IgG4-related orbital disease masquerading as thyroid eye disease, vice versa, or both?

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IgG4-related orbital disease masquerading as thyroid eye disease, vice versa, or both?

Orbit. 2017 Oct 20;:1-4

Authors: Khandji J, Campbell AA, Callahan AB, Sirinek P, Kazim M

Abstract
A 40 year-old male presented after one year of unilateral, progressive, steroid-responsive, orbital inflammatory disease causing proptosis, extraocular muscle (EOM) restriction, and compressive optic neuropathy. The development of anti-thyroidal antibodies prompted the diagnosis of thyroid eye disease (TED); however, the prolonged active phase, remarkable reversibility of ophthalmic features with high-dose corticosteroids, unilaterally of disease, uncharacteristic EOM involvement (including both obliques), and the absence of autoimmune thyroid disease provoked consideration of alternative diagnoses. Inferior oblique biopsy stained positive for IgG4 with histologic features atypical of TED. The patient received rituximab for presumed IgG4-related orbital disease (IgG4-ROD) with subsequent reversal of compressive optic neuropathy, near complete resolution of EOM restriction, and improved proptosis, the latter two of which are not routinely anticipated in advanced TED. The possible role for B-cell depletion in both TED and IgG4-ROD suggests a degree of overlap in the underlying immune-related pathophysiology that is yet to be defined.

PMID: 29053038 [PubMed - as supplied by publisher]

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Longitudinal study of Staphylococcus aureus colonization and infection in a cohort of swine veterinarians in the United States.

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Longitudinal study of Staphylococcus aureus colonization and infection in a cohort of swine veterinarians in the United States.

BMC Infect Dis. 2017 Oct 19;17(1):690

Authors: Sun J, Yang M, Sreevatsan S, Bender JB, Singer RS, Knutson TP, Marthaler DG, Davies PR

Abstract
BACKGROUND: People working with pigs are at elevated risk of harboring methicillin resistant S. aureus (MRSA) in their nose, which is attributable to occupational exposure to animals harboring livestock adapted S. aureus. To obtain insight into the biological nature of occupationally related nasal culture positivity, we conducted a longitudinal study of 66 swine veterinarians in the USA.
METHODS: The study cohort resided in 15 US states and worked predominantly with swine. Monthly for 18 months, participants self-collected nasal swabs and completed a survey to report recent exposure to pigs and other animals; the occurrence of work related injuries; and any relevant health events such as skin and soft tissue infections or confirmed staphylococcal infections. Nasal swabs were cultured using selective methods to determine the presence of MRSA and methicillin susceptible S. aureus (MSSA), and isolates were characterized by spa typing and MLST.
RESULTS: Prevalences of S. aureus (64%, monthly range from 58 to 82%) and MRSA (9.5%; monthly range from 6 to15%) were higher than reported for the US population (30% and 1.5% respectively). Predominant spa types were t034 (ST398, 37%), t002 (ST5, 17%) and t337 (ST9/ST398 13%), a distribution similar to that found in a concurrent study in pigs in the USA. Veterinarians were classified into three groups: Persistent carriers (PC, 52%), Intermittent carriers (IC, 47%) and Non-carriers (NC, 1%). Persistent carriage of a single spa type was observed in 14 (21%) of participants, and paired (first and last) isolates from PC subjects had minor genetic differences. Swabs from PC veterinarians carried higher numbers of S. aureus. Among IC veterinarians, culture positivity was significantly associated with recent contact with pigs.
CONCLUSIONS: Exposure to pigs did not lead to prolonged colonization in most subjects, and the higher numbers of S. aureus in PC subjects suggests that unknown host factors may determine the likelihood of prolonged colonization by S. aureus of livestock origin. Exposure to S. aureus and persistent colonization of swine veterinarians was common but rarely associated with S. aureus disease.

PMID: 29052523 [PubMed - in process]

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What is the role of Staphylococcus aureus and herpes virus infections in the pathogenesis of atopic dermatitis?

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What is the role of Staphylococcus aureus and herpes virus infections in the pathogenesis of atopic dermatitis?

Future Microbiol. 2017 Oct 20;:

Authors: Saintive S, Abad E, C Ferreira D, Stambovsky M, Cavalcante FS, Gonçalves LS, Vidal F, Dos Santos KR

Abstract
Atopic dermatitis (AD) is a chronic, relapsing disease. Genetic, environmental and immunological factors are involved in its pathophysiology. Individuals with AD have an increased predisposition to colonization and/or infection of the skin by various pathogens, especially Staphylococcus aureus and herpes simplex virus. The composition of their skin microbiome is also different, and changes during flares. The disease severity can be related to the degree of colonization by S. aureus. In addition, the presence of this bacterial species can predispose the host to more severe and disseminated viral infections. This article reviews the role of S. aureus and herpes virus infections and the skin microbiome in the pathogenesis of AD and their importance in the treatment and prevention strategies of this dermatosis.

PMID: 29052452 [PubMed - as supplied by publisher]

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Programming the shape-shifting of flat soft matter

Publication date: Available online 21 October 2017
Source:Materials Today
Author(s): Teunis van Manen, Shahram Janbaz, Amir A. Zadpoor
Shape-shifting of flat materials into the desired 3D configuration is an alternative design route for fabrication of complex 3D shapes, which provides many benefits such as access to the flat material surface and the ability to produce well-described motions. The advanced production techniques that primarily work in 2D could then be used to add complex surface features to the flat material. The combination of complex 3D shapes and surface-related functionalities has a wide range of applications in biotechnology, actuators/sensors, and engineering of complex metamaterials. Here, we categorize the different programming strategies that could be used for planning the shape-shifting of soft matter based on the type of stresses generated inside the flat material and present an overview of the ways those mechanisms could be used to achieve the desired 3D shapes. Stress gradients through the thickness of the material, which generate out-of-plane bending moments, and compressive in-plane stresses that result in out-of-plane buckling constitute the major mechanisms through which shape-shifting of the flat matter could be programmed. We review both programming strategies with a focus on the underlying physical principles, which are highly scalable and could be applied to other structures and materials. The techniques used for programming the time sequence of shape-shifting are discussed as well. Such types of so-called "sequential" shape-shifting enable achieving more complex 3D shapes, as the kinematics of the movements could be planned in time to avoid collisions. Ultimately, we discuss what 3D shapes could be achieved through shape-shifting from flat soft matter and identify multiple areas of application.

Graphical abstract

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Hierarchically porous composites fabricated by hydrogel templating and viscous trapping techniques

Publication date: 5 January 2018
Source:Materials & Design, Volume 137
Author(s): Benjamin R. Thompson, Tommy S. Horozov, Simeon D. Stoyanov, Vesselin N. Paunov
Two methods for the preparation of hierarchically porous composites have been developed and explored. The first involved templating mixed slurries of hydrogel beads with two different average bead size distributions with gypsum slurry which allows for precise control over the porosity, pore size distributions and hierarchical microstructure of the hardened composite after the evaporation of the water from the hydrogel beads. The other technique utilised the viscosity of methylcellulose solution to suspend gypsum particles as they form an interlocked network. By varying the volume percentage of methylcellulose solution used, it is possible to control the porosity of the dried sample. The mechanical and thermal insulation properties of the composites as a function of both their porosity and pore size were investigated. Both methods demonstrate an inexpensive approach for introducing porosity in gypsum composites which reduces their thermal conductivity, improves their insulation properties and allows economic use of the matrix material whilst controlling their mechanical properties. Such composites allow for tuneable porosity without significantly compromising their strength which could find applications in the building industry as well as structuring of other composites for a variety of consumer products.

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Axon mimicking hydrophilic hollow polycaprolactone microfibres for diffusion magnetic resonance imaging

Publication date: 5 January 2018
Source:Materials & Design, Volume 137
Author(s): Feng-Lei Zhou, Zhanxiong Li, Julie E. Gough, Penny L. Hubbard Cristinacce, Geoff J.M. Parker
Highly hydrophilic hollow polycaprolactone (PCL) microfibres were developed as building elements to create tissue-mimicking test objects (phantoms) for validation of diffusion magnetic resonance imaging (MRI). These microfibres were fabricated by the co-electrospinning of PCL-polysiloxane-based surfactant (PSi) mixture as shell and polyethylene oxide as core. The addition of PSi had a significant effect on the size of resultant electrospun fibres and the formation of hollow microfibres. The presence of PSi in both co-electrospun PCL microfibre surface and cross-section, revealed by X-ray energy dispersive spectroscopy (EDX), enabled water to wet these fibres completely (i.e., zero contact angle) and remained active for up to 12 months after immersing in water. PCL and PCL-PSi fibres with uniaxial orientation were constructed into water-filled phantoms. MR measurement revealed that water molecules diffuse anisotropically in the PCL-PSi phantom. Co-electrospun hollow PCL-PSi microfibres have desirable hydrophilic properties for the construction of a new generation of tissue-mimicking dMRI phantoms.

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Euphorbia lunulata extract acts on multidrug resistant gastric cancer cells to inhibit cell proliferation, migration and invasion, arrest cell cycle progression, and induce apoptosis

Publication date: 15 February 2018
Source:Journal of Ethnopharmacology, Volume 212
Author(s): Zhaoying Fu, Xiaodong Han, Juan Du, Xiaoxiao Han, Weipeng Liu, Shumei Shao, Xiaobin Liu
Ethnopharmacological relevanceThe milky sap or the aboveground part of the plant Euphorbia lunulata has long been used by Chinese people to treat noncancerous growths and cancerous ailments but the specific mode of action and the action mechanism remain to be elucidated.Aim of the studyTo investigate the effects of Euphorbia lunulata extract on cell proliferation, migration, invasion, cell cycle progression, and apoptosis of multidrug resistant human gastric cancer cells; To study the mechanism of apoptosis induction by Euphorbia lunulata extract in multidrug resistant human gastric cancer cells.Materials and methodsThe aboveground part of fresh Euphorbia lunulata plant was extracted first with ethanol and then with n-hexane. The aseptic extract at varying concentrations was used to treat the multidrug resistant human gastric cancer SGC7901/ADR cells. After treatment, the inhibition of cell proliferation was examined by MTT assay. The inhibitions of cell migration and invasion were detected by Transwell method. The alteration of cell cycle progression was studied by flow cytometry. The morphological changes of cell nuclei were observed with fluorescence microscopy following Hoechst 33258 staining and the apoptotic indexes were calculated. The activation of caspase enzymes was analyzed by spectrophotometry. The sub-cellular distribution of cytochrome complex and the expression of Bax and Bcl-2 proteins were determined by Western blot.ResultsThe proliferation, migration, and invasion of SGC7901/ADR cells were significantly inhibited by Euphorbia lunulata extract, which showed time- and dose-dependent manners. Cell cycle was arrested in G2/M phase. Significant apoptotic morphological changes were observed in the nuclei of the treated cells, and apoptotic indexes were increased significantly; these changes were diminished when Z-VAD-FMK, a caspase inhibitor, was also presented. The activities of caspase-3, caspase-8, and caspase-9 were increased. The sub-cellular distribution of cytochrome complex was altered----reduced in the mitochondria and increased in the cytoplasm. The expression of Bax was upregulated, while that of Bcl-2 was downregulated.ConclusionEuphorbia lunulata extract inhibited the proliferation, migration, and invasion of SGC7901/ADR cells, arrested cell cycle progression, and induced cell apoptosis; the mechanism of apoptosis induction involved both the extrinsic and the intrinsic pathways.

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Revitalization of plant growth promoting rhizobacteria for sustainable development in agriculture

Publication date: Available online 17 October 2017
Source:Microbiological Research
Author(s): Sushanto Gouda, Rout George Kerry, Gitishree Das, Spiros Paramithiotis, Han-Seung Shin, Jayanta Kumar Patra
The progression of life in all forms is not only dependent on agricultural and food security but also on the soil characteristics. The dynamic nature of soil is a direct manifestation of soil microbes, bio-mineralization, and synergistic co-evolution with plants. With the increase in world's population the demand for agriculture yield has increased tremendously and thereby leading to large scale production of chemical fertilizers. Since the use of fertilizers and pesticides in the agricultural fields have caused degradation of soil quality and fertility, thus the expansion of agricultural land with fertile soil is near impossible, hence researchers and scientists have sifted their attention for a safer and productive means of agricultural practices. Plant growth promoting rhizobacteria (PGPR) has been functioning as a co-evolution between plants and microbes showing antagonistic and synergistic interactions with microorganisms and the soil. Microbial revitalization using plant growth promoters had been achieved through direct and indirect approaches like bio-fertilization, invigorating root growth, rhizoremediation, disease resistance etc. Although, there are a wide variety of PGPR and its allies, their role and usages for sustainable agriculture remains controversial and restricted. There is also variability in the performance of PGPR that may be due to various environmental factors that might affect their growth and proliferation in the plants. These gaps and limitations can be addressed through use of modern approaches and techniques such as nano-encapsulation and micro-encapsulation along with exploring multidisciplinary research that combines applications in biotechnology, nanotechnology, agro biotechnology, chemical engineering and material science and bringing together different ecological and functional biological approaches to provide new formulations and opportunities with immense potential.



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SawR a new regulator controlling pyomelanin synthesis in Pseudomonas aeruginosa

Publication date: January 2018
Source:Microbiological Research, Volume 206
Author(s): Yossi Ben-David, Elena Zlotnik, Itzhak Zander, Gal Yerushalmi, Sivan Shoshani, Ehud Banin
Surface Acoustic Waves (SAW) were previously shown to inhibit biofilm formation, increase bacterial susceptibility to antibiotic treatment and alter the transcription pattern of Pseudomonas aeruginosa. Here we characterize one gene, sawR (PA3133), that is highly overexpressed when P. aeruginosa is exposed to SAW. SawR is a putative transcription factor belonging to the TetR regulator family. When overexpressed sawR causes numerous phenotypes, including the accumulation of a brown pigment which we identified as pyomelanin. In this study we describe how sawR regulates pyomelanin synthesis. We show that sawR down-regulates the expression levels of hmgA and this causes the accumulation of homogentisic acid which in turn undergoes oxidation and polymerization to pyomelanin. Using bioinformatics, we were able to identify a specific amino acid, arginine 23, which is found within the sawR DNA binding domain and is crucial for its regulatory activity. Our results indicate that sawR does not affect any other genes in the phenylalanine/tyrosine metabolic pathway and its repressive ability on hmgA is not mediated by the hmgA repressor PA2010 (i.e. hmgR). Taken together, our results shed light on the regulatory cascade controlling pyomelanin synthesis and uncover yet another unknown regulator involved in its regulation.



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Endophytism or saprophytism: Decoding the lifestyle transition of the generalist fungus Phomopsis liquidambari

Publication date: January 2018
Source:Microbiological Research, Volume 206
Author(s): Jun Zhou, Xin Li, Peng-Wei Huang, Chuan-Chao Dai
Filamentous ascomycete Phomopsis sp. are common inhabitants of natural ecosystems and, as saprophytes, are largely responsible for the destructive decay of litterfall, promoting the carbon and nitrogen cycles. Phomopsis liquidambari B3 can establish mutualistic symbiosis with a broad spectrum of crop plants. Colonizing dynamics observations and a growth promotion assay of rice and Arabidopsis thaliana revealed that the B3 colonization strategy is host-adapted and resulted in different growth promotions influenced by N availability. However, the biochemical mechanisms and underlying genetics of the saprophyte transition to an endophyte are poorly understood. Here, the transcriptome features of generalist P. liquidambari and highlighted gene sets involved in the lifestyle transition from saprophytism to endophytism were reported. Most notable were genes for translation, ribosome biogenesis and MAPK signaling, several of which were only up-regulated in endophytic B3. Coordinated up-regulation of genes encoding enzymes involved in phenylalanine, tyrosine and tryptophan biosynthesis were preceded by secondary metabolite induction, which was encountered with host defense. Quantitative PCR validates the reliability of RNA-seq. Dissection at the molecular level facilitated a deeper understanding of P. liquidambari adaptation to hosts and the complex natural environment to play a role in sustainable agriculture and carbon and nitrogen cycles.



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Composition of lactic acid bacteria during spontaneous curly kale (Brassica oleracea var. sabellica) fermentation

Publication date: Available online 16 October 2017
Source:Microbiological Research
Author(s): Magdalena Michalak, Klaudia Gustaw, Adam Waśko, Magdalena Polak-Berecka
The present work is the first report on spontaneous fermentation of curly kale and characteristics of autochthonous lactic acid bacteria (LAB). Our results indicate that curly kale fermentation is the new possibility of the technological use of this vegetable. Bacteria representing ten different species were isolated from three phases of curly kale fermentation and identified by MALDI-TOF mass spectrometry and 16S rRNA gene sequencing. Among them, four species were identified as Lactobacillus spp. (Lb. plantarum 332, Lb. paraplantarum G2114, Lb. brevis R413, Lb. curvatus 154), two as Weissella spp. (W. hellenica 152, W. cibaria G44), two as Pediococcus spp. (P. pentosaceus 45AN, P. acidilactici 2211), one as Leuconostoc mesenteroides 153, and one as Lactococcus lactis 37BN. The functional properties of isolates, i.e. acid, NaCl and bile salt tolerance, enzyme activities, adhesion to hydrocarbons, and antibiotic resistance, were examined. Among the tested strains, Lb. plantarum 332, Lb. paraplantarum G2114, P. pentosaceus 2211, and Lb. brevis R413 exhibited the best hydrophobicity value and high tolerance to bile salts, NaCl, and low pH.



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Phosphatidylcholine absence affects the secretion of lipodepsipeptide phytoxins in Pseudomonas syringae pv. syringae van Hall CFCC 1336

Publication date: January 2018
Source:Microbiological Research, Volume 206
Author(s): Fang Cao, Min Xiong, Shunyi Li, Huawan Cai, Yufang Sun, Sheng Yang, Xin Liu, Rong Zhu, Xuejing Yu, Xingguo Wang
Pseudomonas syringae pv. syringae van Hall CFCC 1336 (Pss 1336) is the causal agent of bacterial disease of stone fruit trees, and also able to elicit hypersensitive response (HR) in non-host tobacco. It is known that this pathogen uses PCS-pathway to synthesize phosphatidylcholine (PC), and mutation of the pcs gene abolishes bacterial PC synthesis. Previous study also found that the 1336 pcs⁻ mutant lacking PC in its membrane phospholipids was unable to secrete HrpZ harpin and elicit HR in non-host plants. In this study, we further analyzed virulence of lipodepsipeptide phytoxins of Pss 1336 wild type (pcs⁺), the 1336RM (pcs−/+) and the 1336 pcs− mutant, and found that the 1336 pcs− mutant was unable to cause necrosis of Chinese date fruits and inhibit fungal growth. HPLC analysis also showed that the 1336 pcs− mutant markedly reduced its secretion of lipodepsipeptide phytoxins. Analysis of semi-quantitative RT-PCR revealed that PC presence or absence did not affect gene expressions of SyrD, PseABC and PseEF efflux systems at transcriptional level. However, western blotting assays found that PseE and PseF present only in the cytoplasmic fractions but undetectable in the membrane extract of the 1336 pcs− mutant. PC absence obviously interrupted the translocation of two membrane-associated proteins PseE and PseF from cytoplasm to cell membranes to form an intact PseEF efflux system in bacterial membranes. Failure to form PseEF efflux system could be a major factor for less lipopeptide-phytoxin secretion. Our results demonstrate that PC in bacterial membrane phospholipids plays an important role in maintaining physiological functions of PseEF efflux system.



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The outer membrane protein OprF and the sigma factor SigX regulate antibiotic production in Pseudomonas fluorescens 2P24

Publication date: Available online 16 October 2017
Source:Microbiological Research
Author(s): Xu Li, Gao-Qi Gu, Wei Chen, Li-Juan Gao, Xue-Hong Wu, Li-Qun Zhang
Pseudomonas fluorescens 2P24 produces 2,4-diacetylphloroglucinol (2,4-DAPG) as the major antibiotic compound that protects plants from soil-borne diseases. Expression of the 2,4-DAPG biosynthesis enzymes, which are encoded by the phlACBD locus, is under the control of a delicate regulatory network. In this study, we identified a novel role for the outer membrane protein gene oprF, in negatively regulating the 2,4-DAPG production by using random mini-Tn5 mutagentsis. A sigma factor gene sigX was located immediately upstream of the oprF gene and shown to be a positive regulator for oprF transcription and 2,4-DAPG production. Genetic analysis of an oprF and sigX double-mutant indicated that the 2,4-DAPG regulation by oprF was dependent on SigX. The sigX gene did not affect PhlA and PhlD expression, but positively regulated the level of malonyl-CoA, the substrate of 2,4-DAPG synthesis, by influencing the expression of acetyl-CoA carboxylases. Further investigations revealed that sigX transcription was induced under conditions of salt starvation or glycine addition. All these findings indicate that SigX is a novel regulator of substrate supplements for 2,4-DAPG production.



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Electronic medical record reminders and smoking cessation activities in primary care

Publication date: February 2018
Source:Addictive Behaviors, Volume 77
Author(s): Jaeyong Bae, Eric W. Ford, Hadi H.K. Kharrazi, Timothy R. Huerta
PurposeThe purpose of this paper is to assess electronic medical record (EMR) automatic reminder use in relation to smoking cessation activities among primary-care providers.BackgroundPrimary-care physicians are in the frontline of efforts to promote smoking cessation. Moreover, doctors' prescribing privileges give them additional tools to help patients successfully quit smoking. New EMR functions can provide automated reminders for physicians to counsel smokers and provide prescriptions to support quit attempts.Sample and methodsLogit regression is used to analyze the 2012 National Ambulatory Medical Care Survey (NAMCS). Variables related to the EMR's clinical reminder capability, patient's smoking status, the provision of cessation counseling and the prescribing of drugs that support quitting are analyzed.ResultsFor primary care visit documents, smoking status was recorded 77.7% of the time. Smoking cessation counseling was ordered/provided 16.4% of the time in physicians' offices using electronic reminders routinely compared to 9.1% in those lacking the functionality. Smoking cessation medication was ordered/prescribed for 3.7% of current smokers when reminders were routinely used versus 2.1% when no reminder was used. All the differences were statistically significant.ConclusionsThe presence of an EMR equipped with automated clinical reminders is a valuable resource in efforts to promote smoking cessation. Insurers, regulators, and organizations promulgating clinical guidelines should include the use of EMR technology as part of their programs.



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Instructions to Authors

Publication date: November 2017
Source:The Kaohsiung Journal of Medical Sciences, Volume 33, Issue 11





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Source:The Kaohsiung Journal of Medical Sciences, Volume 33, Issue 11





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Source:The Kaohsiung Journal of Medical Sciences, Volume 33, Issue 11





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Publication date: November 2017
Source:The Kaohsiung Journal of Medical Sciences, Volume 33, Issue 11





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Publication date: November 2017
Source:The Kaohsiung Journal of Medical Sciences, Volume 33, Issue 11





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To use the brief psychiatric rating scale to detect disorganized speech in schizophrenia: Findings from the REAP-AP study

Publication date: Available online 20 October 2017
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Yong Chon Park, Shigenobu Kanba, Mian-Yoon Chong, Adarsh Tripathi, Roy Abraham Kallivayalil, Ajit Avasthi, Sandeep Grover, Kok Yoon Chee, Andi J. Tanra, Marigarita M. Maramis, Shu-yu Yang, Norman Sartorius, Chay-Hoon Tan, Naotaka Shinfuku, Seon-Cheol Park
Our study aimed to assess the psychometric validity of the conceptual disorganization item and other items of the Brief Psychiatric Rating Scale (BPRS) for detecting disorganized speech in patients with schizophrenia. We included 357 schizophrenia patients with disorganized speech and 1082 without disorganized speech from the survey centers in India, Indonesia, Japan, Malaysia, and Taiwan, using the data from the Research on Asian Psychotropic Patterns for Antipsychotics (REAP-AP) study. After adjusting the effects of confounding variables, a binary logistic regression model was fitted to identify BPRS items independently associated with disorganized speech. Receiver operating characteristic (ROC) curves were used to identify optimum cut-off scores and their sensitivities and specificities for detecting disorganized speech. After adjusting the effects of confounding variables, the fitted binary logistic regression model indicated that conceptual disorganization (P < 0.0001), uncooperativeness (P = 0.010) and excitement (P = 0.001) were independently associated with disorganized speech. The ROC curve revealed that the conceptual disorganization item could accurately detect disorganized speech in patients with schizophrenia both separately and in combination with uncooperativeness and excitement. The subscale for conceptual disorganization, uncooperativeness and excitement items in the BPRS is a promising psychometric tool for detecting disorganized speech.



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Beau's lines in nails: An indicator of recent Docetaxel and 5-FU use

Publication date: Available online 17 October 2017
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Neng-Sheng Chu, I-Chen Wu, Li-Tzong Chen, Yi-Ying Chin




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Erratum to ‘Limitations and opportunities for immune checkpoint inhibitors in pediatric malignancies’ [Cancer Treat. Rev. 58C (2017) 22–33]

Publication date: Available online 21 October 2017
Source:Cancer Treatment Reviews
Author(s): Jeong A Park, Nai-Kong V. Cheung




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Composition and estimate of daily mineral intake from samples of Brazilian rice

Publication date: March 2018
Source:Microchemical Journal, Volume 137
Author(s): Iago José Santos da Silva, Ana Paula Silveira Paim, Maria José da Silva
Rice is one of the most produced and consumed cereals in the world, making the control of its chemical composition, especially of minerals, important. A method of rice digestion using nitric acid and hydrogen peroxide to determine metals (Al, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb and Zn) using Inductively Coupled Plasma Optical Emission Spectrometry (ICP OES) was developed. The optimized conditions were established using a factorial design 2³, obtaining the following digestion conditions as the most adequate: digestion time (20min), concentration of HNO3 (8molL⁻¹) and H2O2 volume (2.5mL). Recovery values ranging from 80 to 120% with RSD<5.1% were obtained for most elements of interest and limits of detection of the method were in the range of 0.02mgkg⁻¹ (Mn) to 5.6mgkg⁻¹ (Ca). A table of metal composition for the different types of processed rice (white, parboiled and brown) was established through an analysis of 54 rice samples. Brown rice contributed significantly to the Recommended Dietary Allowances (RDA) of Mn (61%) and Mg (20%), parboiled rice with Cu (45%) and white rice with Mn (14%). In addition, the daily intake estimated through rice consumption, for all detected metals, was much lower than the Tolerable Upper Intake Level. The rice samples could be differentiated by their type of processing, based on their mineral composition using Principal Component Analysis (PCA).



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Validation of Dosimetric Leaf Gap (DLG) prior to its implementation in Treatment Planning System (TPS): TrueBeam™ millennium 120 leaf MLC

Publication date: November–December 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 6
Author(s): Ravindra Shende, Ganesh Patel
AimObjective of present study is to determine optimum value of DLG and its validation prior to being incorporated in TPS for Varian TrueBeam™ millennium 120 leaves MLC.BackgroundPartial transmission through the rounded leaf ends of the Multi Leaf Collimator (MLC) causes a conflict between the edges of the light field and radiation field. Parameter account for this partial transmission is called Dosimetric Leaf Gap (DLG). The complex high precession technique, such as Intensity Modulated Radiation Therapy (IMRT), entails the modeling of optimum value of DLG inside Eclipse Treatment Planning System (TPS) for precise dose calculation.Materials and methodsDistinct synchronized uniformed extension of sweeping dynamic MLC leaf gap fields created by Varian MLC shaper software were use to determine DLG. DLG measurements performed with both 0.13cc semi-flex ionization chamber and 2D-Array I-Matrix were used to validate the DLG; similarly, values of DLG from TPS were estimated from predicted dose. Similar mathematical approaches were employed to determine DLG from delivered and TPS predicted dose. DLG determined from delivered dose measured with both ionization chamber (DLGIon) and I-Matrix (DLGI-Matrix) compared with DLG estimate from TPS predicted dose (DLGTPS). Measurements were carried out for all available 6MV, 10MV, 15MV, 6MVFFF and 10MVFFF beam energies.ResultsMaximum and minimum DLG deviation between measured and TPS calculated DLG was found to be 0.2mm and 0.1mm, respectively. Both of the measured DLGs (DLGIon and DLGI-Matrix) were found to be in a very good agreement with estimated DLG from TPS (DLGTPS).ConclusionsProposed method proved to be helpful in verifying and validating the DLG value prior to its clinical implementation in TPS.



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Increased proportion of a CD38highIgD+ B cell subset in peripheral blood is associated with clinical and immunological features in patients with primary Sjögren's syndrome

Publication date: Available online 20 October 2017
Source:Clinical Immunology
Author(s): Eriko Ishioka-Takei, Keiko Yoshimoto, Katsuya Suzuki, Ayumi Nishikawa, Hidekata Yasuoka, Kunihiro Yamaoka, Tsutomu Takeuchi
We investigated the correlation between the increased proportion of peripheral B cell subsets and clinical and immunological features in primary Sjögren's syndrome (pSS). We found that the proportion of CD19⁺ B cells was significantly increased in pSS as compared with HC and was correlated with serum IgG levels. Moreover, in vitro IgG production by CD19⁺ B cells was significantly increased in pSS and was positively and significantly correlated with serum IgG levels. FACS analysis revealed that the proportions of peripherally CD38^highIgD⁺ B cells and CD38^highIgD⁻ B cells were significantly increased in pSS. In addition, the proportion of CD38^highIgD⁺ B cells positively correlated with ESSDAI scores and serum levels of IgG, anti-Ro/SSA and anti-La/SSB antibodies while that of CD38^highIgD⁻ B cells showed no correlation with these parameters. Our data suggest that increased proportion of CD38^highIgD⁺ B cells in pSS is involved in IgG overproduction including autoantibodies, and correlates with disease progression.



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The Endovenous Literature: A Perfect Storm of Limited Effectiveness Data, Rapid Technological Evolution and Potential Conflict of Interest

Publication date: Available online 20 October 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): David C. Bosanquet, Christopher P. Twine




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A Huge Thoracic Aortic Aneurysm

Publication date: Available online 20 October 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Anne Lejay, Nabil Chakfé




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Open Abdomen Therapy with Vacuum and Mesh Mediated Fascial Traction After Aortic Repair: an International Multicentre Study

Publication date: Available online 21 October 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Stefan Acosta, Arne Seternes, Maarit Venermo, Leena Vikatmaa, Karl Sörelius, Anders Wanhainen, Mats Svensson, Khatereh Djavani, Martin Björck
ObjectivesOpen abdomen therapy may be necessary to prevent or treat abdominal compartment syndrome (ACS). The aim of the study was to analyse the primary delayed fascial closure (PDFC) rate and complications after open abdomen therapy with vacuum and mesh mediated fascial traction (VACM) after aortic repair and to compare outcomes between those treated with open abdomen after primary versus secondary operation.MethodsThis was a retrospective cohort, multicentre study in Sweden, Finland, and Norway, including consecutive patients treated with open abdomen and VACM after aortic repair at six vascular centres in 2006–2015. The primary endpoint was PDFC rate.ResultsAmong 191 patients, 155 were men. The median age was 71 years (IQR 66–76). Ruptured abdominal aortic aneurysm (RAAA) occurred in 69.1%. Endovascular/hybrid and open repairs were performed in 49 and 142 patients, respectively. The indications for open abdomen were inability to close the abdomen (62%) at primary operation and ACS (80%) at secondary operation. Duration of open abdomen was 11 days (IQR 7–16) in 157 patients alive at open abdomen termination. The PDFC rate was 91.8%. Open abdomen initiated at primary (N=103), compared with secondary operation (N=88), was associated with less severe initial open abdomen status (p=.006), less intestinal ischaemia (p=.002), shorter duration of open abdomen (p=.007), and less renal replacement therapy (RRT, p<.001). In hospital mortality was 39.3%, and after entero-atmospheric fistula (N=9) was 88.9%. Seven developed graft infection within 6 months, 1 year mortality was 28.6%. Intestinal ischaemia (OR 3.71, 95% CI 1.55–8.91), RRT (OR 3.62, 95% CI 1.72–7.65), and age (OR 1.12, 95% CI 1.06–1.12), were independent factors associated with in hospital mortality, but not open abdomen initiated at primary versus secondary operation.ConclusionsVACM was associated with a high PDFC rate after prolonged open abdomen therapy following aortic repair. Patient outcomes seemed better when open abdomen was initiated at primary, compared with secondary operation but a selection effect is possible.



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Pasireotide for the Treatment of Refractory Hypoglycemia from Malignant Insulinoma

Abstract

Insulinomas are rare, usually solitary benign tumors. The presence of metastases defines malignant insulinomas⁽¹⁾. Medical therapy primarily treats symptomatic hypoglycemia, alleviates symptoms, and improves the quality of life in affected individuals. While diazoxide is used as first-line therapy, the incomplete response rate and complications associated with diazoxide provide a role for somatostatin analogues in difficult-to-treat hypoglycemia_.

This article is protected by copyright. All rights reserved.

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Long-Term Safety of Growth Hormone – A Combined Registry Analysis

Abstract

Objectives

Preliminary data from the French cohort of the Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) study raised concerns regarding the safety of recombinant human GH, suggesting that GH may increase mortality and incidence of stroke in patients treated during childhood for GH deficiency or short stature. We evaluated published safety data, focusing on mortality, neoplasms, cerebrovascular events and diabetes across a number of large-scale pharmaceutical company GH registries.

Design

A literature review was conducted using PubMed, EMBASE and Google Scholar to identify all relevant safety data from manufacturers' GH registries published between 1988 and April 2016. Results were hand-sorted to exclude non-relevant publications; bibliographic references from retrieved articles were evaluated for any additional references.

Results

The published data do not support an increased risk of mortality in children or adults treated with GH. There was no evidence of an increased risk of stroke, new malignancy, leukaemia, non-leukaemic extracranial tumours or recurrence of intracranial malignancy in patients without risk factors. The risk of a second neoplasm is increased, particularly if patients have received radiation therapy for a central nervous system tumour. There may be an increased risk of type 2 diabetes in GH-treated patients, but this appears to be confined to those with pre-existing risk factors.

Conclusions

Patients with risk factors for malignancy or type 2 diabetes should be treated with caution and monitored during follow-up, but current published data provide reassurance on the long-term safety profile of GH in patients receiving GH treatment.

This article is protected by copyright. All rights reserved.

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Data on fluoride concentration levels in cold and warm season in rural area of Shout (West Azerbaijan, Iran)

Publication date: December 2017
Source:Data in Brief, Volume 15
Author(s): Farzaneh Baghal Asghari, Ali Akbar Mohammadi, Zahra Aboosaedi, Mehdi Yaseri, Mahmood Yousefi
The aim of this study was to determine the concentration of fluoride in drinking water, the distribution system, in 22 villages in Shout (A city in West Azerbaijan province). Sampling of springs and underground water was carried out in two warm and cold seasons. Fluoride concentration were determined through spectrophotometer with a model, DR/5000.The fluoride concentration were compared with Iranian standards and WHO guidelines for drinking water.



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Synthesis and biological evaluation of Santacruzamate-A based analogues

Publication date: Available online 20 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Rosario Randino, Patrizia Gazzerro, Ralph Mazitschek, Manuela Rodriquez
Several derivatives of Santacruzamate-A, a natural product that is structurally related to SAHA, were synthesized to explore the potential of carbamates and oxalylamides as novel biasing element for targeting the catalytic site of zinc-dependent histone deacetylases (HDAC). An additional class of Santacruzamate-A derivatives was synthesized to investigate the influence of the cap group and the linker element on HDAC inhibitory activity. All compounds were evaluated in dose response for their in vitro cytotoxic activity in MTT assay in HCT116 cells. HDAC inhibitory activity was evaluated in vitro by western blot analysis for histone hyperacetylation assay and biochemically for representative human HDACs isoforms. Two novel compounds were identified to exhibit potent time dependent anti proliferative activity. However, unlike hydroxamic acid analogues, the tested Santacruzamate-A derivatives showed no noticeable HDAC inhibitory activity. The ethylcarbamate moiety as unusual zinc-binding group displayed no ability to coordinate the zinc ion and thus, presumably, was not able to reproduce known inhibitor-substrate zinc-binding group interactions with the HDAC catalytic site. This study confirmed that the accommodation of the zinc-binding group is deeply critical of the positioning of the linker and the projection of the cap group toward the different surface pockets of the enzyme.

Graphical abstract

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Identification of an allosteric benzothiazoloprymidone inhibitor of the oncogenic protein tyrosine phosphatase SHP2

Publication date: Available online 20 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Jonathan R. LaRochelle, Michelle Fodor, Jana M. Ellegast, Xiaoxi Liu, Vidyasiri Vemulapalli, Morvarid Mohseni, Travis Stams, Sara J. Buhrlage, Kimberly Stegmaier, Matthew J. LaMarche, Michael G. Acker, Stephen C. Blacklow
The PTPN11 oncogene encodes the cytoplasmic protein tyrosine phosphatase SHP2, which, through its role in multiple signaling pathways, promotes the progression of hematological malignancies and other cancers. Here, we employ high-throughput screening to discover a lead chemical scaffold, the benzothiazolopyrimidones, that allosterically inhibits this oncogenic phosphatase by simultaneously engaging the C-SH2 and PTP domains. We improved our lead to generate an analogue that suppresses SHP2 activity in vitro. Suppression of Erk phopsphorylation by the lead compound is also consistent with SHP2 inhibition in AML cells. Our findings provide an alternative starting point for therapeutic intervention and will catalyze investigations into the relationship between SHP2 conformational regulation, activity, and disease progression.

Graphical abstract

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Design, synthesis, and anticancer properties of isocorydine derivatives

Publication date: Available online 21 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Qian Yan, Ruxia Li, Aiyi Xin, Yin Han, Yanxia Zhang, Junxi Liu, Wenguang Li, Duolong Di
Isocorydine (ICD), an aporphine alkaloid, is widely distributed in nature. Its ability to target side population (SP) cells found in human hepatocellular carcinoma (HCC) makes it and its derivative 8-amino-isocorydine (NICD) promising chemotherapeutic agents for the treatment of HCC. To improve the anticancer activity of isocorydine derivatives, twenty derivatives of NICD were designed and synthesized through chemical structure modifications of the aromatic amino group at C-8. The anti-proliferative activities of all synthesized compounds against human hepatocellular (HepG2), cervical (HeLa), and gastric (MGC-803) cancer cell lines were evaluated using an MTT assay. The results showed that all the synthetic compounds had some tumor cell growth inhibitory activity. The compound COM33 (24) was the most active with IC50 values under 10 μM (IC50 for HepG2 = 7.51 µM; IC50 for HeLa = 6.32 µM). FICD (12) and COM33 (24) were selected for further investigation of their in vitro and in vivo activities due to their relatively good antiproliferative properties. These two compounds significantly downregulated the expression of four key proteins (C-Myc, β-Catenin, CylinD1, and Ki67) in HepG2 cells. The tumor inhibition rate of COM33 (24) in vivo was 73.8% after a dose 100 mg/kg via intraperitoneal injection and the combined inhibition rate of COM33 (24) (50 mg/kg) with sorafenib (50 mg/kg) was 66.5%. The results indicated that these isocorydine derivatives could potentially be used as targeted chemotherapy agents or could be further developed in combination with conventional chemotherapy drugs to target cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT), the main therapeutic targets in HCC.

Graphical abstract

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Nanoscale metal–organic frameworks for phototherapy of cancer

Publication date: Available online 21 October 2017
Source:Coordination Chemistry Reviews
Author(s): Guangxu Lan, Kaiyuan Ni, Wenbin Lin
Phototherapy involves the irradiation of tissues with light and is commonly implemented in the forms of photodynamic therapy (PDT) and photothermal therapy (PTT). Photosensitizers (PSs) are often needed to improve the efficacy and selectivity of phototherapy via enhanced singlet oxygen generation in PDT and photothermal responses in PTT. In both cases, efficient and selective delivery of PSs to the diseased tissues is of paramount importance. Nanoscale metal–organic frameworks (nMOFs), a new class of hybrid materials built from metal connecting points and bridging ligands, have been examined as nanocarriers for drug delivery due to their compositional and structural tunability, highly porous structures, and good biocompatibility. This review summarizes recent advances on using nMOFs as nanoparticle PSs for PDT and PTT.

Graphical abstract

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Characterization and molecular mechanism of therapeutic peptide functionalized gold nanoparticle inhibiting p53-HDM2 interaction in retinoblastoma

Publication date: Available online 20 October 2017
Source:Molecular Therapy - Nucleic Acids
Author(s): Sushma Kalmodia, Sowmya Parameswaran, Kalaivani Ganapathy, Wenrong Yang, Colin J. Barrow, Jagat Kanwar, Kislay Roy, Madavan Vasudevan, Kirti Kulkarni, Sailaja V. Elchuri, Subramanian Krishnakumar
Inhibition of p53-HDM2 interactions is an effective therapeutic strategy in cancers such as retinoblastoma (RB) that harbor a wild-type p53 protein. Nanoparticle based delivery of therapeutic molecules has been shown to be advantageous in localized delivery, including to the eye, by overcoming the ocular barriers. In this study, we utilized biocompatible gold nanoparticles (GNP), to deliver anti-HDM2 peptide to RB cells. Characterization studies suggested that GNP-HDM2 was stable in biologically relevant solvents and had optimal cellular internalization capability, the primary requirement of any therapeutic molecule. GNP-HDM2 treatment in RB cells in vitro suggested that they function by arresting RB cells at the G2M phase of the cell cycle and initiating apoptosis. Analysis of molecular changes in the GNP-HDM2 treated cells by quantitative reverse transcription PCR and western blotting revealed that the p53 protein was upregulated; however, trans-activation of its downstream targets was minimal, except for the PUMA-BCl2 and Bax axis. Global gene expression and in silico bioinformatic analysis of the GNP-HDM2 treated cells suggested that upregulation of p53 might mediate apoptosis presumptively, through the induction of p53 inducible miRNAs.



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Ecomorphological analysis of bovid mandibles from Laetoli Tanzania using 3D geometric morphometrics: Implications for hominin paleoenvironmental reconstruction

Publication date: January 2018
Source:Journal of Human Evolution, Volume 114
Author(s): Frances L. Forrest, Thomas W. Plummer, Ryan L. Raaum
The current study describes a new method of mandibular ecological morphology (ecomorphology). Three-dimensional geometric morphometrics (3D GM) was used to quantify mandibular shape variation between extant bovids with different feeding preferences. Landmark data were subjected to generalized Procrustes analysis (GPA), principal components analysis (PCA), and discriminant function analysis (DFA). The PCA resulted in a continuum from grazers to browsers along PC1 and DFA classified 88% or more of the modern specimens to the correct feeding category. The protocol was reduced to a subset of landmarks on the mandibular corpus in order to make it applicable to incomplete fossils. The reduced landmark set resulted in greater overlap between feeding categories but maintained the same continuum as the complete landmark model. The DFA resubstitution and jackknife analyses resulted in classification success rates of 85% and 80%, respectively. The reduced landmark model was applied to fossil mandibles from the Upper Laetolil Beds (∼4.3–3.5 Ma) and Upper Ndolanya Beds (∼2.7–2.6 Ma) at Laetoli, Tanzania in order to assess antelope diet, and indirectly evaluate paleo-vegetation structure. The majority of the fossils were classified by the DFA as browsers or mixed feeders preferring browse. Our results indicate a continuous presence of wooded habitats and are congruent with recent environmental studies at Laetoli indicating a mosaic woodland-bushland-grassland savanna ecosystem.



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Climatic controls on Later Stone Age human adaptation in Africa's southern Cape

Publication date: January 2018
Source:Journal of Human Evolution, Volume 114
Author(s): Brian M. Chase, J. Tyler Faith, Alex Mackay, Manuel Chevalier, Andrew S. Carr, Arnoud Boom, Sophak Lim, Paula J. Reimer
Africa's southern Cape is a key region for the evolution of our species, with early symbolic systems, marine faunal exploitation, and episodic production of microlithic stone tools taken as evidence for the appearance of distinctively complex human behavior. However, the temporally discontinuous nature of this evidence precludes ready assumptions of intrinsic adaptive benefit, and has encouraged diverse explanations for the occurrence of these behaviors, in terms of regional demographic, social and ecological conditions. Here, we present a new high-resolution multi-proxy record of environmental change that indicates that faunal exploitation patterns and lithic technologies track climatic variation across the last 22,300 years in the southern Cape. Conditions during the Last Glacial Maximum and deglaciation were humid, and zooarchaeological data indicate high foraging returns. By contrast, the Holocene is characterized by much drier conditions and a degraded resource base. Critically, we demonstrate that systems for technological delivery – or provisioning – were responsive to changing humidity and environmental productivity. However, in contrast to prevailing models, bladelet-rich microlithic technologies were deployed under conditions of high foraging returns and abandoned in response to increased aridity and less productive subsistence environments. This suggests that posited links between microlithic technologies and subsistence risk are not universal, and the behavioral sophistication of human populations is reflected in their adaptive flexibility rather than in the use of specific technological systems.



http://ift.tt/2xdiYJ6

Suidae from Kanapoi

Publication date: Available online 21 October 2017
Source:Journal of Human Evolution
Author(s): Denis Geraads, René Bobe
The whole collection of Suidae from Kanapoi is revised in the context of the systematics and evolution of Nyanzachoerus in the Pliocene of Eastern Africa. It contains only two species, Nyanzachoerus kanamensis and Notochoerus jaegeri. The size and morphology of their premolars overlap, but not those of their m3s. No transitional form between them is known in Kenya, but some populations from Uganda and Ethiopia display intermediate characters, suggesting that No. jaegeri could be descended from a kanamensis-like ancestor. However, the cranial remains of No. jaegeri from Kanapoi are insufficient to formally establish the affinities of the species. On the basis of the dentition, Notochoerus euilus could be descended from No. jaegeri. The noticeable absence of Kolpochoerus at Kanapoi (and in the whole Turkana Basin at that time) remains unexplained. The presence of a species with affinity to Nyanzachoerus tulotos at Ekora raises the possibility that uppermost Miocene sediments occur there.



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Antisense oligonucleotide therapy rescues disruptions in organization of exploratory movements associated with Usher syndrome type 1C in mice

Publication date: 15 February 2018
Source:Behavioural Brain Research, Volume 338
Author(s): Tia N. Donaldson, Kelsey T. Jennings, Lucia A. Cherep, Adam M. McNeela, Frederic F. Depreux, Francine M. Jodelka, Michelle L. Hastings, Douglas G. Wallace
Usher syndrome, Type 1C (USH1C) is an autosomal recessive inherited disorder in which a mutation in the gene encoding harmonin is associated with multi-sensory deficits (i.e., auditory, vestibular, and visual). USH1C (Usher) mice, engineered with a human USH1C mutation, exhibit these multi-sensory deficits by circling behavior and lack of response to sound. Administration of an antisense oligonucleotide (ASO) therapeutic that corrects expression of the mutated USH1C gene, has been shown to increase harmonin levels, reduce circling behavior, and improve vestibular and auditory function. The current study evaluates the organization of exploratory movements to assess spatial organization in Usher mice and determine the efficacy of ASO therapy in attenuating any such deficits. Usher and heterozygous mice received the therapeutic ASO, ASO-29, or a control, non-specific ASO treatment at postnatal day five. Organization of exploratory movements was assessed under dark and light conditions at two and six-months of age. Disruptions in exploratory movement organization observed in control-treated Usher mice were consistent with impaired use of self-movement and environmental cues. In general, ASO-29 treatment rescued organization of exploratory movements at two and six-month testing points. These observations are consistent with ASO-29 rescuing processing of multiple sources of information and demonstrate the potential of ASO therapies to ameliorate topographical disorientation associated with other genetic disorders.



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Distribution of cancer mortality rates by province in South Africa

Publication date: December 2017
Source:Cancer Epidemiology, Volume 51
Author(s): Felix Made, Kerry Wilson, Ruxana Jina, Nonhlanhla Tlotleng, Samantha Jack, Vusi Ntlebi, Tahira Kootbodien
IntroductionCancer mortality rates are expected to increase in developing countries. Cancer mortality rates by province remain largely unreported in South Africa. This study described the 2014 age standardised cancer mortality rates by province in South Africa, to provide insight for strategic interventions and advocacy.Methods2014 deaths data were retrieved from Statistics South Africa. Deaths from cancer were extracted using 10th International Classification of Diseases (ICD) codes for cancer (C00-C97). Adjusted 2013 mid-year population estimates were used as a standard population. All rates were calculated per 100 000 individuals.ResultsNearly 38 000 (8%) of the total deaths in South Africa in 2014 were attributed to cancer. Western Cape Province had the highest age standardised cancer mortality rate in South Africa (118, 95% CI: 115–121 deaths per 100 000 individuals), followed by the Northern Cape (113, 95% CI: 107–119 per 100 000 individuals), with the lowest rate in Limpopo Province (47, 95% CI: 45–49 per 100 000). The age standardised cancer mortality rate for men (71, 95% CI: 70–72 per 100 000 individuals) was similar to women (69, 95% CI: 68–70 per 100 000). Lung cancer was a major driver of cancer death in men (13, 95% CI: 12.6–13.4 per 100 000). In women, cervical cancer was the leading cause of cancer death (13, 95% CI: 12.6–13.4 per 100 000 individuals).ConclusionThere is a need to further investigate the factors related to the differences in cancer mortality by province in South Africa. Raising awareness of risk factors and screening for cancer in the population along with improved access and quality of health care are also important.



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Risk of cardiovascular disease among women with endometrial cancer compared to cancer-free women in the Women’s Health Initiative

Publication date: December 2017
Source:Cancer Epidemiology, Volume 51
Author(s): Ashley S. Felix, Amy Lehman, Randi E. Foraker, Michelle J. Naughton, Julie K. Bower, Lewis Kuller, Gloria E. Sarto, Marcia L. Stefanick, Linda Van Horn, Rebecca D. Jackson, Electra D. Paskett
BackgroundThe majority of women diagnosed with endometrial cancer (EC) have low cancer-specific mortality; however, a high prevalence of cardiovascular disease (CVD) risk factors places EC patients at high risk of developing CVD. In the Women's Health Initiative (WHI), we assessed the hypothesis that CVD risk was higher among women who developed EC compared with women who did not develop EC.MethodsWe compared the incidence of fatal and non-fatal CVD events among 1,179 women who developed Type I EC, 211 women who developed Type II EC, and 92,217 women who did not develop EC. We first estimated univariable cause-specific hazard ratios (CHRs) and 95% confidence intervals (CIs) for the association between an EC diagnosis (overall and by EC type) with CVD risk using Cox proportional hazards regression. Potential confounders were examined using a risk factor modeling approach; final multivariable-adjusted models included covariates that changed univariable CHRs for EC diagnosis by≥5%.ResultsIn multivariable-adjusted models, CVD risk did not significantly differ between women who developed EC compared to women who did not develop EC (CHR=1.01, 95% CI=0.87–1.16), particularly for the subgroup of women who developed Type I EC (CHR=0.98, 95% CI=0.84–1.14); however, there was a positive but statistically nonsignificant association for Type II EC (CHR=1.32, 95% CI=0.88–1.97).ConclusionDespite our null findings, women with EC should still receive counseling and support to make lifestyle changes aimed at reducing weight as appropriate, given the high prevalence of CVD risk factors at diagnosis.



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Mathematical models and vaccination strategies

Publication date: Available online 21 October 2017
Source:Vaccine
Author(s): Guillaume Béraud
Infection transmission is a complex and dynamic process, and is therefore difficult to assess. Consequently, mathematical models are a useful tool to understand any leverage on this transmission, such as vaccination. Models can provide guidance to implement an optimal vaccination campaign whether it concerns the fraction of the population or the age-group to be vaccinated. Mathematical models can also provide insights on counter-intuitive collateral effects of vaccination campaign, given the possibility that the overall benefits for the general population may hide deleterious effects on some sub-groups.As a large proportion of the population is now vaccinated, complex modelling taking into account individual and population heterogeneity and behaviour is necessary although challenging. But the most crucial aspect in the future of mathematical modelling still consists in obtaining precise and exhaustive data.



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Hospital-based collaboration for epidemiological investigation of vaccine safety: A potential solution for low and middle-income countries?

Publication date: Available online 21 October 2017
Source:Vaccine
Author(s): Hector S. Izurieta, Pedro L. Moro, Robert T. Chen




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Intratumoral injection of thermogelling and sustained-release carboplatin-loaded hydrogel simplifies the administration and remains the synergistic effect with radiotherapy for mice gliomas

Publication date: January 2018
Source:Biomaterials, Volume 151
Author(s): Hsiang-Kuang Tony Liang, Xue-Shi Lai, Ming-Feng Wei, Szu-Huai Lu, Wen-Fen Wen, Sung-Hsin Kuo, Chung-Ming Chen, Wen-Yih Isaac Tseng, Feng-Huei Lin
BackgroundCarboplatin, an antineoplastic agent, binds DNA and enhances radiotherapy (RT) effects. Carboplatin-loaded hydrogel (oxidized hyaluronic acid/adipic acid dihydrazide) enables the sustained drug release and facilitates the synergistic effect with RT.PurposeWe investigated the effectiveness and convenience of hydrogel carboplatin combined with RT for mice glioma.Materials and methodsMouse glioma cells (ALTS1C1) were subcutaneously implanted in the right thigh of C57BL/6 mice on Day 0. The mice were categorized by treatments: sham, hydrogel, hydrogel carboplatin, aqueous carboplatin, RT, hydrogel carboplatin/RT, and aqueous carboplatin/RT. Hydrogel carboplatin (300 μg single dose on Day 7) or aqueous carboplatin (100 μg daily dose on Days 7, 8, and 9) was administered via intratumoral injection. RT was delivered a daily dose of 10 Gy on Days 8 and 9.ResultsFor mice administered hydrogel carboplatin/RT versus those administered aqueous carboplatin/RT, the 24-day tumor growth control rate and 104-day recurrence-free survival rate were 100% and 50% versus 100% and 66.7% (p = 0.648), respectively. However, mice receiving other treatments showed tumor progression by Day 24 and died within 40 days of tumor cell implantation.ConclusionsHydrogel carboplatin simplified intratumoral drug delivery and remained the synergistic effects with RT, which is potential for clinical applications.



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Creation of a nanoformulated cabotegravir prodrug with improved antiretroviral profiles

Publication date: January 2018
Source:Biomaterials, Volume 151
Author(s): Tian Zhou, Hang Su, Prasanta Dash, Zhiyi Lin, Bhagya Laxmi Dyavar Shetty, Ted Kocher, Adam Szlachetka, Benjamin Lamberty, Howard S. Fox, Larisa Poluektova, Santhi Gorantla, JoEllyn McMillan, Nagsen Gautam, R. Lee Mosley, Yazen Alnouti, Benson Edagwa, Howard E. Gendelman
Long-acting parenteral (LAP) antiretroviral drugs have generated considerable interest for treatment and prevention of HIV-1 infection. One new LAP is cabotegravir (CAB), a highly potent integrase inhibitor, with a half-life of up to 54 days, allowing for every other month parenteral administrations. Despite this excellent profile, high volume dosing, injection site reactions and low body fluid drug concentrations affect broad use for virus infected and susceptible people. To improve the drug delivery profile, we created a myristoylated CAB prodrug (MCAB). MCAB formed crystals that were formulated into nanoparticles (NMCAB) of stable size and shape facilitating avid monocyte-macrophage entry, retention and reticuloendothelial system depot formulation. Drug release kinetics paralleled sustained protection against HIV-1 challenge. After a single 45 mg/kg intramuscular injection to BALB/cJ mice, the NMCAB pharmacokinetic profiles was 4-times greater than that recorded for CAB LAP. These observations paralleled replicate measurements in rhesus macaques. The results coupled with improved viral restriction in human adult lymphocyte reconstituted NOD/SCID/IL2Rγc^−/− mice led us to conclude that NMCAB can improve biodistribution and viral clearance profiles upon current CAB LAP formulations.



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Reduced graphene oxide/BiFeO3 nanohybrids-based signal-on photoelectrochemical sensing system for prostate-specific antigen detection coupling with magnetic microfluidic device

Publication date: 15 March 2018
Source:Biosensors and Bioelectronics, Volume 101
Author(s): Qian Zhou, Youxiu Lin, Kangyao Zhang, Meijin Li, Dianping Tang
A novel magnetic controlled photoelectrochemical (PEC) sensing system was designed for sensitive detection of prostate-specific antigen (PSA) using reduced graphene oxide-functionalized BiFeO3 (rGO-BiFeO3) as the photoactive material and target-triggered hybridization chain reaction (HCR) for signal amplification. Remarkably enhanced PEC performance could be obtained by using rGO-BiFeO3 as the photoelectrode material due to its accelerated charge transfer and improved the visible light absorption. Additionally, efficient and simple operation could be achieved by introducing magnetic controlled flow-through device. The assay mainly involved in anchor DNA-conjugated magnetic bead (MB-aDNA), PSA aptamer/trigger DNA (Apt-tDNA) and two glucose oxidase-labeled hairpins (H1-GOx and H2-GOx). Upon addition of target PSA, the analyte initially reacted with the aptamer to release the trigger DNA, which partially hybridized with the anchor DNA on the MB. Thereafter, the unpaired trigger DNA on the MB opened the hairpin DNA structures in sequence and propagated a chain reaction of hybridization events between two alternating hairpins to form a long nicked double-helix with numerous GOx enzymes on it. Subsequently, the enzymatic product (H2O2) generated and consumed the photo-excited electrons from rGO-BiFeO3 under visible light irradiation to enhance the photocurrent. Under optimal conditions, the magnetic controlled PEC sensing system exhibited good photocurrent responses toward target PSA within the linear range of 0.001 − 100ng/mL with a detection limit of 0.31pg/mL. Moreover, favorable selectivity, good stability and satisfactory accuracy were obtained. The excellent analytical performance suggested that the rGO-BiFeO3-based PEC sensing platform could be a promising tool for sensitive, efficient and low cost detection of PSA in disease diagnostics.



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Hand-in-hand RNA nanowire-based aptasensor for the detection of theophylline

Publication date: 15 March 2018
Source:Biosensors and Bioelectronics, Volume 101
Author(s): Jue Wang, Wenbo Cheng, Fanyu Meng, Mo Yang, Yue Pan, Peng Miao
Theophylline is a popular drug for many respiratory diseases. However, certain toxic side effects may be developed and the narrow safety range raises the demand for sensitive methods to constantly monitor theophylline levels. This study presents an electrochemical approach towards theophylline detection based on the recognition by split RNA aptamers. Target induced construction of hand-in-hand RNA nanowire on the electrode surface could further absorb silver nanoparticles (Ag NPs) as electrochemical species. When theophylline is not present, RNA probes are stable and their conformations remain unchanged. In contrast, theophylline is able to trigger the hairpin opening of RNA probe and subsequent self-assembly of RNA nanowire, which could be captured by DNA tetrahedron on the electrode interface. After further decorating Ag NPs on the nanowire, silver stripping current is measured to reveal initial theophylline concentration. The developed sensing strategy shows excellent specificity and sensitivity with the limit of detection of 50nM. Its practical utility is demonstrated by quantitative determination of theophylline levels in complex biological samples.



http://ift.tt/2yIajSv

Bio-bar-code-based photoelectrochemical immunoassay for sensitive detection of prostate-specific antigen using rolling circle amplification and enzymatic biocatalytic precipitation

Publication date: 15 March 2018
Source:Biosensors and Bioelectronics, Volume 101
Author(s): Kangyao Zhang, Shuzhen Lv, Zhenzhen Lin, Meijin Li, Dianping Tang
Methods based on photoelectrochemistry have been developed for immunoassay, but most involve in a low sensitivity and a relatively narrow detectable range. Herein a new bio-bar-code-based split-type photoelectrochemical (PEC) immunoassay was designed for sensitive detection of prostate-specific antigen (PSA), coupling rolling circle amplification (RCA) with enzymatic biocatalytic precipitation. The bio-bar-code-based immunoreaction was carried out on monoclonal anti-PSA antibody (mAb1)-coated microplate using primer DNA and polyclonal anti-PSA antibody-conjugated gold nanoparticle (pDNA-AuNP-pAb2) with a sandwich-type assay format. Accompanying the immunocomplex, the labeled primer DNA on gold nanoparticle readily triggered RCA reaction in the presence of padlock probe/dNTPs/ligase/polymerase. The RCA product with a long single-stranded DNA could cause the formation of numerous hemin/G-quadruplex-based DNAzyme concatamers. With the assistance of nicking endonuclease, DNAzyme concatamers were dissociated from gold nanoparticle, which catalyzed the precipitation of 4-chloro-1-naphthol in the presence of H2O2 onto CdS nanorods-coated electrode (as the photoanode for the generated holes). The formed insoluble precipitate inhibited the electron transfer from the solution to CdS nanorods-modified electrode by using ascorbic acid as the electron donor. Under the optimum conditions, the photocurrent of the modified electrode decreased with the increasing of PSA concentration. A detectable concentration for target PSA with this system could be achieved as low as 1.8pgmL⁻¹. In addition, our strategy also showed good reproducibility, high specificity and accuracy matched well with commercial PSA ELISA kits for real sample analysis. These remarkable properties revealed that the developed PEC immunoassay has great potential as a useful tool for the detection of PSA in practical application.



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Multiple verrucous lesions of the feet in Waldenström macroglobulinaemia

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Traumatic subungual neuroma

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Scholar : These new articles for Levant are available online

The online platform for Taylor & Francis Online content New for Levant and online now on Taylor & Francis Online: Original Articles Environment, seasonality and hunting strategies as influences on Natufian food procurement: The faunal remains from Shubayqa 1 Lisa Yeomans, Tobias Richter & Louise Martin Pages: 1-29 | DOI: 10.1080/00758914.2017.1368820 Do you have original research that relates to present-day Japan and its recent historical development? Contemporary Japan welcomes your submissions. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Corrections are available online

The online platform for Taylor & Francis Online content New for Corrections and online now on Taylor & Francis Online: Original Articles The Impact of Discretionary Release on Offender Recidivism using Survival Analysis David Marble Pages: 1-14 | DOI: 10.1080/23774657.2017.1361799 Predicting Staff Assault in Juvenile Correctional Facilities David A. Rembert, Howard Henderson, Whitney Threadcraft-Walker & Sherri Simmons-Horton Pages: 1-16 | DOI: 10.1080/23774657.2017.1359126 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Amyloid are available online

The online platform for Taylor & Francis Online content New for Amyloid and online now on Taylor & Francis Online: Letter to the Editor Prevalence of mutant ATTR cardiac amyloidosis in elderly African Americans with heart failure Marios Arvanitis, Gloria G. Chan, Daniel R. Jacobson, John L. Berk , Lawreen H. Connors & Frederick L. Ruberg Pages: 1-3 | DOI: 10.1080/13506129.2017.1391086 Original Article Prognostic impact of immunoparesis at diagnosis and after treatment onset in patients with light-chain amyloidosis Luis Gerardo Rodríguez-Lobato , Carlos Fernández de Larrea , Maria Teresa Cibeira , Natalia Tovar, Ignacio Isola, Juan I. Aróstegui , Laura Rosiñol , Tania Díaz, Ester Lozano , Jordi Yagüe & Joan Bladé Pages: 1-8 | DOI: 10.1080/13506129.2017.1390451 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Voice and Speech Review are available online

The online platform for Taylor & Francis Online content New for Voice and Speech Review and online now on Taylor & Francis Online: Original Articles Stalking the calm buzz: how the polyvagal theory links stage presence, mammal evolution, and the root of the vocal nerve Joanna Cazden Pages: 1-22 | DOI: 10.1080/23268263.2017.1390036 Browse this free access collection on: Communication, Media and Culture in Asia. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Asian Geographer are available online

The online platform for Taylor & Francis Online content New for Asian Geographer and online now on Taylor & Francis Online: Original Articles Probing the position of the Jakarta metropolitan area in global inter-urban networks through the lens of manufacturing firms Galuh Syahbana Indraprahasta & Ben Derudder Pages: 1-21 | DOI: 10.1080/10225706.2017.1387161 Do you have original research that relates to present-day Japan and its recent historical development? Contemporary Japan welcomes your submissions. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for The American Journal of Family Therapy are available online

The online platform for Taylor & Francis Online content New for The American Journal of Family Therapy and online now on Taylor & Francis Online: Original Articles "I'm Not a Gadget": A Grounded Theory on Unplugging Neli Morris & Jaclyn D. Cravens Pickens Pages: 1-19 | DOI: 10.1080/01926187.2017.1365665 2018 Future Directions Forum JOIN US at the 2018 Future Directions Forum for Journal of Clinical Child & Adolescent Psychology - June 15-16, 2018 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : Philosophical Magazine, Volume 97, Issue 33, November 2017 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Philosophical Magazine, Volume 97, Issue 33, November 2017 is now available online on Taylor & Francis Online. This new issue contains the following articles: Part A: Materials Science Semi-coherent interfaces without length misfit accommodation in a lamellar Al–Al2Cu eutectic Roland Bonnet Pages: 3055-3083 | DOI: 10.1080/14786435.2017.1366082 Fracture complexity of pressure vessel steels Arpan Das Pages: 3084-3141 | DOI: 10.1080/14786435.2017.1367857 Void growth via atomistic simulation: will the formation of shear loops still grow a void under different thermo-mechanical constraints? Y. Cui & Z. T. Chen Pages: 3142-3171 | DOI: 10.1080/14786435.2017.1369192 Hardening mechanisms in olivine single crystal deformed at 1090 °C: an electron tomography study | Alexandre Mussi , Patrick Cordier , Sylvie Demouchy & Benoit Hue Pages: 3172-3185 | DOI: 10.1080/14786435.2017.1367858 Love waves in layered flexoelectric structures Wenjun Yang, Xu Liang & Shengping Shen Pages: 3186-3209 | DOI: 10.1080/14786435.2017.1378825 Free access to articles in this Editor's Choice collection from the Journal of Control and Decision. Don't miss it! To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.