Transcriptomic response and immunological responses to chimpanzee adenovirus- and MVA viral-vectored vaccines for RSV in healthy adults.

Cohorts of healthy younger adults (18-50yrs) and healthy older adults (60-75yrs) were immunized intramuscularly or intranasally with an adenovirus-vectored RSV vaccine (PanAd3-RSV) as a prime dose and boosted with PanAd3-RSV or a poxvirus-vectored vaccine (MVA-RSV) encoding the same insert. Whole blood gene expression was measured at baseline, 3- and 7-days post vaccination. Intramuscular prime vaccination with PanAd3-RSV induced differential expression of 643 genes (DEGs, FDR < 0.05). Intranasal prime vaccination with PanAd3-RSV did not induce any differentially expressed genes (DEGs) in blood samples at 3 days post vaccination. Intranasally primed participants showed greater numbers of DEGS on boosting than intramuscularly primed participants. The most highly enriched biological processes related to DEGs after both prime and boost vaccination were type-1 interferon related pathways, lymphocytic and humoral immune responses.

In vitro profiling of endothelial volatile organic compounds under resting and pro-inflammatory conditions.

INTRODUCTION: The evaluation of volatile organic compounds(VOCs) emitted by human body offers a unique tool to set up new non-invasive devices for early diagnosis and long-lasting monitoring of most human diseases. However, their cellular origin and metabolic fate have not been completely elucidated yet, thus limiting their clinical application. Endothelium acts as an interface between blood and surrounding tissues. As such, it adapts its physiology in response to different environmental modifications thus playing a role in the pathogenesis of many metabolic and inflammatory diseases. OBJECTIVES: Since endothelium specifically reshapes its physiologic functions upon environmental changes the objective of this study was to evaluate if and how pro-inflammatory stimuli affect VOC metabolism in endothelial cell in culture. METHODS: Gas chromatography with mass spectrometric detection was applied to profile VOCs in the headspace of cultured endothelial cells (EC) in the absence or presence of the pro-inflammatory stimulus lipopolysaccharide (LPS). RESULTS: We observed that, under resting conditions, EC affected the amount of 58 VOCs belonging to aldehyde, alkane and ketone families. Among these, LPS significantly altered the amount of 15 VOCs. ROC curves show a perfect performance (AUC = 1) for 10 metabolites including 1-butanol, 3-methyl-1-butanol and 2-ethyl-1-hexanol. DISCUSSION: The emission and uptake of the aforementioned VOCs disclose potential unexplored metabolic pathways for EC that deserve to be investigated. Overall, we identified new candidate VOC potentially exploitable, upon experimental confirm in in vivo model of disease, as potential biomarkers of sepsis and pro-inflammatory clinical settings.

Fe3O4/γ-Fe2O3 nanoparticle multilayers deposited by the Langmuir-Blodgett technique for gas sensors application.

Fe3O4/γ-Fe2O3 nanoparticles (NPs) based thin films were used as active layers in solid state resistive chemical sensors. NPs were synthesized by high temperature solution phase reaction. Sensing NP monolayers (ML) were deposited by Langmuir-Blodgett (LB) techniques onto chemoresistive transduction platforms. The sensing ML were UV treated to remove NP insulating capping. Sensors surface was characterized by scanning electron microscopy (SEM). Systematic gas sensing tests in controlled atmosphere were carried out toward NO2, CO, and acetone at different concentrations and working temperatures of the sensing layers. The best sensing performance results were obtained for sensors with higher NPs coverage (10 ML), mainly for NO2 gas showing interesting selectivity toward nitrogen oxides. Electrical properties and conduction mechanisms are discussed.

Is the continuity of the therapist-patient relationship relevant for the discharge outcome in orthopaedic physical rehabilitation?

Continuity of care has been linked to patient satisfaction and self-reported outcomes. Following hip fractures in the elderly, rehabilitation aims at restoring patients' mobility and independence at the pre-fracture level and at the earliest possible time. Despite the potential role of physiotherapists' continuity on functional outcomes, this correlation has not yet been studied in an acute orthopaedic setting. Guaranteeing the presence of the same physical therapist on individual patients is challenging from an organizational point of view. An observational retrospective study was conducted on 129 aged patients (84 ± 8 years) who underwent surgery for proximal hip fracture. Indicators of outcomes were ILOA score at discharge, length of stay and achievement of rehabilitation goals as defined by the Individual Rehabilitation Project. The number of physical therapists taking care of patients was monitored during the patient's hospital stay. No correlation was found between the number of physical therapists and functional goals at discharge. The frequent change of physical therapists providing rehabilitation to elderly patients who underwent surgery for hip fragile fracture is not related to functional outcomes.

Effect of top-down nanomachining on electrical conduction properties of TiO2 nanostructure-based chemical sensors.

The present research was motivated by the growing interest of the scientific community towards the understanding of basic gas-surface interaction mechanisms in 1D nanostructured metal oxide semiconductors, whose significantly enhanced chemical detection sensitivity is known. In this work, impedance spectroscopy (IS) was used to evaluate how a top-down patterning of the sensitive layer can modulate the electrical properties of a gas sensor based on a fully integrated nanometric array of TiO(2) polycrystalline strips. The aim of the study was supported by comparative experimental activity carried out on different thin film gas sensors based on identical TiO(2) polycrystalline sensitive thin films. The impedance responses of the investigated devices under dry air (as the reference environment) and ethanol vapors (as the target gas) were fitted by a complex nonlinear least-squares method using LEVM software, in order to find an appropriate equivalent circuit describing the main conduction processes involved in the gas/semiconductor interactions. Two different equivalent circuit models were identified as completely representative of the TiO(2) thin film and the TiO(2) nanostructure-based gas sensors, respectively. All the circuit parameters were quantified and the related standard deviations were evaluated. The simulated results well approximated the experimental data as indicated by the small mean errors of the fits (in the range of 10(-4)) and the small standard deviations of the circuit parameters. In addition to the substrate capacitance, three different contributions to the overall conduction mechanism were identified for both equivalent circuits: bulk conductivity, intergrain contact and semiconductor-electrode contact, electrically represented by an ideal resistor R(g), a parallel R(gb)C(gb) block and a parallel R(c)-CPE(c) combination, respectively. In terms of equivalent circuit modeling, the sensitive layer patterning introduced an additional parameter in parallel connection with the whole circuit block. Such a circuit element (an ideal inductor, L) has an average value of about 125 µH and exhibits no direct dependence on the analyte gas concentration. Its presence could be due to complex mutual inductance effects occurring both between all the adjacent nanostrips (10 µm spaced) and between the nanostrips and the n-type-doped silicon substrate underneath the thermal oxide (wire/plate effect), where a two order of magnitude higher magnetic permeability of silicon can give L values comparable with those estimated by the fitting procedure. Slightly modified experimental models confirmed that the theoretical background, regulating thin film devices based on metal oxide semiconductors, is also valid for nanopatterned devices.

A preliminary study of the local treatment of preneoplastic and malignant skin lesions using methyl jasmonate.

BACKGROUND: Jasmonates are plant stress hormones. These small hydrophobic compounds exhibit anti-cancer activities, in vitro and in vivo, against cancer cells of various histological origins. Moreover, they show a selective activity against transformed cells and affect drug-resistant cells as well. AIM: The aim of this study was to evaluate the activity of a powerful jasmonate derivative, that is methyl jasmonate. MATERIAL AND METHODS: Methyl jasmonate was applied topically on cancerous and pre-cancerous skin lesions from eight patients. RESULTS: Methyl jasmonate did not cause any meaningful local or systemic side effects. Three patients exhibited positive responses. Two patients had complete recovery and one had a recurrence of the lesion three months post treatment. CONCLUSIONS: Methyl jasmonate is a potentially promising novel topical treatment for prcancerous and cancerous skin lesions. Methyl jasmonate should be evaluated in a larger series of patients.

[Overweight and surgical procedures: a proposal for a compatible dietary regimen]. / Il sovrappeso nel percorso chirurgico: proposta per un trattamento dietetico compatibile.

INTRODUCTION: The very low calorie protein diet essentially supplies a low content of carbohydrates and lipids, and a higher protein intake to produce a rapid weight loss. AIM: This study aims at evaluating the effect of a high protein low calorie diet on glycaemia, creatinine, triglycerides, cholesterol, VLDL, HLDL, systolic and diastolic blood pressure. MATERIALS AND METHODS: We have selected 30 surgical patients with a body mass index equal to 30-50 who underwent a high protein low calorie diet for 40 days a s a complications-preventive strategy before operation. The calories supplied have been in the range of 800-1200 accordingly to the individual workload and urgent need to lose weight. RESULTS: After a diet of 40 days, all the patients showed a definite weight loss and significant glycaemia, creatinine, triglycerides, cholesterol, VLDL and HLDL improvement. In the hypertensive patients, systolic and diastolic blood pressure decreased significantly. DISCUSSION: The very low calorie diet is quite effective to lose [corrected] weight before surgical procedures. This dietary regimen, from a physiological perspective, improves electrolyte balance supporting lean mass preservation and reducing the patient's weakness and hunger,without any wound healing impairiment or weakness. Therefore it is an excellent preventive measure against overweight-due complications and it is advisable and safe as prophylactic measure.

[Deep Oscillation: therapeutic-rehabilitative experiences with a new electrostatic device]. / Deep Oscillation®: esperienze terapeutico-riabilitative con un nuovo innovativo strumento ad azione elettrostatica.

AIM: Deep Oscillation® is an apparatus that produces low frequency electromagnetic radiations able to modulate immune reactions and, therefore, applicable to pain, tumour and inflammation treatments. The aim of this study is to evaluate how the Deep Oscillation® therapy works on conventional therapy resistant patients as the apparatus can be applied either to trauma derived fom surgical wounds or on sports post-traumatic oedema, low back pain and/or sciatalgic pain and cervicobrachial pain. METHODS: In the first part of the study, 34 cases of recent surgical wounds have been treated with Deep Oscillation® with 3 times a week visits for 20 minutes. In the same way 30 cases of sports post-traumatic oedema, 20 cases of low back pain and/or sciatalgic pain and 10 cases of cervicobrachial pain were treated. Among these patients, 15 cases had also undergone contemporaneous nonsteroidal anti-inflammatory drugs intravenous drip, electrolytes and vitamins to verify the probable synergetic efficacy of both treatments. RESULTS: The results confirm that in some cases the Deep Oscillation® treatment is effective since the first/third therapy up to the restitutio ad integrum. It has also been demonstrated that the maximum efficiency of the Deep Oscillation® and nonsteroidal anti-inflammatory drugs synergetic treatment is probably due to the electromagnetic radiations able to facilitate the pharmacological uptake. CONCLUSION: This study confirms the capacity of the electrostatic energy, released by Deep Oscillation®, to stimulate the patient's neurosensory system, raising his pain threshold and facilitating his pharmacological uptake and restoring his functional recovery more quickly.

[Food intolerance: reliability and characteristics of different diagnostic alternative tests]. / Le intolleranze alimentari: caratteristiche e attendibilità dei test diagnostici alternativi

The expression "food intolerance" dates back to the ancient Greece and can be generally defined as a sum of unpleasant symptoms of varying etiology that can onset in some patients after the ingestion of various food products. Adverse reactions to food can be divided into toxic and non-toxic. The last ones are classified as immunologically mediated, called "allergies", and non-immunologically mediated, commonly defined as "intolerances". The gut wall is directly involved in these adverse reactions to some foods, since it plays a key role in food absorption and in the regulation of the immunitary system. In this paper we discuss food intolerances and allergies, evaluating the available diagnostic methods and their scientific reliability and focusing on IgG analysis based immunoenzymatic test which is the most relevant test for intolerance diagnosis.

Short review on face rejuvenation procedures: focus on preoperative antiseptic and anesthetic delivery by JetPeel™-3 (a high pressure oxygen delivery device).

AIM: Nowadays there is great attention in trying to slow and reverse the facial aging process. Esthetic medicine has been primarily based on the surgical approach for many years, but now, in order to solve the problem of aging skin, there is an increasing interest into non-invasive, possibly painless, procedures that can guarantee the patient a quick recovery. In this perspective the use of chemical peeling and dermabrasion, to achieve skin rejuvenation, is growing worldwide. These techniques are also relevant to treat skin pigmentation irregularities and to remove keratoses, lentigines, acne and other skin related conditions. One of the most interesting, safe and painless devices, useful for the effective antiaging face treatment, is JetPeel™-3. The aim of this study was to assess the device efficacy starting from a short review on face rejuvenation procedures. METHODS: The basic action mechanism of this medical device is a constant high pressure air flux delivery, including oxygen, mixed with different chemical compounds such as peeling molecules, antioxidants, vitamins and hyaluronic acid, which are mechanically forced across the skin surface. Here we report a new approach in the clinical use of JetPeel™-3, tested in 20 adult volunteers, consisting in the addition to the standard protocol of an anesthetic, carbocaine and a sterilizing and disinfectant agent, that is chlorexidine. In fact disinfection and sterilization of the skin surface is a peculiar step for every antiaging or therapeutic procedure. The procedure has been completed with multiple hyaluronic acid injections of the skin in order to achieve face rejuvenation. The anesthetic power of the JetPeel™-3-carbocaine protocol has been compared to the Emla cream one. RESULTS: The spontaneous pain sensation perceived by the patients in the hemiface treated with JetPeel™-3 was significantly lower compared to the hemiface treated with Emla cream (P<0.001) showing, consequently, that JetPeel™-3-carbocaine protocol had the best anesthetic performance either in dermal, subdermal or subcutaneous injections compared with Emla cream. CONCLUSION: JetPeel™-3 has proved to be a good non-invasive approach and its use is recommended since it induces local anesthesia in a short time.

Outcome and predictive factors of mortality in hospitalized HIV-patients in Burkina Faso.

BACKGROUND: The aim of this study was to describe the clinical presentation and predictors of death in a HIV population hospitalized in Ouagadougou, Burkina Faso. MATERIALS AND METHODS: Baseline demographics, viro-immunological status, clinical presentations, and outcome have been analyzed by univariate analysis and a multivariate model. RESULTS: A total of 1,071 hospitalizations of HIV-positive patients was recorded between 1 January, 2004 and 31 August, 2006, the majority of whom were female (64.1%). The baseline CD4 cell count/microl was higher in the female patients than in the male ones (166.1 vs 110.9). Gastroenteric symptoms were the first cause of hospitalization (61.7%). The crude mortality rate was higher in males than females (38% vs 25.3%). Baseline World Health Organization clinical stage IV (OR 9.22), neurological syndrome (OR 3.04) or wasting syndrome at admission (OR 2.9), positive malaria film (OR 2.17), and an older age independently predicted death. Weight at admission > 40 kg and a higher platelet count at admission were independently associated with a better outcome. CONCLUSIONS: Females are admitted to hospital earlier than males, probably as an indirect result of the Prevention of Mother-to-Child Transmission (PMTCT) public health initiative. An active search of HIV status in other members of the family (PMTCT-plus) may result in the detection of asymptomatic HIV-infected patients as well. A Plasmodium falciparum-positive smear during admission significantly impacted on outcome as well as low platelet count.

Policies and practices on the programmatic management of LTBI: a survey in the African Region.

BACKGROUND: Although the management of latent tuberculous infection (LTBI) is a core component of the End TB Strategy, there is limited information about the status of implementation of such interventions in most African countries. METHODS: A web-based survey involving the 47 countries of the African Region was conducted between November 2016 and April 2017. RESULTS: The questionnaire was completed by 32/47 (68.1%) National TB Programme managers or their delegates. LTBI guidelines were available in four countries (12.5%), while 13 (40.6%) had an LTBI section in their national TB guidelines; there was no significant association with socio-economic conditions and funding allocation. LTBI diagnosis was mostly based on clinical evaluation to rule out active disease, rather than on systematic use of the tuberculin skin test. Respectively 23 (71.8%) and 17 countries (53.1%) reported providing treatment to child contacts aged <5 years and people living with the human immunodeficiency virus (PLHIV). Over two thirds of respondent countries had ongoing activities targeting at least one of the aforementioned high-risk groups. A recording and reporting system for LTBI-related data on child contacts and PLHIV was available in respectively 14 and 12 countries; 7 countries had an LTBI monitoring and evaluation plan. CONCLUSIONS: These data suggest that greater effort is needed to appropriately scale up LTBI policies in the African Region.

Humoral and cellular immunity to RSV in infants, children and adults.

BACKGROUND: Respiratory syncytial virus (RSV) causes respiratory disease throughout life. Here we report differences in naturally acquired immunity with age and presumed exposure. METHODS: A longitudinal, non-interventional, observational study was performed in healthy adults (20 paediatric healthcare workers and 10 non-healthcare workers), children (10 aged 3-6 years) and infants (5 aged 2-4 months and 20 aged 6-12 months). Blood samples were analysed for RSV-neutralising antibody titre, F/Ga/Gb-specific antibody titres, F-specific IgG/IgA memory B-cell frequencies and T-cell production of IFNγ, IL-4, IL-13 and IL-17. RESULTS: Serum G-specific antibody titres were significantly lower in infants and children than adults. However, serum titres of F-specific and RSV-neutralising antibody and IFNγ-producing T-cell frequencies were low or absent in the infants, but comparable between children and adults. Interestingly, F-specific memory IgA B-cells could not be detected in paediatric samples and in samples from non-healthcare workers, but recordable IgA memory B-cells were found in 9/18 paediatric healthcare workers and 2/8 non-healthcare workers at the end of the RSV season. These responses waned 4-6 months later. By contrast, F-specific IgG memory B-cells were detectable in samples from all adults without significant variation across time points. T-cells producing IL-4, IL-13 and IL-17 responses were not detectable in peripheral blood from a subset of volunteers. CONCLUSIONS: Repeated RSV exposure in early life generates immune responses that are inversely related to frequency of severe disease. Induction of F-specific antibody and cellular immune responses through infant vaccination might help to accelerate the development of protective immune responses at an early age. Clinicaltrials.gov reference NCT01563692 and NCT01640652.

Effectiveness and cost-effectiveness of screening migrants for active tuberculosis and latent tuberculous infection.

With the advent of the World Health Organization End TB strategy, there has been renewed interest in screening for active tuberculosis (TB), and particularly latent tuberculous infection (LTBI). In low-incidence countries, a high proportion of TB cases are notified among migrants, which often occurs due to LTBI reactivation. We aimed to review the effectiveness and cost-effectiveness of screening migrants for active TB LTBI to inform and support the TB elimination strategy in low-incidence countries. We carried out a narrative review of English language articles published between 1 January 2000 and 31 June 2016 using the PubMed database. All studies that described the effectiveness or cost-effectiveness of active TB or LTBI screening among migrants were included. We identified 55 studies, and included 40 for the effectiveness of screening, 11 for cost-effectiveness and 4 that reported both. Screening for active TB can be effective and cost-effective depending on the setting, target group and screening approach. Pre-entry screening programmes have some impact on the epidemiology of the receiving countries. The effectiveness and cost-effectiveness of LTBI screening as predicted in mathematical models is also highly setting-specific, with best potential results achieved if screening is restricted to high-risk groups and/or to migrants from high-burden countries.

Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in patients with breast cancer.

BACKGROUND: Polyunsaturated fatty acids of the omega-6 (omega-6) class, as found in corn and safflower oils, can act as precursors for intermediates involved in the growth of mammary tumors when fed to animals, whereas polyunsaturated fatty acids of the omega-3 (omega-3) class, as found in fish oil, can inhibit these effects. The effects of dietary intervention on the ratios of these fatty acids in breast and other adipose tissues have not previously been prospectively studied. PURPOSE: The present investigation was conducted to study the impact on the ratio of omega-3 and omega-6 polyunsaturated fatty acid in plasma and in adipose tissue of the breast and buttocks when women with breast cancer consume a low-fat diet and fish oil supplements. METHODS: Twenty-five women with high-risk localized breast cancer were enrolled in a dietary intervention program that required them to eat a low-fat diet and take a daily fish oil supplement throughout a 3-month period. Breast and gluteal fat biopsy specimens were obtained from each woman before and after dietary intervention. The fatty acid compositions of specimens of plasma, breast fat, and gluteal fat were determined by gas-liquid chromatography. Statistical analysis involved use of a two-sided paired t test. RESULTS: After dietary intervention, a reduction in the level of total omega-6 polyunsaturated fatty acids in the plasma was observed (P<.0003); moreover, total omega-3 polyunsaturated fatty acids increased approximately three-fold (P<.0001) and the omega-3/omega-6 polyunsaturated fatty acids ratio increased approximately fourfold (i.e., mean values increased from 0.09 to 0.41; P = .0001). An increase in total omega-3 polyunsaturated fatty acids in breast adipose tissue was observed following dietary intervention (P = .04); the omega-3/omega-6 polyunsaturated fatty acid ratio increased from a mean value of 0.05 to 0.07 (P = .0001). An increase in total omega-3 polyunsaturated fatty acids was observed in gluteal adipose tissue following the intervention (P = .05); however, the ratio of omega-3 to omega-6 polyunsaturated fatty acids (mean ratio values of 0.036-0.045; P = .06) was unchanged. CONCLUSION: Short-term dietary intervention can lead to statistically significant increases in omega-3/omega-6 polyunsaturated fatty acid ratios in plasma and breast adipose tissue. Breast adipose tissue changed more rapidly than gluteal adipose tissue in response to the dietary modification tested in this study. Therefore, gluteal adipose tissue may not be a useful surrogate to study the effect of diet on breast adipose tissue.

CD161(int)CD8+ T cells: a novel population of highly functional, memory CD8+ T cells enriched within the gut.

The C-type lectin-like receptor CD161 is expressed by lymphocytes found in human gut and liver, as well as blood, especially natural killer (NK) cells, T helper 17 (Th17) cells, and a population of unconventional T cells known as mucosal-associated invariant T (MAIT) cells. The association of high CD161 expression with innate T-cell populations including MAIT cells is established. Here we show that CD161 is also expressed, at intermediate levels, on a prominent subset of polyclonal CD8+ T cells, including antiviral populations that display a memory phenotype. These memory CD161(int)CD8+ T cells are enriched within the colon and express both CD103 and CD69, markers associated with tissue residence. Furthermore, this population was characterized by enhanced polyfunctionality, increased levels of cytotoxic mediators, and high expression of the transcription factors T-bet and eomesodermin (EOMES). Such populations were induced by novel vaccine strategies based on adenoviral vectors, currently in trial against hepatitis C virus. Thus, intermediate CD161 expression marks potent polyclonal, polyfunctional tissue-homing CD8+ T-cell populations in humans. As induction of such responses represents a major aim of T-cell prophylactic and therapeutic vaccines in viral disease and cancer, analysis of these populations could be of value in the future.

Bacteriophage lambda display of complex cDNA libraries: a new approach to functional genomics.

We describe the construction and characterization of two lambda surface displayed cDNA expression libraries derived from human brain and mouse embryo. cDNA inserts were obtained by tagged random-priming elongation of commercially available cDNA libraries and cloned into a novel lambda vector at the 3' end of the D capsid protein gene, which produced highly complex repertoires (1x10(8) and 2x10(7) phage). These libraries were affinity selected with a monoclonal antibody against the neural specific factor GAP-43 and with polyclonal antibodies that recognize the EMX1 and EMX2 homeoproteins. In both cases rapid identification of specific clones was achieved, which demonstrates the great potential of the lambda display system for generating affinity selectable cDNA libraries from complex genomes.

Safety and immunogenicity of novel respiratory syncytial virus (RSV) vaccines based on the RSV viral proteins F, N and M2-1 encoded by simian adenovirus (PanAd3-RSV) and MVA (MVA-RSV); protocol for an open-label, dose-escalation, single-centre, phase 1 clinical trial in healthy adults.

INTRODUCTION: Respiratory syncytial virus (RSV) infection causes respiratory disease throughout life, with infants and the elderly at risk of severe disease and death. RSV001 is a phase 1 (first-in-man), open-label, dose-escalation, clinical trial of novel genetic viral-vectored vaccine candidates PanAd3-RSV and modified vaccinia virus Ankara (MVA)-RSV. The objective of RSV001 is to characterise the (primary objective) safety and (secondary objective) immunogenicity of these vaccines in healthy younger and older adults. METHODS AND ANALYSIS: Heterologous and homologous 'prime'/boost combinations of PanAd3-RSV and single-dose MVA-RSV are evaluated in healthy adults. 40 healthy adults aged 18-50 years test one of four combinations of intramuscular (IM) or intranasal (IN) PanAd3-RSV prime and IM PanAd3 or IM MVA-RSV boost vaccination, starting at a low dose for safety. The following year an additional 30 healthy adults aged 60-75 years test either a single dose of IM MVA-RSV, one of three combinations of IN or IM PanAd3-RSV prime and PanAd3-RSV or MVA-RSV boost vaccination used in younger volunteers, and a non-vaccinated control group. Study participants are self-selected volunteers who satisfy the eligibility criteria and are assigned to study groups by sequential allocation. Safety assessment includes the daily recording of solicited and unsolicited adverse events for 1 week after vaccination, as well as visit (nursing) observations and safety bloods obtained at all scheduled attendances. Laboratory measures of RSV-specific humoral and cellular immune responses after vaccination will address the secondary end points. All study procedures are performed at the Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Oxford, UK. ETHICS AND DISSEMINATION: RSV001 has clinical trial authorisation from the Medicines and Healthcare Products Regulatory Agency (MHRA) and ethics approval from NRES Berkshire (reference 13/SC/0023). All study procedures adhere to International Conference on Harmonisation (ICH) Good Clinical Practice guidelines. The results of the trial are to be published in peer-reviewed journals, conferences and academic forums. TRIAL REGISTRATION NUMBER: NCT01805921.

Cross-reactive phage-displayed mimotopes lead to the discovery of mimicry between HSV-1 and a brain-specific protein.

We previously reported the selection of several families of phage-displayed peptide mimics (mimotopes) recognized by oligoclonal immunoglobulins present in the CSF of multiple sclerosis (MS) patients. To search for the natural antigens recognized by these antibodies, anti-sera were raised against one of the mimotopes and used as a probe in ELISA, Western blotting and immunoprecipitation experiments. Anti-mimotope IgG were found to cross-react with an epitope shared by a brain-specific factor conserved from rodents to humans, and the surface glycoprotein gB of HSV-1. These findings support the hypothesis that common viral infections are the triggering agents of self-reactive CSF antibodies, whose role in MS still remains to be elucidated.

Thermodynamics of formation of magnesium, calcium, strontium and barium complexes with 2,2'-bipyridyl and 1,10-phenanthroline, at different ionic strengths in aqueous solution.

The formation constants for the complexes of Mg(2+), Ca(2+), Sr(2+) and Ba(2+) with 2,2'-bipyridyl and 1,10-phenanthroline have been determined from pH measurements in aqueous solution, at 10, 25 and 40 degrees and various ionic strengths in the range 0.05-0.95M. The species [MtL)](2+) was found in all systems. The dependence on ionic strength was calculated for all the stability constants, and DeltaH degrees values have been calculated from the temperature dependence of the stability constants. The formation constants are in the order MgL(2+) > CaL(2+) > SrL(2+) > BaL(2+) and M-10, 10-phenanthroline > M-2,2'-bipyridyl.