Palisading neutrophilic and granulomatous dermatitis as a presentation of Hodgkin lymphoma: A case and review

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a histopathological diagnosis, characterized by a pattern of granulomatosis, which may be associated with leukocytoclastic vasculitis. PNGD most commonly occurs in association with systemic inflammatory disorders, typically autoimmune conditions, such as rheumatoid arthritis and systemic lupus erythromatosus. There are very rare reports of PNGD in patients with lymphoma. We report the case of a 53-year-old female with an erythematous, papular eruption occurring in association with Hodgkin lymphoma. Histopathological evaluation of the rash confirmed PNGD. To the best of our knowledge, this is the first case of PNGD occurring in association with Hodgkin lymphoma. Although extremely rare, underlying malignancy should be considered in patients with PNGD, particularly in individuals with constitutional symptoms and the absence of an obvious inflammatory etiology.

http://ift.tt/2ydJwt7

A review of the value of human epidermal growth factor receptor 2 (HER2)-targeted therapies in breast cancer

Publication date: January 2018
Source:European Journal of Cancer, Volume 89
Author(s): N.A. Nixon, M.B. Hannouf, S. Verma
The cost of cancer drugs continues to escalate with the rapid development and approval of novel therapies, especially over the course of the last decade. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, the survival benefits gained by new treatments have been undeniably substantial. It is important to assess the financial value of these therapies for decision making at both the societal and individual level. This information is key for managing resources in resource-limited health care systems, while at the same time supporting patient decision-making and conversations between patient and physicians on cost versus benefit. In this article, we perform a systematic review of cost-effectiveness analyses that have been completed to date on HER2-targeted agents, focussing on those that correlate with standard of care therapy. Our discussion also highlights potential strategies to overcome several limitations associated with measuring value for anticancer drugs.



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Development, characterization, and evaluation of sunscreen cream containing solid lipid nanoparticles of silymarin

Summary

Background

Most of the sunscreen formulations mainly contain chemicals or synthetic molecules. Nowadays, researchers are mainly focussing on herbal formulations due to toxicity of the synthetic molecules. Silymarin is a natural flavonoids having excellent antioxidant properties. Solid lipid nanoparticles are novel drug carriers which improve the drug stability and tolerance effect and also enhance the permeation effect.

Aims

This study aimed at the preparation of solid lipid nanoparticles containing silymarin that will be incorporated into a sunscreen cream and determine its sun protection factor.

Methods

The solid lipid nanoparticles were prepared by micro-emulsion method; here, the glyceryl monostearate was used as lipid, and Tween 80 was used as an emulsifier. The solid lipid nanoparticles were evaluated for drug entrapment, particle size and morphology, zeta potential, and polydispersity index. The dispersion was formulated into sunscreen cream and evaluated for various parameters, such as extrudability, viscosity, spreadability, drug content, in vitro drug release, ex vivo permeation of drug, in vitro and in vivo sun protection factor determination, in vivo skin irritation test, and accelerated stability studies.

Results

The results suggested that as the concentration of emulsifier increased, the entrapment efficiency of silymarin increased. In vitro and in vivo sun protection factor determination showed that SPF of 13.80 and 14.1, respectively. Stability studies were performed under accelerated conditions, and it did not show any appreciable change in parameters.

Conclusion

These results indicated that the sunscreen containing silymarin solid lipid nanoparticles exhibited better photoprotective action.

http://ift.tt/2nOxLJF

Microneedling combined with platelet-rich plasma or trichloroacetic acid peeling for management of acne scarring: A split-face clinical and histologic comparison

Summary

Background

Minimally invasive procedures provide effective, safe, relatively long-lasting, and natural results without large damage to the skin. A combination treatment is considered an approach that includes at least 2 different and unrelated modalities.

Objectives

This study aims to evaluate the use and effectiveness of some combined minimally invasive procedures for management of acne scarring.

Patients/methods

Twenty-four volunteers with postacne atrophic scars were randomly divided into 3 equal groups according to performed procedure on each side of the face (microneedling by dermaroller alone or combined with platelet-rich plasma [PRP] or trichloroacetic acid [TCA] 15% peeling) and received 6 bi-weekly sessions of treatment. Photography and punch biopsies were taken before and after 3 months of treatment for clinical, histological, and histometrical evaluation.

Results

Combined treatment of dermaroller and PRP or dermaroller and TCA 15% showed significant improvement when compared with dermaroller alone (P = .015 and .011 respectively). Epidermal thickness showed statistically significant increase in studied groups, mainly after dermaroller and TCA 15%. Moreover, the 3 studied groups showed more organized collagen bundles and newly formed collagen formation and markedly decreased abnormal elastic fibers.

Conclusions

Based on the clinical, histometrical, and histochemical assessment, inspite that most volunteers showed significant improvement after treatment, however, the combined use of dermaroller and TCA 15% was more effective in postacne atrophic scars than the use of dermaroller and PRP or dermaroller only.

http://ift.tt/2C23k5Z

Non-BRCA1/2 Breast Cancer Susceptibility Genes: A New Frontier with Clinical Consequences for Plastic Surgeons

Summary: Twenty percent of breast cancer cases may be related to a genetic mutation conferring an increased risk of malignancy. The most common and prominent breast cancer susceptibility genes are BRCA1 and BRCA2, found in nearly 40% of such cases. However, continued interest and investigation of cancer genetics has led to the identification of a myriad of different breast cancer susceptibility genes. Additional genes, each with unique significance and associated characteristics, continue to be recognized. Concurrently, advanced genetic testing, while still controversial, has become more accessible and cost-effective. As oncologic and reconstructive advances continue to be made in prophylactic breast reconstructive surgery, patients may present to plastic surgeons with an increasingly more diverse array of genetic diagnoses to discuss breast reconstruction. It is therefore imperative that plastic surgeons be familiar with these breast cancer susceptibility genes and their clinical implications. We, therefore, aim to review the most common non-BRCA1/2 breast cancer susceptibility genetic mutations in an effort to assist plastic surgeons in counseling and managing this unique patient population. Included in this review are syndromic breast cancer susceptibility genes such as TP53, PTEN, CDH1, and STK11, among others. Nonsyndromic breast cancer susceptibility genes herein reviewed include PALB2, CHEK2, and ataxia telangiectasia mutated gene. With this knowledge, plastic surgeons can play a central role in the diagnosis and comprehensive treatment, including successful breast reconstruction, of all patients carrying genetic mutations conferring increased risk for breast malignancies.

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Association between hyper-pronated foot and the degree of severity of disability in patients with non-specific low back pain

Publication date: Available online 9 December 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Arun Prasad Balasundaram, Dipankar Choudhury
BackgroundIt has been established that Hyper-pronation of the foot may lead to postural changes in the lower limbs, with a resultant pelvic ante-version, and a subsequent risk of development of low back pain. However, the association between the presence of a hyper-pronated foot and the severity of disability in low back pain is currently not known.ObjectivesThe purpose of this study was to examine whether the presence of a hyper-pronated foot has any impact on the degree of severity of disability (functional status) in patients with non-specific low back pain.MethodsAn observational study was conducted in an outpatient setting, where patients diagnosed as having non-specific low back pain were included. The degree of severity of disability was measured using the Modified Oswestry Low Back Pain Disability Questionnaire, and the foot hyper-pronation was assessed with the execution of the Navicular Drop test. Descriptive statistics and Linear regression analyses were conducted.ResultsOf the 71 patients included, 14 demonstrated having a unilateral hyper-pronation of the foot. The mean scores for the functional status and hyper-pronation of the foot were 37.15 (SD = 10.40) and 6.06 (SD = 3.42) respectively. An association was not found between the severity of disability and the presence of foot hyper-pronation (B = .87, p = .78).ConclusionsHyper-pronation of the foot could lead to the development of non-specific low back pain, but the degree of severity of the disability is not influenced by the presence of a hyper-pronated foot. The alterations in lower limb mechanics leading to back pain are a complex issue, and thus needs further research.



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A comparison of foot kinetic parameters between pronated and normal foot structures during forward jump landing

Publication date: Available online 9 December 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Hosein Kouhzad Mohammadi, Mohammad Mehravar, Khosro Khademi Kalantari, Sedighe Sadat Naimi, Alireza Akbarzadeh Baghban, Farshad Okhovatian, Asghar Rezasoltani, Mohammad Ali Mohseni Bandpei, Navid Taheri
BackgroundPronated foot is one of the most important factors that may lead to musculoskeletal injuries of the lower extremities. It is known that in a pronated foot, excessive mechanical loads are applied to the lower limb structures, which result in the altered foot biomechanics, including vertical ground reaction forces (VGRFs) and rate of loading (ROL). Therefore, the aim of this study was to determine the changes in foot kinetic parameters in the pronated compared to the normal foot structures.MethodsIn this cross-sectional study, 15 individuals (mean age of 23.27 ± 3.28 years) with asymptomatic pronated feet and 15 normal subjects (mean age of 23.40 ± 3.11 years) were recruited from both genders by using a simple non-random sampling method. VGRF, ROL, and the resultant vector of time to stabilization (RVTTS) were evaluated during the forward jump landing task by using a force plate.ResultsThe findings showed that the following parameters were significantly higher in the group of pronated feet than in the normal subjects: VGRF (3.30 ± 0.17 vs. 2.81 ± 0.15, p = .042), ROL (0.10 ± 0.01 vs. 0.07 ± 0.006, p = .020), and RVTTS (2592.80 ± 141.24 vs. 2114.00 ± 154.77, p = .030).ConclusionAll the measured foot kinetic parameters were higher in the pronated foot subjects than in the normal participants. An impaired movement control and greater forces imposed on the foot region of the pronated foot compared to the normal foot individuals were discovered indicating the former group's possible increase of susceptibility to various musculoskeletal injuries.



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The first MICCAI challenge on PET tumor segmentation

Publication date: Available online 9 December 2017
Source:Medical Image Analysis
Author(s): Mathieu Hatt, Baptiste Laurent, Anouar Ouahabi, Hadi Fayad, Shan Tan, Laquan Li, Wei Lu, Vincent Jaouen, Clovis Tauber, Jakub Czakon, Filip Drapejkowski, Witold Dyrka, Sorina Camarasu-Pop, Frédéric Cervenansky, Pascal Girard, Tristan Glatard, Michael Kain, Yao Yao, Christian Barillot, Assen Kirov, Dimitris Visvikis
IntroductionAutomatic functional volume segmentation in PET images is a challenge that has been addressed using a large array of methods. A major limitation for the field has been the lack of a benchmark dataset that would allow direct comparison of the results in the various publications. In the present work, we describe a comparison of recent methods on a large dataset following recommendations by the American Association of Physicists in Medicine (AAPM) task group (TG) 211, which was carried out within a MICCAI (Medical Image Computing and Computer Assisted Intervention) challenge.Materials and methodsOrganization and funding was provided by France Life Imaging (FLI). A dataset of 176 images combining simulated, phantom and clinical images was assembled. A website allowed the participants to register and download training data (n=19). Challengers then submitted encapsulated pipelines on an online platform that autonomously ran the algorithms on the testing data (n=157) and evaluated the results. The methods were ranked according to the arithmetic mean of sensitivity and positive predictive value.ResultsSixteen teams registered but only four provided manuscripts and pipeline(s) for a total of 10 methods. In addition, results using two thresholds and the Fuzzy Locally Adaptive Bayesian (FLAB) were generated. All competing methods except one performed with median accuracy above 0.8. The method with the highest score was the convolutional neural network-based segmentation, which significantly outperformed 9 out of 12 of the other methods, but not the improved K-Means, Gaussian Model Mixture and Fuzzy C-Means methods.ConclusionThe most rigorous comparative study of PET segmentation algorithms to date was carried out using a dataset that is the largest used in such studies so far. The hierarchy amongst the methods in terms of accuracy did not depend strongly on the subset of datasets or the metrics (or combination of metrics). All the methods submitted by the challengers except one demonstrated good performance with median accuracy scores above 0.8.

Graphical abstract

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Gallic acid modulates phenotypic behavior and gene expression in oral squamous cell carcinoma cells by interfering with leptin pathway

Publication date: Available online 10 December 2017
Source:Pathology - Research and Practice
Author(s): Eliane Macedo Sobrinho Santos, Rogério Gonçalves da Rocha, Hércules Otacílio Santos, Talita Antunes Guimarães, Carlos Alberto de Carvalho Fraga, Luiz Henrique da Silveira, Paulo Ricardo Batista, Paulo Sérgio Lopes de Oliveira, Geraldo Aclécio Melo, Sérgio Henrique Santos, Alfredo Maurício Batista de Paula, André Luiz Sena Guimarães, Lucyana Conceição Farias
Gallic acid is a polyphenolic compost appointed to interfere with neoplastic cells behavior. Evidence suggests an important role of leptin in carcinogenesis pathways, inducing a proliferative phenotype. We investigated the potential of gallic acid to modulate leptin-induced cell proliferation and migration of oral squamous cell carcinoma cell lines. The gallic acid effect on leptin secretion by oral squamous cell carcinoma cells, as well as the underlying molecular mechanisms, was also assessed. For this, we performed proliferation, migration, immunocytochemical and qPCR assays. The expression levels of cell migration-related genes (MMP2, MMP9, Col1A1, and E-cadherin), angiogenesis (HIF-1α, mir210), leptin signaling (LepR, p44/42 MAPK), apoptosis (casp-3), and secreted leptin levels by oral squamous cell carcinoma cells were also measured. Gallic acid decreased proliferation and migration of leptin-treated oral squamous cell carcinoma cells, and reduced mRNA expression of MMP2, MMP9, Col1A1, mir210, but did not change HIF-1α. Gallic acid decreased levels of leptin secreted by oral squamous cell carcinoma cells, accordingly with downregulation of p44/42 MAPK expression. Thus, gallic acid appears to break down neoplastic phenotype of oral squamous cell carcinoma cells by interfering with leptin pathway.



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Design and synthesis of a potent, highly selective, orally bioavailable, retinoic acid receptor alpha agonist

Publication date: Available online 9 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Earl Clarke, Christopher I. Jarvis, Maria B. Goncalves, S. Barret Kalindjian, David R. Adams, Jane T. Brown, Jason J. Shiers, David M.A. Taddei, Elodie Ravier, Stephanie Barlow, Iain Miller, Vanessa Smith, Alan D. Borthwick, Jonathan P.T. Corcoran
A ligand-based virtual screening exercise examining likely bioactive conformations of AM 580 (2) and AGN 193836 (3) was used to identify the novel, less lipophilic RARα agonist 4-(3,5-dichloro-4-ethoxybenzamido)benzoic acid 5, which has good selectivity over the RARβ, and RARγ receptors. Analysis of the medicinal chemistry parameters of the 3,5-substituents of derivatives of template 5 enabled us to design a class of drug-like molecules with lower intrinsic clearance and higher oral bioavailability which led to the novel RARα agonist 4-(3-chloro-4-ethoxy-5-isopropoxybenzamido)-2-methylbenzoic acid 56 that has high RARα potency and excellent selectivity versus RARβ (2 orders of magnitude) and RARγ (4 orders of magnitude) at both the human and mouse RAR receptors with improved drug-like properties. This RARα specific agonist 56 has high oral bioavailability (>80%) in both mice and dogs with a good PK profile and was shown to be inactive in cytotoxicity and genotoxicity screens.

Graphical abstract

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5-HT1A and 5-HT2A receptors affinity, docking studies and pharmacological evaluation of a series of 8-acetyl-7-hydroxy-4-methylcoumarin derivatives

Publication date: Available online 9 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Kinga Ostrowska, Dawid Grzeszczuk, Monika Głuch-Lutwin, Anna Gryboś, Agata Siwek, Anna Leśniak, Mariusz Sacharczuk, Bartosz Trzaskowski
In this work we describe the synthesis, docking studies and biological evaluation of a focused library of novel arylpiperazinyl derivatives of 8-acetyl-7-hydroxy-4-methylcoumarin. The new compounds were screened for their 5-HT1A and 5-HT2A receptor affinity. Among the evaluated compounds, six displayed high affinities to 5-HT1A receptors (4a-0.9 nM, 6a-0.5 nM, 10a-0.6 nM, 3b-0.9 nM, 6b-1.5 nM, 10b-1 nM). Compound 6a and 10a bearing a bromo- or methoxy- substituent in ortho position of the piperazine phenyl ring, were identified as potent antagonists of the 5-HT1A receptors. In the tail suspension test, mice injected with 6a showed a dose-dependent increase in depressive-like behavior that was related to a decrease in locomotor activity. Compound 10a did not decrease or prolong immobility time nor did it affect home cage activity. Molecular docking studies using 5-HT1A and 5-HT2A homology models revealed structural basis of the high affinity of ortho-substituted derivatives and subtle changes in amino acid interactions patterns depending on the length of the alkyl linker.

Graphical abstract

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HPV vaccination strategies targeting hard-to-reach populations: Out-of-school girls in LMICs

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Kimberly Bonner, Cecily Banura, Nicole E. Basta




http://ift.tt/2jna3Tw

Diphtheria vaccine: WHO position paper, August 2017 – Recommendations

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): World Health Organization
This article presents the World Health Organization's (WHO) recommendations on the use of diphtheria vaccines excerpted from the Diphtheria vaccines: WHO position paper, August 2017, published in the Weekly Epidemiological Record (Diphtheria vaccine, 2017) [1]. This position paper replaces the 2006 WHO position paper on diphtheria vaccine (Diphtheria vaccine, 2006) [2].The position paper incorporates recent evidence on diphtheria and provides revised recommendations on the optimal number of doses and timing of diphtheria vaccination. In view of the widespread use of combination vaccines, it provides guidance on the alignment of vaccination schedules for different antigens included in routine childhood immunization programmes.Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of diphtheria vaccines were discussed by SAGE in April 2017; evidence presented at these meetings can be accessed at:http://ift.tt/2vZkvTh.



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Cardioprotective effect of influenza and pneumococcal vaccination in patients with cardiovascular diseases

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Andrzej Ciszewski
Due to the wide interaction between the respiratory and the circulatory systems, influenza and pneumococcal vaccinations are recommended in the prevention and treatment of cardiovascular diseases. The review summarizes the results of recent studies and meta-analyses demonstrating that in this group of high-risk patients both vaccinations have potentially beneficial properties. However, in the era of Evidence Base Medicine, there is still a lack of randomized prospective clinical trials, especially those evaluating the effect of pneumococcal vaccination. As the burden of cardiovascular diseases represents various pathologies, it is important to point that the beneficial effect of vaccination is more pronounced in the atherosclerotic etiology, especially in patients after recent coronary events. This information contributes significantly to the appreciation of the role of the adaptive and innate immunity in atherosclerosis, which is now considered as immuno-inflammatory process driven by LDL-cholesterol intimal infiltration and macrophages activation. The mechanism of the cardioprotective effect of vaccination may not only be associated with the elimination of infections and their complications, but also related to the modification of the immuno-inflammatory model of atherosclerosis.



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Editorial Board/Aims and Scope

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2





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A quality improvement initiative to increase Tdap (tetanus, diphtheria, acellular pertussis) vaccination coverage among direct health care providers at a children’s hospital

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Changhong Jiang, LaQuita Whitmore-Sisco, Aditya H. Gaur, Elisabeth E. Adderson
ObjectivesHealth care providers (HCP) are at high risk of acquiring and transmitting pertussis to susceptible family members, co-workers, and patients. Public health authorities recommend administering a single dose of Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccine to all adults, including HCP, to increase adult immunity to pertussis. We set a quality improvement goal to increase Tdap vaccination coverage among HCP who provided direct patient care at a children's hospital from 58% to 90% over 18 months.DesignA multidisciplinary working group comprised of Occupational Health Program (OHP) staff and representatives of various medical services drew from a variety of qualitative methods and previous studies of vaccination programs in the healthcare system to understand barriers to Tdap vaccination within the institution and to develop interventions to increase vaccination rates.InterventionsInterventions included changes to OHP processes, a general education campaign, improved access to vaccine, and personal engagement of HCP by task force members.ResultsOverall vaccination rates increased to 90% over 15 months, a rate that has been sustained by systematically assessing new employees' vaccination status and vaccinating those without documentation of previous Tdap vaccination.ConclusionsTdap vaccination coverage in our institution was significantly increased by an intensive, multipronged educational campaign, and by improving processes of screening and vaccination of HCP. The use of direct engagement of vaccine hesitant populations to increase vaccination rates warrants further study.



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Whole-cell or acellular pertussis vaccination in infancy determines IgG subclass profiles to DTaP booster vaccination

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Saskia van der Lee, Elisabeth A.M. Sanders, Guy A.M. Berbers, Anne-Marie Buisman
IntroductionDuration of protection against pertussis is shorter in adolescents who have been immunized with acellular pertussis (aP) in infancy compared with adolescents who received whole-cell pertussis (wP) vaccines in infancy, which is related to immune responses elicited by these priming vaccines. To better understand differences in vaccine induced immunity, we determined pertussis, diphtheria, and tetanus (DTaP) vaccine antigen-specific IgG subclass responses in wP- and aP-primed children before and after two successive DTaP booster vaccinations.MethodsBlood samples were collected in a cross-sectional study from wP- or aP-primed children before and 1 month after the pre-school DTaP booster vaccination at age 4 years. Blood samples were collected from two different wP- and aP-primed groups of children before, 1 month and 1 year after an additional pre-adolescent Tdap booster at age 9 years. IgG subclass levels against the antigens included in the DTaP vaccine have been determined with fluorescent-bead-based multiplex immunoassays.ResultsAt 4 years of age, the IgG4 proportion and concentration for pertussis, diphtheria and tetanus vaccine antigens were significantly higher in aP-primed children compared with wP-primed children. IgG4 concentrations further increased upon the two successive booster vaccinations at 4 and 9 years of age in both wP- and aP-primed children, but remained significantly higher in aP-primed children.ConclusionsThe pertussis vaccinations administered in the primary series at infancy determine the vaccine antigen-specific IgG subclass profiles, not only against the pertussis vaccine antigens, but also against the co-administered diphtheria and tetanus vaccine antigens. These profiles did not change after DTaP booster vaccinations later in childhood. The different immune response with high proportions of specific IgG4 in some aP-primed children may contribute to a reduced protection against pertussis.ISRCTN65428640; ISRCTN64117538; NTR4089.



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Efficacy and safety of simultaneous vaccination with two modified live virus vaccines against porcine reproductive and respiratory syndrome virus types 1 and 2 in pigs

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Charlotte S. Kristensen, L.K. Kvisgaard, M. Pawlowski, S. Holmgaard Carlsen, C.K. Hjulsager, P.M.H. Heegaard, A. Bøtner, T. Stadejek, S. Haugegaard, L.E. Larsen
The objective of the study was to compare responses of pigs vaccinated with a PRRS MLV vaccine against PRRSV-1 or PRRSV-2 with the responses of pigs vaccinated simultaneously with both vaccines. Furthermore, the efficacy of the two PRRSV MLV vaccination strategies was assessed following challenge. The experimental design included four groups of 4-weeks old SPF-pigs. On day 0 (DPV0), groups 1–3 (N=18 per group) were vaccinated with modified live virus vaccines (MLV) containing PRRSV-1 virus (VAC-T1), PRRSV-2 virus (VAC-T2) or both (VAC-T1T2). One group was left unvaccinated (N=12). On DPV 62, the pigs from groups 1–4 were mingled in new groups and challenged (DPC 0) with PRRSV-1, subtype 1, PRRSV-1, subtype 2 or PRRSV-2. On DPC 13/14 all pigs were necropsied. Samples were collected after vaccination and challenge. PRRSV was detected in all vaccinated pigs and the majority of the pigs were positive until DPV 28, but few of the pigs were still viremic 62 days after vaccination. Virus was detected in nasal swabs until DPV 7–14. No overt clinical signs were observed after challenge. PRRSV-2 vaccination resulted in a clear reduction in viral load in serum after PRRSV-2 challenge, whereas there was limited effect on the viral load in serum following challenge with the PRRSV-1 strains. Vaccination against PRRSV-1 had less impact on viremia following challenge. The protective effects of simultaneous vaccination with PRRSV Type 1 and 2 MLV vaccines and single PRRS MLV vaccination were comparable. None of the vaccines decreased the viral load in the lungs at necropsy. In conclusion, simultaneous vaccination with MLV vaccines containing PRRSV-1 and PRRSV-2 elicited responses comparable to single vaccination and the commercial PRRSV vaccines protected only partially against challenge with heterologous strains. Thus, simultaneous administration of the two vaccines is an option in herds with both PRRSV types.



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Measuring the cost of a pediatric vaccine administration in the UK

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): S. Mokiou, B. Standaert, X. Li, E. De Cock
The administration of a vaccine dose involves a series of activities prior to and on the day of vaccine delivery. Total vaccination cost should include the cost of each activity, which is often not done or poorly reported.To calculate those costs a field study was performed in 6 United Kingdom (UK) sites (General Practitioner (GP) practices) during a 4-month period (April–June 2015). First, a workflow map of all the relevant vaccine-related activities per site was obtained through interviews. Second, time estimates for activities happening prior to the vaccination day were obtained through interviews and associated costs were calculated. A prospective, non-interventional study using Time & Motion (T&M) methodology was used to measure time for activities happening on the day of vaccination. Consumables, wastage, and guardian time were also collected. Third, the time for each task and for all tasks combined during the T&M study was analyzed using a random intercept model to account for site effect.Hundred and twenty-three T&M observations with approximately 20 per site were collected and were equally stratified by vaccination visit during the first year of a baby's life. Total cost per visit was £11.9 (site range: £8.6–£17.0) when supply cost and time for activities prior to the vaccination day were included. Time per dose administrated was 7.1 min (site range: 5.7–9.2) and the associated cost was £4.3 (site range: £3.1–£6.2).The study demonstrates an accurate reflection of the time and cost involved in a vaccine dose administration in a pediatric setting in the UK. The amount measured is consistent with the current National Health Services fee schedule.



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The impact of the recommendation of routine rotavirus vaccination in Germany: An interrupted time-series analysis

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Phillip Alexander Kittel
BackgroundRotavirus is a highly contagious virus causing gastroenteritis, mostly in children under the age of 5. Since 2006, two vaccines are available in Germany. In 2013, these were included into the German national vaccination schedule. The aim of this intervention is to reduce the incidence and hospitalization among children under 5 years caused by rotavirus. The effectiveness of the intervention was analyzed in this study.MethodsNational surveillance data of laboratory confirmed rotavirus infections among children under the age of 5 were analyzed using interrupted time-series analysis. Weekly incidence from 2011 to 2017 and monthly hospital discharge rates from 2005 to 2015 were analyzed using a segmented generalized linear model with Poisson distribution.ResultsAfter adjusting for seasonal effects the incidence were approximately 22% (95% CI: 13.2–30.1) lower than expected following the intervention. The hospitalizations were approximately 27% (95% CI: 14.9–39.7) lower than expected following the intervention. The long-term effects of the intervention were nearly zero. The incidence changed in trend by −0.2% (95% CI: −0.1 to (−0.3)) and the hospitalizations by +0.2% (95% CI: 1.2–(−0.8)) following the intervention.ConclusionAfter the inclusion of the vaccines into the national vaccination schedule significant immediate effects of this intervention were found. The weekly incidences and monthly hospitalization caused by the rotavirus were more than 20% lower than expected. The long-term effects of the intervention however were found to be nearly zero. This could be caused by a low vaccination rate in the German population.



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A novel antigenic cathepsin B protease induces protective immunity in Trichinella-infected mice

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Zhaoshou Yang, Wenjie Li, Zifan Yang, Aihua Pan, Wanqin Liao, Xingwang Zhou
Trichinellosis is a foodborne disease that remains a public health hazard and an economic problem in food safety. Vaccines against the parasite can be an effective way to control this disease; however, commercial vaccines against Trichinella infection are not yet available. Trichinella cathepsin B proteins appear to be promising targets for vaccine development. Here, we reported for the first time the characterization of a novel cDNA that encodes Trichinella spiralis (T. spiralis) cathepsin B-like protease 2 gene (TsCPB2). The recombinant mature TsCPB2 protein was successfully expressed in E. coli system and purified with Ni-affinity chromatography. TsCPB2 expression was detected at all the developmental stages of T. spiralis and it was expressed as an excretory–secretory protein of T. spiralis muscle larvae. Immunization with TsCPB2 antigen induced a combination of humoral and cellular immune responses, which manifested as a mixed Th1/Th2 response, as well as remarkably elevated IgE level. Moreover, vaccination of mice with TsCPB2 that were subsequently challenged with T. spiralis larvae resulted in a 52.3% (P < .001) reduction in worm burden and a 51.2% (P < .001) reduction in muscle larval burden. Our results suggest that TsCPB2 induces protective immunity in Trichinella-infected mice and might be a novel vaccine candidate against trichinellosis.



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The efficacy of two different dosages of hepatitis B immunoglobulin combined with hepatitis B vaccine in preventing mother-to-child transmission of hepatitis B virus: A prospective cohort study

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Kai-Ping Wei, Feng-Cai Zhu, Jian-Xun Liu, Ling Yan, Ying Lu, Xiang-Jun Zhai, Zhan-Jun Chang, Ying Zeng, Jie Li, Hui Zhuang
Background/aimsA birth dose of hepatitis B immunoglobulin (HBIG), in combination with hepatitis B vaccine (HepB), is recommended for infants born to hepatitis B surface antigen (HBsAg)-positive mothers. However, the optimal dosage of HBIG remains to be resolved. This prospective cohort study aimed to compare the efficacy of two dosages of HBIG combined with HepB to prevent mother-to-child transmission (MTCT) of HBV.MethodsFrom 2009 to 2011, we prospectively enrolled mother-infant pairs with positive maternal HBsAg in China. Infants were assigned to receive one dose of 100 IU or 200 IU HBIG within 12 h of birth according to maternal numbering, followed by completion of the 3-dose 10 μg HepB series. At 7 months, post-vaccination serologic testing (PVST) was performed in 545 and 632 infants in 100 IU and 200 IU HBIG groups, respectively, among whom, 451 and 529 were followed up to 12 months.ResultsMaternal and birth characteristics were comparable between infants in 100 IU and 200 IU HBIG groups. At 7 months, the rates of perinatal infection were 1.5% (8/545) and 1.9% (12/632) in 100 IU and 200 IU HBIG groups, respectively (p = .568). One non-responder infant in 200 IU HBIG group became newly infected at 12 months. The antibody to hepatitis B surface antigen (anti-HBs) positive rates were 98.5% (529/537) and 98.2% (609/620) in 100 IU and 200 IU HBIG groups at 7 months, respectively (p = .704), and the corresponding figures were 98.2% (431/439) and 97.1% (496/511) at 12 months (p = .266). The anti-HBs geometric mean concentrations were comparable between two groups at 7 months (707.95 mIU/mL vs. 602.56 mIU/mL, p = .062) and 12 months (245.47 mIU/mL vs. 229.09 mIU/mL, p = .407).ConclusionsOne birth dose of 100 IU HBIG, combined with the HepB series, might be enough for preventing MTCT of HBV in infants born to HBsAg-positive mothers.



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Influence of the intestinal microbiota on the immunogenicity of oral rotavirus vaccine given to infants in south India

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Edward P.K. Parker, Ira Praharaj, Anna Zekavati, Robin P. Lazarus, Sidhartha Giri, Darwin J. Operario, Jie Liu, Eric Houpt, Miren Iturriza-Gómara, Beate Kampmann, Jacob John, Gagandeep Kang, Nicholas C. Grassly
Oral rotavirus vaccines have consistently proven to be less immunogenic among infants in developing countries. Discrepancies in the intestinal microbiota, including a greater burden of enteropathogens and an altered commensal community composition, may contribute to this trend by inhibiting the replication of vaccine viruses. To test this possibility, we performed a nested case–control study in Vellore, India, in which we compared the intestinal microbiota of infants who responded serologically or not after two doses of Rotarix delivered at 6 and 10 weeks of age as part of a clinical trial (CTRI/2012/05/002677). The prevalence of 40 bacterial, viral, and eukaryotic pathogen targets was assessed in pre-vaccination stool samples from 325 infants using singleplex real-time PCR on a Taqman array card (TAC). In a subset of 170 infants, we assessed bacterial microbiota composition by sequencing the 16S rRNA gene V4 region. Contrary to expectations, responders were more likely than non-responders to harbor ≥1 bacterial enteropathogen at dose 1 (26% [40/156] vs 13% [21/157] of infants with TAC results who completed the study per protocol; χ², P = .006), although this was not apparent at dose 2 (24% [38/158] vs 23% [36/158]; P = .790). Rotavirus shedding after dose 1 was negatively correlated with the replication of co-administered oral poliovirus vaccine (OPV). We observed no consistent differences in composition or diversity of the 16S bacterial microbiota according to serological response, although rotavirus shedding was associated with slightly more bacterial taxa pre-vaccination. Overall, our findings demonstrate an inhibitory effect of co-administered OPV on the first dose of Rotarix, consistent with previous studies, but in the context of OPV co-administration we did not find a strong association between other components of the intestinal microbiota at the time of vaccination and Rotarix immunogenicity.



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The effect of probiotics and zinc supplementation on the immune response to oral rotavirus vaccine: A randomized, factorial design, placebo-controlled study among Indian infants

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Robin P. Lazarus, Jacob John, E. Shanmugasundaram, Anand K. Rajan, S. Thiagarajan, Sidhartha Giri, Sudhir Babji, Rajiv Sarkar, P. Saravankumar Kaliappan, Srinivasan Venugopal, Ira Praharaj, Uma Raman, Meghana Paranjpe, Nicholas C. Grassly, Edward P.K. Parker, Umesh D. Parashar, Jacqueline E. Tate, Jessica A. Fleming, A. Duncan Steele, Jayaprakash Muliyil, Asha M. Abraham, Gagandeep Kang
BackgroundStrategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function.MethodsInfants 5weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5mg), probiotic (10¹⁰Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix®, GlaxoSmithKline Biologicals) given at 6 and 10weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14weeks of age based on detection of VP6-specific IgA at ≥20U/ml in previously seronegative infants or a fourfold rise in concentration.ResultsThe study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): −1.4%, 16.2%), p=0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: −4.4%, 13.2%), p=0.272). 16 serious adverse events were recorded, none related to study interventions.ConclusionsZinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation.Trial registrationThe trial was registered in India (CTRI/2012/05/002677).



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Early impact of universal varicella vaccination on childhood varicella and herpes zoster hospitalizations in Brazil

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Marcelo Comerlato Scotta, Rolando Paternina-de la Ossa, Magali Santos Lumertz, Marcus Herbert Jones, Rita Mattiello, Leonardo Araújo Pinto
IntroductionThe Brazilian childhood National Immunization Program (NIP) introduced live and attenuated varicella vaccination in a single dose, combined as tetraviral vaccine, at 15 months of age in the whole country, during September to December of 2013. The aim of this study was to report trends in incidence of childhood hospital admissions related to varicella and zoster in Brazil from 2003 to 2016, including the first three years after vaccine introduction.MethodsThe number and incidence of hospital admission in patients aged less than 20 years in Brazilian public health system with an admission diagnosis of varicella and zoster from 2003 to 2016 were analyzed and pre (2003–2013) and post-vaccination periods (2014–2016) were compared. The data were obtained from DATASUS, a Brazilian government's open-access public health database system, and analyzed adjusting for secular trend and seasonality if a statistically significant change was found.ResultsDuring the study period, 69,791 admissions due to varicella and herpes zoster occurred in the children younger than 20 years. After adjusting for seasonality, the incidence of hospitalizations decreased from 27.33 to 14.33 per 100000 per year, which corresponds to a reduction of 47.6% (95% confidence interval 18.19–77.04%, p < 0.001) in the vaccinated age group (1–4 years) in 2014–2016 compared to pre-vaccination period. The changes were not significant in the unvaccinated age groups.ConclusionThe hospitalizations due to varicella and herpes zoster were decreased by half early after the introduction of a single dose of tetraviral vaccine in NIP in the vaccinated children. Further studies may assess duration and intensity of this effect, as well as the indirect effect in the unvaccinated age groups.



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Immunogenic response in obese patients undergoing rabies post-exposure prophylaxis with combined equine rabies immunoglobulin and rabies vaccination

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Jatuporn Sirikun, Yupin Suputtamongkol, Ploypailin Rattanachinakorn, Athiwat Primsirikunawut
BackgroundObesity is a risk factor for increased morbidity and mortality associated with many vaccine preventable infectious diseases such as influenza. Moreover, higher volume of passive rabies immunoglobulin (RIG) due to weight based dosing might suppress vaccine-induced immune responses in obese patients. This study aimed to evaluate the effect of obesity on humoral immune responses to combined equine RIG and rabies vaccine treatment among patients with WHO category III exposure to a rabies suspected animal.MethodsA single centre, prospective, open-labelled study among WHO category III rabies exposed patients was conducted to compare serum rabies virus neutralizing antibody (RVNA) responses measured by rapid fluorescent focus inhibition test between obese (body mass index, BMI > 30 kg/m²) and control (BMI < 25 kg/m²) patients after combined immunization with equine rabies immunoglobulin and purified chick-embryo cell rabies vaccine for post exposure prophylaxis treatment.ResultsPost-vaccination geometric mean titer (GMT) of RVNA concentrations between two groups at day 7 were 0.33 (95% CI: 0.23, 0.46) vs 0.39 (95% CI: 0.27, 0.55), 4.61 (95% CI: 3.20, 6.63) vs 3.78 (95% CI: 2.77, 5.16) at day 14, and 7.45 (95% CI: 5.86, 9.49) vs 5.93 (95%CI: 4.46–7.90) at day 28 for obese and control patients, respectively. There was no statistically significant difference of RVNA GMT between two groups. Seroconversion to at least adequate concentration (RVNA titer ≥0.5 IU/mL) rates were 34% at day 7 and 100% at days 14 and 28 in both groups. There were no immediate hypersensitivity reaction and no serious adverse events observed during the study period.ConclusionsThere was no evidence of immunosuppression of antibodies' responses in obese patients. Combined ERIG and rabies virus vaccination for post exposure treatment is safe.



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Addition of C3d-P28 adjuvant to a rabies DNA vaccine encoding the G5 linear epitope enhances the humoral immune response and confers protection

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Guillermo Galvez-Romero, Mónica Salas-Rojas, Ericka N. Pompa-Mera, Karina Chávez-Rueda, Álvaro Aguilar-Setién
Rabies DNA vaccines based on full-length glycoprotein (G) induce virus neutralizing antibody (VNA) responses and protect against the virus challenge. Although conformational epitopes of G are the main target of VNAs, some studies have shown that a polypeptide linear epitope G5 is also able to induce VNAs. However, a G5 DNA vaccine has not been explored. While multiple doses of DNA vaccines are required in order to confer a protective immune response, this could be overcome by the inclusion of C3d-P28, a molecular adjuvant is know to improve the antibody response in several anti-viral vaccine models. To induce and enhance the immune response against rabies in mice, we evaluated two DNA vaccines based on the linear epitope G5 of Rabies Virus (RABV) glycoprotein (pVaxG5 vaccine) and another vaccine consisting of G5 fused to the molecular adjuvant C3d-P28 (pVaxF1 vaccine). VNA responses were measured in mice immunized with both vaccines. The VNA levels from the group immunized with pVaxG5 decreased gradually, while those from the group vaccinated with pVaxF1 remained high throughout the experimental study. After challenge with 22 LD50 of the Challenge Virus Strain (CVS), the survival rate of mice immunized with pVaxG5 and pVaxF1 was increased by 27% and 50% respectively, in comparison to the PBS group. Furthermore, the in vitro proliferation of anti-rabies specific spleen CD4+ and CD8+ T cells from mice immunized with pVaxF1 was observed. Collectively, these results suggest that the linear G5 epitope is a potential candidate vaccine. Furthermore, the addition of a C3d-P28 adjuvant contributed to enhanced protection, the sustained production of VNAs, and a specific T-cell proliferative response.



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Anxiety-related adverse events following immunization (AEFI): A systematic review of published clusters of illness

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Anagha Loharikar, Tiffany A. Suragh, Noni E. MacDonald, Madhava R. Balakrishnan, Oleg Benes, Smaragda Lamprianou, Terri B. Hyde, Michael M. McNeil
BackgroundClusters of anxiety-related adverse events following immunization (AEFI) have been observed in several countries and have disrupted country immunization programs. We conducted a systematic literature review to characterize these clusters, to generate prevention and management guidance for countries.MethodsWe searched seven peer-reviewed databases for English language reports of anxiety-related AEFI clusters (≥2 persons) with pre-specified keywords across 4 categories: symptom term, cluster term, vaccine term, and cluster AEFI phenomenon term/phrase. All relevant reports were included regardless of publication date, case-patient age, or vaccine. Two investigators independently reviewed abstracts and identified articles for full review. Data on epidemiologic/clinical information were extracted from full text review including setting, vaccine implicated, predominant case-patient symptoms, clinical management, community and media response, and outcome/impact on the vaccination program.ResultsOf 1472 abstracts reviewed, we identified eight published clusters, from all six World Health Organization (WHO) regions except the African Region. Seven clusters occurred among children in school settings, and one was among adult military reservists. The size and nature of these clusters ranged from 7 patients in one school to 806 patients in multiple schools. Patients' symptoms included dizziness, headache, and fainting with rapid onset after vaccination. Implicated vaccines included tetanus (2), tetanus-diphtheria (1), hepatitis B (1), oral cholera (1), human papillomavirus (1), and influenza A (H1N1)pdm09 (2). In each report, all affected individuals recovered rapidly; however, vaccination program disruption was noted in some instances, sometimes for up to one year.ConclusionsAnxiety-related AEFI clusters can be disruptive to vaccination programs, reducing public trust in immunizations and impacting vaccination coverage; response efforts to restore public confidence can be resource intensive. Health care providers should have training on recognition and clinical management of anxiety-related AEFI; public health authorities should have plans to prevent and effectively manage anxiety-related AEFI clusters. Prompt management of these occurrences can be even more important in an era of social media, in which information is rapidly spread.



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Evaluating interest in an influenza A(H5N1) vaccine among laboratory workers who work with highly-pathogenic avian influenza viruses in the United States

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Kate E. Russell, J.S. Bresee, J.M. Katz, S.J. Olsen
BackgroundHighly pathogenic avian influenza A (HPAI) viruses found in poultry and wild birds occasionally infect humans and can cause serious disease. In 2014, the Advisory Committee on Immunization Practices (ACIP) reviewed data from one licensed ASO3-adjuvanted influenza A(H5N1) vaccine for consideration of use during inter-pandemic periods among persons with occupational exposure. To guide vaccine policy decisions, we conducted a survey of laboratory workers to assess demand for HPAI vaccination.MethodsWe designed an anonymous web survey (EpiInfo 7.0) to collect information on demographics, type of work and time spent with HPAI viruses, and interest in HPAI vaccination. Eligible participants were identified from 42 entities registered with United States Department of Agriculture's Agricultural Select Agent program in 2016 and emailed electronic surveys. Personnel with Biosafety Level 3 enhanced (BSL-3E) laboratory access were surveyed. Descriptive analysis was performed.ResultsOverall, 131 responses were received from 33 principal investigators, 26 research scientists, 24 technicians, 15 postdoctoral fellows, 6 students, and 27 others. The estimated response rate was 15% among the laboratory personnel of responding principal investigators. One hundred respondents reported working in a BSL-3E area where HPAI experiments occurred with a mean time of 5.1–11.7 h per week. Overall, 49% were interested in receiving an A(H5N1) vaccine. By role, interest was highest among students (80%) and among those who spent >50% of their time in a BSL-3E area (64%). Most (61%) of those who said they might be or were not interested in vaccine believed it would not provide additional protection to current safety practices.ConclusionsHalf of responding laboratory workers was interested in receiving an influenza A(H5N1) vaccine. HPAI vaccination of laboratory workers at risk of occupational exposure could be used along with existing safety practices to protect this population.



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The generation of a simian adenoviral vectored HCV vaccine encoding genetically conserved gene segments to target multiple HCV genotypes

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Annette von Delft, Timothy A. Donnison, José Lourenço, Claire Hutchings, Caitlin E. Mullarkey, Anthony Brown, Oliver G. Pybus, Paul Klenerman, Senthil Chinnakannan, Eleanor Barnes
BackgroundHepatitis C virus (HCV) genomic variability is a major challenge to the generation of a prophylactic vaccine. We have previously shown that HCV specific T-cell responses induced by a potent T-cell vaccine encoding a single strain subtype-1b immunogen target epitopes dominant in natural infection. However, corresponding viral regions are highly variable at a population level, with a reduction in T-cell reactivity to these variants. We therefore designed and manufactured second generation simian adenovirus vaccines encoding genomic segments, conserved between viral genotypes and assessed these for immunogenicity.MethodsWe developed a computer algorithm to identify HCV genomic regions that were conserved between viral subtypes. Conserved segments below a pre-defined diversity threshold spanning the entire HCV genome were combined to create novel immunogens (1000–1500 amino-acids), covering variation in HCV subtypes 1a and 1b, genotypes 1 and 3, and genotypes 1–6 inclusive. Simian adenoviral vaccine vectors (ChAdOx) encoding HCV conserved immunogens were constructed. Immunogenicity was evaluated in C57BL6 mice using panels of genotype-specific peptide pools in ex-vivo IFN-ϒ ELISpot and intracellular cytokine assays.ResultsChAdOx1 conserved segment HCV vaccines primed high-magnitude, broad, cross-reactive T-cell responses; the mean magnitude of total HCV specific T-cell responses was 1174 SFU/10⁶ splenocytes for ChAdOx1-GT1-6 in C57BL6 mice targeting multiple genomic regions, with mean responses of 935, 1474 and 1112 SFU/10⁶ against genotype 1a, 1b and 3a peptide panels, respectively. Functional assays demonstrated IFNg and TNFa production by vaccine-induced CD4 and CD8 T-cells. In silico analysis shows that conserved immunogens contain multiple epitopes, with many described in natural HCV infection, predicting immunogenicity in humans.ConclusionsSimian adenoviral vectored vaccines encoding genetic segments that are conserved between all major HCV genotypes contain multiple T-cell epitopes and are highly immunogenic in pre-clinical models. These studies pave the way for the assessment of multi-genotypic HCV T-cell vaccines in humans.



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Immunogenicity of Vibrio cholerae outer membrane vesicles secreted at various environmental conditions

Publication date: 4 January 2018
Source:Vaccine, Volume 36, Issue 2
Author(s): Rezaei Adriani, Seyed Latif Mousavi Gargari, Shahram Nazarian, Samaneh Sarvary, Nafiseh Noroozi
Cholera is caused by toxigenic Vibrio cholerae. It is a significant health problem and an important cause of mortality of children in developing countries. Annually, about 5–7 million people are being infected worldwide, leading to death of 100,000 to 120,000. Immunization using the currently available cholera vaccines has been recommended by World Health Organization (WHO) in areas where cholera is endemic or at risk of outbreaks. Gram-negative bacteria secrete outer membrane vesicles (OMVs) that play important roles in virulence and host-pathogen interaction. The content of protein and lipid in OMVs are affected by purification methods and bacterial growth condition. OMVs released from V. cholerae are an appropriate candidate for vaccine development. The protection conferred by a new vaccine candidate prepared using different methods and in two different growth conditions with nanoparticles in an experimental model of cholera in mice was investigated. OMVs were encapsulated in chitosan-tripolyphosphate (TPP) nanoparticles prepared by an ionic gelation method and coated with Eudragit as an enteric polymer. OMVs loaded into nanoparticles (NP-OMVs) were homogeneous and spherical in shape, with a size of 417nm. BALB/c mice (male, 20–24g) were immunized via intraperitoneal (10µg) or oral route (50µg) with free or encapsulated OMVs. Seventy-eight days after first administration, serum of mice was infected with infection dose of V. cholerae (≥10⁷ CFU). The new vaccine was able to protect fully against infection when it was administered via mucosa. By intraperitoneal route, the unpolymerized OMVs increased the protection against these bacteria.



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A face identity hallucination (palinopsia) generated by intracerebral stimulation of the face-selective right lateral fusiform cortex

Publication date: Available online 9 December 2017
Source:Cortex
Author(s): Jacques Jonas, Hélène Brissart, Gabriela Hossu, Sophie Colnat-Coulbois, Jean-Pierre Vignal, Bruno Rossion, Louis Maillard
We report the case of a patient (MB, young female human subject) who systematically experienced confusion between perceived facial identities specifically when electrically stimulated inside the lateral section of the right fusiform gyrus. In the presence of a face stimulus (an experimenter or a photograph), intracerebral electrical stimulation in this region generated a perceptual hallucination of an individual facial part integrated within the whole perceived face, i.e. facial palinopsia. In the presence of a distracting stimulus (visual scene or object picture), the patient also experienced an individual face percept superimposed on the non-face stimulus. The stimulation site evoking this category-selective transient palinopsia was localized in a region showing highly selective responses to faces both with functional magnetic resonance imaging ("Fusiform Face Area", "FFA") and intracerebral electrophysiological recordings during fast periodic visual stimulation (FPVS). Importantly, the largest electrophysiological response to fast periodic changes of facial identity was also found at this location. Altogether, these observations suggest that the face-selective right lateral fusiform gyrus plays a role in generating vivid percepts of individual faces, supporting the active role of this region in individual face representation.



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Embodied language and perspective taking in light of movement disorders

Publication date: Available online 9 December 2017
Source:Cortex
Author(s): Claudia Gianelli
Growing evidence supports the idea of a strict interplay between linguistic and motor systems, with an impact on participant's neurophysiological and motor responses. Despite the increasing evidence, the translation of these results into the clinical domain - especially that of movement disorders - is still limited. One possible source of limitation is constituted by the contextual and task dependency of embodied language effects, for instance when it comes to evaluating if different linguistic perspectives modulate the processing of action language. By reviewing and discussing the existing literature, I outline how a fruitful application of action-language paradigms to movement disorders is not hindered but indeed can take advantage of these contextual dependencies and of fine-grained motor measures.



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Atmospheric PAHs, NPAHs, and OPAHs at an urban, mountainous, and marine sites in Northern China: Molecular composition, sources, and ageing

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Junmei Zhang, Lingxiao Yang, Abdelwahid Mellouki, Jianmin Chen, Xiangfeng Chen, Ying Gao, Pan Jiang, Yanyan Li, Hao Yu, Wenxing Wang
18 gaseous and particulate polycyclic aromatic hydrocarbons (PAHs), 16 nitro-derivative (NPAHs), and 7 oxy-derivative (OPAHs) were analyzed by Gas Chromatography-Mass Spectrometry (GC-MS) at three locations in Northern China, an urban site (Jinan), a marine site (Tuoji island), and a mountain site (Mt. Tai). The combined gas and particulate concentrations of 18 PAHs, 16 NPAHs, and 7 OPAHs were highest at the urban site (305.91, 2.80, and 9.05 ng/m³, respectively) and lowest at the mountain location (37.83, 0.27, and 1.59 ng/m³, respectively). A noticeable increase in the high molecular weight PAHs was observed during polluted conditions compared to clean conditions. Diagnostic ratios clearly demonstrated that coal/biomass combustion was the major PAH source in Northern China. The particulate PAHs were the most aged at the mountain site due to long-distance atmospheric transport. The formation rate of NPAHs was most efficient at the mountain location and during heavily polluted days at the urban and marine sites. In addition, the main formation pathway for NPAHs was through the OH initiated secondary reaction. NO3 radicals most significantly contributed to the NPAHs formation at night, during clear weather, and at the mountain site. The logKp value was lowest at the urban site for most individual compounds and highest at the mountain site. Higher logKp was found for NPAHs and OPAHs compared with their corresponding parent PAHs. The linear regression of logKp vs logPL⁰ at the three sites suggested that the gas-particle partitioning of PAHs might be in non-equilibrium.

Graphical abstract

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Potential air quality benefits from increased solar photovoltaic electricity generation in the Eastern United States

Publication date: February 2018
Source:Atmospheric Environment, Volume 175
Author(s): David Abel, Tracey Holloway, Monica Harkey, Arber Rrushaj, Greg Brinkman, Phillip Duran, Mark Janssen, Paul Denholm
We evaluate how fine particulate matter (PM2.5) and precursor emissions could be reduced if 17% of electricity generation was replaced with solar photovoltaics (PV) in the Eastern United States. Electricity generation is simulated using GridView, then used to scale electricity-sector emissions of sulfur dioxide (SO2) and nitrogen oxides (NOX) from an existing gridded inventory of air emissions. This approach offers a novel method to leverage advanced electricity simulations with state-of-the-art emissions inventories, without necessitating recalculation of emissions for each facility. The baseline and perturbed emissions are input to the Community Multiscale Air Quality Model (CMAQ version 4.7.1) for a full accounting of time- and space-varying air quality changes associated with the 17% PV scenario. These results offer a high-value opportunity to evaluate the reduced-form AVoided Emissions and geneRation Tool (AVERT), while using AVERT to test the sensitivity of results to changing base-years and levels of solar integration. We find that average NOX and SO2 emissions across the region decrease 20% and 15%, respectively. PM2.5 concentrations decreased on average 4.7% across the Eastern U.S., with nitrate (NO3⁻) PM2.5 decreasing 3.7% and sulfate (SO4²⁻) PM2.5 decreasing 9.1%. In the five largest cities in the region, we find that the most polluted days show the most significant PM2.5 decrease under the 17% PV generation scenario, and that the greatest benefits are accrued to cities in or near the Ohio River Valley. We find summer health benefits from reduced PM2.5 exposure estimated as 1424 avoided premature deaths (95% Confidence Interval (CI): 284 deaths, 2 732 deaths) or a health savings of $13.1 billion (95% CI: $0.6 billion, $43.9 billion) These results highlight the potential for renewable energy as a tool for air quality managers to support current and future health-based air quality regulations.



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Effects of novel nitrification and urease inhibitors (DCD/TZ and 2-NPT) on N2O emissions from surface applied urea: An incubation study

Publication date: February 2018
Source:Atmospheric Environment, Volume 175
Author(s): Kang Ni, Henning Kage, Andreas Pacholski
A 41-day incubation trial was conducted to test the single and combined effects of the novel urease (N-(2-Nitrophenyl) phosphoric triamide, 2-NPT) and nitrification inhibitors (mixture of dicyandiamide and 1H-1,2,4-triazole, DCD/TZ) on N2O emissions and underlying soil processes from a North German sandy loam soil. The effects of treatment on N2O emission were determined using static closed chamber incubation and detected using a photo-acoustic gas monitor. The emission processes were strongly related to soil mineral N and pH dynamics, obtained from destructive sampling of replicate incubation chambers. The combined use of urease and nitrification inhibitors slightly increased the reduction of N2O compared with single use of the nitrification inhibitor (69% vs. 61%). The small amount of soil used in the incubation and the depletion of labile carbon by air drying and pre-incubation caused very low initial N2O emissions, and glucose addition significantly stimulated N2O emission by supplying labile carbon. The urease inhibitor significantly reduced simultaneously determined qualitative NH3 emissions in either urea alone (90%) or urea plus nitrification inhibitor treatment (82%). These results highlighted the potential of the combined use of urease and nitrification inhibitors with urea application to mitigate soil NH3 and N2O emissions.



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What controls the atmospheric methane seasonal variability over India?

Publication date: February 2018
Source:Atmospheric Environment, Volume 175
Author(s): Tania Guha, Yogesh K. Tiwari, Vinu Valsala, Xin Lin, Michel Ramonet, Anoop Mahajan, Amey Datye, K. Ravi Kumar
Atmospheric CH4 observations from two ground-based stations within Indian subcontinent, namely, Sinhagad (SNG) and Cape Rama station (CRI) showed a strong seasonality with a minima (∼1800 ± 20 ppb) during southwest monsoon (SWM; i.e. June–September, JJAS) and a maxima (2000 ± 30 ppb) during northeast monsoon (NEM i.e. December–February, DJF) with a peak-to-peak seasonality close to 200 ppb. The Indian summer (winter) monsoon is characterized with strong southwesterly (northeasterly) winds of oceanic (land) origin at the surface level and strong easterly (westerly) jet streams aloft. The monsoon dynamics has pronounced impact on CH4 variability over India and is analyzed with winds, Lagrangian trajectories, and 3-dimentional distributions of CH4 simulated by a general circulation model. The model simulations suggest a consistent annual vertical structure (mean and sub-seasonal uncertainty) of CH4 over India with a stark contrast in concentration from summer to winter at surface levels (below 750 mb) in confirmation with what is identified by the ground-based observations. During SWM (NEM) the air with comparatively lower (higher) CH4 concentrations from southern (northern) hemisphere reduces the CH4 over India by 1814 ± 26 ppb (enhances by 1950 ± 51 ppb). The contribution of local fluxes to this seasonality appears to be albeit weak as the synthesized CH4 fluxes (from EDGAR dataset) of the Indian peninsula itself show a peak in summer and a dip in winter. Similar property of CH4 is also common to nearby oceanic region (i.e. over Arabian Sea, 1765 ± 10 ppb during summer) suggesting the role of monsoon dynamics as the controlling factor. Further the mixing and convection carries the CH4 to the upper atmosphere and advect inward or outward aloft according the seasonal monsoon dynamics.

Graphical abstract

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Understanding the PM2.5 imbalance between a far and near-road location: Results of high temporal frequency source apportionment and parameterization of black carbon

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): U.M. Sofowote, R.M. Healy, Y. Su, J. Debosz, M. Noble, A. Munoz, C.-H. Jeong, J.M. Wang, N. Hilker, G.J. Evans, P.K. Hopke
The differences in PM2.5 concentrations between two relatively close stations, one situated near a major highway and the other much more distant were used to develop a protocol for determining the impact of highway traffic on particulate matter concentrations at the roadside. The roadside station was <15 m away from the edge of a major highway while the other was located ∼170 m away. The roadside station contains a suite of continuous instrumentation capable of near-real-time speciation of PM2.5. The particulate matter difference, formally termed the PM2.5 imbalance was arbitrarily defined as a case wherein |Near-road PM2.5 - Far from road PM2.5|/Near-road PM2.5≳50%. Of interest was the variation of multi-time factors based on ME2 analyses of the speciation data from the roadside station during these imbalance events. Of the 7 mass-contributing ME2 factors, a black carbon factor was determined to be the major cause of the PM2.5 imbalance and was especially dominant for the case when PM2.5 concentrations at the roadside station were greater than the farther-station PM2.5. The black carbon concentrations observed during these specific events were further regressed against other traffic-related and meteorological parameters with two nonlinear optimization algorithms (generalized reduced gradient and rules ensemble) in our attempts to model any potential relationships. It was observed that the traffic counts of heavy duty vehicles (predominantly diesel-powered) dominated the relationship with black carbon while contributions from light duty vehicles were negligible during these [PM2.5]Roadside > [PM2.5]Farther events at the roadside station. This work details the most critical ways that highway traffic can contribute to local ambient PM2.5 concentrations that commuters are exposed to and will be important in informing policies and strategies for particulate matter pollution reduction.



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Editorial board

Publication date: January 2018
Source:Atmospheric Environment, Volume 173





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Angiotensin II receptor blocker valsartan ameliorates cardiac fibrosis partly by inhibiting miR-21 expression in diabetic nephropathy mice

Publication date: Available online 9 December 2017
Source:Molecular and Cellular Endocrinology
Author(s): Jinyang Wang, Lijun Duan, Yanbin Gao, Shuhong Zhou, Yongming Liu, Suhong wei, Siqin An, Jing Liu, Liming Tian, Shaocheng Wang
Cardiac fibrosis with diabetic nephropathy (DN) is one of major diabetic complications. miR-21 and MMP-9 were closely associated with fibrosis diseases. Angiotensin II receptor blockers (ARB) have cardioprotective effects. However, it remains unclear whether miR-21 was involved in the mechanism of cardiac fibrosis with DN by target MMP-9 and ARB ameliorates cardiac fibrosis partly by inhibiting miR-21 expression. In this study, In Situ Hybridization(ISH), RT-PCR, cell transfection, western blotting and laser confocal telescope were used, respectively. ISH showed that miR-21, concentrated in cytoplasmic foci in the proximity of the nucleus, was mainly localized in cardiac fibroblasts and at relatively low levels in cardiomyocytes within cardiac tissue with DN. RT-PCR showed that miR-21 expression was significantly enhanced in cardiac tissue with DN, accompanied by the increase of col-IV, FN, CVF, PVCA, LVMI, HWI and NT-pro-BNP (p < 0.05). Bioinformatics analysis and Luciferase reporter gene assays showed that MMP-9 was a validated target of miR-21. Furthermore, cell transfection experiments showed that miR-21 overexpression directly decreased MMP-9 expression. Interestingly, miR-21 levels in cardiac tissue was positively correlated with ACR (r = -0.870, P = 0.003), whereas, uncorrelated with SBP, HbA1C and T-Cho (p > 0.05). More importantly, ARB can significantly decrease miR-21 expression in cardiac tissue, cardiac fibroblasts and serum. Overall, our results suggested that miR-21 may contribute to the pathogenesis of cardiac fibrosis with DN by target MMP-9, and that miR-21 may be a new possible therapeutic target for ARB in cardiac fibrosis with DN.



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Comparison of radiation therapy modalities for hepatocellular carcinoma with portal vein thrombosis: A meta-analysis and systematic review

Publication date: Available online 9 December 2017
Source:Radiotherapy and Oncology
Author(s): Chai Hong Rim, Chul Yong Kim, Dae Sik Yang, Won Sup Yoon
PurposeWe performed a meta-analysis and systematic review to compare the radiotherapy (RT) modalities for hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT).Materials and methodsWe searched the PubMed, EMBASE, Medline, and Cochrane library databases. The primary endpoint was the 1-year overall survival (OS), and response rate (RR), local control (LC), 2-year OS, and grade ≥3 toxicity incidence were evaluated as secondary endpoints.ResultsThirty-seven studies comprising 2513 patients were included. The pooled 1-year OS rates for the 3-dimensional conformal RT (3DCRT), selective internal RT (SIRT), and stereotactic body RT (SBRT) groups were 43.8% [95% confidence interval (CI): 37.6–50.2], 46.5% (95% CI: 37.7–55.6), and 48.5% (95% CI: 39.4–57.8). These inter-group differences were not statistically significant (p = 0.635). The pooled response rates were 51.3% (95% CI: 45.7–57.0), 33.3% (95% CI: 18.0–53.2), and 70.7 (95% CI: 63.7–76.8) for 3DCRT, SIRT, and SBRT groups, respectively; p = 0.001 and 0.031 for 3DCRT vs. SBRT and SIRT, respectively. The most common grade ≥ 3 complications were lymphocytopenia and bilirubin abnormalities in the 3DCRT and SIRT groups, respectively. Grade ≥ 3 complication was rare in SBRT group.ConclusionsOS did not differ among the modalities, although the response rates vary among modalities.



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Exploring the relationship between frontal asymmetry and emotional dampening

Publication date: Available online 9 December 2017
Source:International Journal of Psychophysiology
Author(s): James P. Loveless, Alexandra J. Nicoletta, Andrea R. Winters, Robert A. Carels, Karl L. Wuensch, Matthew C. Whited, James A. McCubbin, D. Erik Everhart
Cardiovascular emotional dampening is the term used to describe the inverse relationship between resting blood pressure and emotional responsivity which extends from normotensive to hypertensive ranges. Little is known about its underlying physiological mechanisms, but it is thought to involve some disruption in emotion processing. One area that has yet to be explored in the literature is the relationship between emotional dampening and frontal asymmetry, a psychophysiological indicator for motivational direction and emotional valence bias. The present study explored that relationship using data from a sample of 48 healthy college students. Measures of baseline resting blood pressure and frontal cortical activity were recorded, after which participants completed a series of emotion-related tasks. Results revealed a significant relationship between resting systolic blood pressure and left frontal activity. Likewise, left frontal activity was associated with neutral appraisal of emotionally valenced stimuli within the tasks. The findings from the present study yield support for a link between emotional dampening and left frontal activity. Implications are discussed.



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Discussion on Raposo et al

Publication date: Available online 23 November 2017
Source:Seminars in Oncology
Author(s): Chand Khanna




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Mind the Graph. Foregone Health Gains in Lung Cancer

Publication date: Available online 6 December 2017
Source:Seminars in Oncology
Author(s): Laird Cameron, Richard Sullivan, Brendan Luey, Ben Solomon




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Circadian peak dopaminergic activity response at the biological clock pacemaker (suprachiasmatic nucleus) area mediates the metabolic responsiveness to a high fat diet

Abstract

Among vertebrate species of the major vertebrate classes in the wild, a seasonal rhythm of whole body fuel metabolism, oscillating from lean to obese condition, is a common biological phenomenon. This annual cycle is driven in part by annual changes in the circadian dopaminergic signaling at the suprachiasmatic nuclei (SCN), with diminution of circadian peak dopaminergic activity at the SCN facilitating development of the seasonal obese insulin resistant condition. The present study investigated whether such an ancient circadian dopamine-SCN activity system for expression of the seasonal obese, insulin resistant phenotype may be operative in animals made obese, insulin resistant by high fat feeding and if so whether reinstatement of the circadian dopaminergic peak at the SCN would be sufficient to reverse the adverse metabolic impact of the high fat diet without alteration of caloric intake. First, we identified the supramammillary nucleus as a novel site providing the majority of dopaminergic neuronal input to the SCN. We further identified dopamine D2 receptors within the peri-SCN region as functional in mediating SCN responsiveness to local dopamine. In lean, insulin sensitive rats the peak in the circadian rhythm of dopamine release at the peri-SCN coincided with the daily peak in SCN electrophysiological responsiveness to local dopamine administration. However, in rats made obese, insulin resistant by high fat diet feeding, these coincident circadian peak activities were both markedly attenuated or abolished. Reinstatement of the circadian peak in dopamine level at the peri-SCN by its appropriate circadian-timed daily microinjection to this area, but not outside this circadian time-interval, abrogated the obese, insulin resistant condition without altering consumption of the high fat diet. These findings suggest that the circadian peak of dopaminergic activity at the peri-SCN/SCN is a key modulator of metabolism and of responsiveness to adverse metabolic consequences of high fat diet consumption.

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Initial Observations of Salivary BDNF Levels in Rett Syndrome

Publication date: Available online 8 December 2017
Source:Pediatric Neurology
Author(s): Breanne Byiers, Chantel Barney, Michael Ehrhardt, Angela Panoskaltsis-Mortari, Timothy Feyma, Arthur Beisang, Frank J. Symons




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Smear layer-deproteinizing improves bonding of one-step self-etch adhesives to dentin

Publication date: Available online 9 December 2017
Source:Dental Materials
Author(s): Ornnicha Thanatvarakorn, Taweesak Prasansuttiporn, Suppason Thittaweerat, Richard M. Foxton, Shizuko Ichinose, Junji Tagami, Keiichi Hosaka, Masatoshi Nakajima
ObjectivesSmear layer deproteinizing was proved to reduce the organic phase of smear layer covered on dentin surface. It was shown to eliminate hybridized smear layer and nanoleakage expression in resin–dentin bonding interface of two-step self-etch adhesive. This study aimed to investigate those effects on various one-step self-etch adhesives.MethodsFour different one-step self-etch adhesives were used in this study; SE One (SE), Scotchbond™ Universal (SU), BeautiBond Multi (BB), and Bond Force (BF). Flat human dentin surfaces with standardized smear layer were prepared. Smear layer deproteinizing was carried out by the application of 50ppm hypochlorous acid (HOCl) on dentin surface for 15s followed by Accel^® (p-toluenesulfinic acid salt) for 5s prior to adhesive application. No surface pretreatment was used as control. Microtensile bond strength (μTBS) and nanoleakage under TEM observation were investigated. The data were analyzed by two-way ANOVA and Tukey's post-hoc test and t-test at the significant level of 0.05.ResultsSmear layer deproteinizing significantly improved μTBS of SE, SU, and BB (p<0.001). Hybridized smear layer observed in control groups of SE, BB, and BF, and reticular nanoleakage presented throughout the hybridized complex in control groups of BB and BF were eliminated upon the smear layer deproteinizing.SignificanceSmear layer deproteinizing by HOCl and Accel^® application could enhance the quality of dentin for bonding to one-step self-etch adhesives, resulting in the improving μTBS, eliminating hybridized smear layer and preventing reticular nanoleakage formation in resin–dentin bonding interface.



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Effect of tetracalcium phosphate/monetite toothpaste on dentin remineralization and tubule occlusion in vitro

Publication date: Available online 9 December 2017
Source:Dental Materials
Author(s): L. Medvecky, R. Stulajterova, M. Giretova, J. Mincik, M. Vojtko, J. Balko, J. Briancin
ObjectivesTo investigate the tubule occlusion and remineralization potential of a novel toothpaste with active tetracalcium phosphate/monetite mixtures under de/remineralization cycling.MethodsDentin de/remineralization cycling protocol consisted of demineralization in 1% citric acid at pH 4.6 with following remineralization with toothpastes and soaking in artificial saliva. Effectiveness of toothpastes to promote remineralization was evaluated by measurement of microhardness recovery, analysis of surface roughness, thickness of coating and scanning electron microscopy.ResultsThe novel tetracalcium phosphate/monetite dentifrice had comparable remineralization potential as commercial calcium silicate/phosphate (SENSODYNE^®) and magnesium aluminum silicate (Colgate^®) toothpastes and significantly higher than control saliva (p<0.02). Surface roughness was significantly lower after treatment with prepared and SENSODYNE^® dentifirice (p<0.05). The coatings on dentin surfaces was significantly thicker after applying toothpastes as compared to negative control (p<0.001).ConclusionsThe new fluoride toothpaste formulation with bioactive tetracalcium phosphate/monetite calcium phosphate mixture effectively occluded dentin tubules and showed good dentin remineralization potential under de/remineralization cycling. It could replace professional powder preparation based on this mixture. It was demonstrated that prepared dentifrice had comparable properties with commercial fluoride calcium silicate/phosphate or magnesium aluminum silicate dentifrices.



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