Publication date: February 2016
Source:Journal of Electromyography and Kinesiology, Volume 26
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Παρασκευή 12 Φεβρουαρίου 2016
Standards for Reporting EMG Data
Tumor radio-sensitivity assessment by means of volume data and magnetic resonance indices measured on prostate tumor bearing rats
Purpose:
Radiation therapy is one of the most common treatments in the fight against prostate cancer, since it is used to control the tumor (early stages), to slow its progression, and even to control pain (metastasis). Although many factors (e.g., tumor oxygenation) are known to influence treatment efficacy, radiotherapy doses and fractionation schedules are often prescribed according to the principle "one-fits-all," with little personalization. Therefore, the authors aim at predicting the outcome of radiation therapy a priori starting from morphologic and functional information to move a step forward in the treatment customization.
Methods:
The authors propose a two-step protocol to predict the effects of radiation therapy on individual basis. First, one macroscopic mathematical model of tumor evolution was trained on tumor volume progression, measured by caliper, of eighteen Dunning R3327-AT1 bearing rats. Nine rats inhaled 100% O2 during irradiation (oxy), while the others were allowed to breathe air. Second, a supervised learning of the weight and biases of two feedforward neural networks was performed to predict the radio-sensitivity (target) from the initial volume and oxygenation-related information (inputs) for each rat group (air and oxygen breathing). To this purpose, four MRI-based indices related to blood and tissue oxygenation were computed, namely, the variation of signal intensity in interleaved blood oxygen level dependent and tissue oxygen level dependent (IBT) sequences as well as changes in longitudinal and transverse relaxation rates.
Results:
An inverse correlation of the radio-sensitivity parameter, assessed by the model, was found with respect the (−0.65) for the oxy group. A further subdivision according to positive and negative values of showed a larger average radio-sensitivity for the oxy rats with and a significant difference in the two distributions (p neural networks.
Conclusions:
While preliminary, these specific results suggest that subjects affected by the same pathology can benefit differently from the same irradiation modalities and support the usefulness of IBT in discriminating between different responses.
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Dog Named Mercy
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David Grafman with his puppy Mercy.
Mercy quickly helped David get up and moving.
ST. LOUIS - Knowing the symptoms of heart disease isn't new to David Grafman; it runs in his family. However, when he started having stomach pains he didn't think about heart issues.
The 54-year-old hockey referee used a sports analogy to explain. "If someone tells me to watch No. 12 because he plays dirty, I'm going to watch No. 12 but might miss what No. 22 is doing behind me," Grafman explained. "That's what happened. I missed the heart symptoms because I was focused on my stomach."
When he finally had a stress test for his heart, he only made it for eight minutes before he was drenched with sweat and curled up in a fetal position on the table. "They didn't hit the panic button, but everyone was moving very quickly," he said.
Grafman was immediately admitted for a cardiac catheterization procedure. He said he was in good spirits, even joking while he was on the table. But that's when he realized the seriousness of the situation. The cath procedure couldn't help him; he would need open heart surgery as soon as possible.
"I had 100 percent blockage in one artery, 95 and 90 in the other two," Grafman said. "The doctor said he wasn't sure how I was still alive."
He met with cardiothoracic surgeon Dr. Mark Blucher to discuss his options and was quickly scheduled for surgery.
After his procedure, he woke up with a nurse in his room. "She said, 'I'm Emily and I'll be your nurse,'" Grafman choked up. "My mother's name was Emily, so it was really emotional and a great sign."
Grafman couldn't stop gushing about his care – the doctors, nurses, techs and more, "even the people who brought my food were great. The food was even good. You always hear those stories about 'that one nurse' and I never had that. Everyone I encountered was terrific."
The experience he had leads the story to his new puppy. Once home, Grafman's wife went to get some salt-free spices and stopped in the pet store on a whim. She messaged him with a picture of a puppy and he surprisingly agreed getting to the dog.
"I've always heard dogs are great for therapy, and I knew it would give me something to focus on, get me out walking and be a symbol of my recovery," Grafman recalled.
But what to name the new puppy wasn't as easy. He joked about naming the dog Blucher to honor his doctor, but didn't want it to be taken the wrong way. They ultimately decided on Mercy.
"I have never heard of a dog named Mercy," Grafman said. "Now she will always remind me of the excellent care I received, and that without the dedicated people and their wonderful attitudes, things might have been different."
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Potential reference measurement procedures for PBDE in surface water at levels required by the EU Water Frame Directive
Publication date: 15 May 2016
Source:Talanta, Volume 152
Author(s): Claudia Swart, Fanny Gantois, Panayot Petrov, John Entwisle, Heidi Goenaga-Infante, Marjaana Nousiainen, Mine Bílsel, Burcu Binici, Adriana Gonzalez-Gago, Daniel Pröfrock, Ahmet C. Gören
Polybrominated diphenylethers (PBDE), used as flame retardants, are named as priority substances in the Directive 2000/60/EC of the European parliament and of the council establishing a framework for Community action in the field of water policy. An annual average environmental quality standard (EQS) for inland surface waters of 0.0005µg/L (0.0002µg/L for other surface waters) for PBDE congeners involved in the technical penta-PBDE mixtures containing PBDE with five bromine atoms has been established. The directives focus especially on the congeners PBDE 28, 47, 99, 100, 153 and 154 contained in the penta-PBDE mixture. Up to now, no reference measurement procedures have been established reaching the limits of quantification (LOQs) and the associated uncertainties as defined in the directives with results traceable to the SI. Within a recent European project on metrology, different approaches for the traceable quantification of PBDE, based on liquid/liquid or solid phase extraction followed by the detection with gas chromatography coupled to either inductively coupled plasma mass spectrometry or triple quadrupole mass spectrometry, were investigated and the related LOQs and expanded uncertainties of the results were compared. A complete uncertainty budget for each method was estimated according to the Guide to the Expression of Uncertainty in Measurement (GUM). All presented analytical procedures can serve as reference measurement procedures regarding the LOQs and their associated expanded uncertainties for monitoring the six priority PBDEs named above. LOQs as low as 0.026ng/kg with an associated expanded uncertainty of 0.002ng/kg could be achieved
Graphical abstract
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Influence of the linking spacer length and type on the enantioseparation ability of β-cyclodextrin functionalized monoliths
Publication date: 15 May 2016
Source:Talanta, Volume 152
Author(s): Jialiang Guo, Yuan Xiao, Yuanjing Lin, Qiaoxuan Zhang, Yiqun Chang, Jacques Crommen, Zhengjin Jiang
In order to investigate the effect of the linking spacer on the enantioseparation ability of β-cyclodextrin (β-CD) functionalized polymeric monoliths, three β-CD-functionalized organic polymeric monoliths with different spacer lengths were prepared by using three amino-β-CDs, i.e. mono-6-amino-6-deoxy-β-CD, mono-6-ethylenediamine-6-deoxy-β-CD, mono-6-hexamethylenediamine-6-deoxy-β-CD, as starting materials. These amino-β-CDs reacted with glycidyl methacrylate to produce functional monomers which were then copolymerized with ethylene dimethacrylate. The enantioseparation ability of the three monoliths was evaluated using 14 chiral acidic compounds, including mandelic acid derivatives, nonsteroidal anti-inflammatory drugs, N-derivatized amino acids, and chiral herbicides under optimum chromatographic conditions. Notably, the poly(GMA-NH2-β-CD-co-EDMA) column provides higher enantioresolution and enantioselectivity than the poly(GMA-EDA-β-CD-co-EDMA) and poly(GMA-HDA-β-CD-co-EDMA) columns for most tested chiral analytes. Furthermore, the enantioseparation performance of triazole-linker containing monoliths was compared to that of ethylenediamine-linker containing monoliths. The results indicate that the enantioselectivity of β-CD monolithic columns is strongly related to the length and type of spacer tethering β-CD to the polymeric support.
Graphical abstract
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Emulsion-cryogelation technique for fabricating a versatile toolbox of hierarchical polymeric monolith and its application in chromatography
Publication date: 15 May 2016
Source:Talanta, Volume 152
Author(s): Yaping Li, Li Qi, Nan Li, Huimin Ma
A novel poly (glycidyl methacrylate-co-ethylene dimethacrylate) monolith has been fabricated via the environmental friendly cryogelation-emulsion technique. The polymerization process is assisted by self-assembly of typical tri-block copolymer Pluronic F127 at sub-zero temperature using ice crystal as template, which can avoid consumption of organic porogenic solvents and thermal unstability of emulsion system. The developed monolith possesses hierarchical networks, which is confirmed by nitrogen adsorption measurement, mercury intrusion porosimetry, scanning electron microscopy and permeability testing. Further, the effect of the amounts of Pluronic F127 on the microstructure has been investigated. Moreover, the prepared polymer monolith undergoes acidic hydrolysis of epoxy groups into hydroxyl groups on the surface and its liquid chromatographic performance is explored by separating model analytes. The results indicate that the unique porous polymer monolith with hierarchical networks could be prepared via an organic porogen-free approach and used for analysis of polar and nonpolar molecules, extending the application of cryogelation-emulsion technique and methacrylate-based monolith.
Graphical abstract
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Editorial board
Publication date: 1 March 2016
Source:Bioorganic & Medicinal Chemistry, Volume 24, Issue 5
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Randomized Trial Comparing Performance of Molecular Markers for Indeterminate Thyroid Nodules
Condition: Thyroid
Interventions: Other: Afirma GEC; Other: ThyroSeq v.2
Sponsor: Jonsson Comprehensive Cancer Center
Not yet recruiting - verified February 2016
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Interventions: Other: Afirma GEC; Other: ThyroSeq v.2
Sponsor: Jonsson Comprehensive Cancer Center
Not yet recruiting - verified February 2016
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Phase II Trial of Thalidomide Combined With Concurrent Chemoradiotherapy in Esophageal Cancer
Condition: Esophageal Cancer
Interventions: Other: chemoradiotherapy; Drug: thalidomide; Other: without thalidomide
Sponsor: Changzhou No.2 People's Hospital
Recruiting - verified February 2016
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Interventions: Other: chemoradiotherapy; Drug: thalidomide; Other: without thalidomide
Sponsor: Changzhou No.2 People's Hospital
Recruiting - verified February 2016
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Viruses, Vol. 8, Pages 51: Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein
A history of infectious mononucleosis (IM), symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses. Antibody responses towards cellular antigens using a HEp-2 based indirect immunofluorescence assay and native myelin oligodendrocyte glycoprotein (MOG) using a flow cytometry-based assay were determined in 35 patients with IM and in 23 control subjects. We detected frequent immunoglobulin M (IgM) reactivity to vimentin, a major constituent of the intermediate filament family of proteins, in IM patients (27/35; 77%) but rarely in control subjects (2/23; 9%). IgG autoantibodies binding to HEp-2 cells were absent in both groups. In contrast, IgG responses to native MOG, present in up to 40% of children with inflammatory demyelinating diseases of the central nervous system (CNS), were detectable in 7/35 (20%) patients with IM but not in control subjects. Normalization of anti-vimentin IgM levels to increased total IgM concentrations during IM resulted in loss of significant differences for anti-vimentin IgM titers. Anti-MOG specific IgG responses were still detectable in a subset of three out of 35 patients with IM (9%), even after normalization to increased total IgG levels. Vimentin-specific IgM and MOG-specific IgG responses decreased following clinical resolution of acute IM symptoms. We conclude from our data that MOG-specific memory B cells are activated in subset of patients with IM.
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Invasive pneumococcal disease: Clinical outcomes and patient characteristics 2–6 years after introduction of 7-valent pneumococcal conjugate vaccine compared to the pre-vaccine period, the Netherlands
Source:Vaccine, Volume 34, Issue 8
Author(s): Gertjan H.J. Wagenvoort, Elisabeth A.M. Sanders, Bart J. Vlaminckx, Karin E. Elberse, Hester E. de Melker, Arie van der Ende, Mirjam J. Knol
BackgroundImplementation of 7-valent pneumococcal conjugate vaccine (PCV7) in the Dutch national immunization program for infants led to a shift from vaccine to non-vaccine serotypes in invasive pneumococcal disease (IPD) in all age groups. We studied the impact of the serotype shift on clinical syndromes and outcomes.MethodsPneumococcal isolates from hospitalized IPD patients obtained from nine sentinel microbiology laboratories, covering 25% of the Dutch population, were serotyped. Clinical syndromes, outcomes and patient characteristics in the post-PCV7 (2008–2012) period were compared with the pre-PCV7 period (2004–2006). Serotype specific propensity of the association with empyema, meningitis and death was calculated.ResultsInvasive pneumonia incidence significantly decreased in children <5 years and elderly ≥65 years, but increased in 5–64 years old from 4.92 to 5.58 cases/100.000/year (RR 1.13 95% CI 0.99–1.29). Empyema incidence significantly increased in elderly 65 years and older from 0.61 to 2.60 cases/100.000/year (RR 4.28 95% CI 1.97–9.33), mainly due to serotype 1. The incidence of meningitis only declined significantly in children <5 years. IPD case-fatality decreased in children <5 years from 5% to 3%, in 5–64 years old from 9% to 7% and in elderly ≥65 years significantly from 22% to 17%, due to lower case-fatality rates for most emerging non-PCV7 serotypes.ConclusionsAn increase in empyema incidence was observed in persons ≥65 years old in the post-PCV7 era, mainly due to the emergence of serotype 1, although overall IPD case-fatality decreased. Extended conjugate vaccines that target serotype 1 or serotypes with high case-fatality may offer further reduction of pneumococcal disease burden.
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Agronomy, Vol. 6, Pages 8: Agro-Morphological Evaluation of Rice (Oryza sativa L.) for Seasonal Adaptation in the Sahelian Environment
In the Sahel zone of West Africa that extends from Senegal to Chad, temperatures can vary from less than 15 °C to 25 °C from November to February. These low temperatures affect the growth, development and yield of rice plants, and therefore constitute a major constraint to rice production in the Sahel. In order to identify rice varieties tolerant to cold stress at different developmental stages, a diverse set of 224 rice germplasm was evaluated for yield and yield-related traits in Ndiaye, Senegal, using three different sowing dates. The first sowing date (October 2010), was chosen so as to expose the rice plants to cold stress at the reproductive stage while the rice crop planted at the second sowing date (January 2011) experienced cold stress at the vegetative stage. The third sowing date (July 2011) was the normal planting date for irrigated rice in the Sahel and it served as the control date when the crop does not experience any cold stress throughout its growth cycle. Among the data collected, significant genetic variation was detected and genotype-by-environment interaction was also significant for the traits. At the vegetative stage, cold stress reduced tillering and plant vigor and delayed flowering but increased yield, whereas at the reproductive stage, aside from delaying flowering, cold stress also inhibited panicle exsertion and reduced panicle length, spikelet fertility, grain filling and strongly reduced yields. Principal Component Analysis and correlation analysis using agro-morphological traits helped to identify genotypes that were tolerant to cold stress at either the vegetative or the reproductive stage and the traits associated with high yield under cold stress at each of these stages. Our results can be used to develop cold tolerant rice varieties adapted to double cropping in the Sahelian zone of West Africa.
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Remote Sensing, Vol. 8, Pages 141: JPSS-1 VIIRS Pre-Launch Response Versus Scan Angle Testing and Performance
The Visible Infrared Imaging Radiometer Suite (VIIRS) instruments on-board both the Suomi National Polar-orbiting Partnership (S-NPP) and the first Joint Polar Satellite System (JPSS-1) spacecraft, with launch dates of October 2011 and December 2016 respectively, are cross-track scanners with an angular swath of ±56.06°. A four-mirror Rotating Telescope Assembly (RTA) is used for scanning combined with a Half Angle Mirror (HAM) that directs light exiting from the RTA into the aft-optics. It has 14 Reflective Solar Bands (RSBs), seven Thermal Emissive Bands (TEBs) and a panchromatic Day Night Band (DNB). There are three internal calibration targets, the Solar Diffuser, the BlackBody and the Space View, that have fixed scan angles within the internal cavity of VIIRS. VIIRS has calibration requirements of 2% on RSB reflectance and as tight as 0.4% on TEB radiance that requires the sensor's gain change across the scan or Response Versus Scan angle (RVS) to be well quantified. A flow down of the top level calibration requirements put constraints on the characterization of the RVS to 0.2%–0.3% but there are no specified limitations on the magnitude of response change across scan. The RVS change across scan angle can vary significantly between bands with the RSBs having smaller changes of ~2% and some TEBs having ~10% variation. Within a band, the RVS has both detector and HAM side dependencies that vary across scan. Errors in the RVS characterization will contribute to image banding and striping artifacts if their magnitudes are above the noise level of the detectors. The RVS was characterized pre-launch for both S-NPP and JPSS-1 VIIRS and a comparison of the RVS curves between these two sensors will be discussed.
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Viruses, Vol. 8, Pages 50: Structural Proteomics of Herpesviruses
Herpesviruses are highly prevalent viruses associated with numerous pathologies both in animal and human populations. Until now, most of the strategies used to prevent or to cure these infections have been unsuccessful because these viruses have developed numerous immune evasion mechanisms. Therefore, a better understanding of their complex lifecycle is needed. In particular, while the genome of numerous herpesviruses has been sequenced, the exact composition of virions remains unknown for most of them. Mass spectrometry has recently emerged as a central method and has permitted fundamental discoveries in virology. Here, we review mass spectrometry-based approaches that have recently allowed a better understanding of the composition of the herpesvirus virion. In particular, we describe strategies commonly used for proper sample preparation and fractionation to allow protein localization inside the particle but also to avoid contamination by nonstructural proteins. A collection of other important data regarding post-translational modifications or the relative abundance of structural proteins is also described. This review also discusses the poorly studied importance of host proteins in herpesvirus structural proteins and the necessity to develop a quantitative workflow to better understand the dynamics of the structural proteome. In the future, we hope that this collaborative effort will assist in the development of new strategies to fight these infections.
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Workshop report: Schistosomiasis vaccine clinical development and product characteristics
Source:Vaccine, Volume 34, Issue 8
Author(s): Annie X. Mo, Daniel G. Colley
A schistosomiasis vaccine meeting was organized to evaluate the utility of a vaccine in public health programs, to discuss clinical development paths, and to define basic product characteristics for desirable vaccines to be used in the context of schistosomiasis control and elimination programs. It was concluded that clinical evaluation of a schistosomiasis vaccine is feasible with appropriate trial design and tools. Some basic Preferred Product Characteristics (PPC) for a human schistosomiasis vaccine and for a veterinary vaccine for bovine use were also proposed.
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Development of a cost-effective vaccine candidate with outer membrane vesicles of a tolA-disrupted Shigella boydii strain
Source:Vaccine
Author(s): Soma Mitra, Ritam Sinha, Jiro Mitobe, Hemanta Koley
Our previous studies on outer membrane vesicles based vaccine development against shigellosis, revealed the inability of Shigella to release significant amount of vesicles naturally, during growth. Disruption of tolA, one of the genes of the Tol–Pal system of Gram negative bacterial membrane, has increased the vesicle release rate of a Shigella boydii type 4 strain to approximately 60% higher. We also noticed the vesicles, released from tolA-disrupted strain captured more OmpA protein and lipopolysaccharide, compared to the vesicles released from its wild type prototype. Six to seven weeks old BALB/c mice, immunized with 25μg of three oral doses of the vesicles, released by tolA mutant, conferred 100% protection against lethal homologous challenge through nasal route, compared to only 60% protection after the same dose of wild type immunogen. Mice, immunized with the vesicles from tolA-mutant, manifested significant secretion of mucosal IgG and IgA. A sharp and significant response of pro-inflammatory cytokines (TNF-α, IL-6, IFN-γ) were also observed in the lung lavage of these groups of mice, within 6h post challenge; but at 24h, these inflammatory cytokines showed the sign of subsidence and the system was taken over by the release of anti-inflammatory cytokines (IL-4 and IL-10). Studies with naïve peritoneal macrophages, proved further, the potency of these vesicles to stimulate nitric oxide and TNF-α, IL-12p70, IL-6 and IL-10 productions in-vitro. The ability of these vesicles to trigger polarization of CD4+ T cells toward Th1 adaptive immune response had also been observed along with the presence of anti-inflammatory cytokines in the system. Our study demonstrated, the vesicles from tolA-disrupted Shigella were able to suppress Shigella-mediated inflammation in the host and could balance between inflammation and anti-inflammation, promoting better survival and health of the infected mice. Outer membrane vesicles from tolA-mutant, could be a potential cost-effective vaccine candidate against shigellosis.
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The key role of rubella virus glycoproteins in the formation of immune response, and perspectives on their use in the development of new recombinant vaccines
Source:Vaccine, Volume 34, Issue 8
Author(s): Ekaterina K. Petrova, Anastasia A. Dmitrieva, Ekaterina A. Trifonova, Nikolai A. Nikitin, Olga V. Karpova
Rubella is a highly contagious viral disease which is mostly threatens to women of reproductive age. Existent live attenuated vaccines are effective enough, but have some drawbacks and are unusable for a certain group of people, including pregnant women and people with AIDS and other immunodeficiency. Thereby the development of alternative non-replicating, recombinant vaccines undoubtedly is needed. This review discusses the protein E1 and E2 role in formation of immune response and perspectives in development of new generation recombinant vaccines using them.
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Glyceradehyde-3-phosphate dehydrogenase as a suitable vaccine candidate for protection against bacterial and parasitic diseases
Source:Vaccine, Volume 34, Issue 8
Author(s): Jose Perez-Casal, Andrew A. Potter
The enzyme glyceraldehyde-3-P-dehydrogenase (GAPDH) has been identified as having other properties in addition to its key role in glycolysis. The ability of GAPDH to bind to numerous extracellular matrices, modulation of host-immune responses, a role in virulence and surface location has prompted numerous investigators to postulate that GAPDH may be a good vaccine candidate for protection against numerous pathogens. Although immune responses against GAPDH have been described for many microorganisms, vaccines containing GAPDH have been successfully tested in few cases including those against the trematode—Schistosoma mansoni, the helminth—Enchinococcus multilocularis; the nematode filaria— Litomosoides sigmodontis; fish pathogens such as Aeromonas spp., Vibrio spp., Edwarsiella spp., and Streptococcus iniae; and environmental streptococci, namely, Streptococcus uberis and Streptococcus dysgalactiae. Before GAPDH-based vaccines are considered viable options for protection against numerous pathogens, we need to take into account the homology between the host and pathogen GAPDH proteins to prevent potential autoimmune reactions, thus protective GAPDH epitopes unique to the pathogen protein must be identified.
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The 5As: A practical taxonomy for the determinants of vaccine uptake
Source:Vaccine, Volume 34, Issue 8
Author(s): Angus Thomson, Karis Robinson, Gaëlle Vallée-Tourangeau
Suboptimal vaccine uptake in both childhood and adult immunisation programs limits their full potential impact on global health. A recent progress review of the Global Vaccine Action Plan stated that "countries should urgently identify barriers and bottlenecks and implement targeted approaches to increase and sustain coverage". However, vaccination coverage may be determined by a complex mix of demographic, structural, social and behavioral factors. To develop a practical taxonomy to organise the myriad possible root causes of a gap in vaccination coverage rates, we performed a narrative review of the literature and tested whether all non-socio-demographic determinants of coverage could be organised into 4 dimensions: Access, Affordability, Awareness and Acceptance. Forty-three studies were reviewed, from which we identified 23 primary determinants of vaccination uptake. We identified a fifth domain, Activation, which captured interventions such as SMS reminders which effectively nudge people towards getting vaccinated. The 5As taxonomy captured all identified determinants of vaccine uptake. This intuitive taxonomy has already facilitated mutual understanding of the primary determinants of suboptimal coverage within inter-sectorial working groups, a first step towards them developing targeted and effective solutions.
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Editorial Board/Aims and Scope
Source:Vaccine, Volume 34, Issue 8
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Innocuity of a commercial live attenuated vaccine for epizootic hemorrhagic disease virus serotype 2 in late-term pregnant cows
Source:Vaccine
Author(s): Massimo Spedicato, Irene Carmine, Liana Teodori, Alessandra Leone, Ottavio Portanti, Valeria Marini, Maura Pisciella, Alessio Lorusso, Giovanni Savini
Epizootic hemorrhagic disease (EHD) is an arthropod-borne infectious non-contagious viral disease sustained by the epizootic hemorrhagic disease virus (EHDV). The only commercially available vaccines are manufactured for EHDV-2, either live or inactivated vaccines. In this study we wanted to test the innocuity for fetuses of a live attenuated EHDV-2 vaccine in five late-term pregnant cows. Whole blood and serum were regularly collected from dams and screened for the presence of EHDV-2 RNA, infectious virus and antibodies. After calving, whole blood and serum samples collected from calves, before and after colostrum intake, were tested for antibodies and for virus detection. In dams, neither fever nor clinical signs were observed. All of them seroconverted and a strong humoral response was detected throughout the sampling period. All blood samples tested negative for EHDV-2 except for one sample collected from a dam 11 days post-vaccination which tested positive at virus isolation at the third cell passage following two rounds of blind passages. Unexpectedly, although they had free access to colostrum, calves tested serologically negative for EHDV-2 during the entire course of the experiment. Overall, the tested live attenuated vaccine can be safely administered to late-term pregnant cows as it was not demonstrated to cross the placental barrier. The safety of the live-attenuated vaccine is further confirmed by the emergence of Ibaraki virus in 2013 in Japan which is not related to the vaccine strain used for decades in Japan.
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Seasonal influenza vaccine effectiveness estimates: Development of a parsimonious case test negative model using a causal approach
Source:Vaccine, Volume 34, Issue 8
Author(s): C.R. Lane, K.S. Carville, N. Pierse, H.A. Kelly
BackgroundInfluenza vaccine effectiveness (VE) is increasingly estimated using the case-test negative study design. Cases have a symptom complex consistent with influenza and test positive for influenza, while non-cases have the same symptom complex but test negative. We aimed to determine a parsimonious logistic regression model for this study design when applied to patients in the community.MethodsTo determine the minimum covariate set required, we used a previously published systematic review to find covariates and restriction criteria commonly included in case-test negative logistic regression models. Covariates were assessed for inclusion using a directed acyclic graph. We used data from the Victorian Influenza Sentinel Practice Network from 2007 to 2013, excluding the pandemic year of 2009, to test the model. VE was estimated as (1−adjusted OR) * 100%. Changes in model fit from addition of specified covariates were examined. Restriction criteria were examined using change in VE estimate. VE was estimated for each year, all years aggregated, and for influenza type and sub-type.ResultsUsing publicly available software, the directed acyclic graph indicated that covariates specifying age, time within the influenza season, immunocompromising comorbid conditions and year or study site, where applicable, were required for closure. The inclusion of sex was not required. Inclusions and exclusions were validated when testing the variables (when collected) with our data. Restriction by time between onset and swab was supported by the data. VE for all years aggregated was estimated as 53% (95%CI 38, 64). VE was estimated as 42% (95%CI 19, 59) for H3N2, 75% (95%CI 51, 88) for H1N1pdm09 and 63% (95%CI 38, 79) for influenza B.ConclusionTheoretical covariates specified by the directed acyclic graph were validated when tested against surveillance data. A parsimonious model using the case test negative design allows regular estimates of VE and aggregated estimates by year.
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Global epidemiology of capsular group W meningococcal disease (1970–2015): Multifocal emergence and persistence of hypervirulent sequence type (ST)-11 clonal complex
Source:Vaccine
Author(s): Mustapha M. Mustapha, Jane W. Marsh, Lee H. Harrison
Following an outbreak in Mecca Saudi Arabia in 2000, meningococcal strains expressing capsular group W (W) emerged as a major cause of invasive meningococcal disease (IMD) worldwide. The Saudi Arabian outbreak strain (Hajj clone) belonging to the ST-11 clonal complex (cc11) is similar to W cc11 causing occasional sporadic disease before 2000. Since 2000, W cc11 has caused large meningococcal disease epidemics in the African meningitis belt and endemic disease in South America, Europe and China. Traditional molecular epidemiologic typing suggested that a majority of current W cc11 burden represented global spread of the Hajj clone. However, recent whole genome sequencing (WGS) analyses revealed significant genetic heterogeneity among global W cc11 strains. While continued spread of the Hajj clone occurs in the Middle East, the meningitis belt and South Africa have co-circulation of the Hajj clone and other unrelated W cc11 strains. Notably, South America, the UK, and France share a genetically distinct W cc11 strain. Other W lineages persist in low numbers in Europe, North America and the meningitis belt. In summary, WGS is helping to unravel the complex genomic epidemiology of group W meningococcal strains. Wider application of WGS and strengthening of global IMD surveillance is necessary to monitor the continued evolution of group W lineages.
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Risk factors for measles in children aged 8 months–14 years in China after nationwide measles campaign: A multi-site case-control study, 2012–2013
Source:Vaccine
Author(s): Lixin Hao, Chao Ma, Kathleen A. Wannemuehler, Qiru Su, Zhijie An, Lisa Cairns, Linda Quick, Lance Rodewald, Yuanbao Liu, Hanqing He, Qing Xu, Yating Ma, Wen Yu, Ningjing Zhang, Li Li, Ning Wang, Huiming Luo, Huaqing Wang, Christopher J. Gregory
IntroductionEndemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated more than 100 million children in 2010. In 2011, almost half of the 9943 measles cases in China occurred in children eligible for measles vaccination. We conducted a case-control study during 2012–2013 to identify risk factors for measles infection in children aged 8 months–14 years.MethodsChildren with laboratory-confirmed measles were age- and neighborhood-matched with three controls. We interviewed parents of case and control infants on potential risk factors for measles. We calculated adjusted matched odds ratios and 95% confidence intervals of risk factors. We calculated attributable fractions for risk factors that could be interpreted as causal and vaccine efficacy (VE) for the measles containing vaccine (MCV) used in the Chinese immunization program.ResultsIn all, 969 case-patients and 2845 controls were enrolled. In multivariable analysis, lack of measles vaccination both overall (mOR 22.7 [16.6, 31.1] and when stratified by region (east region, mOR 74.2 [27.3, 202]; central/western regions mOR 17.4 [12.5, 24.3]), hospital exposure (mOR 63.0, 95% CI [32.8, 121]), and migration among counties (overall mOR 3.0 [2.3, 3.9]) were significant risk factors. The calculated VE was 91.9–96.1% for a single dose of MCV and 96.6–99.5% for 2 doses.ConclusionsLack of vaccination was the leading risk factor for measles infection, especially in children born since the 2010 supplementary immunization activity. Reducing missed vaccination opportunities, improving immunization access for migrant children, and strengthening school/kindergarten vaccine checks are needed to strengthen the routine immunization program and maintain progress toward measles elimination in China.
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Factors associated with a successful expansion of influenza vaccination among pregnant women in Nicaragua
Source:Vaccine, Volume 34, Issue 8
Author(s): Carmen S. Arriola, Nancy Vasconez, Mark Thompson, Sara Mirza, Ann C. Moen, Joseph Bresee, Ivy Talavera, Alba María Ropero
BackgroundPregnant women are at risk of severe influenza disease and are a priority group for influenza vaccination programs. Nicaragua expanded recommendations to include influenza vaccination to all pregnant women in the municipality of Managua in 2013.MethodsWe carried out a survey among 1,807 pregnant women who delivered at public hospitals in the municipality of Managua to evaluate the uptake of influenza vaccination and factors associated with vaccination.ResultsWe observed a high (71%) uptake of influenza vaccination among this population, with no differences observed by age, education or parity of the women. Having four antenatal visits and five or more visits were associated with receipt of influenza vaccination (AORs: 2.58; 95% CI: 1.15, 5.81, and 2.37; 95% CI: 1.12, 5.0, respectively). Also, receipt of influenza vaccination recommendation from a health care provider was positively associated with receipt of influenza vaccination (AOR: 14.22; 95% CI: 10.45, 19.33).ConclusionsThe successful expansion of influenza vaccination among pregnant women in the municipality of Managua may be due to ready access to free medical care and health care providers' recommendation for vaccination at health care clinics that received influenza vaccine.
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Immunogenicity of dimorphic and C-terminal fragments of Plasmodium falciparum MSP2 formulated with different adjuvants in mice
Source:Vaccine
Author(s): Saidou Balam, Ali Jafarshad, Catherine Servis, Geraldine Frank, Steve Reed, Richard Pink, Pierre Druilhe, François Spertini, Giampietro Corradin
BackgroundPlasmodium falciparum MSP2 is a blood stage protein that is associated with protection against malaria. It was shown that the MSP2 dimorphic (D) and constant (C) regions were well recognized by immune human antibodies, and were characterized by major conserved epitopes in different endemic areas and age groups. These Abs recognized merozoite-derived proteins in WB and IFA. Here, the goal was to determine in mice the immunogenicity of the two allelic MSP2 D and C domains formulated with different adjuvants, for their possible use in future clinical studies.MethodFemale A/J, C3H, and ICR mice were immunized subcutaneously 3 times at 3-week interval with a mixture of allelic and conserved MSP2 long synthetic peptides formulated with different adjuvants. One week after the third injection, sera from each group were obtained and stored at −20°C for subsequent testing.ResultsBoth domains of the two MSP2 families are immunogenic and the fine specificity and intensity of the Ab responses are dependent on mouse strains and adjuvants. The major epitopes were restricted to the sequences of 20-mer sequences of peptide comprising the last 8aa of D and first 12aa of C of the two allelic families and the first 20aa of the C region, this for most strains and adjuvants. Strong immune responses were associated with GLA-SE adjuvant and its combination with other TLR agonists (CpG or GDQ) compared to alhydrogel and Montanide. Further, the elicited Abs were also capable of recognizing Plasmodium-derived MSP2 and inhibiting parasite growth in ADCI.ConclusionThe data provide a valuable opportunity to evaluate in mice different adjuvant and antigen formulations of a candidate vaccine containing both MSP2 D and C fragments. The formulations with GLA-SE seem to be a promising option to be compared with the alhydrogel one in human clinical trials.
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Stability and efficacy of the 3′-UTR A4G-G5A variant of viral hemorrhagic septicemia virus (VHSV) as a live attenuated immersion VHSV vaccine in olive flounder (Paralichthys olivaceus)
Source:Vaccine, Volume 34, Issue 8
Author(s): Sung-Hyun Kim, Meesun Kim, Go-Eun Choi, Jeong Ho Lee, Jung-Ha Kang, Øystein Evensen, Woo-Jai Lee
Viral hemorrhagic septicemia virus (VHSV) is the causative agent of viral hemorrhagic septicemia in fish, a disease that affects a number of teleost fish species including olive flounder (Paralichthys olivaceus). In this study, we assessed the safety and efficacy of two recombinant attenuated VHSV strains, termed A4G-G5A and ΔNV, with the purpose to select the most suitable vaccine strain. The virus strains were passaged in two commercially available cell lines, EPC and RTG-2, and the strains were also tested for residual virulence in zebrafish (Danio rerio). The A4G-G5A strain showed an attenuated growth profile in both the EPC and RTG-2 cell lines compared to wild-type (WT) VHSV (JF-09, genotype IVa), whereas the growth profile of ΔNV was comparable to the WT strains in RTG-2 cells in contrast to EPC cells. Moreover, ΔNV had higher residual virulence compared to A4G-G5A and was highly pathogenic to zebrafish. The A4G-G5A strain was chosen as vaccine candidate and tested for efficacy in in vivo fish studies in the target species, olive flounder, using an immersion vaccine scheme. Groups of fish were immunized with 102.5, 103.5, 104.5, and 105.5 TCID50/ml of A4G-G5A giving 5–13.3 cumulative percent mortality (CPM) post immunization. Immunization was followed by a challenge experiment using VHSV-WT. The relative percent survival (RPS) in immunized groups ranged from 81.6% to 100%, correlating with vaccination dose. This study demonstrates that while strain A4G-G5A has retained some residual virulence it confers high level of protection in immunized olive flounder.
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Immune responses against hepatitis C virus genotype 3a virus-like particles in mice: A novel VLP prime-adenovirus boost strategy
Source:Vaccine, Volume 34, Issue 8
Author(s): Anuj Kumar, Soma Das, Ranajoy Mullick, Priyanka Lahiri, Ranjitha Tatineni, Debashree Goswami, Prasanna Bhat, Joseph Torresi, Eric James Gowans, Anjali Anoop Karande, Saumitra Das
Chronic hepatitis C virus (HCV) infection represents a major health threat to global population. In India, approximately 15–20% of cases of chronic liver diseases are caused by HCV infection. Although, new drug treatments hold great promise for HCV eradication in infected individuals, the treatments are highly expensive. A vaccine for preventing or treating HCV infection would be of great value, particularly in developing countries. Several preclinical trials of virus-like particle (VLP) based vaccine strategies are in progress throughout the world. Previously, using baculovirus based system, we have reported the production of hepatitis C virus-like particles (HCV-LPs) encoding structural proteins for genotype 3a, which is prevalent in India. In the present study, we have generated HCV-LPs using adenovirus based system and tried different immunization strategies by using combinations of both kinds of HCV-LPs with other genotype 3a-based immunogens. HCV-LPs and peptides based ELISAs were used to evaluate antibody responses generated by these combinations. Cell-mediated immune responses were measured by using T-cell proliferation assay and intracellular cytokine staining. We observed that administration of recombinant adenoviruses expressing HCV structural proteins as final booster enhances both antibody as well as T-cell responses. Additionally, reduction of binding of VLP and JFH1 virus to human hepatocellular carcinoma cells demonstrated the presence of neutralizing antibodies in immunized sera. Taken together, our results suggest that the combined regimen of VLP followed by recombinant adenovirus could more effectively inhibit HCV infection, endorsing the novel vaccine strategy.
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Heat shock protein complex vaccines induce antibodies against Neisseria meningitidis via a MyD88-independent mechanism
Source:Vaccine
Author(s): Jia-Xi Han, Garrett Z. Ng, Paola Cecchini, Yok Teng Chionh, Muhammad A. Saeed, Lisbeth M. Næss, Michael Joachim, Lucy E. Blandford, Richard A. Strugnell, Camilo A. Colaco, Philip Sutton
BackgroundNeisseria meningitidis are common colonisers of the human nasopharynx. In some circumstances, N. meningitidis becomes an opportunistic pathogen that invades tissues and causes meningitis. While a vaccine against a number of serogroups has been in effective use for many years, a vaccine against N. meningitidis group B has not yet been universally adopted. Bacterial Heat shock protein complex (HSPC) vaccines comprise bacterial HSPs, purified with their chaperoned protein cargo. HSPC vaccines use the intrinsic adjuvant activity of their Hsp, thought to act via Toll-like receptors (TLR), to induce an immune response against their cargo antigens. This study evaluated HspC vaccines from N. meningitidis and the closely related commensal N. lactamica.ResultsThe protein composition of N. lactamica and N. meningitidis HSPCs were similar. Using human HEK-293 cells we found that both HSPCs can induce an innate immune response via activation of TLR2. However, stimulation of TLR2 or TLR4 deficient murine splenocytes revealed that HSPCs can activate an innate immune response via multiple receptors. Vaccination of wildtype mice with the Neisseria HSPC induced a strong antibody response and a Th1-restricted T helper response. However, vaccination of mice deficient in the major TLR adaptor protein, MyD88, revealed that while the Th1 response to Neisseria HSPC requires MyD88, these vaccines unexpectedly induced an antigen-specific antibody response via a MyD88-independent mechanism.ConclusionsN. lactamica and N. meningitidis HSPC vaccines both have potential utility for immunising against neisserial meningitis without the requirement for an exogenous adjuvant. The mode of action of these vaccines is highly complex, with HSPCs inducing immune responses via both MyD88-dependent and -independent mechanisms. In particular, these HSPC vaccines induced an antibody response without detectable T cell help.
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Effects of meditation practice on spontaneous eyeblink rate
Abstract
A rapidly growing body of research suggests that meditation can change brain and cognitive functioning. Yet little is known about the neurochemical mechanisms underlying meditation-related changes in cognition. Here, we investigated the effects of meditation on spontaneous eyeblink rates (sEBR), a noninvasive peripheral correlate of striatal dopamine activity. Previous studies have shown a relationship between sEBR and cognitive functions such as mind wandering, cognitive flexibility, and attention–functions that are also affected by meditation. We therefore expected that long-term meditation practice would alter eyeblink activity. To test this, we recorded baseline sEBR and intereyeblink intervals (IEBI) in long-term meditators (LTM) and meditation-naive participants (MNP). We found that LTM not only blinked less frequently, but also showed a different eyeblink pattern than MNP. This pattern had good to high degree of consistency over three time points. Moreover, we examined the effects of an 8-week course of mindfulness-based stress reduction on sEBR and IEBI, compared to an active control group and a waitlist control group. No effect of short-term meditation practice was found. Finally, we investigated whether different types of meditation differentially alter eyeblink activity by measuring sEBR and IEBI after a full day of two kinds of meditation practices in the LTM. No effect of meditation type was found. Taken together, these findings may suggest either that individual difference in dopaminergic neurotransmission is a self-selection factor for meditation practice, or that long-term, but not short-term meditation practice induces stable changes in baseline striatal dopaminergic functioning.
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Differential heart rate responses to social and monetary reinforcement in women with obesity
Abstract
Obesity is often accompanied by weight stigmatization; subsequently, individuals with obesity frequently face social rejection. It has been shown that recurrent negative social experiences can alter the perception of social cues. However, the way individuals with obesity process social stimuli is not well understood. This study aims to investigate obesity-related alterations in social compared to nonsocial information processing. Women with obesity (n = 14) and without obesity (n = 14) participated in a social and a monetary incentive delay task in which they anticipated and received positive, negative, and neutral outcomes in the form of faces or money. During the experiment, phasic heart rate changes and reaction times were measured. Women with obesity, compared to lean women, exhibited a stronger differentiation during the anticipation of monetary and social reinforcement, showing slower reaction times to social cues compared to monetary cues. During the outcome processing phase, women with obesity relative to controls demonstrated diminished heart rate responses particularly to negative social outcomes. Interestingly, differences in cardiac responses in participants with obesity were moderated by weight-related teasing experiences. In women with obesity, a higher BMI was associated with blunted cardiac responses to social cues relative to monetary cues only if they reported more emotional pain after weight-related teasing. Our results contribute to a better understanding of social information processing in obesity and give first evidence for the role of negative social experiences in reinforcement processing.
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Senescence associated secretory phenotype profile from primary lung mice fibroblasts depends on the senescence induction stimuli
Abstract
Cellular senescence is a multifactorial phenomenon of growth arrest and distorted function, which has been recognized as an important feature during tumor suppression mechanisms and a contributor to aging. Senescent cells have an altered secretion pattern called Senescence-Associated Secretory Phenotype (SASP) that comprises a complex mix of factors including cytokines, growth factors, chemokines, and matrix metalloproteinases. SASP has been related with local inflammation that leads to cellular transformation and neurodegenerative diseases. Various pathways for senescence induction have been proposed; the most studied is replicative senescence due to telomere attrition called replicative senescence (RS). However, senescence can be prematurely achieved when cells are exposed to diverse stimuli such as oxidative stress (stress-induced premature senescence, SIPS) or proteasome inhibition (proteasome inhibition-induced premature senescence, PIIPS). SASP has been characterized in RS and SIPS but not in PIIPS. Hence, our aim was to determine SASP components in primary lung fibroblasts obtained from CD-1 mice induced to senescence by PIIPS and compare them to RS and SIPS. Our results showed important variations in the 62 cytokines analyzed, while SIPS and RS showed an increase in the secretion of most cytokines, and in PIIPS only 13 were incremented. Variations in glutathione-redox balance were also observed in SIPS and RS, and not in PIIPS. All senescence types SASP displayed a pro-inflammatory profile and increased proliferation in L929 mice fibroblasts exposed to SASP. However, the behavior observed was not exactly the same, suggesting that the senescence induction pathway might encompass dissimilar responses in adjacent cells and promote different outcomes.
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Perceived Stress, Coping, and Cortisol Reactivity in Daily Life: A Study of Adolescents during the First Year of College
Source:Biological Psychology
Author(s): Michael R. Sladek, Leah D. Doane, Linda J. Luecken, Nancy Eisenberg
Adolescents change how they cope with stress across different situations, but also differ from one another in their general capacity to cope. The current study examined whether cortisol reactivity to perceived daily stress varies with both situational (within-person) and individual (between-person) differences in coping. First-year college students (N=63;Mage=18.85) provided 15 stress-coping diaries and 15 corresponding saliva samples across 3 weekdays. Results from hierarchical linear growth models revealed that perceiving greater stress than usual in the last hour was significantly associated with elevations in cortisol (relative to diurnal patterning) only during situations characterized by greater than usual diary-reported engagement coping. Regarding individual differences, perceiving greater stress than usual was significantly associated with elevations in cortisol only for adolescents below average on trait measures of engagement coping or belief in their ability to handle stress. Findings indicate that cortisol reactivity to daily stress varies with both situational variation and individual differences in coping.
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Maurizio Battino and Hojjat Adeli being named a Thomson Reuters Highly Cited Researcher
IOS Press congratulates Maurizio Battino, Editor-in-Chief of Journal of Berry Research and Mediterranean Journal of Nutrition and Metabolism, and Hojjat Adeli, founder and Editor-in-Chief of Integrated Computer-Aided Engineering, on being recognized as a 2015 Thomson Reuters Highly Cited Researcher.
Thomson Reuters carefully analyzed citation data over an 11-year period using Thomson Reuters Web of ScienceTM and InCitesTM to identify some of the best and brightest scientific minds of our time.
Maurizio Battino and Hojjat Adeli were selected due to the number of citations their work has received from their fellow researchers and their contributions have been identified as being among the most valuable and significant in the field of Agricultural Sciences.
List containing Maurizio Battino's publications.
List containing Hojjat Adeli's publications.
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Research discovers neuroprotective protein in blood is biomarker of Alzheimer’s disease
A new discovery by Tel Aviv University, Technion (Rambam Medical Center), and Harvard University researchers takes the medical community a leap forward in the process of effectively screening and diagnosing Alzheimer's disease. The new study, published in the Journal of Alzheimer's Disease, proposes a new biomarker for cognitive aging and Alzheimer's disease: activity-dependent neuroprotective protein (ADNP), the levels of which can be easily monitored in routine blood tests. The study also found that ADNP levels tested in the blood correlate with higher IQ in healthy older adults.
The research was led by Prof. Illana Gozes, the incumbent of the Lily and Avraham Gildor Chair for the Investigation of Growth Factors and former director of the Adams Super Center for Brain Studies at TAU's Sackler Faculty of Medicine and a member of TAU's Sagol School of Neuroscience, conducted by TAU PhD student Anna Malishkevich and spearheaded by Dr. Gad Marshall, Dr. Aaron Schultz, and Prof. Reisa Sperling of Harvard University, and Prof. Judith Aharon-Peretz of Rambam Medical Center – The Technion Institute of Technology.
A step to early intervention
Significant increases in ADNP RNA levels were observed in patients ranging from mild cognitive impairment (MCI) to Alzheimer's dementia. ADNP levels tested in plasma and serum samples, as well as white blood cell RNA levels, distinguished among cognitively normal elderly, MCI, and Alzheimer's dementia participants.
For the purpose of the cross-sectional study, the investigators analyzed blood samples taken from 42 healthy adults, MCI patients, and Alzheimer's disease patients at Rambam Medical Center in Israel. After comparing the ADNP expression in the blood samples, the researchers prepared plasma samples and once again compared the protein levels.
"This study has provided the basis to detect this biomarker in routine, non-invasive blood tests, and it is known that early intervention is invaluable to Alzheimer's patients," said Prof. Gozes. "We are now planning to take these preliminary findings forward into clinical trials — to create a pre-Alzheimer's test that will help to tailor potential preventative treatments."
Builds on original research
This new research is based on Prof. Gozes' earlier investigation of neuronal plasticity and nerve cell protection at the molecular, cellular, and system level, and her discovery of novel families of proteins, including ADNP, associated with cross-communication among neural nerve cells and their support cells.
Prof. Gozes focused on the potential utility of blood ADNP levels as an Alzheimer's biomarker. "The more ADNP RNA found in the blood cells, the fewer aggregates found in the brain of elderly cognitively normal individuals," said Prof. Gozes. "Interestingly, we also found that the more ADNP in the serum, the higher the person's IQ level."
These findings are corroborated by a separate study by an independent group that found that the ADNP protein is present in lesser quantities in serum samples from select mild Alzheimer's disease patients. However, in Prof. Gozes' studies, which approach advanced Alzheimer's disease patients, the ADNP mRNA levels in white blood cells dramatically rose above the levels measured in cognitively normal individuals. This finding suggests that dramatically increased ADNP mRNA blood levels in Alzheimer's patients may be either insufficient or damaging.
"We have found a clear connection between ADNP levels in the blood and amyloid plaques in the brain," said Prof. Gozes. "Our study is the first to assess ADNP in elderly individuals at risk for Alzheimer's disease, and its results open the door for further validation in larger, more informative studies."
The researchers are currently exploring larger clinical trials to better determine the ability of ADNP to predict cognitive decline and disease progression.
###
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Changes over lactation in breast milk serum proteins involved in the maturation of immune and digestive system of the infant
Publication date: Available online 12 February 2016
Source:Journal of Proteomics
Author(s): Lina Zhang, Marita de Waard, Hester Verheijen, Sjef Boeren, Jos A. Hageman, Toon van Hooijdonk, Jacques Vervoort, Johannes B. van Goudoever, Kasper Hettinga
To objective of this study was to better understand the biological functions of breast milk proteins in relation to the growth and development of infants over the first six months of life. Breast milk samples from four individual women collected at seven time points in the first six months after delivery were analyzed by filter aided sample preparation and dimethyl labeling combined with liquid chromatography tandem mass spectrometry. A total of 247 and 200 milk serum proteins were identified and quantified, respectively. The milk serum proteome showed a high similarity (80% overlap) on the qualitative level between women and over lactation. The quantitative changes in milk serum proteins were mainly caused by three groups of proteins, enzymes, and transport and immunity proteins. Of these 21 significantly changed proteins, 30% were transport proteins, such as serum albumin and fatty acid binding protein, which are both involved in transporting nutrients to the infant. The decrease of the enzyme bile salt-activated lipase as well as the immunity proteins immunoglobulins and lactoferrin coincide with the gradual maturation of the digestive and immune system of infants. The human milk serum proteome didn't differ qualitatively but it did quantitatively, both between mothers and as lactation advanced. The changes of the breast milk serum proteome over lactation corresponded with the development of the digestive and immune system of infants.Biological significanceBreast milk proteins provide nutrition, but also contribute to healthy development of infants. Despite the previously reported large number of identified breast milk proteins and their changes over lactation, less is known on the changes of these proteins in individual mothers. This study is the first to determine the qualitative and quantitative changes of milk proteome over lactation between individual mothers. The results indicate that the differences in the milk proteome between individual mothers are more related to the quantitative level than qualitative level. The correlation between the changes of milk proteins and the gradual maturation of the gastrointestinal tract and immune system in infants, contributes to a better understanding of the biological functions of human milk proteins for the growth and development of infants.
Graphical abstract
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Toxicovenomics and antivenom profiling of the Eastern green mamba snake (Dendroaspis angusticeps)
Publication date: Available online 12 February 2016
Source:Journal of Proteomics
Author(s): Line P. Lauridsen, Andreas H. Laustsen, Bruno Lomonte, José María Gutiérrez
A toxicovenomic study was performed on the venom of the green mamba, Dendroaspis angusticeps. Forty-two different proteins were identified in the venom of D. angusticeps, in addition to the nucleoside adenosine. The most abundant proteins belong to the three-finger toxin (3FTx) (69.2%) and the Kunitz-type proteinase inhibitor (16.3%) families. Several sub-subfamilies of the 3FTxs were identified, such as Orphan Group XI (Toxin F-VIII), acetylcholinesterase inhibitors (fasciculins), and aminergic toxins (muscarinic toxins, synergistic-like toxins, and adrenergic toxins). Remarkably, no α-neurotoxins were identified. Proteins of the Kunitz-type proteinase inhibitor family include dendrotoxins. Toxicological screening revealed a lack of lethal activity in all RP-HPLC fractions, except one, at the doses tested. Thus, the overall toxicity depends on the synergistic action of various types of proteins, such as dendrotoxins, fasciculins, and probably other synergistically-acting toxins. Polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of venom-induced lethality. These antivenoms also showed a pattern of broad immunorecognition of the different HPLC fractions by ELISA and immunoprecipitated the crude venom by gel immunodiffusion. The synergistic mechanism of toxicity constitutes a challenge for the development of effective recombinant antibodies, as it requires the identification of the most relevant synergistic toxins.Biological significanceEnvenomings by elapid snakes of the genus Dendroaspis, collectively known as mambas, represent a serious medical problem in sub-Saharan Africa. The development of novel antivenoms and of recombinant neutralizing antibodies demands the identification of the most relevant toxins in these venoms. In this study, a bottom-up approach was followed for the study of the proteome of the venom of the Eastern green mamba, D. angusticeps. Forty-two different proteins were identified, among which the three-finger toxin (3FTx) family, characteristic of elapid venoms, was the most abundant, followed by the Kunitz-type proteinase inhibitor family. In addition, several other protein families were present in the venom, together with the nucleoside adenosine. No α-neurotoxins were identified within the family of 3FTxs in the venom of D. angusticeps, in contrast to the venom of Dendroaspis polylepis, in which α-neurotoxins are largely responsible for the toxicity. With one exception, HPLC fractions from D. angusticeps venom did not kill mice at the doses tested. This underscores that the toxicity of the whole venom is due to the synergistic action of various components, such as fasciculins and dendrotoxins, and probably other synergistically-acting toxins. Thus, the venoms of these closely related species (D. angusticeps and D. polylepis) seem to have different mechanisms to subdue their prey, which may be related to different prey preferences, as D. angusticeps is predominantly arboreal, whereas D. polylepis lives mostly in open bush country and feeds mainly on mammals. It is therefore likely that the predominant clinical manifestations of human envenomings by these species also differ, although in both cases neurotoxic manifestations predominate. Polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of venom-induced lethality in mice and showed a pattern of broad immunorecognition of the various venom fractions. It is necessary to identify the toxins responsible for the synergistic mode of toxicity in this venom, since they are the targets for the development of recombinant antibodies for the treatment of envenomings.
Graphical abstract
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Melanoma can control development of metastasis - fact or myth?
Publication date: Available online 12 February 2016
Source:Medical Hypotheses
Author(s): Leo Čabrijan, Tanja Batinac, Jasna Lipozenčić
The malignant melanoma spreading process cannot explain occurrence of metastases several years following local surgical therapy of primary malignancy. But, this complex process of delayed metastases is still challenging and not completely understood. We hypothese that melanoma metastases occur early in disease, probably at the same time with the occurrence of the primary melanoma. We suggest that dissemination of metastatic "seed cells" occur at an early stage of the disease together with the development of primary melanoma and cannot be detected by standard diagnostic methods. These cells are masked between healthy cells and have the potential to proceed in true metastasis following the activation triggered by signal from primary tumor or other source. Other possibility includes the existence of two different genes, one responsible for development of primary melanoma, and the other with a roll in development of metastases. We believe that future investigation should be directed toward better understanding of mechanisms involved in metastases development keeping in mind that melanoma behavior is irrational and defies logical thinking.
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A new concentric double prosthesis for sutureless, magnetic-assisted aortic arch inclusion
Publication date: Available online 11 February 2016
Source:Medical Hypotheses
Author(s): Marco Cirillo
Acute dissection of the ascending aorta is a life-threatening condition in which the aortic wall develops one or more tears of the intima associated with intramural rupture of the media layer with subsequent formation of a two lumina vessel. The remaining outer layer is just the adventitia, with high risk of complete rupture. Vital organs may be under-perfused. Mortality rate in this acute event is about 50% if an emergent surgical procedure is not performed as soon as possible to replace the tract affected by the primary rupture. Nevertheless, the emergent surgical procedure is affected by high risk of mortality or severe neurologic sequelae, due to the need for deep hypothermia and cardiocirculatory arrest and different methods of cerebral protection. If the patient survives the acute event, a frequent outcome is the establishment of a chronic aortic dissection in the remaining aorta and late chronic dissecting aneurysm, usually starting from the surgical suture itself. Traumatism of surgical stitches and of direct blood flow pressure on weak aortic wall can be important contributing factors of the chronic disease. In conclusions, the majority of these patients undergoes a high risk operation without a complete solution of the disease.We hypothesize that excluding the aortic layers from the blood direct flow and using an anastomotic technique which does not include surgical stitches could help to significantly reduce the recurrence of aortic dissection after the acute event and shorten hypothermic arrest duration. We devised a double tubular prosthesis consisting of two concentric artificial tubes between which the aortic wall is confined and excluded from direct blood flow. We also devised a magnetic assisted sutureless anastomotic technique that seals the aortic tissue between the two prostheses and avoids the perforation of the fragile aortic wall with surgical stitches. We are presenting here this new prototype and draw a few different models. Both acute and chronic diseases of the aorta could benefit from the proposed technique, although acute dissection is the ideal scenario for its use.
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Promising Link Between Selenium and Peroxisome Proliferator Activated Receptor Gamma in the Treatment Protocols of Obesity as well as Depression
Publication date: Available online 12 February 2016
Source:Medical Hypotheses
Author(s): M.M. Donma, O. Donma
Considerable interest has been given to the significance of peroxisome proliferator activated receptors (PPARs) in macronutrient metabolism, however, there is not sufficient data concerning the interactions between PPARs and micronutrients. Investigations performed on PPARγ and one of the essential micronutrients selenium (Se) have shown that both parameters may lead to alterations in obesity-related or mood disorders. Therefore, it is plausible to consider PPARγ and Se together as a powerful combination during the treatment of two associated diseases; obesity and depression.PPARγ has been shown to be involved in the antidepressant-like activity. It is also an important parameter to be considered in obesity as the master regulator of adipogenesis. The mechanism of action of PPARγ is initiated by ligand binding which induces a conformational change in the receptor. Se is capable of alleviating inflammatory signaling pathways. Obesity is associated with chronic low-grade inflammation. Depression is also defined as an inflammatory disorder. Inflammatory mediators such as tumor necrosis factor-alpha (TNFα) participate in the progression of depression. They are also obesity-associated parameters. Due to TNFα induced depressive-like behaviors and the positive association between this proinflammatory cytokine and obesity, TNFα-activated signaling pathways and those inhibiting them have recently gained importance as potential targets and therapeutic tools, respectively.More studies are necessary to develop compounds with therapeutic nature against depressive disorders and obesity. PPARγ is an important signaling pathway that occurs at the crossroads of depression and obesity. Se, aside from its anti-inflammatory, anticarcinogenic and antioxidative nature, affects also the way of PPARγ action. Se supplementation or fortification as well as the development of the partial agonists of PPARγ in which lipophilic Se compounds are used as ligand followed by experimental trials and human studies using the newly developed compounds will be promising approaches for future hope during the treatment of these diseases.
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Maurizio Battino and Hojjat Adeli being named a Thomson Reuters Highly Cited Researcher
IOS Press congratulates Maurizio Battino, Editor-in-Chief of Journal of Berry Research and Mediterranean Journal of Nutrition and Metabolism, and Hojjat Adeli, founder and Editor-in-Chief of Integrated Computer-Aided Engineering, on being recognized as a 2015 Thomson Reuters Highly Cited Researcher.
Thomson Reuters carefully analyzed citation data over an 11-year period using Thomson Reuters Web of ScienceTM and InCitesTM to identify some of the best and brightest scientific minds of our time.
Maurizio Battino and Hojjat Adeli were selected due to the number of citations their work has received from their fellow researchers and their contributions have been identified as being among the most valuable and significant in the field of Agricultural Sciences.
List containing Maurizio Battino's publications.
List containing Hojjat Adeli's publications.
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Research discovers neuroprotective protein in blood is biomarker of Alzheimer’s disease
A new discovery by Tel Aviv University, Technion (Rambam Medical Center), and Harvard University researchers takes the medical community a leap forward in the process of effectively screening and diagnosing Alzheimer's disease. The new study, published in the Journal of Alzheimer's Disease, proposes a new biomarker for cognitive aging and Alzheimer's disease: activity-dependent neuroprotective protein (ADNP), the levels of which can be easily monitored in routine blood tests. The study also found that ADNP levels tested in the blood correlate with higher IQ in healthy older adults.
The research was led by Prof. Illana Gozes, the incumbent of the Lily and Avraham Gildor Chair for the Investigation of Growth Factors and former director of the Adams Super Center for Brain Studies at TAU's Sackler Faculty of Medicine and a member of TAU's Sagol School of Neuroscience, conducted by TAU PhD student Anna Malishkevich and spearheaded by Dr. Gad Marshall, Dr. Aaron Schultz, and Prof. Reisa Sperling of Harvard University, and Prof. Judith Aharon-Peretz of Rambam Medical Center – The Technion Institute of Technology.
A step to early intervention
Significant increases in ADNP RNA levels were observed in patients ranging from mild cognitive impairment (MCI) to Alzheimer's dementia. ADNP levels tested in plasma and serum samples, as well as white blood cell RNA levels, distinguished among cognitively normal elderly, MCI, and Alzheimer's dementia participants.
For the purpose of the cross-sectional study, the investigators analyzed blood samples taken from 42 healthy adults, MCI patients, and Alzheimer's disease patients at Rambam Medical Center in Israel. After comparing the ADNP expression in the blood samples, the researchers prepared plasma samples and once again compared the protein levels.
"This study has provided the basis to detect this biomarker in routine, non-invasive blood tests, and it is known that early intervention is invaluable to Alzheimer's patients," said Prof. Gozes. "We are now planning to take these preliminary findings forward into clinical trials — to create a pre-Alzheimer's test that will help to tailor potential preventative treatments."
Builds on original research
This new research is based on Prof. Gozes' earlier investigation of neuronal plasticity and nerve cell protection at the molecular, cellular, and system level, and her discovery of novel families of proteins, including ADNP, associated with cross-communication among neural nerve cells and their support cells.
Prof. Gozes focused on the potential utility of blood ADNP levels as an Alzheimer's biomarker. "The more ADNP RNA found in the blood cells, the fewer aggregates found in the brain of elderly cognitively normal individuals," said Prof. Gozes. "Interestingly, we also found that the more ADNP in the serum, the higher the person's IQ level."
These findings are corroborated by a separate study by an independent group that found that the ADNP protein is present in lesser quantities in serum samples from select mild Alzheimer's disease patients. However, in Prof. Gozes' studies, which approach advanced Alzheimer's disease patients, the ADNP mRNA levels in white blood cells dramatically rose above the levels measured in cognitively normal individuals. This finding suggests that dramatically increased ADNP mRNA blood levels in Alzheimer's patients may be either insufficient or damaging.
"We have found a clear connection between ADNP levels in the blood and amyloid plaques in the brain," said Prof. Gozes. "Our study is the first to assess ADNP in elderly individuals at risk for Alzheimer's disease, and its results open the door for further validation in larger, more informative studies."
The researchers are currently exploring larger clinical trials to better determine the ability of ADNP to predict cognitive decline and disease progression.
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Role of reactive oxygen species in age-related neuromuscular deficits
Abstract
Although it is now clear that reactive oxygen species (ROS) are not the key determinants of longevity, a number of studies have highlighted the key role that these species play in age-related diseases and more generally in determining individual health span. Age-related loss of skeletal muscle mass and function is a key contributor to physical frailty in older individuals and our current understanding of the key areas in which ROS contribute to age-related deficits in muscle is through defective redox signalling and key roles in maintenance of neuromuscular integrity. This topical review will describe how ROS stimulate adaptations to contractile activity in muscle that include up-regulation of short-term stress responses, an increase in mitochondrial biogenesis and an increase in some catabolic processes. These adaptations occur through stimulation of redox-regulated processes that lead to activation of transcription factors such as NF-κB, AP-1 and HSF1 which mediate changes in gene expression. They are attenuated during ageing and this appears to occur through an age-related increase in mitochondrial hydrogen peroxide production. The potential for redox-mediated cross-talk between motor neurons and muscle is also described to illustrate how ROS released from muscle fibres during exercise may help maintain the integrity of axons and how the degenerative changes in neuromuscular structure that occur with ageing may contribute to mitochondrial ROS generation in skeletal muscle fibres.
This article is protected by copyright. All rights reserved
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Exploring the biophysical evidence that mammalian two pore channels are NAADP-activated calcium-permeable channels
Abstract
Nicotinic acid adenine dinucleotide phosphate (NAADP) potently releases Ca2+ from acidic intracellular endo-lysosomal Ca2+-stores. It is widely accepted that two types of two pore channels, termed TPC1 and TPC2, are responsible for the NAADP-mediated Ca2+-release but the underlying mechanisms regulating their gating appear to be different. For example, although both TPC1 and TPC2 are activated by NAADP, TPC1 appears to be additionally regulated by cytosolic Ca2+. Ion conduction and permeability also differ markedly. TPC1 and TPC2 are permeable to a range of cations although biophysical experiments suggest that TPC2 is slightly more selective for Ca2+ over K+ than TPC1 and hence capable of releasing greater quantities of Ca2+ from acidic stores. TPC1 is also permeable to H+ and therefore may play a role in regulating lysosomal and cytosolic pH, possibly creating localised acidic domains. The significantly different gating and ion conducting properties of TPC1 and TPC2 suggest that these two ion channels may play complementary physiological roles as Ca2+ release channels of the endo-lysosomal system.
This article is protected by copyright. All rights reserved
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Evaluation of rapid tests for diagnosis of acute hepatitis E
Journal of Clinical Virology
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Repeated measurements of hepatitis B surface antigen identify carriers of inactive HBV during long-term follow-up
Clinical Gastroenterology and Hepatology
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Performance of the new aptima HCV quant Dx assay in comparison to the COBAS TaqMan HCV2 assay for use with the high pure system in the detection and quantification of HCV RNA in plasma or serum
Journal of Clinical Microbiology
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Clostridium difficile associated risk of death score (CARDS): a novel severity score to predict mortality among hospitalised patients with C. difficile infection
Alimentary Pharmacology and Therapeutics
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Defining swallowing-related quality of life profiles in individuals with amyotrophic lateral sclerosis
Dysphagia
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