An Ancient Family of RNA-Binding Proteins: Still Important!

Publication date: Available online 14 January 2017
Source:Trends in Biochemical Sciences
Author(s): Melissa L. Wells, Lalith Perera, Perry J. Blackshear
RNA-binding proteins are important modulators of mRNA stability, a crucial process that determines the ultimate cellular levels of mRNAs and their encoded proteins. The tristetraprolin (TTP) family of RNA-binding proteins appeared early in the evolution of eukaryotes, and has persisted in modern eukaryotes. The domain structures and biochemical functions of family members from widely divergent lineages are remarkably similar, but their mRNA 'targets' can be very different, even in closely related species. Recent gene knockout studies in species as distantly related as plants, flies, yeasts, and mice have demonstrated crucial roles for these proteins in a wide variety of physiological processes. Inflammatory and hematopoietic phenotypes in mice have suggested potential therapeutic approaches for analogous human disorders.



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IOP-details

Publication date: February 2017
Source:International Journal of Psychophysiology, Volume 112





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Editorial Board

Publication date: February 2017
Source:International Journal of Psychophysiology, Volume 112





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Instructions to Authors

Publication date: February 2017
Source:International Journal of Psychophysiology, Volume 112





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Bottom-Up Synthesis of Carbon Nanoparticles with Higher Doxorubicin Efficacy

Publication date: Available online 14 January 2017
Source:Journal of Controlled Release
Author(s): Samer Bayda, Mohamad Hadla, Stefano Palazzolo, Vinit Kumar, Isabella Caligiuri, Emmanuele Ambrosi, Enrico Pontoglio, Marco Agostini, Tiziano Tuccinardi, Alvise Benedetti, Pietro Riello, Vincenzo Canzonieri, Giuseppe Corona, Giuseppe Toffoli, Flavio Rizzolio
Nanomedicine requires intelligent and non-toxic nanomaterials for real clinical applications. Carbon materials possess interesting properties but with some limitations due to toxic effects. Interest in carbon nanoparticles (CNPs) is increasing because they are considered green materials with tunable optical properties, overcoming the problem of toxicity associated with quantum dots or nanocrystals, and can be utilized as smart drug delivery systems. Using black tea as a raw material, we synthesized CNPs with a narrow size distribution, tunable optical properties covering visible to deep red absorption, non-toxicity and easy synthesis for large-scale production. We utilized these CNPs to label subcellular structures such as exosomes. More importantly, these new CNPs can escape lysosomal sequestration and rapidly distribute themselves in the cytoplasm to release doxorubicin (doxo) with better efficacy than the free drug. The release of doxo from CNPs was optimal at low pH, similar to the tumour microenvironment. These CNPs were non-toxic in mice and reduced the tumour burden when loaded with doxo due to an improved pharmacokinetics profile. In summary, we created a new delivery system that is potentially useful for improving cancer treatments and opening a new window for tagging microvesicles utilized in liquid biopsies.

Graphical abstract

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Dating and intimate partner violence among young persons ages 15–30: Evidence from a systematic review

Publication date: Available online 14 January 2017
Source:Aggression and Violent Behavior
Author(s): Wesley G. Jennings, Chidike Okeem, Alex R. Piquero, Christine S. Sellers, Delphine Theobald, David P. Farrington
While there has been much empirical research on adult dating violence, only recently has research began to also focus on young adult dating violence in general and teen dating violence specifically. With recognition of the growing research and media attention toward youth and young adult dating violence, the current study provides a systematic review of the extant literature devoted toward examinations of dating/intimate partner violence among individuals aged 15 to 30 and, more narrowly, on the prior research that has tested the effectiveness of dating/intimate partner violence interventions with this age group. Results from a comprehensive literature search of a number of existing databases revealed 169 studies that met the inclusion criteria, and 42 of these 169 studies were also characterized as intervention studies. Descriptive results are discussed for the 169 studies overall, and for the 42 intervention studies in particular in greater detail. Evidence gleaned from this systematic review revealed a number of similarities and differences between the studies in general, but also pointed toward the potential effectiveness of interventions to prevent the occurrence and re-occurrence of dating/intimate partner violence. Study limitations and directions for future research are also discussed.



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Unraveling the link between maltreatment and juvenile antisocial behavior: A meta-analysis of prospective longitudinal studies

Publication date: Available online 14 January 2017
Source:Aggression and Violent Behavior
Author(s): Teresa Braga, Leonel Cunha Gonçalves, Miguel Basto-Pereira, Ângela Maia
The maltreatment-antisocial behavior relationship has been a focus of research for decades. However, understanding this association has been largely based on individual empirical studies or on reviews of maltreatments' broad consequences or of delinquency's diverse risk factors. To thoroughly examine the relationship between maltreatment and juvenile antisocial behaviors, we conducted a meta-analysis exclusively of prospective longitudinal studies and explored moderator effects. Overall maltreatment, physical, sexual and emotional abuse, and neglect were included, and general and aggressive antisocial behaviors were considered. The final data set consisted of 33 studies, including 23,973 youth, and 69 correlations. Results showed that maltreatment is associated with higher rates of general antisocial behaviors (r=0.11; 95% CI [0.08, 0.14]) and aggressive antisocial behaviors (r=0.11; 95% CI [0.07, 0.14]), and the relationship holds in the presence of potential confounders, as common risk factors and methodological variations. Furthermore, sexual and physical abuse were more strongly linked to aggressive rather than general antisocial behaviors, while neglected youth had an increased risk of general antisocial involvement. The causal mechanisms underlying these dissimilar relationships warrant further research to prevent the adverse antisocial consequences of maltreatment.



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Systematic review of early risk factors for life-course-persistent, adolescence-limited, and late-onset offenders in prospective longitudinal studies

Publication date: Available online 14 January 2017
Source:Aggression and Violent Behavior
Author(s): Darrick Jolliffe, David P. Farrington, Alex R. Piquero, Rolf Loeber, Karl G. Hill
This paper builds on our previous systematic review of prospective longitudinal studies and examines the early risk factors associated with life-course persistent offending (LCP), adolescence-limited (AL) and late-onset (LO) offending. Out of the 55 prospective longitudinal studies which theoretically could possess the relevant information, only four provided information about risk factors associated with the different offending types. An additional three provided data so that relevant analyses could be conducted. The results suggested that there was little evidence that specific early risk factors were associated with specific offending types. There was also limited evidence that specific risk factors predicted specific offending types when criminal career duration was included in the definitions of LCP, AL, and LO offending. However, LCP offenders tended to have a greater number of risk factors, and the magnitude of these was somewhat greater than for AL offenders, who in turn tended to have more risk factors (and of a greater magnitude) than LO offenders. LCP and AL offenders may differ more in degree (in the number and magnitude of risk factors) than in kind (in the specific risk factors that are predictive). Importantly, as the potential criminal career duration was increased in defining the offending types, those with longer careers tended to have more risk factors, but, LCP and AL offenders were not predicted by different risk factors. Much more research is needed on risk factors for offending types defined according to criminal career durations.



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Elemental characterisation of Andalusian wine vinegars with protected designation of origin by ICP-OES and chemometric approach

Publication date: May 2017
Source:Food Control, Volume 75
Author(s): P. Paneque, M.L. Morales, P. Burgos, L. Ponce, R.M. Callejón
Wine vinegars from three Protected Designations of Origin (PDO), Vinagre de Jerez (J), Vinagre de Montilla-Moriles (MM) and Vinagre del Condado de Huelva (CH) from Andalusia, Southern Spain, were investigated for their mineral elements content. Al, As, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, P, Pb, S, Sr, V and Zn were determined by inductively coupled plasma optical-emission (ICP-OES). Jerez vinegars had a statistically significant higher Sr content than the others, while with respect to B the same was true for Montilla-Moriles vinegars. Moreover, the ageing time of the vinegars clearly played a role in vinegar mineral content, with higher mineral levels found in aged vinegars than in young ones, especially in samples from Condado de Huelva. Multivariate analysis was performed in order to assess if the vinegars' geographical classification was possible through their elemental profile. Classification models were obtained by LDA and SVM, achieving good prediction abilities, 73 and 80%, respectively.



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Phosphorylation of chitosan/HEMA interpenetrating polymer network prepared by γ-radiation for metal ions removal from aqueous solutions

Publication date: 15 April 2017
Source:Carbohydrate Polymers, Volume 162
Author(s): Ahmed M. Elbarbary, Mohamed Mohamady Ghobashy
Interpenetrating polymer network (IPN) hydrogels, based on chitosan (CS) and 2-hydroxyethyl methacrylate (HEMA), have been prepared by γ-radiation followed by chemical modification via phosphorylation reaction and used for adsorption of Ca(II), Cu(II) and Zn(II) ions from their aqueous solutions. The gel content (%) increases with increasing the HEMA concentration. The maximum swelling (%) observed at the ratio (70/30) (CS/HEMA). CS/pHEMA IPN showed a higher thermal stability than CS. The phosphorylated hydrogel, Phos-(CS/pHEMA), characterized by XRD, EDS, SEM, DSC and TGA techniques. FT-IR spectra before and after adsorption of metal ions have been studied. Factors affecting the maximum adsorption capacity were also investigated. The maximum adsorption capacity using 0.01g Phos-(CS/pHEMA) was 66.3, 57.6 and 48.7 (mg/g) for Cu(II), Zn(II) and Ca(II) ions, respectively. The adsorption isotherms were simulated by Langmuir and Freundlich models and the adsorption kinetics were simulated by the pseudo-first-order and pseudo-second-order kinetics. The adsorption follows Langmuir models and pseudo-second order. The IPN hydrogels showed effective adsorption of the three metal ions from aqueous solution.



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Interplay of bifurcated hydrogen bonds in making of inclusion/pseudo-inclusion complexes of Ni(II), Cu(II) and Zn(II) of a salophen type ligand: Crystal structures and spectral aspects

Publication date: 15 April 2017
Source:Journal of Molecular Structure, Volume 1134
Author(s): K.U. Ambili, M. Sithambaresan, M.R. Prathapachandra Kurup
Three novel photoluminescent materials were synthesized by treating Ni(II), Cu(II) and Zn(II) acetate salts with a Schiff base prepared from 3-ethoxysalicylaldehyde and 2-aminobenzylamine. Among the prepared complexes, Ni(II) and Cu(II) complexes are inclusion compounds while Zn(II) complex is a pseudo-inclusion compound. They were characterized by elemental analysis, IR, UV–visible and EPR spectra. Single crystal XRD studies of these complexes suggest that Ni(II) and Cu(II) are in a distorted square planar environment while the spatial arrangement of donor atoms in Zn(II) complex is best described as distorted square based pyramid although significant distortion towards trigonal bipyramid is noticed. Stabilized crystal packing of the complexes is established via supramolecular interactions. The metal chelate rings as the π system for C–H···π interactions found in Cu(II) and Zn(II) complexes explicit the concept of metalloaromaticity. TG-DTG studies reveal that all the complexes are thermally stable. Both ligand and complexes exhibit intense photoluminescence in near UV region. However, Zn(II) complex giving an intense blue-green emission spectrum at maximum wavelength of 518 nm with shoulder peaks, could be used for optoelectronic applications.

Graphical abstract

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Advances and Challenges in Oral Biofilm Control

Abstract

Purpose of Review

The paper aims to critically study the literature published over the past 3 years as relevant to oral biofilm control. The emphasis of this review is the interests and importance of new findings, seeking the following answers: (i) what is the major challenge in oral biofilm control?, (ii) what are the new anti-biofilm approaches?, and (iii) what are the further researches?

Recent Findings

In addition to mechanical plaque removal and the use of chemical agents against pathogenic biofilm, there is a need for development of new anti-biofilm approaches. The majority of the new studies aiming to control oral biofilm have been performed with the characterization of the extracellular matrix components. Exopolysaccharides (EPS), proteins, lipids, nucleic acids (eDNA), lipoteichoic acids (LTA), and lipopolysaccharides have been identified in the matrices of bacterial biofilms and are considered the current targets to oral biofilm control.

Summary

The extracellular matrix is essential for the existence of the biofilm and by its virulence both in bacterial and fungal pathogens. The better understanding of the biomechanical properties of the EPS matrix is the main advance and is leading to new chemical and/or biological approaches to remove or disorganize cariogenic biofilms. Recently, researches are focusing on the extracellular matrix for oral biofilm control with further clinical applicability.

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Adrenal Teratoma: a Case Series and Review of the Literature

Abstract

Adrenal teratomas are rare neoplasms and there is limited data on their surgical outcomes and long-term prognosis. We aimed to review our institutional experience and compare this to the existing literature on adrenal teratomas in adults and children. An institutional pathology database was searched for cases of adrenal teratoma (June 1956–July 2016). Clinical and imaging data were abstracted from the medical records and pathology slides were obtained for review. In addition, a PubMed search for "adrenal teratoma" from June 1952 to July 2016 was performed to identify reports of primary adrenal teratoma in patients of all ages. Of 7706 patients who underwent adrenalectomy during the study period at our institution, three patients were identified with adrenal teratoma. Patients were 24, 26, and 29 years of age, respectively. Two patients presented with abdominal pain and two of the three underwent a laparoscopic adrenalectomy. A pathologic examination revealed mature cystic teratomas that frequently displayed well-differentiated respiratory, digestive, and squamous epithelia. Eighteen case reports in the literature were identified in patients 17–61 years of age. Patients presented most frequently with abdominal or flank pain (63.6%). Median tumor diameter was 9.0 cm and tumors were frequently left-sided (81.8%), cystic (63.6%), and calcified (72.7%) on either radiologic or pathologic examination. Primary adrenal teratomas are rare neoplasms that typically present as large, left-sided nodules with cystic and calcified components seen radiographically. Although the data are limited, they are generally amenable to laparoscopic resection and have a very favorable prognosis.

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Resident Perspectives of an Interactive Case Review following Independent Didactic Study as a Method of Teaching a Pediatric Imaging Curriculum

Publication date: Available online 14 January 2017
Source:Current Problems in Diagnostic Radiology
Author(s): Aleksandr Rozenberg, Sachin Dheer, Levon N. Nazarian, Suzanne S. Long




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The High-Performing Radiology Residency: A Case Study

Publication date: Available online 14 January 2017
Source:Current Problems in Diagnostic Radiology
Author(s): Lu Anne V. Dinglasan, Mary H. Scanlon




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Unexpected Presentation of Perianal Granular Cell Tumor in a Young Woman

Publication date: Available online 14 January 2017
Source:Current Problems in Diagnostic Radiology
Author(s): Laila Rashidi, Darren Pollock, Sarah Bastawrous
Granular cell tumors (GCT) originate from Schwann cells of the soft tissues and are rarely observed in the perianal region. Often, correct diagnosis can be challenging due to non specific clinical symptoms and imaging characteristics, as well as its ability to mimic other malignant lesions histologically. We describe the case of a previously healthy 36-year-old woman who presents with a slow growing, painless lump in her perianal region who underwent surgical excision and was found to have a GCT on microscopic evaluation. This case highlights the importance for radiologists, pathologist, surgeons and other health care providers to be aware of this rare neoplasm and consider it in the differential diagnosis when encountering perianal masses.



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Adaptation of primocane fruiting raspberry plants to environmental factors under the influence of Bacillus strains in Western Siberia

Abstract

In geographical locations with a short vegetative season and continental climate that include Western Siberia, growing primocane fruiting raspberry varieties becomes very important. However, it is necessary to help the plants to overcome the environmental stress factors. This study aimed to evaluate the impact of the pre-planting treatment of primocane fruiting raspberry root system with Bacillus strains on the following plant development under variable environmental conditions. In 2012, Bacillus subtilis RCAM В-10641, Bacillus amyloliquefaciens RCAM В-10642, and Bacillus licheniformis RCAM В-10562 were used for inoculating the root system of primocane fruiting raspberry cultivar Nedosyagaemaya before planting. The test suspensions were 10⁵ CFU/ml for each bacterial strains. The effects of this treatment on plant growth and crop productivity were estimated in 2012–2015 growing seasons differed by environmental conditions. The pre-planting treatment by the bacterial strains increased the number of new raspberry canes and the number of plant generative organs as well as crop productivity compared to control. In addition, these bacilli acted as the standard humic fertilizer. Variable environmental factors such as air temperature, relative humidity, and winter and spring frosts seriously influenced the plant biological parameters and crop productivity of control plants. At the same time, the pre-planting primocane fruiting root treatment by Bacillus strains decreased the negative effects of abiotic stresses on plants in all years of the research. Of the three strains studied, B. subtilis was shown to reveal the best results in adaptation of primocane fruiting raspberry plants to environmental factors in Western Siberia. For the first time, the role of Bacillus strains in enhancing frost resistance in primocane fruiting raspberry plants was shown. These bacilli are capable of being the basis of multifunctional biological formulations for effective plant and environmental health management in growing primocane fruiting raspberry.

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Investigation of diethylstilbestrol residue level in human urine samples by a specific monoclonal antibody

Abstract

Diethylstilbestrol (DES) is used as a kind of animal feed additive and affects people's health through the food chain. The purpose of this study is to detect the residue level of DES in 576 human urine samples directly. DES-BSA was used to immunize Balb/c mice. The monoclonal antibody was produced by hybridoma that was screened through cell fusion techniques. Finally, we developed the indirect competitive ELISA method to analyze 576 human urine samples from Zhejiang Province, China. The IC₅₀ of this method was 3.33 ng/mL. The LOD and LOQ were 0.16 and 0.54 ng/mL. Linear range of the standard curve was from LOD to 12.50 ng/mL. There was no cross-reactivity with two kinds of estrogens and two structural analogs with DES. Five hundred seventy-six urine samples were analyzed by the indirect competitive ELISA method, and the detection rate was 98.78%. The mean concentration and geometric mean were 4.70 and 3.50 ng/mL. The indirect competitive ELISA method based on monoclonal antibody was sensitive and reliable for the detection of DES in human urine samples. The results warned us to pay more attention to human health and food safety.

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Bio-based degradation of emerging endocrine-disrupting and dye-based pollutants using cross-linked enzyme aggregates

Abstract

In this study, manganese peroxidase (MnP) from an indigenous white-rot fungus Ganoderma lucidum IBL-05 was insolubilized in the form of cross-linked enzyme aggregates (CLEAs) using various aggregating agents, i.e., acetone, ammonium sulfate, ethanol, 2-propanol, and tert-butanol, followed by glutaraldehyde (GA) cross-linking. The precipitant type, MnP, and GA concentrations affected the CLEAs activity recovery and aggregation yield. Among precipitants used, acetone appeared to be the most efficient aggregation agent, providing the highest activity recovery and aggregation yield of 31.26 and 73.46%, respectively. Optimal cross-linking was noticed using 2.0% (v/v) GA and 8:1 (v/v) MnP to GA ratio at 3.0 h cross-linking time under continuous agitation at 4 °C. The highest recovered activity and aggregation yield were determined to be 47.57 and 81.26%, respectively. The MnP-CLEAs, thus synthesized, were tested to investigate their bio-catalytic capacity for removing two known endocrine-disrupting chemicals (EDCs), e.g., nonylphenol and triclosan in a packed bed reactor system. The insolubilized MnP efficiently catalyzed the biodegradation of both EDCs, transforming over 80% in the presence of MnP-based system. A maximal of 100% decolorization was recorded for Sitara textile (SIT-based) effluent, followed by 95.5% for Crescent textile (CRT-based) effluent, 88.0% for K&N textile (KIT-based) effluent, and 84.2% for Nishat textile (NIT-based) effluent.

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Validated electrochemical and chromatographic quantifications of some antibiotic residues in pharmaceutical industrial waste water

Abstract

Realistic implementation of ion selective electrodes (ISEs) into environmental monitoring programs has always been a challenging task. This could be largely attributed to difficulties in validation of ISE assay results. In this study, the electrochemical response of amoxicillin trihydrate (AMX), ciprofloxacin hydrochloride (CPLX), trimethoprim (TMP), and norfloxacin (NFLX) was studied by the fabrication of sensitive membrane electrodes belonging to two types of ISEs, which are polyvinyl chloride (PVC) membrane electrodes and glassy carbon (GC) electrodes. Linear response for the membrane electrodes was in the concentration range of 10⁻⁵–10⁻² mol/L. For the PVC membrane electrodes, Nernstian slopes of 55.1, 56.5, 56.5, and 54.0 mV/decade were achieved over a pH 4–8 for AMX, CPLX, and NFLX, respectively, and pH 3–6 for TMP. On the other hand, for GC electrodes, Nernstian slopes of 59.1, 58.2, 57.0, and 58.2 mV/decade were achieved over pH 4–8 for AMX, CPLX, and NFLX, respectively, and pH 3–6 for TMP. In addition to assay validation to international industry standards, the fabricated electrodes were also cross-validated relative to conventional separation techniques; high performance liquid chromatography (HPLC), and thin layer chromatography (TLC)-densitometry. The HPLC assay was applied in concentration range of 0.5–10.0 μg/mL, for all target analytes. The TLC-densitometry was adopted over a concentration range of 0.3–1.0 μg/band, for AMX, and 0.1–0.9 μg/band, for CPLX, NFLX, and TMP. The proposed techniques were successfully applied for quantification of the selected drugs either in pure form or waste water samples obtained from pharmaceutical plants. The actual waste water samples were subjected to solid phase extraction (SPE) for pretreatment prior to the application of chromatographic techniques (HPLC and TLC-densitometry). On the other hand, the fabricated electrodes were successfully applied for quantification of the antibiotic residues in actual waste water samples without any pretreatment. This finding assures the suitability of the fabricated ISEs for environmental analysis.

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Lactucopicrin potentiates neuritogenesis and neurotrophic effects by regulating Ca2+/CaMKII/ATF1 signaling pathway

Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Ramu Venkatesan, Won-Sik Shim, Eui-Ju Yeo, Sun Yeou Kim
Ethno-pharmacological relevanceLactucopicrin is one of constitutes in Cichorium intybus L, which is commonly known as chicory in worldwide. It has been used for traditional usage such as antianalgesics, antidepressants and antihyperglycemicsAim of studyWe investigated the neurotrophin-mediated neuroprotective effect of lactucopicrin in in vitro and examined for the underlying mechanism.Materials and methodTo verify the neuroprotective effect of lactucopicrin, we investigated the inhibitory AChE activity, neurite outgrowth-related downstream signaling in murine neuroblastoma N2a and neurotrophins secretion in rat C6 glioma cells.ResultsLactucopicrin inhibited the AChE activity and increased intracellular Ca²⁺ levels with a substantial rise in muscarinic acetylcholine receptor M1 (CHRM1) expression in N2a cells. Moreover, lactucopicrin actively promoted neurite outgrowth via Ca²⁺-mediated activation of Ca²⁺/calmodulin-dependent protein kinase-II (CaMKII). It further activates transcription factor 1 (ATF1) along with modulating the levels of tropomyosin receptor kinase A, extracellular signal-regulated kinase 1 and 2, AKT, and synaptophysin 1 in N2a cells. Additionally, the levels of neurotrophins including NGF, BDNF, and NT3 were increased by treatment of lactucopicrin in C6 cells. The effects of lactucopicrin on NGF secretion and neuritogenesis were maintained even in the presence of phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002, indicating that lactucopicrin exerts its effect on neuritogenesis in a PI3K-independent manner.ConclusionOur results suggest that the natural compound lactucopicrin may be a promising neurotrophin-mediated neuroprotective candidate for neurodegenerative diseases.

Graphical abstract

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Aqueous seed extract of Hunteria umbellata (K. Schum.) Hallier f. (Apocynaceae) palliates hyperglycemia, insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome in rats

Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): T.O. Ajiboye, A.A. Hussaini, B.Y. Nafiu, O.B. Ibitoye
Ethnopharmacological relevanceHunteria umbellata is used in the management and treatment of diabetes and obesity in Nigeria. This study evaluates the effect of aqueous seed extract of Hunteria umbellata on insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndromeMaterials and methodsRats were randomized into seven groups (A-G). Control (group A) and group C rats received control diet for nine weeks while rats in groups B, D – G were placed on high-fructose diet for 9 weeks. In addition to the diets, groups C – F rats orally received 400, 100, 200 and 400mg/kg body weight aqueous seed extract of Hunteria umbellata for 3 weeks starting from 6th – 9th week.ResultsHigh-fructose diet (when compared to control rats) mediated a significant (p<0.05) increase in body weight, body mass index and abdominal circumference. Similarly, levels of blood glucose, insulin, leptin, adiponectin and insulin resistance were increased. It also caused a significant increase in the levels of cholesterol, triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic index, cardiac index and coronary artery index while high-density lipoprotein cholesterol was decreased significantly. Levels of proinflammatory factor, tumour necrosis factor-α, interleukin-6 and 8 were also increased by the high fructose diet. Moreover, it mediated decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose 6-phosphate dehydrogenase and level of glutathione reduced. Conversely, levels of malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl and fragmented DNA were elevated. Aqueous seed extract of Hunteria umbellata significantly ameliorated the high fructose diet-mediated alterations.ConclusionsFrom this study, it is concluded that aqueous seed extract of Hunteria umbellata possesses hypoglycemic, hypolipidemic and antioxidants abilities as evident from its capability to extenuate insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome rats.

Graphical abstract

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Activation and pathogenic manipulation of the sensors of the innate immune system

Publication date: Available online 14 January 2017
Source:Microbes and Infection
Author(s): Charlotte Odendall, Jonathan C. Kagan
The innate immune system detects the presence of microbes through different families of pattern-recognition receptors (PRRs). PRRs detect pathogens of all origins and trigger signaling events that activate innate and adaptive immunity. These signaling pathways are initiated by the recruitment of adaptor proteins and enzymes to the site of ligand encounter, in large complexes termed supramolecular organizing centers (SMOCs). These events need to be tightly regulated in order to ensure optimal activation when required, and minimal signaling in the absence of microbial encounters. This regulation is achieved, at least in part, through the precise subcellular localization of receptors and adaptors. Consequently, mislocalization of these proteins inhibits innate immune pathways, and pathogens have evolved to alter host protein localization as a strategy to evade immune detection. This review describes the importance of subcellular localization of various PRR families and their adaptors, and highlights pathogenic immune evasion strategies that operate by altering immune proteins localization.



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Direct and indirect effects of wastewater use and herd environment on the occurrence of animal diseases and animal health in Pakistan

Abstract

The use of wastewater for rearing domestic animals is a common phenomenon in most of the developing countries like Pakistan that face a serious shortage of freshwater resources. However, most of the literature has only focused on the indirect effects of wastewater use on animal health or productivity, and literature on the direct effects of wastewater use is rare. Therefore, this study aims to investigate the direct and indirect effects of wastewater usage on the prevalence of animal diseases and animal health in Pakistan. The study is based on a household-level survey of 360 domestic water buffalo herds collected from 12 districts of Punjab Province, Pakistan. We tested the prevalence of the animal's diseases, animal's health, and wastewater-use preference with various econometric tools, such as the Poisson, negative binomial, and logistic regressions. The findings of the study show that the majority of the farmers use wastewater for buffalo bathing due to the shortage of freshwater resources. Results explore the prevalence of diseases such as clinical mastitis, tick infestation, and foot and mouth disease at the farm level significantly associated with buffalo bathing in the wastewater. Moreover, bathing in wastewater pre- and post-milking also plays a role in the occurrence of diseases. Particularly, if the buffalo's access to wastewater for bathing is within 60 min after milking, the probability of the animals being exposed to mastitis is higher. Furthermore, on investigation, a number of factors are found, such as the distance to the water source, power shortage, groundwater availability, and the education of farmers that influence farmers' behavior of letting their animals take a bath in wastewater. Moreover, the use of different preventive measures improves the animal's health.

http://ift.tt/2iUAuKO

Palliative effects of extra virgin olive oil, gallic acid, and lemongrass oil dietary supplementation on growth performance, digestibility, carcass traits, and antioxidant status of heat-stressed growing New Zealand White rabbits

Abstract

This study explored the effects of supplemental dietary extra virgin olive oil (EVOO), gallic acid (GA), or lemongrass essential oil (LGEO) on growth performance, nutrient digestibility, carcass traits, lipid peroxidation, hematological, and antioxidative status in growing rabbits under heat stress conditions. A total of 48 male growing New Zealand White rabbits were randomly divided into four equal groups, which received a basal diet without any supplementation or supplemented with 15 g EVOO, 500 mg GA, or 400 mg LGEO/kg of diet, for eight consecutive weeks. Results revealed that the overall mean of temperature humidity index was 84.67 ± 0.35, reflecting a state of severe heat stress. Moreover, dietary supplementation with EVOO, GA, or LGEO significantly increased live body weight and daily body weight gain but decreased both feed conversion ratio and daily water consumption. Additionally, a significant increase in both organic matter and crude protein digestibility besides a remarkable elevation in the nutritive values of digestible crude protein, total digestible nutrients, and digestible energy, as well as an increase in the numbers of WBCs, lymphocytes, and heterophils was significant in EVOO-supplemented rabbits. Supplementation with EVOO, GA, or LGEO in the heat-stressed growing rabbit's diet enhanced catalase activity and reduced glutathione content, whereas EVOO-treated rabbits had the highest values. Also, malondialdehyde activity was reduced in response to all tested additives. In conclusion, these findings suggested that addition of EVOO, GA, or LGEO in growing rabbit's diet could be used effectively to alleviate negative impacts of heat stress load on performance, nutrient digestibility, oxidative status, and hemato-biochemical features. Furthermore, among these additives, EVOO achieved the best effects.

http://ift.tt/2jRaww6

Porous nano-cerium oxide wood chip biochar composites for aqueous levofloxacin removal and sorption mechanism insights

Abstract

The adsorption removal of levofloxacin (LEV), a widely used fluoroquinolone antibiotic, by using the biochars derived from the pyrolysis of pine wood chip pretreated with cerium trichloride was investigated through batch sorption experiments and multiple characterization techniques. The differences in the basic physicochemical properties between Ce-impregnated biochars and the pristine biochars were confirmed by the analysis of elemental compositions, specific surface areas, energy dispersive spectrometry, X-ray diffraction, and thermo-gravimetry. FT-IR spectra of the pre- and post-sorption biochars confirmed the chemical adsorption for LEV sorption onto the biochars. Large shifts in the binding energy of Ce_3d, O_1s, C_1s, and N_1s regions on the pre- and post-sorption biochars indicated the surface complexation of LEV molecule onto the biochars. The binding species of Ce⁴⁺ and Ce³⁺ identified by X-ray photoelectron spectroscopy reflect the role of Ce oxides during sorption. Batch adsorption showed the significant enhancement of adsorption capacity for LEV after the Ce modification. Batch adsorption kinetic data fitted well with the pseudo-second-order model. Both the Langmuir and the Freundlich models reproduced the isotherm data well. Findings from this work indicated that Ce-impregnated biochars can be effective for the removal of aqueous LEV.

http://ift.tt/2iUMEDw

Comparative assessment of metallurgical recovery of metals from electronic waste with special emphasis on bioleaching

Abstract

Waste electrical and electronic equipment (WEEE) or electronic waste (e-waste) is one of the fastest growing waste streams in the urban environment worldwide. The core component of printed circuit board (PCB) in e-waste contains a complex array of metals in rich quantity, some of which are toxic to the environment and all of which are valuable resources. Therefore, the recycling of e-waste is an important aspect not only from the point of waste treatment but also from the recovery of metals for economic growth. Conventional approaches for recovery of metals from e-waste, viz. pyrometallurgical and hydrometallurgical techniques, are rapid and efficient, but cause secondary pollution and economically unviable. Limitations of the conventional techniques have led to a shift towards biometallurgical technique involving microbiological leaching of metals from e-waste in eco-friendly manner. However, optimization of certain biotic and abiotic factors such as microbial species, pH, temperature, nutrients, and aeration rate affect the bioleaching process and can lead to profitable recovery of metals from e-waste. The present review provides a comprehensive assessment on the metallurgical techniques for recovery of metals from e-waste with special emphasis on bioleaching process and the associated factors.

http://ift.tt/2jRePHx

Genotypic differences in cadmium transport in developing barley grains

Abstract

Genotypic differences in cadmium (Cd) transport in developing grains of barley (Hordeum vulgare L.) were investigated using detached ears cultured in a nutrient solution containing 0.5 and 5 μM Cd. Cd concentration in each part of the ear in W6nk2 (a low-grain-Cd-accumulation genotype) was much less than in Zhenong8 (a high accumulator) with 0.5 μM Cd treatment. However, Cd concentration in W6nk2 grains increased with an increase in external Cd level and was similar to Zhenong8 with 5 μM Cd treatment. Awn removal, a high relative humidity (RH, 90%) and addition of sucrose markedly decreased grain Cd concentration in Zhenong8 but less affected Cd transport to grain in W6nk2. Stem girdling reduced Cd transport to developing grains with 5 μM Cd treatment, especially for W6nk2, whereas no effect was found in either genotype with low Cd treatment. Our results suggested that higher grain Cd in Zhenong8 is closely related to a larger capacity for xylem transport and is connected with Cd translocation in xylem and phloem sap.

http://ift.tt/2iUOep1

Biodegradability of fluoxetine, mefenamic acid, and metoprolol using different microbial consortiums

Abstract

The biodegradation of fluoxetine, mefenamic acid, and metoprolol using ammonium-nitrite-oxidizing consortium, nitrite-oxidizing consortium, and heterotrophic biomass was evaluated in batch tests applying different retention times. The ammonium-nitrite-oxidizing consortium presented the highest biodegradation percentages for mefenamic acid and metoprolol, of 85 and 64% respectively. This consortium was also capable to biodegrade 79% of fluoxetine. The heterotrophic consortium showed the highest ability to biodegrade fluoxetine reaching 85%, and it also had a high potential for biodegrading mefenamic acid and metoprolol, of 66 and 58% respectively. The nitrite-oxidizing consortium presented the lowest biodegradation of the three pharmaceuticals, of less than 48%. The determination of the selected pharmaceuticals in the dissolved phase and in the biomass indicated that biodegradation was the major removal mechanism of the three compounds. Based on the obtained results, the biodegradation kinetics was adjusted to pseudo-first-order for the three pharmaceuticals. The values of k _biol for fluoxetine, mefenamic acid, and metoprolol determined with the three consortiums indicated that ammonium-nitrite-oxidizing and heterotrophic biomass allow a partial biodegradation of the compounds, while no substantial biodegradation can be expected using nitrite-oxidizing consortium. Metoprolol was the less biodegradable compound. The sorption of fluoxetine and mefenamic acid onto biomass had a significant contribution for their removal (6–14%). The lowest sorption coefficients were obtained for metoprolol indicating that the sorption onto biomass is poor (3–4%), and the contribution of this process to the global removal can be neglected.

http://ift.tt/2jRkJbN

Zeolitic tuffs for acid mine drainage (AMD) treatment in Ecuador: breakthrough curves for Mn 2+ , Cd 2+ , Cr 3+ , Zn 2+ , and Al 3+

Abstract

Zeolitic tuff constitutes a technical and economical feasible alternative to manage acidic waters in initial phases of generation. A study of cation exchange with two zeolitic tuffs from Ecuador and one from Cuba has been conducted using breakthrough curve methodology. Cations Mn²⁺, Cd²⁺, Cr³⁺, Zn²⁺, and Al³⁺ have been chosen owing to their presence in underground water in exploration activities (decline development) in Fruta del Norte (Ecuador). Zeolites characterized by X-ray diffraction and thermal stability after heating overnight as heulandites show a similar exchange behavior for the five cations studied. The clinoptilolite sample Tasajeras shows a relevant cation exchange performance expressed in the important increment of spatial time to reach the breakthrough point in comparison with heulandite samples. The maximum length of unused beds was found for Cr³⁺ and Zn²⁺ cations showing, therefore, a lower adsorption performance in relation with Mn²⁺ and Cd²⁺. A final disposal method of metal-loaded zeolites with cement is proposed.

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Lethal Dysregulation of Energy Metabolism During Embryonic Vitamin E Deficiency

Publication date: Available online 14 January 2017
Source:Free Radical Biology and Medicine
Author(s): Melissa McDougall, Jaewoo Choi, Hye-Kyeong Kim, Gerd Bobe, J. Frederik Stevens, Enrique Cadenas, Robert Tanguay, Maret G. Traber
Vitamin E (α-tocopherol, VitE) was discovered in 1922 for its role in preventing embryonic mortality. We investigated the underlying mechanisms causing lethality using targeted metabolomics analyses of zebrafish VitE-deficient embryos over five days of development, which coincided with their increased morbidity and mortality. VitE deficiency resulted in peroxidation of docosahexaenoic acid (DHA), depleting DHA-containing phospholipids, especially phosphatidylcholine, which also caused choline depletion. This increased lipid peroxidation also increased NADPH oxidation, which depleted glucose by shunting it to the pentose phosphate pathway. VitE deficiency was associated with mitochondrial dysfunction with concomitant impairment of energy homeostasis. The observed morbidity and mortality outcomes could be attenuated, but not fully reversed, by glucose injection into VitE-deficient embryos at developmental day one. Thus, embryonic VitE deficiency in vertebrates leads to a metabolic reprogramming that adversely affects methyl donor status and cellular energy homeostasis with lethal outcomes.



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Joining aluminum alloy 5052 sheets via novel hybrid resistance spot clinching process

Publication date: 15 March 2017
Source:Materials & Design, Volume 118
Author(s): Yu Zhang, He Shan, Yang Li, Jing Guo, Zhen Luo, Cheng Yong Ma
Aluminum alloy 5052 sheets (thickness: 1mm) were joined using a novel method (resistance spot clinching) that combines mechanical clinching and resistance spot welding processes. A pair of molds combine with processing tapes were exerted in this process. The microstructure of the fusion zone under novel process presents more portion of equiaxed dendritic zone compared with that of the resistance spot welded joint, which is due to the different temperature gradient feature during solidification. The mechanical properties of the joints were evaluated via orthogonal trials of tensile shear tests performed on the joints. The results revealed that, even under lower heat input, the load-bearing capacity of the resistance spot clinching joints is superior to that of the traditional resistance spot welding joints. Digital image correlation was used to evaluate the distortion behavior of the weld joints during testing. Compared with the stiffness of traditional joints, the higher stiffness of the resistance spot clinching joint generated a higher tensile stress component in the periphery of the fusion zone during testing (which resulted in a higher peak load).

Graphical abstract

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A rare complication of middle ear cholesteatoma – Pseudoaneurysm of petrous internal carotid artery

Publication date: Available online 13 January 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): L.Y. Lim, I. Mohamad, J.H. Lau, I.P. Tang
ObjectivesTo report a rare complication of middle ear cholesteatoma resulting pseudoaneurysm of petrous internal carotid artery (ICA).Case reportA 39year old lady presented with sudden profuse bleeding from the right ear. Previously, she had been having bilateral intermittent foul smelling ear discharge for a year. Otoscope finding was insignificant as only blood seen. Computed tomography of temporal bone and magnetic resonance imaging of brain suggested locally aggressive cholesteatoma. Right ICA angiography showed pseudoaneurysm of petrous part of ICA. She underwent coil embolisation followed by bilateral modified radical mastoidectomy a month later. She recovered well after surgery and remained symptoms free.ConclusionsPseudoaneurysm of petrous ICA as a complication of middle ear cholesteatoma is extremely rare. Spontaneous profuse bleeding maybe the only clinical presentation. Radiological imaging is important to diagnose and assist in treatment. Endovascular technique may be required, followed by surgical treatment for infection control



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Δ14CO2 from dark respiration in plants and its impact on the estimation of atmospheric fossil fuel CO2

Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): Xiaohu Xiong, Weijian Zhou, Peng Cheng, Shugang Wu, Zhenchuan Niu, Hua Du, Xuefeng Lu, Yunchong Fu, George S. Burr
Radiocarbon (¹⁴C) has been widely used for quantification of fossil fuel CO2 (CO2ff) in the atmosphere and for ecosystem source partitioning studies. The strength of the technique lies in the intrinsic differences between the ¹⁴C signature of fossil fuels and other sources. In past studies, the ¹⁴C content of CO2 derived from plants has been equated with the ¹⁴C content of the atmosphere. Carbon isotopic fractionation mechanisms vary among plants however, and experimental study on fractionation associated with dark respiration is lacking. Here we present accelerator mass spectrometry (AMS) radiocarbon results of CO2 respired from 21 plants using a lab-incubation method and associated bulk organic matter. From the respired CO2 we determine Δ¹⁴Cres values, and from the bulk organic matter we determine Δ¹⁴Cbom values. A significant difference between Δ¹⁴Cres and Δ¹⁴Cbom (P < 0.01) was observed for all investigated plants, ranging from −42.3‰ to 10.1‰. The results show that Δ¹⁴Cres values are in agreement with mean atmospheric Δ¹⁴CO2 for several days leading up to the sampling date, but are significantly different from corresponding bulk organic Δ¹⁴C values. We find that although dark respiration is unlikely to significantly influence the estimation of CO2ff, an additional bias associated with the respiration rate during a plant's growth period should be considered when using Δ¹⁴C in plants to quantify atmospheric CO2ff.



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Nanoporous hydroxyapatite/sodium titanate bilayer on titanium implants for improved osteointegration

Publication date: Available online 13 January 2017
Source:Dental Materials
Author(s): A. Carradò, F. Perrin-Schmitt, Q.V. Le, M. Giraudel, C. Fischer, G. Koenig, L. Jacomine, L. Behr, A. Chalom, L. Fiette, A. Morlet, G. Pourroy
ObjectiveThe aim of this study was to improve the strength and quality of the titanium–hydroxyapatite interface in order to prevent long-term failure of the implanted devices originating from coating delamination and to test it in an in-vivo model.MethodsTi disks and dental commercial implants were etched in Kroll solution. Thermochemical treatments of the acid-etched titanium were combined with sol–gel hydroxyapatite (HA) coating processes to obtain a nanoporous hydroxyapatite/sodium titanate bilayer. The sodium titanate layer was created by incorporating sodium ions onto the Ti surface during a NaOH alkaline treatment and stabilized using a heat treatment. HA layer was added by dip-coating in a sol–gel solution. The bioactivity was assessed in vitro with murine MC3T3-E1 and human SaOs-2 cells. Functional and histopathological evaluations of the coated Ti implants were performed at 22, 34 and 60days of implantation in a dog lower mandible model.ResultsNanoporous hydroxyapatite/sodium titanate bilayer on titanium implants was sensitive neither to crack propagation nor to layer delamination. The in vitro results on murine MC3T3-E1 and human SaOs-2 cells confirm the advantage of this coating regarding the capacity of cell growth and differentiation. Signs of progressive bone incorporation, such as cancellous bone formed in contact with the implant over the existing compact bone, were notable as early as day 22. Overall, osteoconduction and osteointegration mean scores were higher for test implants compared to the controls at 22 and 34 days.SignificanceNanoporous hydroxyapatite/sodium titanate bilayer improves the in-vivo osteoconduction and osteointegration. It prevents the delamination during the screwing and it could increase HA-coated dental implant stability without adhesive failures. The combination of thermochemical treatments with dip coating is a low-cost strategy.



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Mechanical and microbiological properties and drug release modeling of an etch-and-rinse adhesive containing copper nanoparticles

Publication date: Available online 13 January 2017
Source:Dental Materials
Author(s): M.F. Gutiérrez, P. Malaquias, T.P. Matos, A. Szesz, S. Souza, J. Bermudez, A. Reis, A.D. Loguercio, P.V. Farago
ObjectivesTo evaluate the effect of addition of copper nanoparticles (CN) at different concentrations into a two-step etch-and-rinse (2-ER) adhesive on antimicrobial activity (AMA), copper release (CR), ultimate tensile strength (UTS), degree of conversion (DC), water sorption (WS), solubility (SO), as well as the immediate (IM) and 1-year resin–dentin bond strength (μTBS) and nanoleakage (NL).MethodsSeven adhesives were formulated according to the addition of CN (0, 0.0075, 0.015, 0.06, 0.1, 0.5 and 1wt%) in adhesive. The AMA was evaluated against Streptococcus mutans using agar diffusion assay. For CR, WS and SO, specimens were constructed and tested for 28 days. For UTS, specimens were tested after 24h and 28 days. For DC, specimens were constructed and tested after 24h by FTIR. After enamel removal, the ER was applied to dentin. After composite resin build-ups, specimens were sectioned to obtain resin–dentin sticks. For μTBS and NL, specimens were tested after 24h and 1-year periods. All data were submitted to statistical analysis (α=0.05).ResultsThe addition of CN provided AMA to the adhesives at all concentrations. Higher CR was observed in adhesives with higher concentration of CN. UTS, DC, WS and SO were not influenced. For μTBS an increase was observed in 0.1 and 0.5% copper group. For NL, a significant decrease was observed in all groups in comparison with control group. After 1-year, no significant reductions of μTBS and no significant increases of NL were observed for copper containing adhesives compared to the control group.SignificanceThe addition of CN in concentrations up to 1wt% in the 2-ER adhesive may be an alternative to provide AMA and preserve the bonding to dentin, without reducing adhesives' mechanical properties evaluated.



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Application of close-packed structures in dental resin composites

Publication date: Available online 14 January 2017
Source:Dental Materials
Author(s): Ruili Wang, Eric Habib, X.X. Zhu
ObjectiveThe inorganic filler particles in dental resin composites serve to improve their mechanical properties and reduce polymerization shrinkage during their use. Efforts have been made in academia and industry to increase the filler particle content, but, few studies examine the theoretical basis for the maximum particle loading.MethodsThis work evaluates the packing of spherical particles in a close-packed state for highly loaded composites.ResultsCalculations show that for low dispersity particles, the maximum amount of particles is 74.05vol%, regardless of the particle size. This can be further improved by using a mix of large and small particles or by the use of non-spherical particles. For representative spherical particles with a diameter of 1000nm, two types of secondary particles with respective sizes of 414nm (dI) and 225nm (dII) are selected. The results show that after embedding secondary particles I & II into primary spherical particles, the packing factor is increased to 81.19% for the close-packed structures, which shows an improvement of 9.64%, compared to the 74.05% obtained only with primary spherical particles. This packing factor is also higher than either structure with the embedded secondary particles I or II.SignificanceExamples of these mixtures with different spherical particle sizes are shown as a theoretical estimation, serving as a guideline for the design and formulation of new dental resin composites with better properties and improved performance.

Graphical abstract

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Influence of enamel/dentin thickness on the toxic and esthetic effects of experimental in-office bleaching protocols

Abstract

Objectives

This paper aims to assess the whitening effectiveness and toxicity of tooth-bleaching protocols applied to enamel/dentin disks simulating mandibular incisors (ICs) and premolars (PMs).

Materials and methods

A 10% hydrogen peroxide (H₂O₂) gel was applied for 3 × 15, 1 × 15, or 1 × 5 min to enamel/dentin disks simulating mandibular ICs and PMs, and the trans-enamel and trans-dentinal diffusion products were applied to human dental pulp cells (1 h). Professional therapy (35% H₂O₂—3 × 15 min) was used as positive control, and non-bleached samples were used as negative control. Cell viability and morphology, oxidative stress generation, and odontoblastic marker expression were assessed. The H₂O₂ diffusion and enamel color change (ΔE) were also analyzed.

Results

The 10% H₂O₂ gel induced significant cell viability reduction only when applied 3 × 15 min, with the intensity of oxidative stress and down-regulation of odontoblastic markers being higher in the IC group. The other experimental bleaching protocols caused slight alterations regarding the cell parameters evaluated, with intensity being related to enamel/dentin thickness. These effects were also correlated with higher H₂O₂ diffusion in the IC group. ΔE values similar as positive control were found for the 10% 3 × 15 and 1 × 15 protocols on IC group, after 4 and 6 sessions.

Conclusion

Application of a 10% H₂O₂ bleaching gel for 15 or 45 min to thin dental substrate significantly minimizes cell toxicity in comparison with highly concentrated gels associated with similar esthetic outcomes by increasing the number of bleaching sessions.

Clinical relevance

Bleaching gels with 10% H₂O₂ applied in small teeth for short periods may be an interesting alternative to obtain whitening effectiveness without causing toxicity to pulp cells, which may be able to reduce the tooth hypersensitivity claimed by patients.

http://ift.tt/2ixiBUs

Repeated applications of photodynamic therapy on Candida glabrata biofilms formed in acrylic resin polymerized

Abstract

Previous studies have been suggested that photodynamic therapy (PDT) can be used as an adjuvant treatment for denture stomatitis. In this study, we evaluated the effects of multiple sessions of PDT on Candida glabrata biofilms in specimens of polymerized acrylic resin formed after 5 days. Subsequently, four applications of PDT were performed on biofilms in 24-h intervals (days 6–9). Also, we evaluated two types of PDT, including application of laser and methylene blue or light-emitting diode (LED) and erythrosine. The control groups were treated with physiological solution. The effects of PDT on biofilm were evaluated after the first and fourth application of PDT. The biofilm analysis was performed by counting the colony-forming units. The results showed that between the days 6 and 9, the biofilms not treated by PDT had an increase of 5.53 to 6.05 log (p = 0.0271). Regarding the treatments, after one application of PDT, the biofilms decreased from 5.53 to 0.89 log. When it was done four applications, the microbial reduction ranged from 6.05 log to 0.11 log. We observed that one application of PDT with laser or LED caused a reduction of 3.36 and 4.64 compared to the control groups, respectively (p = 0.1708). When it was done four applications of PDT, the reductions achieved were 1.57 for laser and 5.94 for LED (p = 0.0001). It was concluded that repeated applications of PDT on C. glabrata biofilms showed higher antimicrobial activity compared to single application. PDT mediated by LED and erythrosine was more efficient than the PDT mediated by laser and methylene blue.

http://ift.tt/2jimmhN

Dynamic optical absorption characteristics of blood after slow and fast heating

Abstract

Laser treatment is the most effective therapy in dermatology for vascular skin disorders, such as port-wine stains (PWS). Changes in heat-induced absorbance in blood must be determined for accurate numerical simulation and implementation of multi-pulse laser therapy for treatment of PWS. Thermally induced absorbance changes in hemoglobin in blood were compared in vitro between slow water bath heating and fast heating irradiated by using sub-millisecond Nd:YAG laser. Blood composition at different temperatures was calculated by comparing blood absorption spectra with those of pure HbO₂, Hb, and metHb at room temperature. Blood absorbance to heat energy were categorized into three stages distinguished by metHb and coagulation points, which are the validity and security thresholds of the optimized therapy, respectively. Rapid laser heating can distinctively enhance blood absorbance by photochemically induced strong instability compared with slow heating at a constant temperature. Slow heating facilitates metHb point at 70 °C and coagulation point at 75 °C as the temperature of the water bath increases. However, the temperature at which metHb or coagulation point shifts to higher than 10 °C when pulses and fluence in laser irradiation change. Laser fluence less than 20 J/cm² and more than 50 J/cm² is unsuitable for laser treatment because of its low probability to coagulate vascular hyperplasia and high probability to damage normal tissues adjacent to target lesions, respectively. Few bubbles formed after mediate fluence is beneficial to minimize adverse side-effects. Considering blood absorbance, temperature evolution, and bubble formation, we recommend 30–40 J/cm² and 2–4 Hz frequency as the optimal laser parameters in sub-millisecond Nd:YAG laser.

http://ift.tt/2jt2BRY

Outcome of early surgery in infantile esotropia: Our experience in tertiary care hospital

Publication date: Available online 13 January 2017
Source:Medical Journal Armed Forces India
Author(s): Anirudh Singh, J.K.S. Parihar, S.K. Mishra, R. Maggon, Anurag Badhani
BackgroundInfantile esotropia is a convergent strabismus presenting before 6 months of age and is the most common strabismus disorder presenting in the ophthalmology OPD. The dilemma of whether to go for early surgery and how early has been a matter of research for the last 50 years. We describe our results of surgery in infantile esotropia at variable age groups, as well as with different reoperation rates and compare with the results in western literature.MethodsA prospective study was carried out through a review of 113 cases operated for infantile esotropia between February 2013 and August 2014. The variables studied were: age at surgery, type of fixation, refractive error, associated nystagmus, inferior oblique overaction or dissociated vertical deviation (DVD), type of surgery performed and pre- and postoperative deviation angles.ResultsThere were 67 male and 46 female cases of infantile esotropia. The age group of patients varied from 6 months to 12 years. Latent nystagmus was seen in 22 cases, inferior oblique overaction in 49 cases and DVD (mild) in 14 cases. Bimedial rectus recession was done in 78 cases and recession–resection in non-dominant eye in remaining 35 cases. The postoperative residual deviation was <10 PD in 102 cases, between 10 and 16 PD in 5 cases and more than 16 PD in 6 cases. Only 6 cases (5.3%) required reoperation for correction of residual deviation.ConclusionThe authors recommend surgery before 12 months in all cases of infantile esotropia. The reoperation rates in the current study were considerably low.



http://ift.tt/2isflqj

Smoking as a Risk Factor for Breast Reduction: An Analysis of 13,503 Cases

Reduction mammaplasty is one of the most common reconstructive procedures performed by plastic surgeons. Over 100,000 procedures are performed annually. Although important for relieving the painful symptoms associated with macromastia, complication rates of this procedure are not insignificant. They are reported in up to half of cases. Reported risk factors for adverse outcomes include obesity, preoperative wound infection, and advanced ASA status. Smoking has been described as a risk factor for breast reduction.

http://ift.tt/2iouyhb

Sexual segregation in foraging giraffe

Publication date: February 2017
Source:Acta Oecologica, Volume 79
Author(s): Rosemary Peter Mramba, Obeid Mahenya, Annetjie Siyaya, Karen Marie Mathisen, Harry Peter Andreassen, Christina Skarpe
Sexual segregation in giraffe is known to vary between savannas. In this study, we compared sexual segregation in giraffe in one nutrient-rich savanna, the Serengeti National Park, one nutrient-poor, Mikumi National Park, and one medium rich savanna, Arusha National Park, (from here on referred to just by name) based on effects of sexual size dimorphism and related hypotheses. Data were collected in the wet and dry seasons, by driving road transects and making visual observations of browsing giraffe. Additional data were collected from literature (plant chemistry; mammal communities). There was a noticeable difference in browsing by females and males and in browsing between the three savannas. Females browsed a higher diversity of tree species in Serengeti whereas males browsed a higher diversity in Arusha, while the diversity of species browsed in Mikumi was high and about the same in both sexes. Females selected for high concentrations of nitrogen and low concentrations of tannins and phenolics compared to males in Serengeti but selection in Mikumi was more complex. Males browsed higher in the canopy than females in all sites, but the browsing height was generally higher in Serengeti than Mikumi and Arusha. Season had an effect on the browsing height independent of sex in Mikumi, where giraffes browsed higher in the dry season compared to the wet season. Males spent more time browsing per tree compared to females in all three sites; however, browsing time in Mikumi was also affected by season, where giraffes had longer browsing bouts in the wet season compared to the dry season. We suggest that sexual differences in forage requirement and in foraging interacts with differences in tree chemistry and in competing herbivore communities between nutrient rich and nutrient poor savanna in shaping the sexual segregation.



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OX40: Structure and function – What questions remain?

Publication date: March 2017
Source:Molecular Immunology, Volume 83
Author(s): Jane Willoughby, Jordana Griffiths, Ivo Tews, Mark S. Cragg
OX40 is a type 1 transmembrane glycoprotein, reported nearly 30 years ago as a cell surface antigen expressed on activated T cells. Since its discovery, it has been validated as a bone fide costimulatory molecule for T cells and member of the TNF receptor family. However, many questions still remain relating to its function on different T cell sub-sets and with recent interest in its utility as a target for antibody-mediated immunotherapy, there is a growing need to gain a better understanding of its biology.Here, we review the expression pattern of OX40 and its ligand, discuss the structure of the receptor:ligand interaction, the downstream signalling it can elicit, its function on different T cell subsets and how antibodies might engage with it to provide effective immunotherapy.



http://ift.tt/2jjb253

Enhancement of NK cell-mediated lysis of non-small lung cancer cells by nPKC activator, ingenol 3,20 dibenzoate

Publication date: March 2017
Source:Molecular Immunology, Volume 83
Author(s): Chenyuan Gong, Chao Yao, Zihang Xu, Zhongya Ni, Xiaowen Zhu, Lixin Wang, Xuewei Yan, Wuxiong Zhou, Shiguo Zhu
The IFN-γ production is crucial for NK cell-mediated lysis of cancer cells. Thus increasing the IFN-γ production by NK cells may be an ideal strategy to improve their tumoricidal effect. Since the focus on new drug development has shifted towards natural products, limited information is out there about natural products that enhance the IFN-γ production by NK cells. In this study, through a high-throughput screening, we have identified a natural product ingenol 3,20 dibenzoate (IDB), an activator of tumor suppressor protein kinase C (PKC) isozymes, could increase the IFN-γ production and degranulation by NK cells, especially when NK cells were stimulated by non-small lung cancer (NSCLC) cells. IDB also significantly enhanced the NK cell-mediated lysis of NSCLC cells. Furthermore, PKC inhibitor, sotrastaurin abrogated IDB-induced IFN-γ production, degranulation and cytotoxicity, but did not affect IFN-γ production by NK cells without IDB treatment and NSCLC cell stimulation. The IFN-γ neutralization reversed the IDB-induced enhancement of NK cell mediated killing. In conclusion, our study indicated that IDB enhanced NK cell-mediated lysis of NSCLC cells is dependent on specific PKC mediated IFN-γ production and degranulation. Thus, IDB may have a promising application in clinic for NK cell-based cancer immunotherapy.

Graphical abstract

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Anti-inflammatory effects of ononin on lipopolysaccharide-stimulated RAW 264.7 cells

Publication date: March 2017
Source:Molecular Immunology, Volume 83
Author(s): Lin Dong, Lei Yin, Yuanbin Zhang, Xueyan Fu, Jincai Lu
Increasing evidence has shown that ononin, a major isoflavone, has anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation. However, the molecular mechanisms underlying the anti-inflammatory effects of ononin are still unclear. In the present study, we investigated these effects and the underlying mechanisms of ononin on LPS-induced inflammatory responses. Mouse RAW 264.7 cells were treated with 1μg/mL LPS and 5, 25, 50, 100 or 150μM ononin for 18h. Cell viability was assessed using MTT assays, and the production of nitric oxide (NO), prostaglandin E2 (PGE2) and the pro-inflammatory cytokines TNF-α, IL-1β and IL-6 in cultures was examined by Griess and ELISA analyses. qRT-PCR was performed to detect the mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). Mitogen-activated protein kinases (MAPKs) and nuclear transcription factor Kappa-B (NF-κB) signalling pathway-related proteins were assessed by western blot assays. The results showed that cell viability was not significantly affected by up to 100μM ononin. The production of NO, PGE2 and the pro-inflammatory cytokines TNF-α, IL-1β and IL-6 in the cultures, the mRNA expression of two major inflammatory mediators, COX-2 and iNOS, and the expression of phosphorylated IκB-α, ERK, JNK, and p38 MAPKs proteins in LPS-treated cells were significantly increased. These changes could be reversed by treatment with ononin in a concentration-dependent manner (P<0.05). The results suggest that ononin has anti-inflammatory effects on LPS-induced inflammatory responses by inhibiting the NF-κB and MAPK pathways and may be a potential treatment for inflammation.

Graphical abstract

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The Effectiveness of the Braden Scale as a Tool for Identifying Nutrition Risk

Publication date: Available online 13 January 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Wendy Phillips, Monica Hershey, Kate Willcutts, Janette Dietzler-Otte




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Using pupil size and heart rate to infer affective states during behavioral neurophysiology and neuropsychology experiments

Publication date: Available online 13 January 2017
Source:Journal of Neuroscience Methods
Author(s): Andrew R. Mitz, Ravi V. Chacko, Philip T. Putnam, Peter H. Rudebeck, Elisabeth A. Murray
BackgroundNonhuman primates (NHPs) are a valuable research model because of their behavioral, physiological and neuroanatomical similarities to humans. In the absence of language, autonomic activity can provide crucial information about cognitive and affective states during single-unit recording, inactivation and lesion studies. Methods standardized for use in humans are not easily adapted to NHPs and detailed guidance has been lacking.New MethodWe provide guidance for monitoring heart rate and pupil size in the behavioral neurophysiology setting by addressing the methodological issues, pitfalls and solutions for NHP studies. The methods are based on comparative physiology to establish a rationale for each solution. We include examples from both electrophysiological and lesion studies.ResultsSingle-unit recording, pupil responses and heart rate changes represent a range of decreasing temporal resolution, a characteristic that impacts experimental design and analysis. We demonstrate the unexpected result that autonomic measures acquired before and after amygdala lesions are comparable despite disruption of normal autonomic function.Comparison with Existing MethodsSpecies and study design differences can render standard techniques used in human studies inappropriate for NHP studies. We show how to manage data from small groups typical of NHP studies, data from the short behavioral trials typical of neurophysiological studies, issues associated with longitudinal studies, and differences in anatomy and physiology.ConclusionsAutonomic measurement to infer cognitive and affective states in NHP is neither off-the-shelf nor onerous. Familiarity with the issues and solutions will broaden the use of autonomic signals in NHP single unit and lesion studies.



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Prefrontal cortex-mediated executive function as assessed by Stroop task performance associates with weight loss among overweight and obese adolescents and young adults

Publication date: 15 March 2017
Source:Behavioural Brain Research, Volume 321
Author(s): Xia Xu, Zhang-Yan Deng, Qin Huang, Wei-Xia Zhang, Chang-zhu Qi, Jia-Ai Huang
People with cognitive deficits or executive dysfunction are often overweight or obese. Several human neuroimaging studies have found that executive function (EF) predicts food intake and weight gain; however, fewer studies have investigated the relationship between EF and weight loss. The Stroop task is a classic measure of EF that is used in many neuroimaging studies. In the present work, functional near infrared spectroscopy (fNIRS) data were collected during performance of the Stroop task from a sample of overweight or obese adolescents and young adults (n=31) who participated in a summer fitness and weight loss camp. We assessed the Stroop effect by interference in the reaction time (RT) to visual challenges, and by alterations in levels of oxygenated hemoglobin, as detected by fNIRS. In line with previous studies, we found that the Stroop effect was successfully induced by different visual task conditions among obese/overweight individuals. Moreover, our results reveal that better Stroop task performance is correlated with greater weight loss over a4-weekfitness intervention. Indeed, behavioral data demonstrated that reduced RT interference predicted a greater percentage of weight loss. Moreover, overweight/obese individuals with a greater hemodynamic response in the left ventrolateral and bilateral dorsolateral prefrontal cortex due to the Stroop effect lost more weight during the short-term fitness intervention than participants with lower levels of activation of these neural regions. Overall, our results support a role for prefrontal cortex-mediated EF in influencing food intake and weight loss outcomes in a population of a previously unstudied age.



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Editorial Board/Aims and Scope

Publication date: 20 January 2017
Source:Vaccine, Volume 35, Supplement 1





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Defining cases of severe pediatric diarrhea for an efficacy trial of an enterotoxigenic Escherichia coli (ETEC) vaccine: Report on an international workshop, Washington DC, March 2016

Publication date: 23 January 2017
Source:Vaccine, Volume 35, Issue 4
Author(s): Thomas F. Wierzba, Alexandra Bourgis
Enterotoxigenic Escherichia coli (ETEC) causes severe acute watery diarrhea. No ETEC vaccine is available but candidates are in development, including ETVAX, an oral, whole-cell inactivated vaccine. ETVAX is being tested in a descending-age trial in Bangladesh. If found safe and immunogenic, investigators may test it for efficacy in children. Like oral rotavirus vaccines, we expect that ETVAX will be most effective at decreasing the incidence of moderate-to-severe ETEC episodes. Thus, for an efficacy trial outcome, it will be necessary to triage patients into moderate-to-severe versus mild disease. A severity scale specific to ETEC does not exist. To develop this scale, PATH convened a committee of international experts for a two-day meeting to strategize on diagnostic scale development. The workshop began with four presentations. The first described existing scales, item selection, and issues related to validation, reliability, and ease of use. The other three presentations provided details on the following published scores: the DHAKA score, validated for use with Bangladeshi children seeking diarrhea treatment; a modified-Vesikari score for evaluating North American outpatient children with diarrhea; and the Community Diarrhea Assessment (CODA) score developed for passive-case surveillance of Peruvian children with diarrhea. Following the presentations and discussion, the committee made several recommendations including: modifying existing scores to make them ETEC-centric; evaluating scoring systems against an objective measure of dehydration (i.e., the percent change in a child's bodyweight following rehydration); and adding an item to the scale measuring ETEC effects on growth faltering. The committee also discussed using available data sets to evaluate scores, but was concerned that if investigators characterized patients using different procedures than prescribed by the score, the results would be difficult to interpret. Committee members suggested new data collection and recommended conducting studies in Sub-Saharan Africa. The study results would be presented for peer-review and to regulatory authorities.



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Moving beyond traditional valuation of vaccination: Needs and opportunities

Publication date: 20 January 2017
Source:Vaccine, Volume 35, Supplement 1
Author(s): David E. Bloom, Logan Brenzel, Daniel Cadarette, Jessica Sullivan
Economic evaluations of vaccination traditionally focus on a relatively narrow set of vaccine benefits, such as averted medical care costs among those who are immunized. In recent years, researchers have identified additional vaccination benefits that should be incorporated into economic evaluations in order to reflect vaccination's full value. Early efforts to estimate the magnitude of these broader benefits suggest that vaccination has been substantially undervalued, which has important implications for public and private vaccine policy and human health and welfare. More and better data will be required to advance this emerging line of research on the value of vaccination. The article discusses promising data sources and methods and research questions needing to be addressed.



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Interest in an Ebola vaccine among a U.S. national sample during the height of the 2014–2016 Ebola outbreak in West Africa

Publication date: 23 January 2017
Source:Vaccine, Volume 35, Issue 4
Author(s): Julia E. Painter, Ralph J. DiClemente, Michael E. von Fricken
To better understand the association between Ebola-related attitudes and interest in receiving an Ebola virus vaccine, a survey was administered to a U.S. national sample using GfK's KnowledgePanel®. Among participants (N=1417), 34.1% expressed interest in an Ebola vaccine for themselves. In the subset of participants with children aged 0–17 (N=410), 38.1% expressed interest in an Ebola vaccine for their child. In multivariable analyses, vaccine interest for oneself was associated with perceived susceptibility to Ebola (p=0.009), beliefs that the U.S. government should spend money to control Ebola (p=0.002), and beliefs Ebola posed a national threat (p=0.007). Vaccine interest for one's child was associated with perceived severity of Ebola (p=0.018) and beliefs that the U.S. government should spend money to control Ebola (p=0.003). Findings highlight the influence of personal and national threat beliefs on vaccine interest. Understanding the impact of threat beliefs may benefit vaccine campaign development during future pandemic threats.



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Negative impact of prior influenza vaccination on current influenza vaccination among people infected and not infected in prior season: A test-negative case-control study in Japan

Publication date: 23 January 2017
Source:Vaccine, Volume 35, Issue 4
Author(s): Nobuo Saito, Kazuhiro Komori, Motoi Suzuki, Kounosuke Morimoto, Takayuki Kishikawa, Takahiro Yasaka, Koya Ariyoshi
BackgroundAccumulating evidences indicate that repeated influenza vaccination has negative impact on the vaccine effectiveness (VE). However no published studies considered past influenza infection when assessing the VE of repeated vaccination.MethodsProspective surveillance was conducted from 2009 to 2012 at a community hospital on a small island in Japan. The study included all outpatients with an influenza-like illness (ILI) who attended the hospital, and a rapid diagnostic test (RDT) was used to diagnose influenza A/B infection. The VE of trivalent inactivated influenza vaccine (TIV) against medically attended influenza A (MA-fluA) was estimated using a test-negative case-control study design. The influence of TIV in the prior season on VE in the current season was investigated in the context of MA-fluA during the prior season.ResultsDuring the three influenza seasons, 5838 ILI episodes (4127 subjects) were analysed. Subjects who had an episode of MA-fluA in the prior season were at a significantly lower risk of MA-fluA in the current season (adjusted odds ratio: 0.38, 95% CI: 0.30–0.50). The overall adjusted VE was 28% (95% CI, 14–40). VE was substantially lower in subjects vaccinated in the prior season compared to those who had not been vaccinated in prior season (19%; 95% CI: 0–35 vs 46%; 95% CI: 26–60, test for interaction, P value <0.05). In subjects who did not have MA-fluA in the prior season showed the attenuation of VE due to repeated vaccination (13%; 95% CI: −7 to 30 vs 44%; 95% CI: 24–59, test for interaction, P<0.05). However this effect was not detected in subjects who had contracted MA-fluA in the prior season.ConclusionsNegative effects of repeated vaccination were significant among those without history of MA-fluA in the prior season.



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Planning and priority setting for vaccine development and immunization

Publication date: 20 January 2017
Source:Vaccine, Volume 35, Supplement 1
Author(s): Charles E. Phelps, Guruprasad Madhavan, Bruce Gellin
We review a sequence of strategic planning efforts over time in the United States, all involving processes to prioritize new vaccine candidates. The Institute of Medicine of the National Academies of Sciences, Engineering, and Medicine has been involved in three priority setting processes, each using different metrics and methodologies: infant mortality equivalents (1985–1986), cost-effectiveness (2000), and more recently, the implementation of a software system based on a broader multi-criteria systems approach that can include either of the earlier metrics among other various considerations (2015). The systems approach offers users the flexibility to select, combine, rank, weigh and evaluate different attributes representing their perspectives, assumptions, and particular needs. This approach also overcomes concerns relating to the previous single-metric ranking approaches that yielded lists that, once published, were static, and could not readily accommodate new information about emerging pathogens, new scientific advances, or changes in the costs and performance features of interventions. We discuss the rationale and reasoning behind the design of this multi-criteria decision support approach, stakeholder feedback about the tool, and highlight the potential advantages from using this expanded approach to better inform and support vaccine policies.



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Hospitalizations within 14days of vaccination among pediatric recipients of the live attenuated influenza vaccine, United States 2010–2012

Publication date: 23 January 2017
Source:Vaccine, Volume 35, Issue 4
Author(s): Alexander J. Millman, Sue Reynolds, Jonathan Duffy, Jufu Chen, Paul Gargiullo, Alicia M. Fry
BackgroundLive attenuated influenza vaccine (LAIV) is safe in healthy children ⩾2years. The original clinical trials excluded individuals with underlying conditions; however, post-marketing data suggest LAIV may be safe for these populations.MethodsWe analyzed MarketScan Commercial Claims Databases from 2010 to 2012 to describe hospitalizations within 14days of vaccination among LAIV recipients. We evaluated LAIV recipients aged 2–18years and defined underlying conditions by presence of inpatient or outpatient ICD-9 code during the previous calendar year. We excluded asthma and immunocompromising conditions. We defined risk windows as 1–7days and 8–14days after vaccination; the control period was 12–4days prior to and 15–23days after vaccination. We conducted a self-controlled case series analysis using a conditional Poisson regression model to estimate incidence-rate ratios (IRR).Results1,216,123 children aged 2–18years received LAIV from 2010 to 2012. 634 children met our inclusion criteria and were hospitalized during the observation period (12days prior to vaccination to 23days after vaccination). Of those hospitalized, 72 (11.4%) had non-asthma, non-immunocompromising underlying conditions. Children with non-asthma, non-immunocompromising underlying conditions had an all-cause hospitalization IRR of 1.1 (95% CI 0.6–2.0, p=0.83) in the 1–7day risk period and 0.9 (95% CI 0.4–1.7, p=0.67) in the 8–14day risk period. Children with no underlying conditions had an all-cause hospitalization IRR of 0.9 (0.8–1.2, p=0.60) in the 1–7day risk period and 1.1 (95% CI 0.9–1.3, p=0.53) in the 8–14day risk period. There were no differences in all-cause hospitalization risk in individuals with non-asthma, non-immunocompromising underlying conditions compared to those without underlying conditions in the 1–7day (p=0.88) or 8–14day (p=0.24) risk period.ConclusionsWe found no evidence of differences in post-LAIV hospitalization risk among children with non-asthma, non-immunocompromising underlying conditions compared to healthy children.



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Editorial Board/Aims and Scope

Publication date: 23 January 2017
Source:Vaccine, Volume 35, Issue 4





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Identification of amino acids in antigen-binding site of class II HLA proteins independently associated with hepatitis B vaccine response

Publication date: 23 January 2017
Source:Vaccine, Volume 35, Issue 4
Author(s): Aiko Sakai, Emiko Noguchi, Takashi Fukushima, Manabu Tagawa, Atsushi Iwabuchi, Masaki Kita, Keisuke Kakisaka, Akio Miyasaka, Yasuhiro Takikawa, Ryo Sumazaki
Background & aimsGenetic factors in class II human leukocyte antigen (HLA) have been reported to be associated with inter-individual variation in hepatitis B virus (HBV) vaccine response. However, the mechanism underlying the associations remains elusive. In particular, the broad linkage disequilibrium in HLA region complicates the localization of the independent effects of genetic variants. Thus, the present study aimed to identify the most probable causal variations in class II HLA loci involved in the immune response to HBV vaccine.MethodsWe performed a case-control study to assess whether HLA-DRB1, -DQB1, and -DPB1 4-digit alleles were associated with the response to primary HBV vaccination in 574 healthy Japanese students. To identify causative variants, we next assessed independently associated amino acid variants in these loci using conditional logistic regression analysis. Furthermore, to clarify the functional effects of these variants on HLA proteins, we performed computational structural studies.ResultsHLA-DRB1^∗01:01, HLA-DRB1^∗08:03, HLA-DQB1^∗05:01, and HLA-DPB1^∗04:02 were significantly associated with sufficient response, whereas HLA-DPB1^∗05:01 was associated with poor response. We then identified amino acids independently associated with sufficient response, namely, leucine at position 26 of HLA-DRβ1 and glycine-glycine-proline-methionine at positions 84–87 of HLA-DPβ1. These amino acids were located in antigen-binding pocket 4 of HLA-DR and pocket 1 of HLA-DP, respectively, which are important structures for selective binding of antigenic peptides. In addition, the detected variations in HLA-DP protein were responsible for the differences in the electrostatic potentials of the pocket, which can explain in part the sufficient/poor vaccine responses.ConclusionHLA-DRβ1 position 26 and HLA-DPβ1 positions 84–87 are independently associated with anti-HBs production against HBV vaccine. Our results suggest that HBsAg presentation through these HLA pocket structures plays an important role in the inter-individual variability of HBV vaccination.



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Achieving a “Grand Convergence” in global health by 2035

Publication date: 20 January 2017
Source:Vaccine, Volume 35, Supplement 1
Author(s): Adel Mahmoud
Historical evidence demonstrates the validity of the concept "Grand Convergence". The Lancet commission identified the major challenges facing low and lower middle income countries including the unfinished agenda, non-communicable diseases and injuries and an approach to funding and achieving these objectives along with progress towards universal health care. The role of vaccines is summarized as a major approach to accomplish a Grand Convergence in a generation.



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Passive antibodies derived from intramuscularly immunized toxoid fusion 3xSTaN12S-dmLT protect against STa+ enterotoxigenic Escherichia coli (ETEC) diarrhea in a pig model

Publication date: 23 January 2017
Source:Vaccine, Volume 35, Issue 4
Author(s): Rahul M. Nandre, Qiangde Duan, Yin Wang, Weiping Zhang
Enterotoxigenic Escherichia coli (ETEC) strains are among the most common causes of children's diarrhea and travelers' diarrhea. Developing effective vaccines against ETEC associated diarrhea becomes a top priority. ETEC heat-labile toxin (LT) and heat-stable toxin (STa) toxoid fusion 3xSTaN12S-dmLT was demonstrated recently to induce neutralizing antitoxin antibodies in intraperitoneally or subcutaneously immunized mice. However, whether antibodies derived from this toxoid fusion are protective against ETEC diarrhea has not been examined. In this study, we intramuscularly immunized pregnant gilts with toxoid fusion 3xSTaN12S-dmLT, challenged suckling piglets with a STa-positive ETEC strain, and assessed protective efficacy of passive acquire antitoxin antibodies against ETEC diarrhea. Data showed all three immunized gilts developed anti-STa IgG and IgA antibodies, and piglets born to the immunized dams acquired anti-STa and anti-LT antibodies. When challenged with a STa+ ETEC strain, none of the piglets born to the immunized dams developed watery diarrhea, with 20 piglets remained normal and the other 8 piglets developed mild diarrhea indicated with stained butt. In contrast, the control dams and born piglets had no anti-STa or anti-LT antibodies detected, and 26 out 32 piglets developed watery diarrhea after challenge of the STa+ ETEC strain. These results indicated that passive acquired anti-STa antibodies are protective against ETEC diarrhea, and suggested potential application of toxoid fusion 3xSTaN12S-dmLT in ETEC vaccine development.



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European strategy for vaccine development against infectious diseases

Publication date: 20 January 2017
Source:Vaccine, Volume 35, Supplement 1
Author(s): Line Matthiessen, Hannu Lång, Maria Klimathianaki, Finnian Hanrahan, Barbara Kerstiëns, Alessandra Martini, Ruxandra Draghia-Akli
Immunisation efforts save millions of lives every year, but vaccines hold the potential to deliver even greater health benefits for mankind. Vaccine research and development is highly complex, and it requires concerted public funding efforts to support. In this paper we discuss EU funding priorities and the resulting recent advancements in European vaccine research, and we lay out the EU strategy for aiding promising vaccine candidates to successfully reach the market.



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Viral vector vaccines protect cockatiels from inflammatory lesions after heterologous parrot bornavirus 2 challenge infection

Publication date: 23 January 2017
Source:Vaccine, Volume 35, Issue 4
Author(s): Solveig Runge, Marita Olbert, Christiane Herden, Sara Malberg, Angela Römer-Oberdörfer, Peter Staeheli, Dennis Rubbenstroth
Avian bornaviruses are causative agents of proventricular dilatation disease (PDD), a chronic neurologic and often fatal disorder of psittacines including endangered species. To date no causative therapy or immunoprophylaxis is available. Our previous work has shown that viral vector vaccines can delay the course of homologous bornavirus challenge infections but failed to protect against PDD when persistent infection was not prevented.The goal of this study was to refine our avian bornavirus vaccination and infection model to better represent natural bornavirus infections in order to achieve full protection against a heterologous challenge infection.We observed that parrot bornavirus 2 (PaBV-2) readily infected cockatiels (Nymphicus hollandicus) by combined intramuscular and subcutaneous injection with as little as 10^2.7foci-forming units (ffu) per bird, whereas a 500-fold higher dose of the same virus administered via peroral and oculonasal route did not result in persistent infection. These results indicated that experimental bornavirus challenge infections with this virus should be performed via the parenteral route.Prime-boost vaccination of cockatiels with Newcastle disease virus (NDV) and modified vaccinia virus Ankara (MVA) vectors expressing the nucleoprotein and phosphoprotein genes of PaBV-4 substantially blocked bornavirus replication following parenteral challenge infection with 10^3.5ffu of heterologous PaBV-2. Only two out of six vaccinated birds had very low viral levels detectable in a few organs. As a consequence, only one vaccinated bird developed mild PDD-associated microscopic lesions, while mock-vaccinated controls were not protected against PaBV-2 infection and inflammation.Our results demonstrate that NDV and MVA vector vaccines can protect against invasive heterologous bornavirus challenge infections and subsequent PDD. These vector vaccines represent a promising tool to combat avian bornaviruses in psittacine populations.



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Informing vaccine decision-making: A strategic multi-attribute ranking tool for vaccines—SMART Vaccines 2.0

Publication date: 20 January 2017
Source:Vaccine, Volume 35, Supplement 1
Author(s): Stacey Knobler, Karin Bok, Bruce Gellin
SMART Vaccines 2.0 software is being developed to support decision-making among multiple stakeholders in the process of prioritizing investments to optimize the outcomes of vaccine development and deployment. Vaccines and associated vaccination programs are one of the most successful and effective public health interventions to prevent communicable diseases and vaccine researchers are continually working towards expanding targets for communicable and non-communicable diseases through preventive and therapeutic modes. A growing body of evidence on emerging vaccine technologies, trends in disease burden, costs associated with vaccine development and deployment, and benefits derived from disease prevention through vaccination and a range of other factors can inform decision-making and investment in new and improved vaccines and targeted utilization of already existing vaccines. Recognizing that an array of inputs influences these decisions, the strategic multi-attribute ranking method for vaccines (SMART Vaccines 2.0) is in development as a web-based tool—modified from a U.S. Institute of Medicine Committee effort (IOM, 2015)—to highlight data needs and create transparency to facilitate dialogue and information-sharing among decision-makers and to optimize the investment of resources leading to improved health outcomes. Current development efforts of the SMART Vaccines 2.0 framework seek to generate a weighted recommendation on vaccine development or vaccination priorities based on population, disease, economic, and vaccine-specific data in combination with individual preference and weights of user-selected attributes incorporating valuations of health, economics, demographics, public concern, scientific and business, programmatic, and political considerations.Further development of the design and utility of the tool is being carried out by the National Vaccine Program Office of the Department of Health and Human Services and the Fogarty International Center of the National Institutes of Health. We aim to demonstrate the utility of SMART Vaccines 2.0 through the engagement of a community of relevant stakeholders and to identify a limited number of pilot projects to determine explicitly defined attribute preferences and the related data and model requirements that are responsive to user needs and able to improve the use of evidence for vaccine-related decision-making and consequential priorities of vaccination options.



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The economic impact of prenatal varicella immunity among pregnant women in Alberta

Publication date: 23 January 2017
Source:Vaccine, Volume 35, Issue 4
Author(s): Amrit Passi, Sabrina S. Plitt, Florence Y. Lai, Kimberley Simmonds, Carmen L. Charlton
In light of the changing epidemiology of varicella, we sought to examine varicella antibody levels in the prenatal population in the Canadian province of Alberta. All prenatal varicella screening tests performed between August 1, 2002 and February 2, 2014 (454,592) were included in this study. Test results, demographics and vaccination status were examined to identify varicella seroprevalence and correlates for being seronegative. An overall seroprevalence for varicella of 95.8% was found across all pregnancy screenings. Significant independent correlates of seronegativity included younger age (AOR: 4.72 (95% CI: 3.87–5.77) for <20years of age vs. >40years of age) and having immigrated to Alberta from Africa or Asia (AOR: 4.55 (95% CI: 4.10–5.05) and AOR: 5.83 (95%CI; 5.48–6.19), respectively). Women who were initially seronegative for varicella antibodies and who received both postnatal vaccination and post-vaccination prenatal screening (2566) were examined to assess seroconversion. 66.3% of women who were tested up to six months post-vaccination were seropositive, however only 36.9% of women tested after 36months were seropositive. Finally, 40.9% of all prenatal varicella specimens tested were deemed redundant, i.e. women had either a history of (1) ⩾2 doses of varicella vaccine, (2) varicella infection, or (3) a previous positive varicella serology. Eliminating this redundant screening could provide an estimated $96,000 in savings annually in laboratory and Public Health follow-up costs alone. As the number of women with vaccine-derived immunity through universal childhood vaccination increase in the prenatal population, screening methods may need to adapt to ensure varicella immunity is accurately conducted and assessed.



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Corrigendum to “Trends in childhood vaccine purchase costs in the US public sector: 1996–2014” [Vaccine 34 (2016) 4706–4711]

Publication date: 23 January 2017
Source:Vaccine, Volume 35, Issue 4
Author(s): Weiwei Chen, Mark Messonnier, Fangjun Zhou




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Introduction to the vaccine supplement

Publication date: 20 January 2017
Source:Vaccine, Volume 35, Supplement 1
Author(s): Rino Rappuoli




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What drivers will influence global immunizations in the era of grand convergence in global health?

Publication date: 20 January 2017
Source:Vaccine, Volume 35, Supplement 1
Author(s): Orin S. Levine
Recent projections suggest that by 2035 global health will look dramatically different than it does today. In what's called a 'grand convergence' the world is likely to be characterized by far more similarities than differences in the prevailing health and medical problems across populations. This manuscript considers how key drivers for vaccine use and uptake might change as a result of the grand convergence and how decisions taken now might anticipate those changes in ways that position immunizations to continue playing an important role in the future.



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Prioritizing vaccines for developing world diseases

Publication date: 20 January 2017
Source:Vaccine, Volume 35, Supplement 1
Author(s): Allan Saul, Katherine L. O'Brien
A major disparity in the burden of health will need to be addressed to achieve the "Grand Convergence" by 2035. In particular people living in low and middle income countries have a much higher burden of infectious diseases. Although vaccines have been very effective in reducing the global burden of infectious disease, there are no registered vaccines to address 60% of the current burden of infectious disease, especially in developing countries. Thus there is a pressing need for new vaccines and for prioritizing vaccine development given that resources for developing new vaccines are strictly limited. As part of the GLOBAL HEALTH 2035: Mission Grand Convergence meeting one working group assessed the SMART vaccine algorithm as a mechanism for prioritizing vaccine development for diseases of priority in the developing world. In particular, the working group considered which criteria in the standard SMART set were considered "key" criteria and whether other criteria should be considered, when prioritizing vaccines for this important set of countries.



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