A Systematic Evaluation of the Two-Component Systems Network Reveals That ArlRS Is a Key Regulator of Catheter Colonization by Staphylococcus aureus.

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A Systematic Evaluation of the Two-Component Systems Network Reveals That ArlRS Is a Key Regulator of Catheter Colonization by Staphylococcus aureus.

Front Microbiol. 2018;9:342

Authors: Burgui S, Gil C, Solano C, Lasa I, Valle J

Abstract
Two-component systems (TCS) are modular signal transduction pathways that allow cells to adapt to prevailing environmental conditions by modifying cellular physiology. Staphylococcus aureus has 16 TCSs to adapt to the diverse microenvironments encountered during its life cycle, including host tissues and implanted medical devices. S. aureus is particularly prone to cause infections associated to medical devices, whose surfaces coated by serum proteins constitute a particular environment. Identification of the TCSs involved in the adaptation of S. aureus to colonize and survive on the surface of implanted devices remains largely unexplored. Here, using an in vivo catheter infection model and a collection of mutants in each non-essential TCS of S. aureus, we investigated the requirement of each TCS for colonizing the implanted catheter. Among the 15 mutants in non-essential TCSs, the arl mutant exhibited the strongest deficiency in the capacity to colonize implanted catheters. Moreover, the arl mutant was the only one presenting a major deficit in PNAG production, the main exopolysaccharide of the S. aureus biofilm matrix whose synthesis is mediated by the icaADBC locus. Regulation of PNAG synthesis by ArlRS occurred through repression of IcaR, a transcriptional repressor of icaADBC operon expression. Deficiency in catheter colonization was restored when the arl mutant was complemented with the icaADBC operon. MgrA, a global transcriptional regulator downstream ArlRS that accounts for a large part of the arlRS regulon, was unable to restore PNAG expression and catheter colonization deficiency of the arlRS mutant. These findings indicate that ArlRS is the key TCS to biofilm formation on the surface of implanted catheters and that activation of PNAG exopolysaccharide production is, among the many traits controlled by the ArlRS system, a major contributor to catheter colonization.

PMID: 29563900 [PubMed]

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Infective Endocarditis Associated with Atopic Dermatitis.

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Infective Endocarditis Associated with Atopic Dermatitis.

Int Heart J. 2018 Mar 20;:

Authors: Aoyagi S, Oda T, Wada K, Nakamura E, Kosuga T, Yasunaga H

Abstract
We report a case of aortic valve infective endocarditis (IE) in a 24-year-old man with atopic dermatitis (AD). He had a history of balloon valvuloplasty for a stenotic bicuspid aortic valve, and had dental caries but no invasive dental procedure before the onset of IE. On admission, skin lesions of AD with itching and scratches were found on the neck, trunk, and extremities. Echocardiography showed a vegetation on the aortic valve with mild steno-regurgitation, but extension of IE to the annulus was not detected. Magnetic resonance imaging identified fresh cerebral infarction without neurological dysfunction, leading us to suspect an embolism. Blood cultures grew methicillin-sensitive Staphylococcus aureus. During emergency surgery, a vegetation attached to the conjoined cusp was observed, and the aortic valve was replaced with a mechanical valve. The patient recovered uneventfully without any complications such as recurrent IE or mediastinitis. We also review previously reported cases of IE associated with AD.

PMID: 29563378 [PubMed - as supplied by publisher]

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Numerical and experimental investigation on thermal shock failure of Y2O3-coated CVD ZnS infrared windows

Publication date: September 2018
Source:International Journal of Heat and Mass Transfer, Volume 124
Author(s): Xing Liu, Jiaqi Zhu, Jiecai Han
Infrared transparent windows on aircraft and missiles can be subjected to extreme aerothermodynamics, which can cause thermal shock failure. Finite element analysis and oxygen–propane flame jet impingement tests were performed to investigate the thermal shock failure of an yttrium oxide-coated chemical vapor deposition (CVD) ZnS infrared window. Good agreement was achieved between the simulation and experimental results, which indicated that thermal shock failure occurs under high temperature differences and thermal stresses. The temperature and stress in the samples increased rapidly in a few seconds and then trended to be stable. The center area of the window surface failed most easily because the maximum temperature and stress both occurred in this area. No delamination of the Y2O3 films occurred during the thermal shock, which indicated good adhesion between the Y2O3 films and CVD ZnS substrate. In the experiment, the center area of the specimen surface was damaged in the form of pits and line cracks.



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Synthesis, characterization, nucleic acid interactions and photoluminescent properties of methaniminium hydrazone Schiff base and its Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes

Publication date: 15 July 2018
Source:Journal of Molecular Structure, Volume 1164
Author(s): M. Sennappan, P. Murali Krishna, Amar A. Hosamani, R. Hari Krishna
An environmental benign and efficient reaction was carried out via amine exchange and condensation reaction in water and methanol mixture (3:1) and absence of catalyst between 1-[3-(2-hydroxy benzylidene)amine)phenyl]ethanone and benzhydrazide yields methaniminium hydrazone Schiff base in high yield. The prepared ligand was structurally characterized by using single crystal XRD, elemental analysis and spectroscopy (UV–Vis, FT-IR, LC-MS and NMR) techniques. The crystal data indicates the ligand crystallizes in orthorhombic system with Pna21 space group. Further, the ligand was used in synthesis of mononuclear Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes and were characterized by elemental analysis, magnetic moment and spectroscopy (UV–Vis, FT-IR and ESR) studies. The spectral data showed that ligand is coordinated to the metal ion through azomethine nitrogen and methaniminium nitrogen. The DNA binding absorption titrations reveals that, ligand, L and its metal complexes, 1–6 are avid binders to CT- DNA. The apparent binding constant values of compounds are in the order of 10⁶ M⁻¹. The nuclease activity of ligand, L and its metal complexes, 1–6 were investigated by gel electrophoresis method using pUC¹⁸ DNA. The photoluminescent properties of the methaniminium hydrazone ligand, L and its various metal complexes, 1–6 were investigated. The emission spectra of both ligand (L) and metal complexes (1-6) exhibits emission in the range of blue to red.

Graphical abstract

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Effect of ultraprecision polishing techniques on coherence times of shallow nitrogen-vacancy centers in diamond

Publication date: Available online 23 March 2018
Source:Diamond and Related Materials
Author(s): G. Braunbeck, S. Mandal, M. Touge, O.A. Williams, F. Reinhard
We investigate the correlation between surface roughness and corresponding T2 times of near-surface nitrogen-vacancy centers (~10 nm/5 keV implantation energy) in diamond. For this purpose we compare five different polishing techniques, including both purely mechanical as well as chemical mechanical approaches, two different substrate sources (Diam2tec and Element Six) and two different surface terminations (O- and H-termination) during nitrogen-vacancy forming. All coherence times are measured and compared before and after an oxygen surface treatment at 520 °C.We find that the coherence times of shallow nitrogen-vacancy centers are surprisingly independent of surface roughness.

Graphical abstract

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The effect of wildfire on population dynamics for two native small mammal species in a coastal heathland in Queensland, Australia

Publication date: April 2018
Source:Acta Oecologica, Volume 88
Author(s): Adam C. Liedloff, John C. Wilson, Richard M. Engeman
The influences of wildfire through population dynamics and life history for two species of small mammals in a south-east Queensland heathland on Bribie Island are presented. Trapping results provided information on breeding, immigration and movement of Melomys burtoni (Grassland melomys) and Rattus lutreolus (Swamp rat). We first investigated and optimized the design of trapping methodology for producing mark-recapture population estimates to compare two adjacent populations, one of which was subjected to an extensive wildfire during the two year study. We consider how well rodents survive wildfire and whether the immediate impacts of fire or altered habitat have the greatest impact on each species. We found the R. lutreolus population was far more influenced by the fire than the M. burtoni population both immediately after the fire and over 18 months of vegetation recovery.



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Pancreaticobiliary Trauma – A Multimodality Imaging Update

Publication date: Available online 23 March 2018
Source:Seminars in Ultrasound, CT and MRI
Author(s): Staci Gagne, Bryan O′Sullivan-Murphy, Hao S. Lo, Lacey J. McIntosh
Pancreaticobiliary injury is an uncommon entity which more often occurs in the setting of blunt than penetrating trauma. We present cases of pancreaticobiliary traumatic injuries from our level one trauma center to illustrate an imaging update on the spectrum of injuries and correlation with current grading systems.



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Multidetector CT Imaging of Bowel and Mesenteric Injury: Review of Key Signs

Publication date: Available online 23 March 2018
Source:Seminars in Ultrasound, CT and MRI
Author(s): Andrew E. Bennett, Robin B. Levenson, Jon D. Dorfman
In contemporary practice, multidetector computed tomography (MDCT) plays a critical role in the diagnostic evaluation of patients with suspected acute mesenteric and bowel trauma. Although less common than solid organ injuries, it may be seen in up to 5% of blunt trauma patients. Evaluation with CT remains challenging even with improvements in technology. The major imaging signs of mesenteric and bowel trauma and what is known about their applicability in clinical practice are reviewed here. Examples illustrate both the subtlety and variable significance of many of the key signs as well as how these are typically integrated into clinical practice.



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ESR2 regulates granulosa cell genes essential for follicle maturation and ovulation

Publication date: Available online 24 March 2018
Source:Molecular and Cellular Endocrinology
Author(s): Vincentaben Khristi, V. Praveen Chakravarthi, Prabhakar Singh, Subhra Ghosh, Archit Pramanik, Anamika Ratri, Shaon Borosha, Katherine F. Roby, Michael W. Wolfe, M.A. Karim Rumi
Estrogen receptor 2 (ESR2) plays a critical role in folliculogenesis and ovulation. Disruption of ESR2-function in the rats results in female infertility due to failure of ovulation. Ovulation failure occurred in two distinct rat models, a null mutant and a DNA binding domain (DBD) mutant of ESR2, indicating that transcriptional regulation by ESR2 is indispensable for ovulation. To define the regulatory role of ESR2 in preovulatory follicular maturation and ovulation, we investigated ovarian responsiveness to exogenous gonadotropins in prepubertal females. Granulosa cells (GCs) play a vital role in follicle maturation and ovulation, and ESR2-dependent estrogen signaling is predominant in GCs, therefore, we examined the differential expression of gonadotropin-induced genes in GCs. Of 32,623 genes detected by RNA-sequencing, 1696 were differentially expressed in Esr2-mutant rats (789 downregulated, and 907 upregulated, absolute fold change 2, FDR p < 0.05). Molecular pathway analyses indicated that these differentially expressed genes are involved in steroidogenesis, follicle maturation, and ovulation. Many of these genes are known regulators of ovarian function and a subset were also disrupted in Esr2-mutant mice. Interestingly, Kiss1 was identified as one of the differentially expressed genes implicating a potential role within the follicle and its regulation by ESR2. Our findings indicate that ESR2 regulates key genes in GCs that are essential for follicle maturation and ovulation in the rat.



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Emodin protects hyperglycemia-induced injury in PC-12 cells by up-regulation of miR-9

Publication date: Available online 23 March 2018
Source:Molecular and Cellular Endocrinology
Author(s): Lei Fan, Huifeng Zhang, Xiaobin Li, Guang Yang, Jingtao Ru, Tao Liu
BackgroundDiabetic foot is a severe complication of diabetes mellitus, mainly caused by diabetic peripheral neuropathy. The objective of this study was to investigate the function of emodin (a neuroprotective agent reported previously) in diabetic peripheral neuropathy.MethodsA neuron-like cell line PC-12 was subjected with high level glucose, before which emodin was applied to treat cells. The expression of miR-9 in cell was overexpressed or suppressed by miRNA transfection. Thereafter, cell viability, apoptosis and autophagy were assessed, respectively.ResultsHigh glucose exhibited cytotoxicity in PC-12 cells. Emodin protected PC-12 cells against high glucose-induced apoptosis and viability impairment. These observations were coupled with the down-regulations of p21, p16, Bax, cleaved caspase-3 and -9, and the up-regulations of CyclinD1 and Bcl-2. Additionally, high glucose-induced autophagy was alleviated by emodin, as Beclin-1 was down-regulated, p62 was up-regulated, and the conversion of LC3-I to LC3-II was decreased. miR-9 was highly expressed in response to emodin treatment. More interestingly, the protective actions of emodin on high glucose-induced injury were reversed by miR-9 suppression. Also, the activation of PI3K/AKT signaling and deactivation of NF-κB signaling induced by emodin were recovered by miR-9 suppression.ConclusionEmodin protected PC-12 cells against high glucose-induced apoptosis and autophagy. The neuroprotective activities might be realized by up-regulation of miR-9, and modulation of PI3K/AKT and NF-κB signaling pathways.



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GW0742 (PPAR-beta agonist) attenuates hepatic endoplasmic reticulum stress by improving hepatic energy metabolism in high-fat diet fed mice

Publication date: Available online 23 March 2018
Source:Molecular and Cellular Endocrinology
Author(s): Flavia Maria Silva-Veiga, Tamiris Lima Rachid, Letícia de Oliveira, Francielle Graus-Nunes, Carlos Alberto Mandarim-de-Lacerda, Vanessa Souza-Mello
Endoplasmic reticulum (ER) stress and hepatic steatosis are intertwined with insulin resistance. PPARs are at the crossroads of these pathways. This study aimed to investigate the effects of GW0742 (PPAR-beta agonist) on hepatic energy metabolism and ER stress in a murine diet-induced obesity model. HF diet caused overweight, hyperinsulinemia, hepatic inflammation (increased NF-kB, TNF-alpha, and IL-6 protein expression) and favored hepatic lipogenesis, leading to ER stress, with ultrastructural and molecular alterations, ending up in proapoptotic stimulus. GW0742 rescued the overweight and the glucose tolerance, tackled hepatic inflammation and favored hepatic beta-oxidation over lipogenesis. These results comply with ER ultrastructure improvement, reducing ER stress and apoptosis in treated animals. Our results indicate that the PPAR-beta/delta activation alleviated the ER stress by improving the insulin sensitivity and maximizing the hepatic energy metabolism with a shift towards beta-oxidation. PPAR-beta/delta activation could be an essential tool to avoid the NAFLD progression and other obesity constraints.



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Multi-locus transcranial magnetic stimulation—theory and implementation

Publication date: Available online 23 March 2018
Source:Brain Stimulation
Author(s): Lari M. Koponen, Jaakko O. Nieminen, Risto J. Ilmoniemi
BackgroundTranscranial magnetic stimulation (TMS) is a non-invasive brain stimulation method: a magnetic field pulse from a TMS coil can excite neurons in a desired location of the cortex. Conventional TMS coils cause focal stimulation underneath the coil centre; to change the location of the stimulated spot, the coil must be moved over the new target. This physical movement is inherently slow, which limits, for example, feedback-controlled stimulation.ObjectiveTo overcome the limitations of physical TMS coil movement by introducing electronic targeting.MethodsWe propose electronic stimulation targeting using a set of large overlapping coils and introduce a matrix-factorisation-based method to design such sets of coils. We built one such device and demonstrated the electronic stimulation targeting in vivo.ResultsThe demonstrated two-coil transducer allows translating the stimulated spot along a 30-mm line segment in the cortex; with five coils, a target can be selected from within a region of the cortex and stimulated in any direction. Thus, far fewer coils are required by our approach than by previously suggested ones, none of which have resulted in practical devices.ConclusionAlready with two coils, we can adjust the location of the induced electric field maximum along one dimension, which is sufficient to study, for example, the primary motor cortex.



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Editorial Board and Contents

Publication date: April 2018
Source:Trends in Cell Biology, Volume 28, Issue 4





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Modulating ion channel function with antibodies and nanobodies

Publication date: June 2018
Source:Current Opinion in Immunology, Volume 52
Author(s): Catelijne Stortelers, Carolina Pinto-Espinoza, Diane Van Hoorick, Friedrich Koch-Nolte
Immune cells express various voltage-gated and ligand-gated ion channels that mediate the influx and efflux of charged ions across the plasma membrane, thereby controlling the membrane potential and mediating intracellular signal transduction pathways. These channels thus present potential targets for experimental modulation of immune responses and for therapeutic interventions in immune disease. Small molecule drugs and natural toxins acting on ion channels have illustrated the potential therapeutic benefit of targeting ion channels on immune cells. Unwanted side effects and immunogenicity have however hampered the application of these molecules. Owing to their high specificity, low immunogenicity and beneficial pharmacodynamics, antibodies targeting membrane and secretory proteins have emerged as potent therapeutics in oncology and inflammation. Nanobodies—single domain fragments derived from heavy chain antibodies naturally occurring in camelids—offer additional benefits versus antibodies, including protrusion into cryptic epitopes and easy formatting of multi-specific reagents. Here we review recent progress in the development and application of antibodies and Nanobodies targeting ion channels on immune cells.



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A Phase I Trial of the IGF‐1R Antibody Ganitumab (AMG 479) in Combination with Everolimus (RAD001) and Panitumumab in Patients with Advanced Cancer

AbstractPurpose.This study evaluated the maximum tolerated dose or recommended phase II dose (RPTD) and safety and tolerability of the ganitumab and everolimus doublet regimen followed by the ganitumab, everolimus, and panitumumab triplet regimen.Materials and Methods.This was a standard 3 + 3 dose escalation trial. Doublet therapy consisted of ganitumab at 12 mg/kg every 2 weeks; doses of everolimus were adjusted according to dose‐limiting toxicities (DLTs). Panitumumab at 4.8 mg/kg every 2 weeks was added to the RPTD of ganitumab and everolimus. DLTs were assessed in cycle 1; toxicity evaluation was closely monitored throughout treatment. Treatment continued until disease progression or undesirable toxicity. Pretreatment and on‐treatment skin biopsies were collected to assess insulin‐like growth factor 1 receptor and mammalian target of rapamycin (mTOR) target modulation.Results.Forty‐three subjects were enrolled. In the doublet regimen, two DLTs were observed in cohort 1, no DLTs in cohort −1, and one in cohort −1B. The triplet combination was discontinued because of unacceptable toxicity. Common adverse events were thrombocytopenia/neutropenia, skin rash, mucositis, fatigue, and hyperglycemia. In the doublet regimen, two patients with refractory non‐small cell lung cancer (NSCLC) achieved prolonged complete responses ranging from 18 to >60 months; one treatment‐naïve patient with chondrosarcoma achieved prolonged stable disease >24 months. In dermal granulation tissue, the insulin‐like growth factor receptor and mTOR pathways were potently and specifically inhibited by ganitumab and everolimus, respectively.Conclusion.The triplet regimen of ganitumab, everolimus, and panitumumab was associated with unacceptable toxicity. However, the doublet of ganitumab at 12 mg/kg every 2 weeks and everolimus five times weekly had an acceptable safety profile and demonstrated notable clinical activity in patients with refractory NSCLC and sarcoma.Implications for Practice.This trial evaluated the maximum tolerated dose or recommended phase II dose and safety and tolerability of the ganitumab and everolimus doublet regimen followed by the ganitumab, everolimus, and panitumumab triplet regimen. Although the triplet regimen of ganitumab, everolimus, and panitumumab was associated with unacceptable toxicity, the doublet of ganitumab at 12 mg/kg every 2 weeks and everolimus at five times weekly had an acceptable safety profile and demonstrated notable clinical activity in patients with refractory non‐small cell lung cancer and sarcoma.

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Alamandine injected into the paraventricular nucleus increases blood pressure and sympathetic activation in spontaneously hypertensive rats

Publication date: Available online 23 March 2018
Source:Peptides
Author(s): Yi-Hui Shen, Xi-Ru Chen, Chun-Xi Yang, Bo-Xun Liu, Peng Li
Alamandine is a newly discovered new component of the renin-angiotensin (Ang) system (RAS) that has been shown to exert vasoactive effects in some areas of the nervous system. The present study investigated whether administration of alamandine to the hypothalamic paraventricular nucleus (PVN) modulates blood pressure and sympathetic activity. Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were recorded in anaesthetized rats. PVN microinjection of alamandine increased MAP and RSNA both in Wistar-Kyoto (WKY) rats and in spontaneously hypertensive rats (SHRs), but to a greater extent in SHRs. Moreover, these effects were blocked by pretreatment with alamandine receptor Mas-related G-protein–coupled receptor, member D (MrgD) antagonist D-Pro⁷-Ang-(1-7), adenylyl cyclase (AC) inhibitor SQ22536, and protein kinase A (PKA) inhibitor rp-adenosine-3′,5′-cyclic monophosphorothionate (Rp-cAMP). Treatment with D-Pro⁷-Ang-(1-7), SQ22536, or Rp-cAMP alone in PVN decreased MAP and RSNA in the SHRs. Conversely cAMP alone increased MAP and RSNA, and pretreatment with cAMP enhanced alamandine's effects. These results indicate that microinjection of alamandine into the PVN increases blood pressure and sympathetic outflow via MrgD and the cAMP-PKA pathway.



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Periodontal and endodontic infectious/inflammatory profile in primary periodontal lesions with secondary endodontic involvement after a calcium hydroxide-based intracanal medication

Abstract

Objective

The aim of the present study was to investigate the effects of a calcium hydroxide-based intracanal medication (ICM) on periodontal and endodontic infectious/inflammatory contents and on periodontal clinical parameters in teeth with primary periodontal lesion and secondary endodontic involvement.

Materials and methods

Ten patients with abnormal pulp test results and deep probing depth derived from primary periodontal disease with secondary endodontic involvement were included. Samples were collected from root canals (RC) and periodontal pockets (PP) in order to investigate the microbiological status, levels of endotoxin (LPS), cytokines, and matrix metalloproteinases (MMP), before and after ICM. PCR was used for microbiological assessment. The kinetic-chromogenic LAL assay was used for LPS quantification. Quantikine ELISA kits were used for measurement of IL-1 α, IL-1 β, TNF-α, PGE₂, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-13 levels. The statistical analyses were made using the Friedman and Wilcoxon tests (p < 0.05). T test was used to compare data on periodontal characteristics.

Results

ICM did not reduce the number of microorganisms in PP and RC, except for Fusobacterium nucleatum in RC. There was a significant reduction in LPS, MMPs, IL-1 β, and TNF-α levels in PP after ICM. In RC, LPS, MMP13, PGE₂, and IL-1β levels remained unaltered (p > 0.05); however, the levels of the other MMPs and cytokines were reduced (p < 0.05). After 1 year of the root canal treatment, tooth mobility was significantly reduced (p ≤ 0.05).

Conclusions

The use of a calcium hydroxide-based ICM showed positive effects for periodontal treatment prognosis, as it reduced LPS, cytokine, and MMP levels in periodontal pockets.

Clinical significance

Patients presenting deep probing depth and undergoing periodontal treatment for at least 6 months, with no positive response to periodontal therapy, might benefit with the endodontic treatment.

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Probabilistic Guidance for Catheter Tip Motion in Cardiac Ablation Procedures

Publication date: Available online 23 March 2018
Source:Medical Image Analysis
Author(s): Mihaela AM Constantinescu, Su-Lin Lee, Sabine Ernst, Apit Hemakom, Danilo Mandic, Guang-Zhong Yang
Radiofrequency catheter ablation is one of the commonly available therapeutic methods for patients suffering from cardiac arrhythmias. The prerequisite of successful ablation is sufficient energy delivery at the target site. However, cardiac and respiratory motion, coupled with endocardial irregularities, can cause catheter drift and dispersion of the radiofrequency energy, thus prolonging procedure time, damaging adjacent tissue, and leading to electrical reconnection of temporarily ablated regions. Therefore, positional accuracy and stability of the catheter tip during energy delivery is of great importance for the outcome of the procedure. This paper presents an analytical scheme for assessing catheter tip stability, whereby a sequence of catheter tip motion recorded at sparse locations on the endocardium is decomposed. The spatial sliding component along the endocardial wall is extracted from the recording and maximal slippage and its associated probability are computed at each mapping point. Finally, a global map is generated, allowing the assessment of potential areas that are compromised by tip slippage. The proposed framework was applied to 40 retrospective studies of congenital heart disease patients and further validated on phantom data and simulations. The results show a good correlation with other intraoperative factors, such as catheter tip contact force amplitude and orientation, and with clinically documented anatomical areas of high catheter tip instability.

Graphical abstract

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A tumor-activatable particle with antimetastatic potential in breast cancer via inhibiting the autophagy-dependent disassembly of focal adhesion

Publication date: June 2018
Source:Biomaterials, Volume 168
Author(s): Yang Wang, Sheng Yin, Li Zhang, Kairong Shi, Jiajing Tang, Zhirong Zhang, Qin He
In attempts to explore the role of autophagy in breast cancer metastasis, we here report a tumor-activatable particle (named as "D/PSP@CQ/CaP") with the ability of efficient autophagy inhibition. D/PSP@CQ/CaP was prepared by coprecipitating chloroquine phosphate (CQ) with calcium chloride, in the form of chloroquine-calcium phosphate coprecipitate (CQ/CaP), onto the surface of a deep-tumor-penetrating doxorubicine (DOX)-loading core particle (named as "D/PSP"). CQ/CaP could partly disintegrate and release CQ within tumor microenvironment and totally be dissolved within lysosomes. Paxillin is a key component of focal adhesion which functions to anchor tumors cells within the primary tumor for limiting cancer cells' detachment from the primary tumor. We tested that autophagy inhibition caused by CQ released from CQ/CaP could reduce the degradation of paxillin by 2.9 folds in vitro and 2.5 folds in vivo (vs. Control), respectively. Thus metastasis could be influenced by exploiting autophagy-dependent paxillin degradation. Data analysis together proved that D/PSP@CQ/CaP decreased the cancer metastatic extent by 7.5 folds (vs. Control) on mice model via inhibiting the autophagy-dependent disassembly of focal adhesion. At the same time, the growth rate of tumors treated by D/PSP@CQ/CaP was inhibited by 9.1 folds (vs. Control), which could be attributed to its effective tumor drug delivery.

Graphical abstract

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Picky eating and food neophobia: Resemblance and agreement in parent/young adult dyads

Publication date: 1 July 2018
Source:Appetite, Volume 126
Author(s): Anjeli Elkins, Hana F. Zickgraf
ObjectiveTo explore selective eating in two samples: young adults and their middle aged parents, including the relationship between food neophobia and picky eating in each, resemblance between children and parents in these eating behaviors, agreement between child self-report and parent report on children's eating, and the relationship between parent eating behavior and parent-report on children's eating. We also explored the relationship between socioeconomic status and picky eating and food neophobia in each sample.MethodUniversity students responded to questionnaires assessing picky eating and food neophobia. Their parents were contacted and asked to complete the same measure about their own picky- and food neophobic behaviors and to report on their child's current picky eating and food neophobia. The final sample included 109 biological parent-child pairs.ResultsThere were large positive correlations between food neophobia and picky eating in both samples. There were positive associations between parents' and children's self-reported selective eating behaviors. There was evidence of parent-child agreement in reporting on the child's selective eating, but also considerable variability between raters. This variability between child self-report and parent report was partially accounted for by parental selective eating. Finally, young adults from a lower-SES background (e.g., lower parent educational attainment and income) reported higher levels of pickiness and food neophobia.ConclusionsYoung adult children and their parents resemble each other in pickiness and food neophobia.



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A literature scoping review of eating practices and food environments in 1 and 2-person households in the UK, Australia and USA

Publication date: 1 July 2018
Source:Appetite, Volume 126
Author(s): Fidelma Breen, John Coveney, Carol Anne Hartwick Pflaum
The purpose of this article is to map the data currently available on the subject of eating practices and food environments in small (i.e. one- and two-person) households. Specifically, the enquiry is focused on commensality; the act of eating together. Research dates from the late 1980s, however, there are few recent publications on this subject. Searching Ovid MEDLINE, PsycINFO, CINAHL, Web of Science, Scopus, ProQuest and Google Scholar, 2949 papers were found, but only 457 discussed any element of the research questions. These were further distilled to a count of 117, by abstract reading to 53 at which point, quality, location and study focus eliminated a further 34 articles leaving 19 articles. After full reading, it was clear that only seven of these focused on the research question in detail and these are marked as four-star articles by bold text. The 19 articles are analysed for quality and their aspects of relevance to the central research question is discussed.



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Assessment of neurohepatic DNA damage in male Sprague–Dawley rats exposed to organophosphates and pyrethroid insecticides

Abstract

The current work was undertaken to test the genotoxic potential of chlorpyrifos (CPF), dimethoate, and lambda cyhalothrin (LCT) insecticides in rat brain and liver using the single cell gel electrophoresis (comet assay). Three groups of adult male Sprague–Dawley rats were exposed orally to one third LD₅₀of CPF, dimethoate, or LCT for 24 and 48 h while the control group received corn oil. Serum samples were collected for estimation of malondialdehyde (MDA) and glutathione peroxidase (GPx); the brain and liver samples were used for comet assay and for histopathological examination. Results showed that signs of neurotoxicity appeared clinically as backward stretching of hind limb and splayed gait in dimethoate and LCT groups, respectively. CPF, LCT, and dimethoate induced oxidative stress indicated by increased MDA and decreased GPx levels. CPF and LCT caused severe DNA damage in the brain and liver at 24 and 48 h indicated by increased percentage of DNA in tail, tail length, tail moment, and olive tail moment. Dimethoate induced mild DNA damage in the brain and liver at 48 h. Histopathological changes were observed in the cerebrum, cerebellum, and liver of exposed rats. The results concluded that CPF, LCT, and dimethoate insecticides induced oxidative stress and DNA damage associated with histological changes in the brain and liver of exposed rats.

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An Evolving Understanding of the S-Glutathionylation Cycle in Pathways of Redox Regulation

Publication date: Available online 23 March 2018
Source:Free Radical Biology and Medicine
Author(s): Jie Zhang, Zhi-wei Ye, Shweta Singh, Danyelle M. Townsend, Kenneth D. Tew
By nature of the reversibility of the addition of glutathione to low pKa cysteine residues, the post-translational modification of S-glutathionylation sanctions a cycle that can create a conduit for cell signaling events linked with cellular exposure to oxidative or nitrosative stress. The modification can also avert proteolysis by protection from over-oxidation of those clusters of target proteins that are substrates. Altered functions are associated with S-glutathionylation of proteins within the mitochondria and endoplasmic reticulum compartments, and these impact energy production and protein folding pathways. The existence of human polymorphisms of enzymes involved in the cycle (particularly glutathione S-transferase P) create a scenario for inter-individual variance in response to oxidative stress and a number of human diseases with associated aberrant S-glutathionylation have now been identified.

Graphical abstract

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Optimizing text for an individual’s visual system: The contribution of visual crowding to reading difficulties

Publication date: Available online 23 March 2018
Source:Cortex
Author(s): Sung Jun Joo, Alex L. White, Douglas J. Strodtman, Jason D. Yeatman
Reading is a complex process that involves low-level visual processing, phonological processing, and higher-level semantic processing. Given that skilled reading requires integrating information among these different systems, it is likely that reading difficulty—known as dyslexia—can emerge from impairments at any stage of the reading circuitry. To understand contributing factors to reading difficulties within individuals, it is necessary to diagnose the function of each component of the reading circuitry. Here, we investigated whether adults with dyslexia who have impairments in visual processing respond to a visual manipulation specifically targeting their impairment. We collected psychophysical measures of visual crowding and tested how each individual's reading performance was affected by increased text-spacing, a manipulation designed to alleviate severe crowding. Critically, we identified a sub-group of individuals with dyslexia showing elevated crowding and found that these individuals read faster when text was rendered with increased letter-, word- and line-spacing. Our findings point to a subtype of dyslexia involving elevated crowding and demonstrate that individuals benefit from interventions personalized to their specific impairments.



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Patterns Of Neural Response In Face Regions Are Predicted By Low-Level Image Properties

Publication date: Available online 23 March 2018
Source:Cortex
Author(s): Katja Weibert, Tessa R. Flack, Andrew W. Young, Timothy J. Andrews
Models of face processing suggest that the neural response in different face regions is selective for higher-level attributes of the face, such as identity and expression. However, it remains unclear to what extent the response in these regions can also be explained by more basic organizing principles. Here, we used fMRI-MVPA to ask whether spatial patterns of response in the core face regions (OFA, FFA, STS) can be predicted across different participants by lower level properties of the stimulus. First, we compared the neural response to face identity and viewpoint, by showing images of different identities from different viewpoints. The patterns of neural response in the core face regions were predicted by the viewpoint, but not the identity of the face. Next, we compared the neural response to viewpoint and expression, by showing images with different expressions from different viewpoints. Again, viewpoint, but not expression, predicted patterns of response in face regions. Finally, we show that the effect of viewpoint in both experiments could be explained by changes in low-level image properties. Our results suggest that a key determinant of the neural representation in these core face regions involves lower-level image properties rather than an explicit representation of higher-level attributes in the face. The advantage of a relatively image-based representation is that it can be used flexibly in the perception of faces.



https://ift.tt/2pzjFKF

Supramodal agnosia for oblique mirror orientation in patients with periventricular leukomalacia

Publication date: Available online 22 March 2018
Source:Cortex
Author(s): E. Castaldi, F. Tinelli, M. Cicchini, M.C. Morrone
Periventricular leukomalacia (PVL) is characterized by focal necrosis at the level of the periventricular white matter, often observed in preterm infants. PVL is frequently associated with motor impairment and with visual deficits affecting primary stages of visual processes as well as higher visual cognitive abilities. Here we describe six PVL subjects, with normal verbal IQ, showing orientation perception deficits in both the haptic and visual domains. Subjects were asked to compare the orientation of two stimuli presented simultaneously or sequentially, using both a two alternative forced choice (2AFC) orientation-discrimination and a matching procedure. Visual stimuli were oriented gratings or bars or collinear short lines embedded within a random pattern. Haptic stimuli comprised two rotatable wooden sticks. PVL patients performed at chance in discriminating the oblique orientation, both for visual and haptic stimuli. Moreover when asked to reproduce the oblique orientation, they often oriented the stimulus along the symmetric mirror orientation. The deficit generalized to stimuli varying in many low level features, was invariant for spatiotopic object orientation, and also occurred for sequential presentations. The deficit was specific to oblique orientations, and not for horizontal or vertical stimuli. These findings show that PVL can affect a specific network involved with the supramodal perception of mirror symmetry orientation.



https://ift.tt/2HW5iH2

Learning for Pitch and Melody Discrimination in Congenital Amusia

Publication date: Available online 23 March 2018
Source:Cortex
Author(s): Kelly L. Whiteford, Andrew J. Oxenham
Congenital amusia is currently thought to be a life-long neurogenetic disorder in music perception, impervious to training in pitch or melody discrimination. This study provides an explicit test of whether amusic deficits can be reduced with training. Twenty amusics and 20 matched controls participated in four sessions of psychophysical training involving either pure-tone (500 Hz) pitch discrimination or a control task of lateralization (interaural level differences for bandpass white noise). Pure-tone pitch discrimination at low, medium, and high frequencies (500, 2000, and 8000 Hz) was measured before and after training (pretest and posttest) to determine the specificity of learning. Melody discrimination was also assessed before and after training using the full Montreal Battery of Evaluation of Amusia, the most widely used standardized test to diagnose amusia. Amusics performed more poorly than controls in pitch but not localization discrimination, but both groups improved with practice on the trained stimulus. Learning was broad, occurring across all three frequencies and melody discrimination for all groups, including those who trained on the non-pitch control task. Following training, 11 of 20 amusics no longer met the global diagnostic criteria for amusia. A separate group of untrained controls (n=20), who also completed melody discrimination and pretest, improved by an equal amount as trained controls on all measures, suggesting that the bulk of learning for the control group occurred very rapidly from the pretest. Thirty-one trained participants (13 amusics) returned to the lab one year later to assess long-term maintenance of pitch and melody discrimination. On average, there was no change in performance between posttest and one-year follow-up, demonstrating that improvements on pitch- and melody-related tasks in amusics and controls can be maintained. The findings indicate that amusia is not always a life-long deficit when using the current standard diagnostic criteria.



https://ift.tt/2pyehYm

Not all errors are the same: ERP sensitivity to error typicality in foreign accented speech perception

Publication date: Available online 22 March 2018
Source:Cortex
Author(s): Sendy Caffarra, Clara D. Martin
Intercultural communication has become more and more frequent in the recent globalized society. When native listeners try to understand non-native speakers, they have to deal with different types of grammatical errors, some being frequently encountered and others being less common. The present ERP study investigated how native listeners process different types of morphosyntactic errors in foreign accented speech and whether they are sensitive to error typicality. Spanish natives listened to Spanish sentences in native and foreign (English) accent. ERPs were recorded in response to morphosyntactic violations that were commonly (gender errors) encountered in English accented Spanish or not (number errors). Although sentence comprehension accuracy did not differ across accents, the ERP responses changed as a function of accent and error type. In line with previous studies, gender and number violations in native accented speech elicited LAN-P600 responses. When speech was uttered by foreign speakers, number violations (uncommon errors) showed a P600 effect, while gender violations (common errors) did not elicit late repair processes (reflected by the P600) but an N400 effect. The present results provide evidence that the neural time course of parsing depends not only on speaker's accent, but also on input error typicality.



https://ift.tt/2HWsRQk

Influence of Task Instructions and Stimuli on the Neural Network of Face Processing: An ALE Meta-analysis

Publication date: Available online 22 March 2018
Source:Cortex
Author(s): Veronika I. Müller, Yvonne Höhner, Simon B. Eickhoff
Many neuroimaging studies have investigated the neural correlates of face processing. However, the location of face-preferential regions differs considerably between studies, possibly due to the use of different stimuli or tasks. By using Activation likelihood estimation meta-analyses, we aimed to a) delineate regions consistently involved in face processing and b) to assess the influence of stimuli and task on convergence of activation patterns. In total, we included 77 neuroimaging experiments in healthy subjects comparing face processing to a control condition. Results revealed a core face-processing network encompassing bilateral fusiform gyrus (FFG), inferior occipital (IOG) gyrus, superior temporal sulcus/middle temporal gyrus (STS/MTG), amygdala, inferior frontal junction (IFJ) and gyrus (IFG), left anterior insula as well as pre-supplementary motor area (pre-SMA). Furthermore, separate meta-analyses showed, that while significant convergence across all task and stimuli conditions was found in bilateral amygdala, right IOG, right mid-FFG, and right IFG, convergence in IFJ, STS/MTG, right posterior FFG, left FFG and pre-SMA differed between conditions. Thus, our results point to an occipito-frontal-amygdalae system that is involved regardless of stimulus and attention, whereas the remaining regions of the face-processing network are influenced by the task-dependent focus on specific facial characteristics as well as the type of stimuli processed.



https://ift.tt/2pzuT21

Editorial Board

Publication date: 15 June 2018
Source:Biosensors and Bioelectronics, Volume 108





https://ift.tt/2pA3096

Acute stress alters the rates of degradation of cardiac muscle proteins

Publication date: Available online 22 March 2018
Source:Journal of Proteomics
Author(s): Bethany Geary, Kieran Magee, Phillip Cash, Holger Husi, Iain S. Young, Phillip D. Whitfield, Mary K. Doherty
Stressful experiences can have detrimental effects on many aspects of health and wellbeing. The zebrafish (Danio rerio) is a widely used model for stress research and a stress phenotype can be induced by manipulating the environmental conditions and social interactions. In this study we have combined a zebrafish stress model with the measurement of degradation rates of soluble cardiac muscle proteins. The results showed that the greater the stress response in the zebrafish the lower the level of overall protein degradation. On comparing the rates of degradation for individual proteins it was found that four main pathways were altered in response to stress conditions with decreased degradation for proteins involved in glucose metabolism, gluconeogenesis, the ubiquitin-proteasome system (UPS) and peroxisomal proliferator-activated receptor (PPAR) signalling pathways. Taken together, these data indicate that under stress conditions zebrafish preserve cardiac muscle proteins required for the 'fight or flight' response together with proteins that play a role in stress mitigation.SignificanceThis study is the first to investigate the impact of stressful experiences on the dynamics of protein turnover in cardiac muscle. Using an established zebrafish model of human stress it has been possible to map key pathways at the protein level. The results show that the rates of degradation of cardiac proteins involved in glucose metabolism, UPS activity, hypoxia and PPAR signalling are decreased in stressed zebrafish. These findings indicate that proteins involved in the 'fight or flight' response to stress are conserved by the heart together with proteins that play a role in stress mitigation. This work provides the basis for more detailed investigations aimed at understanding the molecular effects of stress, which has implications for human health and disease.

Graphical abstract

https://ift.tt/2FYyW1X

Ameliorative effects of nano-elemental selenium against hexavalent chromium-induced apoptosis in broiler liver

Abstract

The current study examined the ameliorative effects of nano-elemental selenium (Nano-Se) against chromium-VI (K₂Cr₂O₇)-induced apoptosis in chickens. The expression of apoptosis-related genes was evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. A total of 60, one-day-old broiler chickens allotted to six equal groups, i.e., control group (standard diet), Cr(VI)-exposed group (K₂Cr₂O₇ via drinking water), Nano-Se group (Nano-Se at 0.5 mg/kg via diet), protection group (K₂Cr₂O₇ + Nano-Se), cure group (K₂Cr₂O₇ for initial 2 weeks and then Nano-Se), and prevention group (opposite to the cure group) and were detected by the activities of pro-apoptosis (Bax, Caspase-3) and anti-apoptosis (Bcl-2) genes expression at day 35 of the experiment. Intense apoptosis was observed in liver tissues of chickens exposed to K₂Cr₂O₇. The Nano-Se supplementation caused a significant decrease (P < 0.01) in the mRNA expression levels of Bax and Caspase-3 genes, while significantly elevated (P < 0.05) mRNA expression level of Bcl-2 gene was observed in Nano-Se experimental groups as compare to control and Cr(VI)-exposed group. The results quantified by the RT-qPCR were further confirmed by the western blot analysis. Altogether, these results suggest anti-apoptotic effects of Nano-Se in the chicken liver, which is interesting for further study. The present findings suggested that Nano-Se has protective effects against K₂Cr₂O₇-induced apoptosis in broilers liver and can serve a key role as a protective agent against apoptosis.

https://ift.tt/2IJySAW

Radioiodine Refractory Differentiated Thyroid Cancer

Publication date: Available online 22 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Yuchen Jin, Douglas Van Nostrand, Lingxiao Cheng, Min Liu, Libo Chen
Differentiated thyroid cancer (DTC) is usually curable with surgery, radioactive iodine (RAI), and thyroid-stimulating hormone (TSH) suppression. However, local recurrence and/or distant metastases occur in approximately 15% of cases during follow-up, and nearly two-thirds of these patients will become RAI-refractory (RR-DTC) with a poor prognosis. This review focuses on the most challenging and rapidly evolving aspects of RR-DTC, and we discuss the considerable improvement in more accurately defining RR-DTC, more effective therapeutic strategies, and describe the diagnosis, pathogenesis, and future prospects of RR-DTC. Along with the detection of serum thyroglobulin and anatomic imaging modalities, such as ultrasound and computer tomography, radionuclide molecular imaging plays a vital role in the evaluation of RR-DTC. In addition, continual progress has been made in the management of RR-DTC, including watchful waiting under appropriate TSH suppression, local treatment approaches, and systemic therapies (molecular targeted therapy, redifferentiation therapy, gene therapy, and cancer immunotherapy). These all hold promise to change the natural history of RR-DTC.



http://ift.tt/2G0O1w4

When and how to treat women with HER2-positive, small (pT1a-b), node-negative breast cancer?

Publication date: Available online 22 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Stefania Gori, Monica Turazza, Alessandra Modena, Simona Duranti, Giuseppe Zamboni, Filippo Alongi, Giovanni Carbognin, Alberto Massocco, Matteo Salgarello, Alessandro Inno
Small (pT1a-b), node-negative (pN0) breast cancer generally has a good prognosis. However, HER2-positive status is associated with an increased risk of relapse and decreased survival even in these tumors. Although there are only few data from prospective randomized trials, results of retrospective studies suggest adjuvant chemotherapy plus trastuzumab may improve outcomes of patients with pT1a-b pN0 HER2-positive breast cancer. On the other hand, trastuzumab is potentially associated with increased cardiac toxicity, especially when combined with anthracycline-based chemotherapy. A valid strategy for improving cardiac safety is the addition of trastuzumab to non-anthracycline chemotherapy, whereas a shorter duration of trastuzumab should be not routinely considered although might represent an option for selected patients at low risk of relapse and very high risk of cardiac events. Therefore, the choice of adjuvant treatment for patients with pT1a-b pN0 HER2-positive breast cancer should be done on individual basis, carefully weighing benefits and risks.



https://ift.tt/2GhkqBY

Biological aspects of chondrosarcoma: leaps and hurdles

Publication date: Available online 22 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Benoîte Mery, Sophie Espenel, Jean-Baptiste Guy, Chloé Rancoule, Alexis Vallard, Marie-Thérèse Aloy, Claire Rodriguez-Lafrasse, Nicolas Magné
Chondrosarcomas are characterized by their chemo- and radioresistance leading to a therapeutic surgical approach which remains the only available treatment with a 10-year survival between 30% and 80% depending on the grade. Non-surgical treatments are under investigation and rely on an accurate biological understanding of drug resistance mechanisms. Novel targeted therapy which represents a new relevant therapeutic approach will open new treatment options by targeting several pathways responsible for processes of proliferation and invasion. Survival pathways such as PI3K, AKT, mTOR and VEGF have been shown to be involved in proliferation of chondrosarcoma cells and antiapoptotic proteins may also play a relevant role. Other proteins such as p53 or COX2 have been identified as potential new targets. This review provides an insight into the biological substantial treatment challenges of CHS and focuses on improving our understanding of CH biology through an overview of major signaling pathways that could represent targets for new therapeutic approaches.



https://ift.tt/2HYqf4m

Trypanosoma cruzi infection of human induced pluripotent stem cell-derived cardiomyocytes: an in vitro model for drug screening for Chagas disease

Publication date: Available online 22 March 2018
Source:Microbes and Infection
Author(s): Leonardo da Silva Lara, Leonardo Andrade-Lima, Claudia Magalhães Calvet, Juliana Borsoi, Thabata Lopes Alberto Duque, Andrea Henriques-Pons, Mirian Claudia Souza Pereira, Lygia Veiga Pereira
Chagas disease, caused by Trypanosoma cruzi, is an important global public health problem which, despite partial efficacy of benznidazole (Bz) in acute phase, urgently needs an effective treatment. Cardiotoxicity is a major safety concern for conduction of more accurate preclinical drug screening platforms. Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM) are a reliable model to study genetic and infectious cardiac alterations and may improve drug development. Herein, we introduce hiPSC-CM as a suitable model to study T. cruzi heart infection and to predict the safety and efficacy of anti-T. cruzi drugs.



https://ift.tt/2Gkus5d

Targeting Long Noncoding RNA HMMR-AS1 Suppresses and Radiosensitizes Glioblastoma

Publication date: May 2018
Source:Neoplasia, Volume 20, Issue 5
Author(s): Junyang Li, Xiangjun Ji, Handong Wang
Emergent evidences revealed that long noncoding RNAs (lncRNAs) participate in neoplastic progression. HMMR is an oncogene that is highly expressed in glioblastoma (GBM) and supports GBM growth. Whether lncRNAs regulate HMMR in GBM remains unknown. Herein, we identify that an HMMR antisense lncRNA, HMMR-AS1, is hyperexpressed in GBM cell lines and stabilizes HMMR mRNA. Knockdown of HMMR-AS1 reduces HMMR expression; inhibits cell migration, invasion, and mesenchymal phenotypes; and suppresses GBM cell growth both in vitro and in vivo. Moreover, knockdown of HMMR-AS1 radiosensitizes GBM by reducing DNA repair proteins ATM, RAD51, and BMI1. Our data demonstrate a mechanism of sense-antisense interference between HMMR and HMMR-AS1 in GBM and suggest that targeting HMMR-AS1 is a potential strategy for GBM treatment.



https://ift.tt/2GhqDO1

Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts

Publication date: May 2018
Source:Neoplasia, Volume 20, Issue 5
Author(s): Simona Corso, Marilisa Cargnelutti, Stefania Durando, Silvia Menegon, Maria Apicella, Cristina Migliore, Tania Capeloa, Stefano Ughetto, Claudio Isella, Enzo Medico, Andrea Bertotti, Francesco Sassi, Ivana Sarotto, Laura Casorzo, Alberto Pisacane, Monica Mangioni, Antonino Sottile, Maurizio Degiuli, Uberto Fumagalli, Giovanni Sgroi, Sarah Molfino, Giovanni De Manzoni, Riccardo Rosati, Michele De Simone, Daniele Marrelli, Luca Saragoni, Stefano Rausei, Giovanni Pallabazzer, Franco Roviello, Paola Cassoni, Anna Sapino, Adam Bass, Silvia Giordano
Patient-Derived Xenografts (PDXs), entailing implantation of cancer specimens in immunocompromised mice, are emerging as a valuable translational model that could help validate biologically relevant targets and assist the clinical development of novel therapeutic strategies for gastric cancer.More than 30% of PDXs generated from gastric carcinoma samples developed human B-cell lymphomas instead of gastric cancer. These lymphomas were monoclonal, Epstein Barr Virus (EBV) positive, originated tumorigenic cell cultures and displayed a mutational burden and an expression profile distinct from gastric adenocarcinomas. The ability of grafted samples to develop lymphomas did not correlate with patient outcome, nor with the histotype, the lymphocyte infiltration level, or the EBV status of the original gastric tumor, impeding from foreseeing lymphoma onset. Interestingly, lymphoma development was significantly more frequent when primary rather than metastatic samples were grafted.Notably, the development of such lympho-proliferative disease could be prevented by a short rituximab treatment upon mice implant, without negatively affecting gastric carcinoma engraftment.Due to the high frequency of human lymphoma onset, our data show that a careful histologic analysis is mandatory when generating gastric cancer PDXs. Such care would avoid misleading results that could occur if testing of putative gastric cancer therapies is performed in lymphoma PDXs. We propose rituximab treatment of mice to prevent lymphoma development in PDX models, averting the loss of human-derived samples.



https://ift.tt/2pBvoI2

Guideline: Protecting, Promoting and Supporting Breastfeeding in Facilities Providing Maternity and Newborn Services.

This guideline provides global, evidence-informed recommendations on protection, promotion and support of optimal breastfeeding in facilities providing maternity and newborn services, as a public health intervention. It is intended to contribute to discussions among stakeholders when selecting or prioritizing appropriate actions in their efforts to achieve the Sustainable Development Goals and the global targets for 2025 as put forward in the Comprehensive implementation plan on maternal, infant and young child nutrition, endorsed by the Sixty-fifth World Health Assembly in 2012, in resolution WHA65.6, the Global strategy for women's, children's, and adolescents' health (2016–2030), and the Global Strategy for infant and young child feeding.

https://ift.tt/2I2c3rc

Guideline: Alternative Mass Drug Administration Regimens to Eliminate Lymphatic Filariasis.

Lymphatic filariasis is a vector-borne neglected tropical disease that causes damage of the lymphatic system and can lead to lymphoedema (elephantiasis) and hydrocele in infected individuals. The global baseline estimate of persons affected by lymphatic filariasis is 25 million men with hydrocele and over 15 million people with lymphoedema. At least 36 million persons remain with these chronic disease manifestations. The disease is endemic in 72 countries. In 2016, an estimated total population of 856 million were living in areas with ongoing transmission of the causative filarial parasites and requiring mass drug administration (MDA). Lymphatic filariasis disfigures and disables, and often leads to stigmatization and poverty. Hundreds of millions of dollars are lost annually due to reduced productivity of affected patients. WHO has ranked the disease as one of the world's leading causes of permanent and long-term disability.

https://ift.tt/2Gio524

Comparing ordinary kriging and inverse distance weighting for soil as pollution in Beijing

Abstract

Spatial interpolation method is the basis of soil heavy metal pollution assessment and remediation. The existing evaluation index for interpolation accuracy did not combine with actual situation. The selection of interpolation methods needs to be based on specific research purposes and research object characteristics. In this paper, As pollution in soils of Beijing was taken as an example. The prediction accuracy of ordinary kriging (OK) and inverse distance weighted (IDW) were evaluated based on the cross validation results and spatial distribution characteristics of influencing factors. The results showed that, under the condition of specific spatial correlation, the cross validation results of OK and IDW for every soil point and the prediction accuracy of spatial distribution trend are similar. But the prediction accuracy of OK for the maximum and minimum is less than IDW, while the number of high pollution areas identified by OK are less than IDW. It is difficult to identify the high pollution areas fully by OK, which shows that the smoothing effect of OK is obvious. In addition, with increasing of the spatial correlation of As concentration, the cross validation error of OK and IDW decreases, and the high pollution area identified by OK is approaching the result of IDW, which can identify the high pollution areas more comprehensively. However, because the semivariogram constructed by OK interpolation method is more subjective and requires larger number of soil samples, IDW is more suitable for spatial prediction of heavy metal pollution in soils.

https://ift.tt/2pzyex4

Nutrigenomics and the Future of Nutrition: Proceedings of a Workshop—in Brief.

On December 5, 2017, the Food Forum of the National Academies of Sciences, Engineering, and Medicine hosted a public workshop in Washington, DC, to review current knowledge in the field of nutrigenomics and to explore the potential impact of personalized nutrition on health maintenance and chronic disease prevention. This publication highlights key points made by individual speakers during the workshop presentations and discussions.

https://ift.tt/2pDI29c

Use of Structured Data Collection for Diabetes Care in General Practice: A Systematic Review [Internet].

The majority of patients with type 2 diabetes in Norway are followed up in primary care. We have investigated the effect of using a structured way of registering clinical data (structured data collection of for example HBA1c and blood pressure) on mortality and morbidity for patients with diabetes type 2.

https://ift.tt/2GkXgue

Intermittent Pneumatic Compression Devices for the Management of Lymphedema: A Review of Clinical Effectiveness and Guidelines [Internet].

There is no cure for lymphedema. The complex decongestive therapy (CDT) is a multimodal therapy, which is recognized as a conservative management of lymphedema and consists of compression therapy (i.e., multilayer bandaging), manual lymphatic drainage (MLD), exercise and skin care. Intermittent pneumatic compression (IPC) can be used in the treatment of lymphedema as an adjunct to CDT, particularly in patients with compromised mobility or physical exercise. Although lymphedema reduces after application, the use of IPC remains controversial due to its adverse effects, including the recurrence of edema due to residual proteins remaining in the interstitial space, and potential lymphatic structure damage due to high pressure application.

https://ift.tt/2pC4jo7

Use of Liverpool Care Pathway at the End of Life [Internet].

Liverpool Care Pathway (LCP) has been promoted as a holistic approach for the care of dying patients and their families at the end of life. We conducted this rapid review to evaluate the effectiveness of LCP on the quality of palliative care.

https://ift.tt/2GfyqvX

Use of Biological Samples in Rehabilitation of Persons Receiving Opioid Maintenance Treatment: A Systematic Review [Internet].

Opioid maintenance treatment is the most common form of treatment for people with opioid dependence in Norway. In opioid maintenance treatment, the patients are offered a suitable replacement drug for the opiate they are dependent on. The treatment is often lifelong and involves that they must give samples of biological material regularly. This systematic review summarises the effects of using biological samples in the rehabilitation of persons that receive opioid maintenance treatment. Biological samples can be urine, saliva, hair or sweat. These are analysed for traces of drugs and medication.

https://ift.tt/2G64eQy

The Effectiveness of Physical Exercise for People with Cancer [Internet].

The National Cancer Strategy for 2013-2017 published by The Norwegian Ministry of Health and Care Services, notes that physical activity is an important adjunctive treatment both during active cancer treatment and after the treatment is completed. We have summarised the results from five systematic reviews, on the effects of exercise for cancer patients during and after cancer treatment, including a total of 119 randomised clinical trials.

https://ift.tt/2GmnSLH

Supported Employment for People with Disabilities: A Systematic Review [Internet].

A large part of The Norwegian Labour and Welfare Administration (NAV)'s budget is used on employment interventions, and most of the recipients need some kind of support in order to enter, and remain in, paid employment. Traditional employment interventions are directed towards sheltered work, work training on a sheltered arena or training, with a more distant goal of competitive employment ("train then place"). The interventions Supported Employment (SE) and Individual Placement and Support (IPS) aim rather to rapidly place the participant in competitive work (paid work in an ordinary work environment, full time or part time), with support and follow-up of employee and employer ("place then train").

https://ift.tt/2pze0Un

Agreement Between Chronological Age and Bone Age Based on the Greulich and Pyle Atlas for Age Estimation: A Systematic Review [Internet].

The Greulich and Pyle atlas is used to estimate the age of children and adolescents. This systematic review summarizes the scientific evidence on the agreement between skeletal age from the Greulich and Pyle atlas (hereafter called GP skeletal age) and chronological age.

https://ift.tt/2GkX0vg

Continuous Monitoring of Pulmonary Artery Pressure Via an Implanted Leadless and Battery Less Pressure Sensor for the Management of Patients with Moderate to Severe Heart Failure (New York Heart Association Class III) [Internet].

Background In Norway the prevalence of chronic heart failure has been estimated to be 2 percent, meaning 80,000-100,000 people. Around 75 percent of heart failure patients are older than 75 years old. Furthermore, patients diagnosed with heart failure account for approximately 5 percent of all hospital admissions in Norway, and at any one time about 20 percent of patients on a medicine department consist of heart failure patients.

https://ift.tt/2pxEBB4

Effect of Respiratory Muscle Training for Acute Traumatic High Spinal Cord Injury: A Systematic Review [Internet].

Pulmonary complications are the leading cause of illness and death in people with traumatic spinal cord injuries, both in the short- and long term after the injury. We have synthesized the available research regarding the effect of various treatment strategies for respiratory management of traumatic, high spinal cord injury within the first eight weeks after injury. We did not include pharmacological or surgical interventions in this report.

https://ift.tt/2Ghq2vL

Hominin hand bone fossils from Sterkfontein Caves, South Africa (1998–2003 excavations)

Publication date: May 2018
Source:Journal of Human Evolution, Volume 118
Author(s): Travis Rayne Pickering, Jason L. Heaton, Ron J. Clarke, Dominic Stratford
We describe eleven hominin metacarpals and phalanges recovered from Jacovec Cavern and Member 4 of the Sterkfontein Formation between 1998 and 2003. Collectively, the fossils date in excess of 2.0 Ma, and are probably attributable to Australopithecus africanus and/or Australopithecus prometheus. When combined with results of previous studies on Australopithecus postcranial functional morphology, the new data presented here suggest that at least some late Pliocene and/or early Pleistocene hominins from Sterkfontein were arboreally adept. This finding accords with the reconstruction of the site's >2.0 Ma catchment area as well-vegetated and containing significant woody components. In addition, most of the new specimens described here evince morphologies that indicate the hands from which they derived lacked complete modern humanlike manual dexterity, which is integral to the manufacture and use of intentionally shaped stone tools. The absence of lithic artifacts from both stratigraphic units from which the fossils were excavated is consistent with this conclusion.



https://ift.tt/2pDnEFh

Lipidomic data on lipid droplet triglyceride remodelling associated with protection of breast cancer cells from lipotoxic stress

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Eva Jarc, Thomas O. Eichmann, Robert Zimmermann, Toni Petan
The data presented here is related to the research article entitled "Lipid droplets induced by secreted phospholipase A2 and unsaturated fatty acids protect breast cancer cells from nutrient and lipotoxic stress" by E. Jarc et al., Biochim. Biophys. Acta 1863 (2018) 247–265. Elevated uptake of unsaturated fatty acids and lipid droplet accumulation are characteristic of aggressive cancer cells and have been associated with the cellular stress response. The present study provides lipidomic data on the triacylglycerol (TAG) and phosphatidylcholine (PC) composition of MDA-MB-231 breast cancer cells exposed to docosahexaenoic acid (DHA; 22:6, ω-3). Datasets provide information on the changes in lipid composition induced by depletion of adipose triglyceride lipase (ATGL) and by exogenous addition of secreted phospholipase A2 (sPLA2) in DHA-treated cells. The presented alterations in lipid composition, mediated by targeting lipid droplet biogenesis and lipolysis, are associated with protection from lipotoxicity and allow further investigation into the role of lipid droplets in the resistance of cancer cells to lipotoxic stress.



https://ift.tt/2pB811k

A resource for sustainable management: De novo assembly and annotation of the liver transcriptome of the Atlantic chub mackerel, Scomber colias

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): André M. Machado, Mónica Felício, Elza Fonseca, Rute R. da Fonseca, L. Filipe C. Castro
Mackerels represent a valuable fishery worldwide. Their ample geographic distribution and capture levels make them an insightful model to address stock management strategies in the context of global changes. Yet, and despite recent impressive genome and transcriptome sequencing efforts from teleost species, available resources from the Scombridae family are comparatively scarce. Here, we generated the first high-quality de novo assembly of the liver transcriptome of the Atlantic chub mackerel (Scomber colias). Through the use of RNA-Seq Illumina technology, 111,124,228 clean reads were obtained for the liver transcriptome. De novo assembly resulted in 93,731 transcripts with an N50 of 1462 bp. This dataset provides an important insight into the context of fisheries management.



https://ift.tt/2pz5KV2

Genome sequence data from 17 accessions of Ensete ventricosum, a staple food crop for millions in Ethiopia

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Zerihun Yemataw, Sadik Muzemil, Daniel Ambachew, Leena Tripathi, Kassahun Tesfaye, Alemayheu Chala, Audrey Farbos, Paul O'Neill, Karen Moore, Murray Grant, David J. Studholme
We present raw sequence reads and genome assemblies derived from 17 accessions of the Ethiopian orphan crop plant enset (Ensete ventricosum (Welw.) Cheesman) using the Illumina HiSeq and MiSeq platforms. Also presented is a catalogue of single-nucleotide polymorphisms inferred from the sequence data at an average density of approximately one per kilobase of genomic DNA.



https://ift.tt/2pzfJJe

Data supporting Ni-NTA magnetic bead-based fluorescent protease assay using recombinant fusion protein substrates

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): János András Mótyán, Márió Miczi, Beáta Bozóki, József Tőzsér
Data provided here are related to the research article entitled as 'A recombinant fusion protein-based, fluorescent protease assay for high throughput-compatible substrate screening'. Here we describe data related to the investigation of the properties of the His6-MBP-VSQNY↓PIVQ-mApple recombinant protein substrate and its interactions with Ni-NTA magnetic beads, including the dependence of substrate attachment on incubation time and concentration. Data on the folding efficiency and conformational stability of the recombinant substrate assessed by tryptic digestion are also presented. We describe here the changes of fluorescent properties and binding abilities upon treatments commonly used for stopping enzymatic reactions: trichloroacetic acid (TCA) or heat treatment.



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Data from a targeted proteomics approach to discover biomarkers in saliva for the clinical diagnosis of periodontitis

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): V. Orti, B. Mertens, J. Vialaret, P. Gibert, A. Relaño-Ginés, S. Lehmann, D. Deville de Périère, C. Hirtz
This study focused on the search for new biomarkers based on liquid chromatography-multiple reaction monitoring (LC-MRM) proteomics profiling of whole saliva from patients with periodontitis compared to healthy subjects. The LC-MRM profiling approach is a new and innovative method that has already been validated for the absolute and multiplexed quantification of biomarkers in several diseases. The dataset for this study was produced using LC-MRM to monitor protein levels in a multiplex assay, it provides clinical information on salivary biomarkers of periodontitis. The data presented here is an extension of our recently published research article (Mertens et al., 2017) [1].

Graphical abstract

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Survey data on teaching strategies and product innovation: A focus on selected university students in Nigeria

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Maxwell Olokundun, Stephen ibidunni, Mercy Ogbari, Fred Peter, Taiye Borishade, Hezekiah Falola, Odunayo Salau, Oladele Kehinde
The main objective of this study was to examine the effectiveness of the teaching methods adopted in motivating university students' in Nigeria to engage in product innovation. Emphasis was laid on Covenant University in Nigeria which is the pioneer institution to offer entrepreneurship education in Nigeria. The study adopted quantitative method with a descriptive research design to establish trends related to the objective of the study. Survey was be used as quantitative research method. The population of this study comprised all students in the selected university which was given as 6401 3. A sample size of 377 students was selected using yard's formula. Reliability and validity were confirmed. Data was analyzed with the use of Statistical Package for Social Sciences (SPSS).Regression analysis was used as statistical tool of analysis. The field data set is made publicly available to enable critical or a more extensive inquiry.



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Neuro-fuzzy inference system Prediction of stability indices and Sodium absorption ratio in Lordegan rural drinking water resources in west Iran

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Afshin Takdastan, Majid Mirzabeygi (Radfard), Mahmood Yousefi, Abbas Abbasnia, Rouhollah Khodadadia, Hamed Soleimani, Amir Hossein Mahvi, Davood Jalili Naghan
According to World Health Organization guidelines, corrosion control is an important aspect of safe drinking-water supplies. Water always includes ingredients, dissolved gases and suspended materials. Although some of these water ingredients is indispensable for human beings, these elements more than permissible limits, could be endanger human health. The aim of this study is to assess physical and chemical parameters of drinking water in the rural areas of Lordegan city, also to determine corrosion indices. This cross-sectional study has carried out with 141 taken samples during 2017 with 13 parameters, which has been analyzed based on standard method and to estimate the water quality indices from groundwater using ANFIS. Also with regard to standard conditions, results of this paper are compared with Environmental Protection Agency and Iran national standards. Five indices, Ryznar Stability Index (RSI), Langlier Saturation Index (LSI), Larson-Skold Index (LS), Puckorius Scaling Index (PSI), and Aggressive Index (AI) programmed by using Microsoft Excel software. Owing to its simplicity, the program, can easily be used by researchers and operators. Parameters included Sulfate, Sodium, Chloride, and Electrical Conductivity respectively were 13.5, 28, 10.5, and 15% more than standard level. The amount of Nitrate, in 98% of cases were in permissible limits and about 2% were more than standard level. Result of presented research indicate that water is corrosive at 10.6%,89.4%,87.2%,59.6% and 14.9% of drinking water supply reservoirs, according to LSI, RSI, PSI, LS and AI, respectively.



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Hyperedge bundling: Data, source code, and precautions to modeling-accuracy bias to synchrony estimates

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Sheng H. Wang, Muriel Lobier, Felix Siebenhühner, Tuomas Puoliväli, Satu Palva, J. Matias Palva
It has not been well documented that MEG/EEG functional connectivity graphs estimated with zero-lag-free interaction metrics are severely confounded by a multitude of spurious interactions (SI), i.e., the false-positive "ghosts" of true interactions [1,2]. These SI are caused by the multivariate linear mixing between sources, and thus they pose a severe challenge to the validity of connectivity analysis. Due to the complex nature of signal mixing and the SI problem, there is a need to intuitively demonstrate how the SI are discovered and how they can be attenuated using a novel approach that we termed hyperedge bundling. Here we provide a dataset with software with which the readers can perform simulations in order to better understand the theory and the solution to SI. We include the supplementary material of [1] that is not directly relevant to the hyperedge bundling per se but reflects important properties of the MEG source model and the functional connectivity graphs. For example, the gyri of dorsal-lateral cortices are the most accurately modeled areas; the sulci of inferior temporal, frontal and the insula have the least modeling accuracy. Importantly, we found the interaction estimates are heavily biased by the modeling accuracy between regions, which means the estimates cannot be straightforwardly interpreted as the coupling between brain regions. This raise a red flag that the conventional method of thresholding graphs by estimate values is rather suboptimal: because the measured topology of the graph reflects the geometric property of source-model instead of the cortical interactions under investigation.



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Peptide data on the disulfide bond analysis of baculovirus produced Pfs25 by LC-MSMS

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Shwu-Maan Lee, Jordan L. Plieskatt, C. Richter King
This article contains the peptide data obtained while performing disulfide bond mapping of the recombinant Plasmodium falciparum protein, Pfs25, produced from the baculovirus expression system. Pfs25 is a malaria transmission-blocking vaccine candidate, with a compact and complex structure including 22 cysteines. This supplementary data is related to the research "Disulfide bond mapping of Pfs25, a recombinant malaria transmission blocking vaccine candidate" (Lee et al., 2018) [1]. In brief, Pfs25 was digested with trypsin/Lys-C and derived peptides separated by High Performance Liquid Chromatography (HPLC) and analyzed by mass spectrometry (MS) by MS^E fragmentation. The theoretical peptides and their respective masses along with disulfide bond locations with linked peptides are presented here alongside the mass spectrometry analysis. The raw mass spectrometry data is made available through the Mass Spectrometry Interactive Virtual Environment (MassIVE) with identifier: MSV000081982.



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The influence of KaiA mutations on its function in the KaiABC circadian clock system

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Qiang Chen, Sen Liu, Liting Yang, Lingya Zhang, Jinkui Li
The core oscillator of the circadian clock of cyanobacteria consists of three proteins, KaiA, KaiB, and KaiC. The KaiABC oscillator can be re-constituted in vitro with the purified proteins in buffer containing ATP and Mg²⁺. The interaction between KaiA and KaiC has not been well studied. In this article, different KaiA mutants were designed and used to elucidate the influence of KaiA structure on its function in the in vitro system. Molecular dynamics simulations were adopted to study the structural flexibility of KaiA homodimer. The data presented in this article provide further experimental supports to our work in Chen et al. (2017) [1].



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Evolution over time in the cost-effectiveness of pneumococcal conjugate vaccine (PCV13) in older Australians due to herd protection from infant vaccination

Publication date: 12 April 2018
Source:Vaccine, Volume 36, Issue 16
Author(s): C. Chen, P. Beutels, A.T. Newall
In many settings, serotype changes as a result of infant 13-valent pneumococcal conjugate vaccine (PCV13) programs are likely to continue after the introduction of adult PCV13 programs. We applied a multi-cohort model to explore how potential serotype changes may impact on the cost-effectiveness of PCV13 use in Australian adults aged over 65 years. We found assumptions around continued herd protection from infant PCV13 programs to be critical when assessing the cost-effectiveness of adult PCV13 vaccination in Australia. Future cost-effectiveness analyses of adult PCV13 programs need to carefully consider how to predict these future changes in serotypes, with Australian data suggesting that the changes post-PCV13 use in infants may be different than post-PCV7.



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Oral Chlamydia vaccination induces transmucosal protection in the airway

Publication date: 12 April 2018
Source:Vaccine, Volume 36, Issue 16
Author(s): Cuiming Zhu, Hui Lin, Lingli Tang, Jianlin Chen, Yimou Wu, Guangming Zhong
Although Chlamydia has been frequently detected in the gastrointestinal tracts of both humans and animals, it is not associated with any gastrointestinal pathology. We have recently shown that gastrointestinal Chlamydiamuridarum is not only non-pathogenic but also induces protective immunity in the genital tract. We now report that the transmucosal immunity induced by a single oral immunization with C.muridarum protected the mouse airway from a subsequent challenge infection. The oral immunization significantly reduced chlamydial burden in the airway as early as day 3 after intranasal challenge. As a result, the airway chlamydial spreading to extra-airway tissues was completely prevented on day 3 and significantly reduced on day 9. The immunized mice were protected from any significant systemic toxicity caused by the intranasal challenge since there was no significant bodyweight drop in the immunized mice. This robust protection correlated well with Chlamydia-specific antibodies that recognize chlamydial organism surface antigens and T cell responses that are dominated with a Th1 phenotype. The immunized mice developed high ratios of IgG2b/c over IgG1 levels and IFNγ-producing over IL-5- or IL-13-producing lymphocytes. Thus, we have demonstrated that oral vaccination with C. muridarum can induce Th1-dominant transmucosal immunity in the airway. Together with previous studies, we propose that non-pathogenic colonization of Chlamydia in the gastrointestinal tract be explored as an oral delivery system for inducing protection against infections and pathologies in extra-gastrointestinal tissues.



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Epidemiological profile and progress toward rubella elimination in China. 10 years after nationwide introduction of rubella vaccine

Publication date: 12 April 2018
Source:Vaccine, Volume 36, Issue 16
Author(s): Qiru Su, Chao Ma, Ning Wen, Chunxiang Fan, Hong Yang, Huaqing Wang, Zundong Yin, Zijian Feng, Lixin Hao, Weizhong Yang
BackgroundRubella-containing vaccine (RCV) became available in China in 1993 and was introduced nationwide into the Expanded Immunization Program (EPI) in 2008. We evaluated implementation and impact of RCV from 2 years prior to nationwide introduction through the 10 years after nationwide introduction.MethodsWe analyzed RCV lot-release (doses distributed) data, 1- and 2-dose RCV coverage, and rubella data from China's nationwide disease surveillance system to describe the current status and changes in rubella epidemiology between 2005 and 2017.ResultsWhile the vaccine was included into the routine immunization program in 2008, its full implementation required 4 years due to sporadic vaccine supply constraints. RCV1 and RCV2 coverage increased from 51.5% and 39.0% in 2008 to >95% during 2012 through 2016. From 2005 to 2017, the annual incidences (per million) of rubella ranged from 91.09 in 2008 down to 1.16 in 2017; reductions occurred in all age groups. The proportion of cases among individuals ≥20 years old increased from 0.97% in 2005 to 31.2% in 2017. In the better-developed eastern China, most cases were among adults; in central and western China, most cases were among children or adolescents.ConclusionsThe marked decrease rubella was a result of inclusion of RCVs into EPI targeting children less than 2 years of age and achieving high level of 2-dose coverage. Rubella was reduced in absolute terms, and its epidemiology was changed to older cases with substantial inter-province variation. Ensuring full vaccination of school children and identifying strategies to reach adults with measles and rubella combined vaccines will be important to hasten elimination of rubella and prevent CRS outbreaks.



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Expression and characterization of a novel truncated rotavirus VP4 for the development of a recombinant rotavirus vaccine

Publication date: 12 April 2018
Source:Vaccine, Volume 36, Issue 16
Author(s): Yijian Li, Miaoge Xue, Linqi Yu, Guoxing Luo, Han Yang, Lianzhi Jia, Yuanjun Zeng, Tingdong Li, Shengxiang Ge, Ningshao Xia
The outer capsid protein VP4 is an important target for the development of a recombinant rotavirus vaccine because it mediates the attachment and penetration of rotavirus. Due to the poor solubility of full-length VP4, VP8 was explored as candidate rotavirus vaccines in the past years. In previous studies, it has been found that the N-terminal truncated VP8 protein, VP8-1 (aa26-231), could be expressed in soluble form with improved immunogenicity compared to the core of VP8 (aa65-223). However, this protein stimulated only a weak immune response when aluminum hydroxide was used as an adjuvant. In addition, it should be noted that the protective efficacy of VP4 was higher than that of VP8 and VP5. In this study, it was found that when the N-terminal 25 amino acids were deleted, the truncated VP4^∗ (aa26-476) containing VP8 and the stalk domain of VP5 could be expressed in soluble form in E. coli and purified to homogeneous trimers. Furthermore, the truncated VP4 could induce high titers of neutralizing antibodies when aluminum adjuvant was used and conferred high protective efficacy in reducing the severity of diarrhea and rotavirus shedding in stools in animal models. The immunogenicity of the truncated VP4 was significantly higher than that of VP8^∗ and VP5^∗ alone. Taken together, the truncated VP4^∗ (aa26-476), with enhanced immunogenicity and immunoprotectivity, could be considered as a viable candidate for further development and has the potential to become a parenterally administered rotavirus vaccine.



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Editorial Board/Aims and Scope

Publication date: 12 April 2018
Source:Vaccine, Volume 36, Issue 16





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Enhancing viral vaccine production using engineered knockout vero cell lines – A second look

Publication date: 12 April 2018
Source:Vaccine, Volume 36, Issue 16
Author(s): F. Hoeksema, J. Karpilow, A. Luitjens, F. Lagerwerf, M. Havenga, M. Groothuizen, G. Gillissen, A.A.C. Lemckert, B. Jiang, R.A. Tripp, C. Yallop
The global adoption of vaccines to combat disease is hampered by the high cost of vaccine manufacturing. The work described herein follows two previous publications (van der Sanden et al., 2016; Wu et al., 2017) that report a strategy to enhance poliovirus and rotavirus vaccine production through genetic modification of the Vero cell lines used in large-scale vaccine manufacturing. CRISPR/Cas9 gene editing tools were used to knockout Vero target genes previously shown to play a role in polio- and rotavirus production. Subsequently, small-scale models of current industry manufacturing systems were developed and adopted to assess the increases in polio- and rotavirus output by multiple stable knockout cell lines. Unlike previous studies, the Vero knockout cell lines failed to achieve desired target yield increases. These findings suggest that additional research will be required before implementing the genetically engineered Vero cell lines in the manufacturing process for polio- and rotavirus vaccines to be able to supply vaccines at reduced prices.



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Characterization of capsid protein (p495) of hepatitis E virus expressed in Escherichia coli and assembling into particles in vitro

Publication date: 12 April 2018
Source:Vaccine, Volume 36, Issue 16
Author(s): Minghua Zheng, Jie Jiang, Xiao Zhang, Nan Wang, Kaihang Wang, Qiong Li, Tingting Li, Qingshan Lin, Yingbin Wang, Hai Yu, Ying Gu, Jun Zhang, Shaowei Li, Ningshao Xia
Hepatitis E virus (HEV) is associated with acute hepatitis disease. Numerous truncated HEV capsid proteins have been successfully expressed using different expression systems. Among these, p495, a protein truncated at its N- and C-termini by 111 and 54 amino acids (aa), respectively (HEV ORF2 aa 112–606) can self-assemble into T = 1 virus-like particles (VLPs) when expressed by insect cells. A shorter p239 (aa 368–606) protein is a particulate antigen that we have previously used in our commercialized HEV vaccine, Hecolin. Here, we sought to express p495 in its soluble form (named Ep495) in E. coli and in baculovirus-infected Tn5 insect cells (named BTp495) as a back-to-back control. Characterization of p495 particles derived from these two expression systems showed similarities in particle size, morphology, and sedimentation coefficient. Antigenicity assays using a panel of anti-HEV monoclonal antibodies also showed similar strong reactivities for Ep495 and BTp495, as well as similar binding profiles that were congruent with p239. Mouse immunization results showed that Ep495 particles had comparable immunogenicity with that of BTp495 VLPs, as well as p239. Overall, our findings suggest that p495 particles produced in E. coli are ideal for the development of next-generation prophylactic vaccines against hepatitis E.



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Influenza vaccination among Saudi Hajj pilgrims: Revealing the uptake and vaccination barriers

Publication date: 12 April 2018
Source:Vaccine, Volume 36, Issue 16
Author(s): Mohammad Alfelali, Osamah Barasheed, Al-Mamoon Badahdah, Hamid Bokhary, Mohammed I. Azeem, Turki Habeebullah, Marwan Bakarman, Atif Asghar, Robert Booy, Harunor Rashid
BackgroundHajj is the world's largest annual mass gathering that attracts two to three million Muslims from around the globe to a religious assemblage in Makkah, Saudi Arabia. The risk of acquisition and transmission of influenza among Hajj pilgrims is high. Therefore, influenza vaccination is recommended, and was monitored frequently among pilgrims from different countries. However, the vaccination uptake among Saudi pilgrims has not been assessed in recent years.ObjectiveThis analysis aims to evaluate influenza vaccine uptake among Saudi Hajj pilgrims, and identify the key barriers to vaccination.MethodData on influenza vaccination were obtained from Saudi pilgrims who took part in a large trial during the Hajj of 2013, 2014 and 2015. Pilgrims were met and recruited in Mina, Makkah during the peak period of Hajj and were asked to complete a baseline questionnaire that recorded their influenza vaccination history, including reason(s) for non-receipt of vaccine.ResultsA total of 6974 Saudi pilgrims aged between 18 and 95 (median 34) years were recruited; male to female ratio was 1:1.2. Of the total, 90.8% declared their influenza vaccination history, 51.3% of them reported receiving influenza vaccine before travel to Hajj. The vaccination rates for the years 2013, 2014 and 2015 were 21.4%, 48.2% and 58.1%, respectively (P < 0.001). Of 1,269 pilgrims who were at higher risk of severe disease, 54.5% received the vaccine. Lack of awareness (47.5%), reliance on natural immunity (15.8%) and being busy (15.5%) were the main reasons for non-receipt.ConclusionThese data from a convenience sample indicate that influenza vaccine uptake among Saudi Hajj pilgrims is increasing over years but still needs further improvement. Lack of awareness and misperceptions are the main barriers. Education of Saudi pilgrims and health professionals is required to raise awareness about influenza vaccination. Further studies are needed to understand pilgrims' misperceptions.



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A DNA prime/protein boost vaccine protocol developed against Campylobacter jejuni for poultry

Publication date: 12 April 2018
Source:Vaccine, Volume 36, Issue 16
Author(s): Marine Meunier, Muriel Guyard-Nicodème, Estelle Vigouroux, Typhaine Poezevara, Véronique Béven, Ségolène Quesne, Michel Amelot, Alberto Parra, Marianne Chemaly, Daniel Dory
Vaccination of broilers is one of the potential ways to decrease Campylobacter intestinal loads and therefore may reduce human disease incidence. Despite many studies, no efficient vaccine is available yet. Using the reverse vaccinology strategy, we recently identified new vaccine candidates whose immune and protective capacities need to be evaluated in vivo. Therefore, the goal of the present study was to develop and evaluate an avian subunit vaccine protocol for poultry against Campylobacter jejuni. For this, flagellin was used as vaccine antigen candidate. A DNA prime/protein boost regimen was effective in inducing a massive protective immune response against C. jejuni in specific pathogen free Leghorn chickens. Contrastingly, the same vaccine regimen stimulated the production of antibodies against Campylobacter in conventional Ross broiler chickens harbouring maternally derived antibodies against Campylobacter, but not the control of C. jejuni colonization. These results highlight the strength of the vaccine protocol in inducing protective immunity and the significance of the avian strain and/or immune status in the induction of this response. Nevertheless, as such the vaccine protocol is not efficient in broilers to induce protection and has to be adapted; this has been done in one of our recent published work.



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The impact of [ 68 Ga]PSMA I&T PET/CT on radiotherapy planning in patients with prostate cancer

Abstract

Purpose

To determine the impact of Gallium-68-labled prostate-specific membrane antigen positron-emission tomography/computed tomography ([⁶⁸Ga]PSMA PET/CT) on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer.

Methods

A total of 106 patients with prostate cancer scheduled for radiation therapy underwent 120 [⁶⁸Ga]PSMA PET/CT scans prior to radiotherapy treatment. In 20 cases, patients underwent [⁶⁸Ga]PSMA PET/CT for primary therapy (PT), 75 cases were referred for biochemical relapse after surgery (RL), and 25 cases were intended for palliative treatment of localized metastases (MD). We retrospectively compared the impact of [⁶⁸Ga]PSMA PET/CT on lesion detection and treatment decision to CT alone.

Results

[⁶⁸Ga]PSMA PET/CT revealed a total of 271 positive lesions, whereas CT detected 86 lesions (32%). Overall, the radiotherapy regime was changed in 55 of 120 cases (46%) based on the higher detection rate of [⁶⁸Ga]PSMA PET/CT: in 15% of cases with PT, in 43% of cases with RL, and in 44% of cases with MD.

Conclusion

[⁶⁸Ga]PSMA PET/CT is superior to CT alone for lesion detection in prostate cancer, thereby significantly impacting on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer.

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Immunogenicity and safety of a Trivalent Influenza HA vaccine in Indonesian infants and children

Publication date: 12 April 2018
Source:Vaccine, Volume 36, Issue 16
Author(s): Soedjatmiko Soedjatmiko, Bernie Endyarni Medise, Hartono Gunardi, Rini Sekartini, Hindra Irawan Satari, Sri Rezeki Hadinegoro, Novilia Sjafri Bachtiar, Rini Mulia Sari
IntroductionHigh rate of influenza infection in children made influenza vaccination strongly recommended for all person aged >6 months in Indonesia. Bio Farma Trivalent Influenza HA (Flubio®) vaccine has been used in adolescents and adults, resulted in increased seroconversion, seroprotection rates and geometric mean titer (GMT). However, no data is available regarding its efficacy and safety in children. This study aimed to assess the immunogenicity and safety of Flubio® vaccine in infants and children.Materials and methodsThis was a phase II, open-labeled, clinical trial conducted on healthy children aged 6 month-11 years, vaccinated with 1 or 2 doses of Influenza HA vaccine, with a 28-day interval. Flubio® vaccine composed of A/California/7/2009 (H1N1) pandemic 09, A/Texas/50/2012 (H3N2), and B/Massachusetts/2/2012 strain. This study was held at East Jakarta, Indonesia from May until July 2014. A Total of 405 subjects were included and divided into three groups: A(6–35 months), B(3–8 years), and C(9–11 years). Antibody titer was measured at visit V1 (Day 0), V2 (28 days/+7days after the first dose) and V3 (28 days/+7days after second dose). The seroprotection and seroconversion rates were assessed. Safety was assessed up to 28 days following each dose.ResultsA total of 404 subjects completed the study. After vaccination, all subjects achieved seroprotection and increased seroconversion rates, with post-vaccination antibody titer of ≥1:40 HI for all strains. The GMT also increased significantly. Within 30 min after vaccination, 14.6% and 2% had local and systemic reactions; meanwhile, between 30 min to 72 h after vaccination, 35.1% and 13.6% subjects had local and systemic reactions, respectively. Most reactions were mild. No serious adverse event (SAE) was reported related to vaccine.ConclusionFlubio® (Influenza HA Trivalent) vaccine is immunogenic and safe for children aged 6 months-11 years.Trial Registration: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT02093260.



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