Medicine by Alexandros G.Sfakianakis: 12/14/15

Δευτέρα 14 Δεκεμβρίου 2015

Review of Surface Enhanced Raman Scattering Applications in Forensic Science

TOC Graphic

Analytical Chemistry

DOI: 10.1021/acs.analchem.5b04131

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Simultaneous detection of single-nucleotide polymorphisms in a DNA bulge structure using a fluorine-modified bisbenzimide derivative

GA?id=C5AN02389K

Analyst, 2016, Advance Article
DOI: 10.1039/C5AN02389K, Communication

Takashi Sakamoto, Daisaku Hasegawa, Kenzo Fujimoto
Single-nucleotide polymorphisms on the bulged-out nucleobase in dsDNA can be detected simultaneously in a ¹⁹F NMR spectrum using 3,5-bis(trifluoromethyl)benzene-modified bisbenzimide H33258.
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In vitro antiviral activity against rotavirus and astrovirus infection exerted by substances obtained from Achyrocline bogotensis (Kunth) DC. (Compositae)

Background: Achyrocline bogotensis has been traditionally used to treat infections of skin, respiratory, tract urinary and other infections, but not to treat viral gastrointestinal disease. In this study, this Colombian native medicinal plant was investigated by its in vitro anti-rotavirus and anti-astrovirus activity. Methods: Several extracts and fractions phytochemically obtained from A. bogotensis were evaluated initially for their cell toxicity on MA104 and Caco2 cells and then for their anti-rotavirus (RRV) and anti-astrovirus (Yuc8) activity following three strategies: pre-treatment of cells (blocking effect), direct viral activity (virucidal effect) and post-treatment of infected cells (reduction of viral yield post-infection). In addition qualitative chemical studies were developed for the active compounds. Results: Non-toxic concentrations of a fraction obtained exhibited antiviral activity against both viruses characterized by a virucidal effect and by the reduction of the infectious particles produced post-infection. Steroids, sterols, terpenes, phenols, flavonoids and sesquiterpenlactones were identified qualitatively in the active fraction. Conclusions: A. bogotensis contains substances with in vitro antiviral activity against rotavirus and astrovirus. This study confirms their anti-microbial properties and describes by the first time its antiviral activity in vitro.

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Characterization of mannanase from Bacillus circulans NT 6.7 and its application in mannooligosaccharides preparation as prebiotic

This study focused on the characterization of mannanase from Bacillus circulans NT 6.7 for mannooligosaccharides (MOS) production. The enzyme from B. circulans NT 6.7 was produced using defatted copra meal as a carbon source. The mannanase was purified by ultrafiltration and column chromatography of Q-Sepharose. The purified protein (M1) was a dimeric protein with a 40 kDa subunit. The purified M1 exhibited optimum pH and temperature at pH 6.0 and 60 °C, respectively. It was activated by Mn 2+, Mg 2+, and Cu 2+ , and as inhibited by EDTA (45–65 %). The purified enzyme exhibited high specificity to beta-mannan: konjac (glucomannan), locust bean gum (galactomannan), ivory nut (mannan), guar gum (galactomannan) and defatted copra meal (galactomannan). The defatted copra meal could be hydrolyzed by purified M1 into mannooligosaccharides which promoted beneficial bacteria, especially Lactobacillus group, and inhibited pathogenic bacteria; Shigella dysenteria DMST 1511, Staphylococcus aureus TISTR 029, and Salmonella enterica serovar Enteritidis DMST 17368. Therefore, the mannanase from B. circulans NT 6.7 would be a novel source of enzymes for the mannooligosaccharides production as prebiotics.

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Predicting the risk of sudden cardiac death

Abstract

Sudden cardiac death (SCD) is the result of a change of cardiac activity from normal (typically sinus) rhythm to a rhythm that does not pump adequate blood to the brain. The most common rhythms leading to SCD are ventricular tachycardia (VT) or ventricular fibrillation (VF). These result from an accelerated ventricular pacemaker or ventricular reentrant waves. Despite significant efforts to develop accurate predictors for the risk of SCD, current methods for risk stratification still need to be improved. In this review we briefly review current approaches to risk stratification. Then we discuss the mathematical basis for dynamical transitions (called bifurcations) that may lead to VT and VF. One mechanism for transition to VT/VF involves a perturbation by a premature ventricular complex (PVC) during sinus rhythm. We describe the main mechanisms of PVCs (reentry, independent pacemakers, and abnormal depolarizations). An emerging approach to risk stratification for SCD involves the development of individualized dynamical models of a patient based on measured anatomy and physiology. Careful analysis and modeling of dynamics of ventricular arrhythmia on an individual basis will be essential in order to improve risk stratification for SCD and to lay a foundation for personalized (precision) medicine in cardiology.

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TRPM7 kinase activity regulates murine mast cell degranulation

Abstract

Transient receptor potential melastatin 7 (TRPM7) is a divalent ion channel with a C-terminally located α-kinase. Heterozygous mice for a TRPM7 kinase deletion (TRPM7^+/∆K) are hypomagnesemic and hyperallergic. In contrast, mice carrying a single point mutation at amino acid 1648, which silences TRPM7 kinase activity (TRPM7^KR), are not hyperallergic and are resistant to systemic magnesium (Mg²⁺) deprivation. Since allergic reactions are triggered by mast cell-mediated histamine release, we investigated the function of TRPM7 on mast cell degranulation and histamine release using wild type (TRPM7^+/+), TRPM7^+/∆K and TRPM7^KR mice. We found that degranulation and histamine release proceeded independently of TRPM7 channel function. Furthermore, extracellular Mg²⁺ ([Mg2+]_e) assured unperturbed IgE-DNP-dependent exocytosis, independently of TRPM7. However, impairment of TRPM7 kinase function suppressed IgE-DNP-dependent exocytosis, slowed the cellular degranulation rate, and diminished the sensitivity to intracellular calcium [Ca²⁺]_i in G protein-induced exocytosis. In addition, G protein-coupled receptor (GPCR) stimulation revealed strong suppression of histamine release, whereas removal of [Mg2+]_e reverted this phenotype. We conclude that the TRPM7 kinase activity regulates murine mast cell degranulation by changing its sensitivity to [Ca²⁺]_i and affecting granular mobility and/or histamine contents.

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Predicting drug-induced QT prolongation and torsades de Pointes

Abstract

Drugs used to treat cardiovascular disease as well as those used in the treatment of multiple other conditions can occasionally produce exaggerated prolongation of the QT interval on the electrocardiogram and the morphologically distinctive polymorphic ventricular tachycardia ("torsades de pointes"). This syndrome of drug-induced long QT syndrome has moved from an interesting academic exercise to become a key element in the development of any new drug entity. The prevailing view, that has driven both clinical care as well as drug regulation, holds that cardiac repolarisation represents a balance between inward currents (primarily through calcium and sodium channels) and outward currents (primarily through rapid and slowed delayed rectifier potassium channels) and that block of the rapid delayed rectifier (I_Kr) is the primary mechanism whereby drugs prolong individual action potentials, manifest on the surface electrocardiogram as QT interval prolongation. Such marked action potential prolongation in individual cardiac cells, in turn, is accompanied by arrhythmogenic afterdepolarisations thought to trigger torsades de pointes. This review will describe the evidence in support of this construct, and will describe the way in which clinical and whole heart experiments have informed molecular mechanisms and vice-versa. New data that challenge these views and that may, as a result, lead to new clinical care and drug screening paradigms, are discussed.

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Sex differences in vascular endothelial function and health in humans: Impacts of exercise

This brief review presents historical evidence for the purported impacts of male and female sex hormones on the vasculature in humans, including effects on macro- and micro-vascular function and health. Impacts of aging on hormonal changes and artery function are considered in the context of the menopause. Physiological data are presented alongside clinical outcomes from large trials, in an attempt to rationalise disparate findings along the bench-to-bedside continuum. Finally, the theoretical likelihood that exercise and hormone treatment may induce synergistic and/or additive vascular adaptations is developed in the context of recent laboratory studies that have compared male and female responses to training. Differences between men and women in terms of the impact of age and cardiorespiratory fitness on endothelial function are addressed. Ultimately, this review highlights the paucity of high quality and compelling evidence regarding the fundamental impact, in humans, of sex differences on arterial function and the moderating impacts of exercise on arterial function, adaptation and health at different ages in either sex.

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Supersensitive and selective detection of picric acid explosive by fluorescent Ag nanoclusters

GA?id=C5AN02251G

Analyst, 2016, Advance Article
DOI: 10.1039/C5AN02251G, Paper

Jian Rong Zhang, Yuan Yuan Yue, Hong Qun Luo, Nian Bing Li
The combination of polyethyleneimine-capped Ag nanoclusters and picric acid (PA) containing a special structure facilitates the detection of PA, with a low detection limit and a remarkably high selectivity over other nitroaromatics.
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Mass spectrometry of modified RNAs: recent developments

GA?id=C5AN01797A

Analyst, 2016, 141,16-23
DOI: 10.1039/C5AN01797A, Minireview

Collin Wetzel, Patrick A. Limbach
A common feature of ribonucleic acids (RNAs) is that they can undergo a variety of chemical modifications, all of which can be detected by mass spectrometry. Here we highlight recent analytical developments in the field, which now enable quantitative characterization of complex mixtures of modified RNAs.
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Probing DNA-stabilized fluorescent silver nanocluster spectral heterogeneity by time-correlated single photon counting

GA?id=C5AN02011E

Analyst, 2016, 141,123-130
DOI: 10.1039/C5AN02011E, Paper

Open Access

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

Miguel R. Carro Temboury, Valentina Paolucci, Emma N. Hooley, Loredana Latterini, Tom Vosch
Average decay time spectra can be used as a tool to characterize the spectral heterogeneity of DNA templated silver nanoclusters (DNA-AgNCs) and assess the sample preparation procedure.
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Emulsion technologies for multicellular tumour spheroid radiation assays

GA?id=C5AN01382H

Analyst, 2016, 141,100-110
DOI: 10.1039/C5AN01382H, Paper

Open Access

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

Kay S. McMillan, Anthony G. McCluskey, Annette Sorensen, Marie Boyd, Michele Zagnoni
Emulsion technology is used to assess the cytotoxic effect of radiation on spheroids by mimicking tumour growth and tumour quiescence.
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Tualang Honey Protects against BPA-Induced Morphological Abnormalities and Disruption of ERα, ERβ, and C3 mRNA and Protein Expressions in the Uterus of Rats

Bisphenol A (BPA) is an endocrine disrupting chemical (EDC) that can disrupt the normal functions of the reproductive system. The objective of the study is to investigate the potential protective effects of Tualang honey against BPA-induced uterine toxicity in pubertal rats. The rats were administered with BPA by oral gavage over a period of six weeks. Uterine toxicity in BPA-exposed rats was determined by the degree of the morphological abnormalities, increased lipid peroxidation, and dysregulated expression and distribution of ERα, ERβ, and C3 as compared to the control rats. Concurrent treatment of rats with BPA and Tualang honey significantly improved the uterine morphological abnormalities, reduced lipid peroxidation, and normalized ERα, ERβ, and C3 expressions and distribution. There were no abnormal changes observed in rats treated with Tualang honey alone, comparable with the control rats. In conclusion, Tualang honey has potential roles in protecting the uterus from BPA-induced toxicity, possibly accounted for by its phytochemical properties.

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Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche

Publication date: December 2015
Source:Neoplasia, Volume 17, Issue 12
Author(s): Zach S. Templeton, Wen-Rong Lie, Weiqi Wang, Yael Rosenberg-Hasson, Rajiv V. Alluri, John S. Tamaresis, Michael H. Bachmann, Kitty Lee, William J. Maloney, Christopher H. Contag, Bonnie L. King
BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche.

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In Vivo Autofluorescence Imaging of Tumor Heterogeneity in Response to Treatment

Publication date: December 2015
Source:Neoplasia, Volume 17, Issue 12
Author(s): Amy T. Shah, Kirsten E. Diggins, Alex J. Walsh, Jonathan M. Irish, Melissa C. Skala
Subpopulations of cells that escape anti-cancer treatment can cause relapse in cancer patients. Therefore, measurements of cellular-level tumor heterogeneity could enable improved anti-cancer treatment regimens. Cancer exhibits altered cellular metabolism, which affects the autofluorescence of metabolic cofactors NAD(P)H and FAD. The optical redox ratio (fluorescence intensity of NAD(P)H divided by FAD) reflects global cellular metabolism. The fluorescence lifetime (amount of time a fluorophore is in the excited state) is sensitive to microenvironment, particularly protein-binding. High-resolution imaging of the optical redox ratio and fluorescence lifetimes of NAD(P)H and FAD (optical metabolic imaging) enables single-cell analyses. In this study, mice with FaDu tumors were treated with the antibody therapy cetuximab or the chemotherapy cisplatin and imaged in vivo two days after treatment. Results indicate that fluorescence lifetimes of NAD(P)H and FAD are sensitive to early response (two days post-treatment, P<.05), compared with decreases in tumor size (nine days post-treatment, P<.05). Frequency histogram analysis of individual optical metabolic imaging parameters identifies subpopulations of cells, and a new heterogeneity index enables quantitative comparisons of cellular heterogeneity across treatment groups for individual variables. Additionally, a dimensionality reduction technique (viSNE) enables holistic visualization of multivariate optical measures of cellular heterogeneity. These analyses indicate increased heterogeneity in the cetuximab and cisplatin treatment groups compared with the control group. Overall, the combination of optical metabolic imaging and cellular-level analyses provide novel, quantitative insights into tumor heterogeneity.

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Combining Optical Reporter Proteins with Different Half-lives to Detect Temporal Evolution of Hypoxia and Reoxygenation in Tumors

Publication date: December 2015
Source:Neoplasia, Volume 17, Issue 12
Author(s): Pierre Danhier, Balaji Krishnamachary, Santosh Bharti, Samata Kakkad, Yelena Mironchik, Zaver M. Bhujwalla
Here we have developed a hypoxia response element driven imaging strategy that combined the hypoxia-driven expression of two optical reporters with different half-lives to detect temporal changes in hypoxia and hypoxia inducible factor (HIF) activity. For this purpose, human prostate cancer PC3 cells were transfected with the luciferase gene fused with an oxygen-dependent degradation domain (ODD-luc) and a variant of the enhanced green fluorescent protein (EGFP). Both ODD-luciferase and EGFP were under the promotion of a poly-hypoxia-response element sequence (5xHRE). The cells constitutively expressed tdTomato red fluorescent protein. For validating the imaging strategy, cells were incubated under hypoxia (1% O2) for 48hours and then reoxygenated. The luciferase activity of PC3-HRE-EGFP/HRE-ODD-luc/tdtomato cells detected by bioluminescent imaging rapidly decreased after reoxygenation, whereas EGFP levels in these cells remained stable for several hours. After in vitro validation, PC3-HRE-EGFP/HRE-ODD-luc/tdtomato tumors were implanted subcutaneously and orthotopically in nude male mice and imaged in vivo and ex vivo using optical imaging in proof-of-principle studies to demonstrate differences in optical patterns between EGFP expression and bioluminescence. This novel "timer" imaging strategy of combining the short-lived ODD-luciferase and the long-lived EGFP can provide a time frame of HRE activation in PC3 prostate cancer cells and will be useful to understand the temporal changes in hypoxia and HIF activity during cancer progression and following treatments including HIF targeting strategies.

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Polyploidy Formation in Doxorubicin-Treated Cancer Cells Can Favor Escape from Senescence

Publication date: December 2015
Source:Neoplasia, Volume 17, Issue 12
Author(s): Grazyna Mosieniak, Malgorzata A. Sliwinska, Olga Alster, Anna Strzeszewska, Piotr Sunderland, Malgorzata Piechota, Halina Was, Ewa Sikora
Cancer cells can undergo stress-induced premature senescence, which is considered to be a desirable outcome of anticancer treatment. However, the escape from senescence and cancer cell repopulation give rise to some doubts concerning the effectiveness of the senescence-induced anticancer therapy. Similarly, it is postulated that polyploidization of cancer cells is connected with disease relapse. We postulate that cancer cell polyploidization associated with senescence is the culprit of atypical cell divisions leading to cancer cell regrowth. Accordingly, we aimed to dissociate between these two phenomena. We induced senescence in HCT 116 cells by pulse treatment with doxorubicin and observed transiently increased ploidy, abnormal nuclear morphology, and various distributions of some proteins (e.g., p21, Ki-67, SA-β-galactosidase) in the subnuclei. Doxorubicin-treated HCT 116 cells displayed an increased production of reactive oxygen species (ROS) possibly caused by an increased amount of mitochondria, which are characterized by low membrane potential. A decrease in the level of ROS by Trolox partially protected the cells from polyploidization but not from senescence. Interestingly, a decreased level of ROS prevented the cells from escaping senescence. We also show that MCF7 cells senesce, but this is not accompanied by the increase of ploidy upon doxorubicin treatment. Moreover, they were stably growth arrested, thus proving that polyploidy but not senescence per se enables to regain the ability to proliferate. Our preliminary results indicate that the different propensity of the HCT 116 and MCF7 cells to increase ploidy upon cell senescence could be caused by a different level of the mTOR and/or Pim-1 kinases.

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Publication date: December 2015
Source:Neoplasia, Volume 17, Issue 12

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Genetic Variations in Inflammatory Response Genes and Their Association with the Risk of Prostate Cancer

Prostate cancer is a common cancer in men. Genetic variations in inflammatory response genes can potentially influence the risk of prostate cancer. We aimed to examine the association between PPARG Pro12Ala, NFKB1 -94 ins/del, NFKBIA -826C/T, COX-1 (50C>T), and COX-2 (-1195G>A) polymorphisms on prostate cancer risk. The genotypes of the polymorphisms were ascertained in 543 prostate cancer patients and 753 controls through PCR-RFLP and the risk association was evaluated statistically using logistic regression analysis. The NFKB1 -94 polymorphism was shown to decrease prostate cancer risk in both heterozygous and homozygous comparison models (odds ratios of 0.74 (95% CI = 0.58–0.96) () and 0.57 (95% CI = 0.42–0.78) (), resp.). An opposite finding was observed for COX-2 (-1195) polymorphism (odds ratios of 1.58 (95% CI = 1.15–2.18) () for heterozygous comparison model and 2.08 (95% CI = 1.48–2.92) () for homozygous comparison model). No association was observed for other polymorphisms. In conclusion, NFKB1 -94 ins/del and COX-2 (-1195G>A) polymorphisms may be, respectively, associated with decreased and increased prostate cancer risk in the Chinese population.

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Can Healthcare Assistant Training (CHAT) improve the relational care of older people? Study protocol for a pilot cluster randomised controlled trial

Background: People aged 75 years and over account for 1 in 4 of all hospital admissions. There has been increasing recognition of problems in the care of older people, particularly in hospitals. Evidence suggests that older people judge the care they receive in terms of kindness, empathy, compassion, respectful communication and being seen as a person not just a patient. These are aspects of care to which we refer when we use the term 'relational care'. Healthcare assistants deliver an increasing proportion of direct care to older people, yet their training needs are often overlooked.Methods/DesignThis study will determine the acceptability and feasibility of a cluster randomised controlled trial of 'Older People's Shoes' a 2-day training intervention for healthcare assistants caring for older people in hospital. Within this pilot, 2-arm, parallel, cluster randomised controlled trial, healthcare assistants within acute hospital wards are randomised to either the 2-day training intervention or training as usual. Registered nurses deliver 'Older People's Shoes' over 2 days, approximately 1 week apart. It contains three components: experiential learning about ageing, exploration of older people's stories, and customer care. Outcomes will be measured at the level of patient (experience of emotional care and quality of life during their hospital stay), healthcare assistant (empathy and attitudes towards older people), and ward (quality of staff/patient interaction). Semi-structured interviews of a purposive sample of healthcare assistants receiving the intervention, and all trainers delivering the intervention, will be undertaken to gain insights into the experiences of both the intervention and the trial, and its perceived impact on practice.DiscussionFew training interventions for care staff have been rigorously tested using randomised designs. This study will establish the viability of a definitive cluster randomised controlled trial of a new training intervention to improve the relational care proided by healthcare assistants working with older people in hospital.Trial registrationThe study was registered as an International Standard Randomised Controlled Trial (ISRCTN10385799) on 29 December 2014.

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IJMS, Vol. 16, Pages 29797-29814: The Mechanisms of Virulence Regulation by Small Noncoding RNAs in Low GC Gram-Positive Pathogens

The discovery of small noncoding regulatory RNAs (sRNAs) in bacteria has grown tremendously recently, giving new insights into gene regulation. The implementation of computational analysis and RNA sequencing has provided new tools to discover and analyze potential sRNAs. Small regulatory RNAs that act by base-pairing to target mRNAs have been found to be ubiquitous and are the most abundant class of post-transcriptional regulators in bacteria. The majority of sRNA studies has been limited to E. coli and other gram-negative bacteria. However, examples of sRNAs in gram-positive bacteria are still plentiful although the detailed gene regulation mechanisms behind them are not as well understood. Strict virulence control is critical for a pathogen's survival and many sRNAs have been found to be involved in that process. This review outlines the targets and currently known mechanisms of trans-acting sRNAs involved in virulence regulation in various gram-positive pathogens. In addition, their shared characteristics such as CU interaction motifs, the role of Hfq, and involvement in two-component regulators, riboswitches, quorum sensing, or toxin/antitoxin systems are described.

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IJMS, Vol. 16, Pages 29787-29796: Identification of Novel Chromosomal Aberrations Induced by 60Co-γ-Irradiation in Wheat-Dasypyrum villosum Lines

Mutations induced by radiation are widely used for developing new varieties of plants. To better understand the frequency and pattern of irradiation-induced chromosomal rearrangements, we irradiated the dry seeds of Chinese Spring (CS)-Dasypyrum villosum nullisomic-tetrasomic (6A/6D) addition (6V) line (2n = 44), WD14, with 60Co-γ-rays at dosages of 100, 200, and 300 Gy. The M0 and M1 generations were analyzed using Feulgen staining and non-denaturing fluorescence in situ hybridization (ND-FISH) by using oligonucleotide probes. Abnormal mitotic behavior and chromosomes with structural changes were observed in the M0 plants. In all, 39 M1 plants had structurally changed chromosomes, with the B genome showing the highest frequency of aberrations and tendency to recombine with chromosomes of the D genome. In addition, 19 M1 plants showed a variation in chromosome number. The frequency of chromosome loss was considerably higher for 6D than for the alien chromosome 6V, indicating that 6D is less stable after irradiation. Our findings suggested that the newly obtained γ-induced genetic materials might be beneficial for future wheat breeding programs and functional gene analyses.

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Genotyping HLA-B*5801 for Allopurinol-Induced Severe Cutaneous Adverse Reactions: An Accurate and Prompt Method

Abstract

Objectives

A new method of HLA-B*5801 genotyping was compared with sequence-based typing (SBT) to find an accurate and prompt method in genotyping HLA-B*5801.

Methods

Two groups of patients from allopurinol-induced cutaneous adverse reactions (SCARs) and allopurinol-tolerant were both genotyped with PG5801 kit and SBT method. The genotyping results of HLA-B*5801 were compared between the two groups.

Results

The PG5801 detection kit results were 100% (79/79) in agreement with the SBT genotyping results for identifying the HLA-B*5801 (+) patients. No false-positive or false-negative errors were found. The sensitivity, specificity, rate of adherence, positive predictive value (PPV) and negative predictive value (NPV) were 100%.

Conclusion

The potential fast screening method is an ideal tool to rule out the high-risk allopurinol-induced SCARs patients. Clin Trans Sci 2015; Volume #: 1–3

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Highly CO2 sensitive extruded fluorescent plastic indicator film based on HPTS

Analyst, 2015, Accepted Manuscript
DOI: 10.1039/C5AN02239H, Paper

Andrew Mills, Yusufu Dilidaer
Highly-sensitive optical fluorescent extruded plastic films are reported for the detection of gaseous and dissolved CO2. The pH-sensitive fluorescent dye used is 8-Hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS, PTS-) coated on...
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IJERPH, Vol. 12, Pages 15860-15874: Autonomic Nervous System Responses to Viewing Green and Built Settings: Differentiating Between Sympathetic and Parasympathetic Activity

This laboratory study explored buffering and recovery effects of viewing urban green and built spaces on autonomic nervous system activity. Forty-six students viewed photos of green and built spaces immediately following, and preceding acute stress induction. Simultaneously recorded electrocardiogram and impedance cardiogram signal was used to derive respiratory sinus arrhythmia (RSA) and pre-ejection period (PEP), indicators of respectively parasympathetic and sympathetic activity. The findings provide support for greater recovery after viewing green scenes, as marked by a stronger increase in RSA as a marker of parasympathetic activity. There were no indications for greater recovery after viewing green scenes in PEP as a marker of sympathetic activity, and there were also no indications of greater buffering effects of green space in neither RSA nor PEP. Overall, our findings are consistent with a predominant role of the parasympathetic nervous system in restorative effects of viewing green space.

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Catalysts, Vol. 5, Pages 2134-2146: Facile Synthesis of Yolk/Core-Shell Structured TS-1@Mesosilica Composites for Enhanced Hydroxylation of Phenol

In the current work, we developed a facile synthesis of yolk/core-shell structured TS-1@mesosilica composites and studied their catalytic performances in the hydroxylation of phenol with H2O2 as the oxidant. The core-shell TS-1@mesosilica composites were prepared via a uniform coating process, while the yolk-shell TS-1@mesosilica composite was prepared using a resorcinol-formaldehyde resin (RF) middle-layer as the sacrificial template. The obtained materials were characterized by X-ray diffraction (XRD), N2 sorption, Fourier transform infrared spectoscopy (FT-IR) UV-Visible spectroscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The characterization results showed that these samples possessed highly uniform yolk/core-shell structures, high surface area (560–700 m2 g−1) and hierarchical pore structures from oriented mesochannels to zeolite micropores. Importantly, owing to their unique structural properties, these composites exhibited enhanced activity, and also selectivity in the phenol hydroxylation reaction.

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JDB, Vol. 3, Pages 129-157: Cell Fate Decision Making through Oriented Cell Division

The ability to dictate cell fate decisions is critical during animal development. Moreover, faithful execution of this process ensures proper tissue homeostasis throughout adulthood, whereas defects in the molecular machinery involved may contribute to disease. Evolutionarily conserved protein complexes control cell fate decisions across diverse tissues. Maintaining proper daughter cell inheritance patterns of these determinants during mitosis is therefore a fundamental step of the cell fate decision-making process. In this review, we will discuss two key aspects of this fate determinant segregation activity, cortical cell polarity and mitotic spindle orientation, and how they operate together to produce oriented cell divisions that ultimately influence daughter cell fate. Our focus will be directed at the principal underlying molecular mechanisms and the specific cell fate decisions they have been shown to control.

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Fibers, Vol. 3, Pages 539-559: The Influence of CFRP Anchorage on Achieving Sectional Flexural Capacity of Strengthened Concrete Beams

This research program is intended to verify the influence of using distributed external U-wrap CFRP anchorage to shift the failure mode from overall debonding to sectional flexural failure for concrete beams externally bonded with CFRP sheets. Premature cover delamination and FRP debonding are predominant failure modes in FRP flexural strengthening that may be delayed or prevented by using FRP anchorage. The present experimental study aims to comparatively prove that proper anchorage of flexural strengthening is anticipated to yield a classical flexural failure by FRP rupture or concrete crushing. Once the cohesion of concrete and/or the adhesion with the FRP is exhausted, the U-wraps are engaged to provide anchorage to the flexural FRP through shear friction. Accordingly, three identical T beams and three identical rectangular beams were designed and constructed to examine the capacity improvement by preventing premature debonding failure. The first specimen in each series was tested as a control beam. The second specimen in each series was strengthened using five layers of flexural CFRP in order to admit a debonding failure. The third specimen in each series was strengthened with the same five layers of flexural CFRP plus additional transverse CFRP U-wraps. This study proved that it is possible to quantify the higher flexural capacity of CFRP strengthened beams using external anchorage.

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Agriculture, Vol. 5, Pages 1277-1288: Selenium Biochemistry and Bioavailability: Implications for Animal Agriculture

Selenium (Se) is an essential trace mineral required for growth, development, immune function, and metabolism. Selenium exerts its biological effects as an integral component of selenoproteins (SePs). Deficiency or low Se status leads to marked changes in many biochemical pathways and a range of pathologies and disorders which are associated with SeP function. Animals, and presumably humans, are able to efficiently utilize nutritionally adequate levels of Se in both organic and inorganic forms. It is now clear that the bioavailability of Se varies depending on the source and chemical form of the Se supplement. There are a range of products available for dietary Se supplementation, however, organic sources have been shown to be assimilated more efficiently than inorganic compounds and are considered to be less toxic and more appropriate as a feed supplement. Yeast enriched with Selenohomoalanthionine (SeHLan) has recently become commercially available, and initial research suggests that it may be an efficacious source for the production of Se enriched animal products.

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Cancers, Vol. 7, Pages 2459-2465: Acute Myeloid Leukemia with Isolated Trisomy 19 Associated with Diffuse Myelofibrosis and Osteosclerosis

Primary myelofibrosis (PMF), per WHO criteria, is a clonal myeloproliferative neoplasm that usually presents with a proliferation of granulocytic and megakaryocytic lineages with an associated fibrous deposition and extramedullary hematopoiesis. The bone marrow histologic findings of this disorder are typically characterized by the presence of myeloid metaplasia with an associated reactive fibrosis, angiogenesis, and osteosclerosis. However, marked myelofibrosis is not solely confined to PMF and may also be associated with other conditions including but not limited to acute megakaryoblastic leukemias (FAB AML-M7). Here, we describe a rare case of a non-megakaryoblastic acute myeloid leukemia with marked myelofibrosis with osteosclerosis and an isolated trisomy 19. A 19-year-old male presented with severe bone pain of one week duration with a complete blood cell count and peripheral smear showing a mild anemia and occasional circulating blasts. A follow up computed tomography (CT) scan showed diffuse osteosclerosis with no evidence of hepatosplenomegaly or lymphadenopathy. Subsequently, the bone marrow biopsy showed markedly sclerotic bony trabeculae and a hypercellular marrow with marked fibrosis and intervening sheets of immature myeloid cells consistent with myeloblasts with monocytic differentiation. Importantly, these myeloblasts were negative for megakaryocytic markers (CD61 and vWF), erythroid markers (hemoglobin and E-cadherin), and lymphoid markers (CD3, CD19, and TdT). Metaphase cytogenetics showed an isolated triosomy 19 with no JAK2 V617F mutation. The patient was treated with induction chemotherapy followed by allogenic hematopoietic stem cell transplantation which subsequently resulted in a rapid resolution of bone marrow fibrosis, suggesting graft-anti-fibrosis effect. This is a rare case of a non-megakaryoblastic acute myeloid leukemia with myelofibrosis and osteosclerosis with trisomy 19 that may provide insights into the prognosis and therapeutic options of future cases.

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Biomolecules, Vol. 5, Pages 3448-3466: On the Role of Glutamate in Presynaptic Development: Possible Contributions of Presynaptic NMDA Receptors

Proper formation and maturation of synapses during development is a crucial step in building the functional neural circuits that underlie perception and behavior. It is well established that experience modifies circuit development. Therefore, understanding how synapse formation is controlled by synaptic activity is a key question in neuroscience. In this review, we focus on the regulation of excitatory presynaptic terminal development by glutamate, the predominant excitatory neurotransmitter in the brain. We discuss the evidence that NMDA receptor activation mediates these effects of glutamate and present the hypothesis that local activation of presynaptic NMDA receptors (preNMDARs) contributes to glutamate-dependent control of presynaptic development. Abnormal glutamate signaling and aberrant synapse development are both thought to contribute to the pathogenesis of a variety of neurodevelopmental disorders, including autism spectrum disorders, intellectual disability, epilepsy, anxiety, depression, and schizophrenia. Therefore, understanding how glutamate signaling and synapse development are linked is important for understanding the etiology of these diseases.

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Biosensors, Vol. 5, Pages 768-790: High Content Imaging (HCI) on Miniaturized Three-Dimensional (3D) Cell Cultures

High content imaging (HCI) is a multiplexed cell staining assay developed for better understanding of complex biological functions and mechanisms of drug action, and it has become an important tool for toxicity and efficacy screening of drug candidates. Conventional HCI assays have been carried out on two-dimensional (2D) cell monolayer cultures, which in turn limit predictability of drug toxicity/efficacy in vivo; thus, there has been an urgent need to perform HCI assays on three-dimensional (3D) cell cultures. Although 3D cell cultures better mimic in vivo microenvironments of human tissues and provide an in-depth understanding of the morphological and functional features of tissues, they are also limited by having relatively low throughput and thus are not amenable to high-throughput screening (HTS). One attempt of making 3D cell culture amenable for HTS is to utilize miniaturized cell culture platforms. This review aims to highlight miniaturized 3D cell culture platforms compatible with current HCI technology.

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Information, Vol. 6, Pages 866-879: Codeword Structure Analysis for LDPC Convolutional Codes

The codewords of a low-density parity-check (LDPC) convolutional code (LDPC-CC) are characterised into structured and non-structured. The number of the structured codewords is dominated by the size of the polynomial syndrome former matrix H T ( D ) , while the number of the non-structured ones depends on the particular monomials or polynomials in H T ( D ) . By evaluating the relationship of the codewords between the mother code and its super codes, the low weight non-structured codewords in the super codes can be eliminated by appropriately choosing the monomials or polynomials in H T ( D ) , resulting in improved distance spectrum of the mother code.

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JSAN, Vol. 4, Pages 378-409: The Efficacy of Epidemic Algorithms on Detecting Node Replicas in Wireless Sensor Networks

A node replication attack against a wireless sensor network involves surreptitious efforts by an adversary to insert duplicate sensor nodes into the network while avoiding detection. Due to the lack of tamper-resistant hardware and the low cost of sensor nodes, launching replication attacks takes little effort to carry out. Naturally, detecting these replica nodes is a very important task and has been studied extensively. In this paper, we propose a novel distributed, randomized sensor duplicate detection algorithm called Discard to detect node replicas in group-deployed wireless sensor networks. Our protocol is an epidemic, self-organizing duplicate detection scheme, which exhibits emergent properties. Epidemic schemes have found diverse applications in distributed computing: load balancing, topology management, audio and video streaming, computing aggregate functions, failure detection, network and resource monitoring, to name a few. To the best of our knowledge, our algorithm is the first attempt at exploring the potential of this paradigm to detect replicas in a wireless sensor network. Through analysis and simulation, we show that our scheme achieves robust replica detection with substantially lower communication, computational and storage requirements than prior schemes in the literature.

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Metals, Vol. 5, Pages 2383-2392: A Simple Up-Scalable Thermal Treatment Method for Synthesis of ZnO Nanoparticles

A simple thermal treatment method, utilizing only zinc nitrate, polyvinyl pyrrolidone (PVP), and deionized water, was used to synthesize ZnO nanoparticles, and their characteristics were investigated by various techniques. The TGA measurement demonstrated that the bulk of the capping agent PVP can be removed at temperatures higher than 500 °C and is consistent with the absence of the majority of PVP absorption peaks in the FT-IR spectra. The formation of almost pure ZnO nanoparticles was established by the presence of single absorption peak in the FT-IR spectra due to being only Zn–O bonds at calcination temperatures of 500 °C and above. The TEM images revealed that the nanoparticles have a spherical shape and the particle size increased from 60.1–83.1 nm with an increase in calcination temperatures from 500–600 °C. The XRD diffraction patterns indicated that the particles are of a wurzite lattice structure. The optical properties were determined by UV-Vis spectrophotometer, and it was found that the band gap of ZnO nanoparticles decreased from 3.249–3.239 eV with an increase in calcination temperature from 500–600 °C.

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Marine Drugs, Vol. 13, Pages 7390-7402: Algal Toxin Azaspiracid-1 Induces Early Neuronal Differentiation and Alters Peripherin Isoform Stoichiometry

Azaspiracid-1 is an algal toxin that accumulates in edible mussels, and ingestion may result in human illness as manifested by vomiting and diarrhoea. When injected into mice, it causes neurotoxicological symptoms and death. Although it is well known that azaspiracid-1 is toxic to most cells and cell lines, little is known about its biological target(s). A rat PC12 cell line, commonly used as a model for the peripheral nervous system, was used to study the neurotoxicological effects of azaspiracid-1. Azaspiracid-1 induced differentiation-related morphological changes followed by a latter cell death. The differentiated phenotype showed peripherin-labelled neurite-like processes simultaneously as a specific isoform of peripherin was down-regulated. The precise mechanism behind this down-regulation remains uncertain. However, this study provides new insights into the neurological effects of azaspiracid-1 and into the biological significance of specific isoforms of peripherin.

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Membranes, Vol. 5, Pages 915-923: NMR Studies of Solvent-Free Ceramic Composite Polymer Electrolytes—A Brief Review

Polyether-based polymer electrolytes containing ceramic inorganic oxide fillers often exhibit improved mechanical and ion transport properties compared to their filler-free counterparts. The nature of local scale interactions that give rise to these enhanced properties is explored by nuclear magnetic resonance measurements.

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Resources, Vol. 4, Pages 939-957: A Standard Characterization Methodology for Respirable Coal Mine Dust Using SEM-EDX

A key consideration for responsible development of mineral and energy resources is the well-being of workers. Respirable dust in mining environments represents a serious concern for occupational health. In particular, coal miners can be exposed to a variety of dust characteristics depending on their work activities, and some exposures may pose risk for lung diseases like CWP and silicosis. As underscored by common regulatory frameworks, respirable dust exposures are generally characterized on the basis of total mass concentration, and also the silica mass fraction. However, relatively little emphasis has been placed on other dust characteristics that may be important in terms of identifying health risks. Comprehensive particle-level analysis to estimate chemistry, size, and shape distributions of particles is possible. This paper describes a standard methodology for characterization of respirable coal mine dust using scanning electron microscopy (SEM) with energy dispersive X-ray (EDX). Preliminary verification of the method is shown based several dust samples collected from an underground mine in Central Appalachia.

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IJMS, Vol. 16, Pages 29797-29814: The Mechanisms of Virulence Regulation by Small Noncoding RNAs in Low GC Gram-Positive Pathogens

Glucose transporters 1, 3, 6, and 10 are expressed in gastric cancer and glucose transporter 3 is associated with UICC stage and survival

Gastric Cancer

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Enteral feeding therapy for maintaining remission in Crohn's disease: A systematic review

Journal of Parenteral and Enteral Nutrition

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Modeling the ecologic niche of plague in sylvan and domestic animal hosts to delineate sources of human exposure in the western United States

Plague has been established in the western United States (US) since 1900 following the West Coast introduction of commensal rodents infected with Yersinia pestis via early industrial shipping. Over the last century, plague ecology has transitioned through cycles of widespread human transmission, urban domestic transmission among commensal rodents, and ultimately settled into the predominantly sylvan foci that remain today where it is maintained alternatively by enzootic and epizootic transmission. While zoonotic transmission to humans is much less common in modern times, significant plague risk remains in parts of the western US. Moreover, risk to some threatened species that are part of the epizootic cycle can be quite substantive. This investigation attempted to predict the risk of plague across the western US by modeling the ecologic niche of plague in sylvan and domestic animals identified between 2000 and 2015. A Maxent machine learning algorithm was used to predict this niche based on climate, altitude, land cover, and the presence of an important enzootic species, Peromyscus maniculatus. This model demonstrated good predictive ability (AUC = 86%) and identified areas of high risk in central Colorado, north-central New Mexico, and southwestern and northeastern California. The presence of P. maniculatus, altitude, precipitation during the driest and wettest quarters, and distance to artificial surfaces, all contributed substantively to maximizing the gain function. These findings add to the known landscape epidemiology and infection ecology of plague in the western US and may suggest locations of particular risk to be targeted for wild and domestic animal intervention.

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Evaluating pharmacological models of high and low anxiety in sheep

New tests of animal affect and welfare require validation in subjects experiencing putatively different states. Pharmacological manipulations of affective state are advantageous because they can be administered in a standardised fashion, and the duration of their action can be established and tailored to suit the length of a particular test. To this end, the current study aimed to evaluate a pharmacological model of high and low anxiety in an important agricultural and laboratory species, the sheep. Thirty-five 8-month-old female sheep received either an intramuscular injection of the putatively anxiogenic drug 1-(m-chlorophenyl)piperazine (mCPP; 1 mg/kg; n = 12), an intravenous injection of the putatively anxiolytic drug diazepam (0.1 mg/kg; n = 12), or acted as a control (saline intramuscular injection n = 11). Thirty minutes after the treatments, sheep were individually exposed to a variety of tests assessing their general movement, performance in a 'runway task' (moving down a raceway for a food reward), response to startle, and behaviour in isolation. A test to assess feeding motivation was performed 2 days later following administration of the drugs to the same animals in the same manner. The mCPP sheep had poorer performance in the two runway tasks (6.8 and 7.7 × slower respectively than control group; p

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Emerging semantics to link phenotype and environment

Understanding the interplay between environmental conditions and phenotypes is a fundamental goal of biology. Unfortunately, data that include observations on phenotype and environment are highly heterogeneous and thus difficult to find and integrate. One approach that is likely to improve the status quo involves the use of ontologies to standardize and link data about phenotypes and environments. Specifying and linking data through ontologies will allow researchers to increase the scope and flexibility of large-scale analyses aided by modern computing methods. Investments in this area would advance diverse fields such as ecology, phylogenetics, and conservation biology. While several biological ontologies are well-developed, using them to link phenotypes and environments is rare because of gaps in ontological coverage and limits to interoperability among ontologies and disciplines. In this manuscript, we present (1) use cases from diverse disciplines to illustrate questions that could be answered more efficiently using a robust linkage between phenotypes and environments, (2) two proof-of-concept analyses that show the value of linking phenotypes to environments in fishes and amphibians, and (3) two proposed example data models for linking phenotypes and environments using the extensible observation ontology (OBOE) and the Biological Collections Ontology (BCO); these provide a starting point for the development of a data model linking phenotypes and environments.

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Analysis of synonymous codon usage patterns in sixty-four different bivalve species

Synonymous codon usage bias (CUB) is a defined as the non-random usage of codons encoding the same amino acid across different genomes. This phenomenon is common to all organisms and the real weight of the many factors involved in its shaping still remains to be fully determined. So far, relatively little attention has been put in the analysis of CUB in bivalve mollusks due to the limited genomic data available. Taking advantage of the massive sequence data generated from next generation sequencing projects, we explored codon preferences in 64 different species pertaining to the six major evolutionary lineages in Bivalvia. We detected remarkable differences across species, which are only partially dependent on phylogeny. While the intensity of CUB is mild in most organisms, a heterogeneous group of species (including Arcida and Mytilida, among the others) display higher bias and a strong preference for AT-ending codons. We show that the relative strength and direction of mutational bias, selection for translational efficiency and for translational accuracy contribute to the establishment of synonymous codon usage in bivalves. Although many aspects underlying bivalve CUB still remain obscure, we provide for the first time an overview of this phenomenon in this large, commercially and environmentally important, class of marine invertebrates.

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Specific labeling: An effective tool to explore the RNA world

Our knowledge about the functional diversity and importance of RNA in biology has grown enormously over the past three decades and has driven efforts to develop better tools to characterize RNAs. Amongst these tools are methods for preparing specifically labeled or chemically modified RNAs, which are essential for basic research, biomedical, and clinical applications. Understanding the potential and limits of these different RNA synthesis and labeling strategies is important in deciding how to approach the preparation of a particular RNA molecule. Here, we review these various labeling methods and future directions of the field.

RNA labeling or modification has become critical in RNA structure-function studies, basic biomedical research, and in development of RNA-based sensors, diagnostics and therapeutics. We discuss the technologies used for RNA labeling, and focus on the potential and limits of these methods.

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Sensors, Vol. 15, Pages 31464-31481: Probabilistic Multi-Sensor Fusion Based Indoor Positioning System on a Mobile Device

Nowadays, smart mobile devices include more and more sensors on board, such as motion sensors (accelerometer, gyroscope, magnetometer), wireless signal strength indicators (WiFi, Bluetooth, Zigbee), and visual sensors (LiDAR, camera). People have developed various indoor positioning techniques based on these sensors. In this paper, the probabilistic fusion of multiple sensors is investigated in a hidden Markov model (HMM) framework for mobile-device user-positioning. We propose a graph structure to store the model constructed by multiple sensors during the offline training phase, and a multimodal particle filter to seamlessly fuse the information during the online tracking phase. Based on our algorithm, we develop an indoor positioning system on the iOS platform. The experiments carried out in a typical indoor environment have shown promising results for our proposed algorithm and system design.

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Sensors, Vol. 15, Pages 31482-31524: Robust 3D Position Estimation in Wide and Unconstrained Indoor Environments

In this paper, a system for 3D position estimation in wide, unconstrained indoor environments is presented that employs infrared optical outside-in tracking of rigid-body targets with a stereo camera rig. To overcome limitations of state-of-the-art optical tracking systems, a pipeline for robust target identification and 3D point reconstruction has been investigated that enables camera calibration and tracking in environments with poor illumination, static and moving ambient light sources, occlusions and harsh conditions, such as fog. For evaluation, the system has been successfully applied in three different wide and unconstrained indoor environments, (1) user tracking for virtual and augmented reality applications, (2) handheld target tracking for tunneling and (3) machine guidance for mining. The results of each use case are discussed to embed the presented approach into a larger technological and application context. The experimental results demonstrate the system's capabilities to track targets up to 100 m. Comparing the proposed approach to prior art in optical tracking in terms of range coverage and accuracy, it significantly extends the available tracking range, while only requiring two cameras and providing a relative 3D point accuracy with sub-centimeter deviation up to 30 m and low-centimeter deviation up to 100 m.

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Sensors, Vol. 15, Pages 31442-31452: Multiple-Parameter Estimation Method Based on Spatio-Temporal 2-D Processing for Bistatic MIMO Radar

A novel spatio-temporal 2-dimensional (2-D) processing method that can jointly estimate the transmitting-receiving azimuth and Doppler frequency for bistatic multiple-input multiple-output (MIMO) radar in the presence of spatial colored noise and an unknown number of targets is proposed. In the temporal domain, the cross-correlation of the matched filters' outputs for different time-delay sampling is used to eliminate the spatial colored noise. In the spatial domain, the proposed method uses a diagonal loading method and subspace theory to estimate the direction of departure (DOD) and direction of arrival (DOA), and the Doppler frequency can then be accurately estimated through the estimation of the DOD and DOA. By skipping target number estimation and the eigenvalue decomposition (EVD) of the data covariance matrix estimation and only requiring a one-dimensional search, the proposed method achieves low computational complexity. Furthermore, the proposed method is suitable for bistatic MIMO radar with an arbitrary transmitted and received geometrical configuration. The correction and efficiency of the proposed method are verified by computer simulation results.

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Viruses, Vol. 7, Pages 6604-6612: Recent Advances in Therapeutic Approaches for Adult T-cell Leukemia/Lymphoma

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma caused by human T-cell leukemia/lymphoma virus type 1 (HTLV-1). ATLL occurs in approximately 3%–5% of HTLV-1 carriers during their lifetime and follows a heterogeneous clinical course. The Shimoyama classification has been frequently used for treatment decisions in ATLL patients, and antiviral therapy has been reportedly promising, particularly in patients with indolent type ATLL; however, the prognosis continues to be dismal for patients with aggressive-type ATLL. Recent efforts to improve treatment outcomes have been focused on the development of prognostic stratification and improved dosage, timing, and combination of therapeutic modalities, such as antiviral therapy, chemotherapy, allogeneic hematopoietic stem cell transplantation, and molecular targeted therapy.

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Uncommon Trimethoxylated Flavonol Obtained from Rubus rosaefolius Leaves and Its Antiproliferative Activity

This study shows the evaluation the antiproliferative effect of the extract, fractions, and uncommon compounds isolated from R. rosaefolius leaves. The compounds were identified by conventional spectroscopic methods such as NMR-H1 and C13 and identified as 5,7-dihydroxy-6,8,4′-trimethoxyflavonol (1), 5-hydroxy-3,6,7,8,4′-pentamethoxyflavone (2), and tormentic acid (3). Both hexane and dichloromethane fractions showed selectivity for multidrug-resistant ovary cancer cell line (NCI-ADR/RES) with total growth inhibition values of 11.1 and 12.6 μg/ml, respectively. Compound 1 also showed selective activity against the same cell line (18.8 μg/ml); however, it was especially effective against glioma cells (2.8 μg/ml), suggesting that this compound may be involved with the in vitro antiproliferative action.

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The Preventive Effect on Ethanol-Induced Gastric Lesions of the Medicinal Plant Plumeria rubra: Involvement of the Latex Proteins in the NO/cGMP/KATP Signaling Pathway

Plumeria rubra (Apocynaceae) is frequently used in folk medicine for the treatment of gastrointestinal disorders, hepatitis, and tracheitis, among other infirmities. The aim of this study was to investigate the gastroprotective potential of a protein fraction isolated from the latex of Plumeria rubra (PrLP) against ethanol-induced gastric lesions and describe the underlying mechanisms. In a dose-dependent manner, the pretreatment with PrLP prevented ethanol-induced gastric lesions in mice after single intravenous administration. The gastroprotective mechanism of PrLP was associated with the involvement of prostaglandins and balance of oxidant/antioxidant factors. Secondarily, the NO/cGMP/ pathway and activation of capsaicin-sensitive primary afferents were also demonstrated as part of the mechanism. This study shows that proteins extracted from the latex of P. rubra prevent gastric lesions induced in experimental animals. Also, the results support the use of the plant in folk medicine.

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Effectiveness of legislative changes obligating notification of prolonged sickness absence and assessment of remaining work ability on return to work and work participation: a natural experiment in Finland

Objectives

Policies have been introduced to reduce sickness absence, but their effectiveness is largely unknown. In a natural experiment, we examined effects of legislative changes on return to work and work participation.

Methods

The source population consisted of up to 72 164 Finnish public sector employees with a permanent job contract in 2008–2011 (before) and in 2013–2014 (after). We used employees with a continuous sickness absence of at least 30 calendar-days (n=5708–6393), 60 compensated days (n=1481–1655) and 90 compensated days (n=766–932). We examined sustainable return to work (a minimum of 28 consecutive working days) with survival analysis as well as monthly work participation after a sickness absence, and annual gain in work participation after the intervention, using trajectory analyses.

Results

Sustainable return to work after 60 days of sickness absence occurred earlier after the legislative changes (p value 0.017), although the effect reduced towards the end of the follow-up. There were no differences in return to work after a 30 or 90 days of sickness absence. The largest annual gain, postintervention versus preintervention, in monthly work participation was observed among employees with 60 days of sickness absence and was 230.9 person-years/10 000 employees. The corresponding annual gains among those with 30 days and 90 days of sickness absence were 51.8 and 39.6, respectively.

Conclusions

Our findings suggest that the legislative changes, obligating early notification of prolonged sickness absences as well as assessment of remaining work ability and possibilities to continue working, may enhance sustainable return to work in the short term. Other measures will be needed to enhance work participation, especially in the long term.

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Extended follow-up of lung cancer and non-malignant respiratory disease mortality among California diatomaceous earth workers

The updated analysis on mortality among 2343 California diatomaceous earth (DE) workers provides useful information and occupational crystalline silica on health.1

Previously followed through 1992,2 the mortality of this cohort was updated through 2011. Results most relevant to crystalline silica exposure are summarised below (table 1).

The deficit of lung cancer mortality in the update period appears to 'balance out' the earlier excess. For chronic obstructive pulmonary disease and pneumoconiosis, earlier increased mortality was not sustained.

Cox proportional hazards analyses controlling for other factors, but not smoking (unknown for half the workers), demonstrated that the earlier excesses of lung cancer and respiratory diseases were concentrated in the highest exposure groups. For lung cancer, only the highest exposure category (>5.6 mg/m³-years), lagged by 15 years, produced a statistically significant hazards ratio (HR) (2.2, 95% CI 1.07 to 4.5). HRs for non-malignant respiratory disease (NMRD) mortality, regardless...

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Pesticide use and risk of end-stage renal disease among licensed pesticide applicators in the Agricultural Health Study

Objectives

Experimental studies suggest a relationship between pesticide exposure and renal impairment, but epidemiological evidence is limited. We evaluated the association between exposure to 39 specific pesticides and end-stage renal disease (ESRD) incidence in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina.

Methods

Via linkage to the US Renal Data System, we identified 320 ESRD cases diagnosed between enrolment (1993–1997) and December 2011 among 55 580 male licensed pesticide applicators. Participants provided information on use of pesticides via self-administered questionnaires. Lifetime pesticide use was defined as the product of duration and frequency of use and then modified by an intensity factor to account for differences in pesticide application practices. Cox proportional hazards models, adjusted for age and state, were used to estimate associations between ESRD and: (1) ordinal categories of intensity-weighted lifetime use of 39 pesticides, (2) poisoning and high-level pesticide exposures and (3) pesticide exposure resulting in a medical visit or hospitalisation.

Results

Positive exposure-response trends were observed for the herbicides alachlor, atrazine, metolachlor, paraquat, and pendimethalin, and the insecticide permethrin. More than one medical visit due to pesticide use (HR=2.13; 95% CI 1.17 to 3.89) and hospitalisation due to pesticide use (HR=3.05; 95% CI 1.67 to 5.58) were significantly associated with ESRD.

Conclusions

Our findings support an association between ESRD and chronic exposure to specific pesticides, and suggest pesticide exposures resulting in medical visits may increase the risk of ESRD.

Clinical trial registration

Clinicaltrials.gov NCT00352924.

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Ambient air pollution and risk of tuberculosis: a cohort study

Objectives

Several respirable hazards, including smoking and indoor air pollution from biomass, were suggested to increase the risk of tuberculosis. Few studies have been conducted on ambient air pollution and tuberculosis. We investigated the association between exposure to ambient air pollution and incidence of active tuberculosis.

Methods

We conducted a cohort study using 106 678 participants of a community-based screening service in Taiwan, 2005–2012. We estimated individual exposure to air pollution using data from the nearest air quality monitoring station and the road intensity within a 500 m buffer zone. The incidence of tuberculosis was ascertained from the national tuberculosis registry.

Results

After a median follow-up of 6.7 years, 418 cases of tuberculosis occurred. Exposure to fine particulate matter (PM_2.5) was associated with increased risk of active tuberculosis (adjusted HR: 1.39/10 μg/m³ (95% CI 0.95 to 2.03)). In addition, traffic-related air pollution including nitrogen dioxide (adjusted HR: 1.33/10 ppb; 95% CI 1.04 to 1.70), nitrogen oxides (adjusted HR: 1.21/10 ppb; 95% CI 1.04 to 1.41) and carbon monoxide (adjusted HR: 1.89/ppm; 95% CI 0.78 to 4.58) was associated with tuberculosis risk. There was a non-significant trend between the length of major roads in the neighbourhood and culture-confirmed tuberculosis (adjusted HR: 1.04/km; 95% CI 0.995 to 1.09).

Conclusions

Our study revealed a possible link between ambient air pollution and risk of active tuberculosis. Since people from developing countries continue to be exposed to high levels of ambient air pollution and to experience high rates of tuberculosis, the impact of worsening air pollution on global tuberculosis control warrants further investigation.

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World Trade Center-related physical and mental health burden among New York City Fire Department emergency medical service workers

Objectives

To describe the health burden among Fire Department of the City of New York (FDNY) emergency medical service (EMS) workers and examine its association with work at the World Trade Center (WTC) disaster site.

Methods

In this observational cohort study, we used FDNY physician diagnoses to estimate the cumulative incidence of physical health conditions including rhinosinusitis, gastroesophageal reflux disease (GERD), obstructive airways disease (OAD) and cancer among EMS workers and demographically similar firefighters who were active on 11 September 2001 (9/11). Validated screening instruments were used to estimate the prevalence of probable post-traumatic stress disorder (PTSD), probable depression and probable harmful alcohol use. We also analysed the association between health conditions and WTC-exposure.

Results

Among 2281 EMS workers, the 12-year post-9/11 cumulative incidence (11 September 2001 to 31 December 2013) of rhinosinusitis was 10.6%; GERD 12.1%; OAD 11.8%; cancer 3.1%. The prevalence of probable PTSD up to 12 years after exposure was 7%; probable depression 16.7%; and probable harmful alcohol use 3%. Compared with unexposed, EMS workers who arrived earliest at the site had higher adjusted relative risks (aRR) for most conditions, including rhinosinusitis (aRR=3.7; 95% CI 2.2 to 6.0); GERD (aRR=3.8; 95% CI 2.4 to 6.1); OAD (aRR=2.4: 95% CI 1.7 to 3.6); probable PTSD (aRR=7.0; 95% CI 3.6 to 13.5); and, probable depression (aRR=2.3; 95% CI 1.6 to 3.1).

Conclusions

In this 12-year study, we documented a high burden of health conditions associated with WTC-exposure among FDNY EMS workers. These findings underscore the importance of continued monitoring and treatment of this workforce.

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Agricultural pesticide exposure and chronic kidney disease: new findings and more questions

The vital importance of agriculture is well-recognised, as is the usefulness of pesticides in increasing agricultural yields and reducing spoilage rates. The usefulness of pesticides in mitigating disease-carrying pests (eg, mosquitos) is also well known. However, there are also risks associated with pesticide use. In addition to causing acute poisoning,1 they are also associated with increased cancer risks,2 among other diseases. A paper by Lebov and colleagues3 provides evidence for another potential risk associated with pesticides, that is, end-stage renal disease (ESRD). To our knowledge, this is the first report using the United States Renal Data System (USRDS) to assess the association between pesticide exposure and ESRD.

Currently, there is little literature available on the nephrotoxic effects of pesticides. The little research that does exist comes from animal studies and case reports of pesticide-poisoned individuals. Fortunately, our understanding of the role of occupational...

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Incidence and mortality risks for circulatory diseases in US radiologic technologists who worked with fluoroscopically guided interventional procedures, 1994-2008

Objectives

Although fluoroscopically guided interventional procedures (FGIP) have provided major advances in the treatment of various common diseases, radiation exposures associated with these procedures may cause adverse health effects in workers. We assess risk of circulatory disease incidence and mortality in medical radiation workers performing FGIP.

Methods

A US nationwide prospective cohort study of 90 957 radiologic technologists who completed a cohort survey during 1994–1998 was followed until completion of a subsequent survey during 2003–2005 for circulatory disease incidence, or until 31 December 2008 for mortality. Incidence analyses were restricted to the 63 482 technologists who completed both the second survey (1994–1998) and the third survey (2003–2005). Cox proportional hazards models were used to assess adjusted HR and 95% CIs for mortality from all causes, all circulatory diseases, all heart diseases, ischaemic heart disease, stroke, acute myocardial infarction and hypertension in participants who reported ever performing FGIP compared to technologists who never performed FGIP procedures. Adjusted HRs were calculated for self-reported hypertension, stroke and myocardial infarction.

Results

We observed a 34% increase in stroke incidence (HR=1.34, 95% CI 1.10 to 1.64) in technologists who performed FGIP compared to those who never performed these procedures. Mortality from stroke was also modestly elevated, although not statistically significant (HR=1.22, 95% CI 0.85 to 1.73). We observed no statistically significant excess risks of incidence or mortality from any other outcome evaluated.

Conclusions

Our finding of elevated risk of stroke in workers performing FGIP needs to be confirmed in studies with individual radiation dose data, but nonetheless underlines the need to keep radiation exposure as low as reasonably achievable without compromising key diagnostic information.

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Heavy lifting at work and risk of retinal detachment: a population-based register study in Denmark

Objectives

To investigate the relationship between rhegmatogenous retinal detachment (RRD) and frequent heavy lifting in a Danish working population through national register data.

Methods

A dynamic cohort of all men aged 20–59 years in Denmark was followed through the Danish Occupational Hospitalisation Register from 1995 to 2010 for diagnosed RRD. Occupational categories were classified according to their potential for heavy lifting in 4 main groups: heavy lifters, manual workers unlikely to be heavy lifters, other manual workers and non-manual workers unlikely to be heavy lifters. The age-standardised rate of diagnosed RRD for heavy lifting occupations was compared with that experienced by the other 3 occupational categories. Rate ratios (RRs) and 95% CIs were estimated through a Poisson regression model adjusted for calendar period and age group.

Results

The highest age-standardised rate of diagnosed RRD was recorded among non-manual workers performing occupational activities unlikely to be associated with heavy lifting (18.0 cases per 100 000 person-years). The RR for workers in jobs expected to entail a high frequency of heavy lifting compared with manual workers whose occupation was unlikely to be associated with heavy lifting was 0.91 (95% CI 0.73 to 1.14), while in comparison with other manual workers, it was 0.93 (95% CI 0.78 to 1.11). The RR compared with non-manual workers in occupations unlikely to entail heavy lifting was 0.51 (95% CI 0.43 to 0.60).

Conclusions

These findings do not support an association of occupational heavy lifting with diagnosed RRD. The epidemiological evidence for this association is still inconclusive. Future studies should use a more specific measure of exposure to resolve the outstanding uncertainties.

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The joint effect of asbestos exposure, tobacco smoking and alcohol drinking on laryngeal cancer risk: evidence from the French population-based case-control study, ICARE

Objective

The objective of the study was to investigate the joint effect of occupational exposure to asbestos, and tobacco and alcohol consumption, on the risk of laryngeal cancer among men.

Methods

We used data from a large population-based case–control study conducted in France. We estimated two-way and three-way interactions between asbestos exposure (never vs ever exposed), tobacco consumption (<20 vs ≥20 pack-years) and alcohol consumption (<5 vs ≥5 drinks per day). The interaction on an additive scale was assessed by estimating the relative excess risk due to interaction (RERI) and the attributable proportion due to interaction, and the interaction on a multiplicative scale was assessed by estimating the multiplicative interaction parameter (). Multiplicative interactions were also assessed using fractional polynomials for alcohol drinking, tobacco smoking and asbestos exposure.

Results

When compared with light-to-moderate smokers and drinkers never exposed to asbestos, the increase in laryngeal cancer risk was smallest among light-to-moderate drinkers and smokers exposed to asbestos (OR=2.23 (1.08 to 4.60)), and highest among heavy smokers and drinkers ever exposed to asbestos (OR=69.39 (35.54 to 135.5)). We found an additive joint effect between asbestos exposure and alcohol consumption (RERI=4.75 (–4.29 to 11.12)), whereas we observed a more than additive joint effect between asbestos exposure and tobacco consumption (RERI=8.50 (0.71 to 23.81)), as well as between asbestos exposure, and tobacco and alcohol consumption (RERI=26.57 (11.52 to 67.88)). However, our results did not suggest any interaction on a multiplicative scale.

Conclusions

Our results suggest that asbestos exposure, in combination with tobacco and alcohol exposure, accounted for a substantial number of laryngeal cancer cases. Our findings therefore highlight the need for prevention in activities, such as construction work, where exposure to asbestos-containing materials remains.

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Effectiveness of workplace interventions in the prevention of upper extremity musculoskeletal disorders and symptoms: an update of the evidence

The burden of disabling musculoskeletal pain and injuries (musculoskeletal disorders, MSDs) arising from work-related causes in many workplaces remains substantial. There is little consensus on the most appropriate interventions for MSDs. Our objective was to update a systematic review of workplace-based interventions for preventing and managing upper extremity MSD (UEMSD). We followed a systematic review process developed by the Institute for Work & Health and an adapted best evidence synthesis. 6 electronic databases were searched (January 2008 until April 2013 inclusive) yielding 9909 non-duplicate references. 26 high-quality and medium-quality studies relevant to our research question were combined with 35 from the original review to synthesise the evidence on 30 different intervention categories. There was strong evidence for one intervention category, resistance training, leading to the recommendation: Implementing a workplace-based resistance training exercise programme can help prevent and manage UEMSD and symptoms. The synthesis also revealed moderate evidence for stretching programmes, mouse use feedback and forearm supports in preventing UEMSD or symptoms. There was also moderate evidence for no benefit for EMG biofeedback, job stress management training, and office workstation adjustment for UEMSD and symptoms. Messages are proposed for both these and other intervention categories.

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Exposure to loud noise, bilateral high-frequency hearing loss and coronary heart disease

Objectives

Bilateral high-frequency hearing loss is an indicator for chronic exposure to loud noise. This study aimed to examine the association between bilateral high-frequency hearing loss and the presence of coronary heart disease (CHD).

Methods

This study included 5223 participants aged 20–69 years who participated in the audiometry examination of the National Health and Nutrition Examination Survey 1999–2004. Bilateral high-frequency hearing loss was defined as the average high-frequency (3, 4 and 6 kHz) hearing threshold ≥25 dB in both ears. CHD was defined as self-reported diagnoses by doctors or other health professionals.

Results

Compared with those with normal high-frequency hearing, participants with bilateral high-frequency hearing loss were more likely to have CHD (OR 1.91; 95% CI 1.28 to 2.85) after adjustment for various covariates. This association was particularly strong for currently employed workers who were exposed to loud occupational noise (OR 4.23; 95% CI 1.32 to 13.55). For this subgroup, there was no significant association of CHD with unilateral high-frequency hearing loss, and unilateral or bilateral low-frequency hearing loss. Furthermore, there was no significant association of CHD with any types of hearing loss for participants who were not exposed to loud noise. Stratified analyses for participants exposed to loud noise showed that the observed association was particularly strong for those who were less than 50 years of age, less educated and current smokers.

Conclusions

On the basis of an objective indicator for personal chronic exposure to loud noise, this study confirmed that exposure to loud occupational noise is associated with the presence of CHD.

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Author response: Extended follow-up of lung cancer and non-malignant respiratory disease mortality among California diatomaceous earth workers

We will address the comments offered by Mundt and Boffetta1 on our manuscript describing findings from an update of mortality among California diatomaceous earth (DE) workers.2 We regard the sustained dose–response trends for lung cancer and non-malignant respiratory disease (NMRD) (tables 3 and 4, respectively) as the most important findings regarding risks associated with crystalline silica. The reduction of overall mortality for these outcomes, indicated by reduced standardised mortality ratios (SMR), is more likely to be a 'depletion of susceptibles' phenomenon than a 'balancing out' effect. We agree that a healthy worker effect is an unlikely explanation for the reduced lung cancer SMR. However, support for the assertion that the healthy worker effect generally declines with employment duration could only be obtained in occupational cohorts where exposure effects and survival effects are sufficiently taken into account, a condition rarely achieved in published studies.

Our application...

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Δευτέρα 14 Δεκεμβρίου 2015

Abstract

Abstract

Abstract

Abstract

Objectives

Methods

Results

Conclusion