Yearly licensing studies from 1997 to 2007 of the inactivated whole virus seasonal influenza vaccine fluval--a useful approach to pandemic vaccine development even in less well developed countries?

OBJECTIVE: Seasonal vaccination has been consistently shown to significantly reduce morbidity and mortality because of influenza epidemics, even in healthy, working adults. Here we report the results of the yearly licensing studies of the past 11 influenza seasons (1997-2007) with a trivalent, inactivated whole virus vaccine with an aluminum phosphate adjuvant system. METHODS: Sixty healthy volunteers per age group (18-60 years and 60 years and older) were enrolled to receive vaccination each year, thus, a total of 1080 subjects were studied. Serum antibody titers were measured by hemagglutination inhibition (HI). RESULTS: The vaccine met the criteria for licensing each year, meaning seroprotection (achievement of an HI titer of >1:40 in >70% of subjects); seroconversion, i.e. a >4-fold increase in HI antibody titer, or reaching a titer of >1:40, in >40% of subjects; and an increase in geometric mean titers by >2.5-fold. Side effects were rare and mild. The same method was used to produce a pre-pandemic vaccine against influenza A (H5N1), which has been shown to be safe and immunogenic in humans. CONCLUSIONS: We conclude that the method presented is safe, effective and may serve as a useful approach to seasonal and pandemic vaccine production even in less well-developed countries by means of technological transfer

Body Mass Index in Multiple Sclerosis modulates ceramide-induced DNA methylation and disease course.

abstract Background: Multiple Sclerosis (MS) results from genetic predisposition and environmental variables, including elevated Body Mass Index (BMI) in early life. This study addresses the effect ofBMI on the epigenome ofmono- cytesand diseasecourseinMS. Methods: Fifty-four therapy-naive Relapsing Remitting (RR)MS patientswith high and normal BMI received clin- ical andMRI evaluation. Blood samples were immunophenotyped, and processed for unbiased plasma lipidomic profiling and genome-wide DNA methylation analysis of circulating monocytes. The main findings at baseline were validated in an independent cohort of 91 therapy-naïve RRMS patients. Disease course was evaluated by a two-year longitudinal follow up and mechanistic hypotheses tested in human cell cultures and in animal models ofMS. Findings: Higher monocytic counts and plasma ceramides, and hypermethylation of genes involved in negative regulation ofcell proliferationwere detected in the high BMI group ofMSpatients compared to normal BMI. Cer- amide treatment of monocytic cell cultures increased proliferation in a dose-dependent manner and was prevented by DNA methylation inhibitors. The high BMI group ofMS patients showed a negative correlation be- tween monocytic counts and brain volume. Those subjects at a two-year follow-up showed increased T1 lesion load, increased disease activity, and worsened clinical disability. Lastly, the relationship between body weight, monocytic infiltration, DNA methylation and disease course was validated in mouse models ofMS. Interpretation: High BMI negatively impacts disease course in Multiple Sclerosis by modulating monocyte cell number through ceramide-induced DNA methylation of anti-proliferative genes

Body Mass Index in Multiple Sclerosis modulates ceramide-induced DNA methylation and disease course

Background: Multiple Sclerosis (MS) results from genetic predisposition and environmental variables, including elevated Body Mass Index (BMI) in early life. This study addresses the effect of BMI on the epigenome of monocytes and disease course in MS. Methods: Fifty-four therapy-naive Relapsing Remitting (RR) MS patients with high and normal BMI received clinical and MRI evaluation. Blood samples were immunophenotyped, and processed for unbiased plasma lipidomic profiling and genome-wide DNA methylation analysis of circulating monocytes. The main findings at baseline were validated in an independent cohort of 91 therapy-na\uefve RRMS patients. Disease course was evaluated by a two-year longitudinal follow up and mechanistic hypotheses tested in human cell cultures and in animal models of MS. Findings: Higher monocytic counts and plasma ceramides, and hypermethylation of genes involved in negative regulation of cell proliferation were detected in the high BMI group of MS patients compared to normal BMI. Ceramide treatment of monocytic cell cultures increased proliferation in a dose-dependent manner and was prevented by DNA methylation inhibitors. The high BMI group of MS patients showed a negative correlation between monocytic counts and brain volume. Those subjects at a two-year follow-up showed increased T1 lesion load, increased disease activity, and worsened clinical disability. Lastly, the relationship between body weight, monocytic infiltration, DNA methylation and disease course was validated in mouse models of MS. Interpretation: High BMI negatively impacts disease course in Multiple Sclerosis by modulating monocyte cell number through ceramide-induced DNA methylation of anti-proliferative genes. Fund: This work was supported by funds from the Friedman Brain Institute, NIH, and Multiple Sclerosis Society

Identifying and Quantifying Neurological Disability via Smartphone

Embedded sensors of the smartphones offer opportunities for granular, patient-autonomous measurements of neurological dysfunctions for disease identification, management, and for drug development. We hypothesized that aggregating data from two simple smartphone tests of fine finger movements with differing contribution of specific neurological domains (i.e., strength & cerebellar functions, vision, and reaction time) will allow establishment of secondary outcomes that reflect domain-specific deficit. This hypothesis was tested by assessing correlations of smartphone-derived outcomes with relevant parts of neurological examination in multiple sclerosis (MS) patients. We developed MS test suite on Android platform, consisting of several simple functional tests. This paper compares cross-sectional and longitudinal performance of Finger tapping and Balloon popping tests by 76 MS patients and 19 healthy volunteers (HV). The primary outcomes of smartphone tests, the average number of taps (per two 10-s intervals) and the average number of pops (per two 26-s intervals) differentiated MS from HV with similar power to traditional, investigator-administered test of fine finger movements, 9-hole peg test (9HPT). Additionally, the secondary outcomes identified patients with predominant cerebellar dysfunction, motor fatigue and poor eye-hand coordination and/or reaction time, as evidenced by significant correlations between these derived outcomes and relevant parts of neurological examination. The intra-individual variance in longitudinal sampling was low. In the time necessary for performing 9HPT, smartphone tests provide much richer and reliable measurements of several distinct neurological functions. These data suggest that combing more creatively-construed smartphone apps may one day recreate the entire neurological examination

Smartphone Level Test Measures Disability in Several Neurological Domains for Patients With Multiple Sclerosis

Our long-term goal is to employ smartphone-embedded sensors to measure various neurological functions in a patient-autonomous manner. The interim goal is to develop simple smartphone tests (apps) and evaluate the clinical utility of these tests by selecting optimal outcomes that correlate well with clinician-measured disability in different neurological domains. In this paper, we used prospectively-acquired data from 112 multiple sclerosis (MS) patients and 15 healthy volunteers (HV) to assess the performance and optimize outcomes of a Level Test. The goal of the test is to tilt the smartphone so that a free-rolling ball travels to and remains in the center of the screen. An accelerometer detects tilting and records the coordinates of the ball at set time intervals. From this data, we derived five features: path length traveled, time spent in the center of the screen, average distance from the center, average speed while in the center, and number of direction changes underwent by the ball. Time in center proved to be the most sensitive feature to differentiate MS patients from HV and had the strongest correlations with clinician-derived scales. Its superiority was validated in an independent validation cohort of 29 MS patients. A linear combination of different Level features failed to outperform time in center in an independent validation cohort. Limited longitudinal data demonstrated that the Level features were relatively stable intra-individually within 4 months, without definitive evidence of learning. In contrast to previously developed smartphone tests that predominantly measure motoric functions, Level features correlated strongly with reaction time and moderately with cerebellar functions and proprioception, validating its complementary clinical value in the MS app suite. The Level Test measures neurological disability in several domains in two independent cross-sectional cohorts (original and validation). An ongoing longitudinal cohort further investigates whether patient-autonomous collection of granular functional data allows measurement of patient-specific trajectories of disability progression to better guide treatment decisions

Rhodococcus opacus B4: a promising bacterium for production of biofuels and biobased chemicals

Bacterial lipids have relevant applications in the production of renewable fuels and biobased oleochemicals. The genus Rhodococcus is one of the most relevant lipid producers due to its capability to accumulate those compounds, mainly triacylglycerols (TAG), when cultivated on different defined substrates, namely sugars, organic acids and hydrocarbons but also on complex carbon sources present in industrial wastes. In this work, the production of storage lipids by Rhodococcus opacus B4 using glucose, acetate and hexadecane is reported for the first time and its productivity compared with Rhodococcus opacus PD630, the best TAG producer bacterium reported. Both strains accumulated mainly TAG from all carbon sources, being influenced by the carbon source itself and by the duration of the accumulation period. R. opacus B4 produced 0.09 and 0.14 g L1 at 24 and 72 h, with hexadecane as carbon source, which was 2 and 3.3 fold higher than the volumetric production obtained by R. opacus PD630. Both strains presented similar fatty acids (FA) profiles in intact cells while in TAG produced fraction, R. opacus B4 revealed a higher variability in fatty acid composition than R. opacus PD630, when both strains were cultivated on hexadecane. The obtained results open new perspectives for the use of R. opacus B4 to produce TAG, in particular using oily (alkane-contaminated) waste and wastewater as cheap raw-materials. Combining TAG production with hydrocarbons degradation is a promising strategy to achieve environmental remediation while producing added value compounds.This work was financially supported by the Portuguese Science Foundation (FCT) and European Social Fund (ESF, POPH-QREN) through the Grant given to A.R. Castro (SFRH/BD/64500/2009), the FCT Strategic Project of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462)

Regional socioeconomic indicators and ethnicity as predictors of regional infant mortality rate in Slovakia

OBJECTIVE: Exploring the associations of regional differences in infant mortality with selected socioeconomic indicators and ethnicity could offer important clues for designing public health policy measures. METHODS: Data included perinatal and infant mortality in the 79 districts of the Slovak population in 2004. Linear regression was used to analyse the contribution of education, unemployment, income and proportion of Roma population on regional differences in perinatal and infant mortality rates. RESULTS: All the explored socioeconomic indicators and ethnicity individually contributed significantly to both perinatal and infant mortality, with the exception of income. In the model exploring the influence of all these variables together on perinatal and infant mortality, only the effect of the proportion of Roma population remained significant. This model explained 34.9% of the variance for perinatal and 36.4% of the variance for infant mortality. CONCLUSIONS: Living in Roma settlements indicates an accumulation of socioeconomic disadvantage. Health literacy, health-related behaviour and many other factors might contribute to the explanation of the differences in infant mortality, and a better understanding of these processes might help us to design tailored interventions