Pregnancy has a minimal impact on the acute transcriptional signature to vaccination.

Vaccination in pregnancy is an effective tool to protect both the mother and infant; vaccines against influenza, pertussis and tetanus are currently recommended. A number of vaccines with a specific indication for use in pregnancy are in development, with the specific aim of providing passive humoral immunity to the newborn child against pathogens responsible for morbidity and mortality in young infants. However, the current understanding about the immune response to vaccination in pregnancy is incomplete. We analysed the effect of pregnancy on early transcriptional responses to vaccination. This type of systems vaccinology approach identifies genes and pathways that are altered in response to vaccination and can be used to understand both the acute inflammation in response to the vaccine and to predict immunogenicity. Pregnant women and mice were immunised with Boostrix-IPV, a multivalent vaccine, which contains three pertussis antigens. Blood was collected from women before and after vaccination and RNA extracted for analysis by microarray. While there were baseline differences between pregnant and non-pregnant women, vaccination induced characteristic patterns of gene expression, with upregulation in interferon response and innate immunity gene modules, independent of pregnancy. We saw similar patterns of responses in both women and mice, supporting the use of mice for preclinical screening of novel maternal vaccines. Using a systems vaccinology approach in pregnancy demonstrated that pregnancy does not affect the initial response to vaccination and that studies in non-pregnant women can provide information about vaccine immunogenicity and potentially safety

Terahertz photometer to observe solar flares in continuum

Solar observations at sub-THz frequencies detected a new flare spectral component peaking in the THz range, simultaneously with the well known microwaves component, bringing challenging constraints for interpretation. Higher THz frequencies observations are needed to understand the nature of the mechanisms occurring in flares. A THz photometer system was developed to observe outside the terrestrial atmosphere on stratospheric balloons or satellites, or at exceptionally transparent ground stations. The telescope was designed to observe the whole solar disk detecting small relative changes in input temperature caused by flares at localized positions. A Golay cell detector is preceded by low-pass filters to suppress visible and near IR radiation, a band-pass filter, and a chopper. A prototype was assembled to demonstrate the new concept and the system performance. It can detect temperature variations smaller than 1 K for data sampled at a rate of 10/second, smoothed for intervals larger than 4 seconds. For a 76 mm aperture, this corresponds to small solar burst intensities at THz frequencies. A system with 3 and 7 THz photometers is being built for solar flare observations on board of stratospheric balloon missions.Comment: 11 pages, 8 figures, accepted by Journal of Infrared, Millimeter, and Terahertz Waves, 9 December 201

Differential transcriptomic and metabolic profiles of M. africanum- and M. tuberculosis-infected patients after, but not before, drug treatment.

The epidemiology of Mycobacterium tuberculosis (Mtb) and M. africanum (Maf) suggests differences in their virulence, but the host immune profile to better understand the pathogenesis of tuberculosis (TB) have not been studied. We compared the transcriptomic and metabolic profiles between Mtb- and Maf-infected TB cases to identify host biomarkers associated with lineages-specific pathogenesis and response to anti-TB chemotherapy. Venous blood samples from Mtb- and Maf-infected patients obtained before and after anti-TB treatment were analyzed for cell composition, gene expression and metabolic profiles. Prior to treatment, similar transcriptomic profiles were seen in Maf- and Mtb-infected patients. In contrast, post treatment, over 1600 genes related to immune responses and metabolic diseases were differentially expressed between the groups. Notably, the upstream regulator hepatocyte nuclear factor 4-alpha (HNF4α), which regulated 15% of these genes, was markedly enriched. Serum metabolic profiles were similar in both group pre-treatment, but the decline in pro-inflammatory metabolites post treatment were most pronounced in Mtb-infected patients. Together, the differences in both peripheral blood transcriptomic and serum metabolic profiles between Maf- and Mtb-infected patients observed over the treatment period, might be indicative of intrinsic host factors related to susceptibility to TB and/or differential efficacy of the standard anti-TB treatment on the two lineages

Different extraction methods of biologically active components from propolis: a preliminary study

Abstract Background Propolis is widely used in apitherapy, preparations, and food and beverage additives. Various extraction techniques were applied in the extraction of the biologically active constituents of poplar type propolis in order to compare their efficiency. The methods employed were: traditional maceration extraction, ultrasound extraction (UE), and microwave assisted extraction (MAE). Results The total amounts of extracted phenolics and flavonoids were determined, and the effectiveness of the methods compared. MAE was very rapid but led to the extraction of a large amount of non-phenolic and non-flavonoid material. UE gave the highest percentage of extracted phenolics. Conclusion Compared to the maceration extraction, MAE and UE methods provided high extraction yield, requiring short timeframes and less labour. UE was shown to be the most efficient method based on yield, extraction time and selectivity.</p

Cost-utility analysis of adjuvant goserelin (Zoladex) and adjuvant chemotherapy in premenopausal women with breast cancer

<p>Abstract</p> <p>Background</p> <p>Increased health care costs have made it incumbent on health-care facilities and physicians to demonstrate both clinical and cost efficacy when recommending treatments. Though studies have examined the cost-effectiveness of adjuvant goserelin with radiotherapy for locally advanced prostate cancer, few have compared the cost-effectiveness of adjuvant goserelin to adjuvant chemotherapy alone in premenopausal breast cancer.</p> <p>Methods</p> <p>In this retrospective study at one hospital, the records of 152 patients with stage Ia to IIIa ER + breast cancer who received goserelin or chemotherapy were reviewed. Survival analysis was assessed by the Kaplan-Meier method. Patients were interviewed to evaluate their quality of life using the European Organization for Research and Treatment Quality of Life questionnaire (EORTC-QLQ-C30, version 4.0), and to obtain the utility value by the standard gamble (SG) and visual scale (VS) methods. Total medical cost was assessed from the (National Health Insurance) NHI payer's perspective.</p> <p>Results</p> <p>Survival at 11 years was significantly better in the groserelin group (<it>P </it>< 0.0012). The lifetime lost was lower in the goserelin group (42 months vs. 66 months). The quality adjusted survival (QAS) of patients who received goserelin was longer (122.5 ± 6.3 vs. 112.2 ± 6.7 months). Total expenses of goserelin were more than cyclophosphamide, methotrexate, 5-fluorouracil (CMF) or 5-fluorouracil, epirubicin, cyclophosphamide (FEC) chemotherapy regimes, but less than docetaxel, epirubicin (TE) or docetaxel, epirubicin, cyclophosphamide (TEC) regimes. The quality-adjusted life-year was higher in the goserelin group.</p> <p>Conclusions</p> <p>Goserelin therapy results in better survival and higher utility-weighted life-years, and is more cost-effective than TC or TEC chemotherapy.</p

Intraocular pressure and ocular pulse amplitude using dynamic contour tonometry and contact lens tonometry

BACKGROUND: The new Ocular Dynamic Contour Tonometer (DCT), investigational device supplied by SMT (Swiss Microtechnology AG, Switzerland) allows simultaneous recording of intraocular pressure (IOP) and ocular pulse amplitude (OPA). It was the aim of this study to compare the IOP results of this new device with Goldmann tonometry. Furthermore, IOP and OPA measured with the new slitlamp-mounted DCT were compared to the IOP and OPA measured with the hand-held SmartLens(®), a gonioscopic contact lens tonometer (ODC Ophthalmic Development Company AG, Switzerland). METHODS: Nineteen healthy subjects were included in this study. IOP was determined by three consecutive measurements with each of the DCT, SmartLens(®), and Goldmann tonometer. Furthermore, OPA was measured three times consecutively by DCT and SmartLens(®). RESULTS: No difference (P = 0.09) was found between the IOP values by means of DCT (mean: 16.6 mm Hg, median: 15.33 mm Hg, SD: +/- 4.04 mm Hg) and Goldmann tonometry (mean: 16.17 mm Hg, median: 15.33 mm Hg, SD: +/- 4.03 mm Hg). The IOP values of SmartLens(® )(mean: 20.25 mm Hg, median: 19.00 mm Hg, SD: +/- 4.96 mm Hg) were significantly higher (P = 0.0008) both from Goldmann tonometry and DCT. The OPA values of the DCT (mean: 3.08 mm Hg, SD: +/- 0.92 mm Hg) were significantly lower (P = 0.0003) than those obtained by SmartLens(® )(mean: 3.92 mm Hg, SD: +/- 0.83 mm Hg). CONCLUSIONS: DCT was equivalent to Goldmann applanation tonometry in measurement of IOP in a small group of normal subjects. In contrast, SmartLens(® )(contact lens tonometry) gave IOP readings that were significantly higher compared with Goldmann applanation tonometer readings. Both devices, DCT and SmartLens(® )provide the measurement of OPA which could be helpful e.g. for the management of glaucoma

Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.

BACKGROUND: Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. METHODS: We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. RESULTS: There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. CONCLUSIONS: Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy trials

Identifying Activated T Cells in Reconstituted RAG Deficient Mice Using Retrovirally Transduced Pax5 Deficient Pro-B Cells

Various methods have been used to identify activated T cells such as binding of MHC tetramers and expression of cell surface markers in addition to cytokine-based assays. In contrast to these published methods, we here describe a strategy to identify T cells that respond to any antigen and track the fate of these activated T cells. We constructed a retroviral double-reporter construct with enhanced green fluorescence protein (EGFP) and a far-red fluorescent protein from Heteractis crispa (HcRed). LTR-driven EGFP expression was used to enrich and identify transduced cells, while HcRed expression is driven by the CD40Ligand (CD40L) promoter, which is inducible and enables the identification and cell fate tracing of T cells that have responded to infection/inflammation. Pax5 deficient pro-B cells that can give rise to different hematopoietic cells like T cells, were retrovirally transduced with this double-reporter cassette and were used to reconstitute the T cell pool in RAG1 deifcient mice that lack T and B cells. By using flow cytometry and histology, we identified activated T cells that had developed from Pax5 deficient pro-B cells and responded to infection with the bacterial pathogen Listeria monocytogenes. Microscopic examination of organ sections allowed visual identification of HcRed-expressing cells. To further characterize the immune response to a given stimuli, this strategy can be easily adapted to identify other cells of the hematopoietic system that respond to infection/inflammation. This can be achieved by using an inducible reporter, choosing the appropriate promoter, and reconstituting mice lacking cells of interest by injecting gene-modified Pax5 deficient pro-B cells

Neutrophil degranulation, NETosis and platelet degranulation pathway genes are co-induced in whole blood up to six months before tuberculosis diagnosis

Mycobacterium tuberculosis (M.tb) causes tuberculosis (TB) and remains one of the leading causes of mortality due to an infectious pathogen. Host immune responses have been implicated in driving the progression from infection to severe lung disease. We analyzed longitudinal RNA sequencing (RNAseq) data from the whole blood of 74 TB progressors whose samples were grouped into four six-month intervals preceding diagnosis (the GC6-74 study). We additionally analyzed RNAseq data from an independent cohort of 90 TB patients with positron emission tomography-computed tomography (PET-CT) scan results which were used to categorize them into groups with high and low levels of lung damage (the Catalysis TB Biomarker study). These groups were compared to non-TB controls to obtain a complete whole blood transcriptional profile for individuals spanning from early stages of M.tb infection to TB diagnosis. The results revealed a steady increase in the number of genes that were differentially expressed in progressors at time points closer to diagnosis with 278 genes at 13-18 months, 742 at 7-12 months and 5,131 detected 1-6 months before diagnosis and 9,205 detected in TB patients. A total of 2,144 differentially expressed genes were detected when comparing TB patients with high and low levels of lung damage. There was a large overlap in the genes upregulated in progressors 1-6 months before diagnosis (86%) with those in TB patients. A comprehensive pathway analysis revealed a potent activation of neutrophil and platelet mediated defenses including neutrophil and platelet degranulation, and NET formation at both time points. These pathways were also enriched in TB patients with high levels of lung damage compared to those with low. These findings suggest that neutrophils and platelets play a critical role in TB pathogenesis, and provide details of the timing of specific effector mechanisms that may contribute to TB lung pathology