The Seroepidemiology of Haemophilus influenzae Type B Prior to Introduction of an Immunization Programme in Kathmandu, Nepal.

Haemophilus influenzae type b (Hib) is now recognized as an important pathogen in Asia. To evaluate disease susceptibility, and as a marker of Hib transmission before routine immunization was introduced in Kathmandu, 71 participants aged 7 months-77 years were recruited and 15 cord blood samples were collected for analysis of anti-polyribosylribitol phosphate antibody levels by enzyme-linked immunosorbent assay. Only 20% of children under 5 years old had levels considered protective (>0.15 µg/ml), rising to 83% of 15-54 year-olds. Prior to introduction of Hib vaccine in Kathmandu, the majority of young children were susceptible to disease

Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP

Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post- translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B’. Results also show that unstructured post- ranslationally modified C-terminal tails are responsible for the dynamics of Sm-B/B’ and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.This work was funded by: BBSRC (OVM), BBSRC and EPSRC (HH and NM), EU Prospects (HH), European Science Foundation (NM), the Royal Society (CVR), and fellowship from JSPS and HFSP (YM and DAPK respectively)

Photo-antagonism of the GABAA receptor

Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation

Operant Sensation Seeking Requires Metabotropic Glutamate Receptor 5 (mGluR5)

Pharmacological and genetic studies have suggested that the metabotropic glutamate receptor 5 (mGluR5) is critically involved in mediating the reinforcing effects of drugs of abuse, but not food. The purpose of this study was to use mGluR5 knockout (KO), heterozygous (Het), and wildtype (WT) mice to determine if mGluR5 modulates operant sensation seeking (OSS), an operant task that uses varied sensory stimuli as a reinforcer. We found that mGluR5 KO mice had significantly reduced OSS responding relative to WT mice, while Het mice displayed a paradoxical increase in OSS responding. Neither KO nor Het mice exhibited altered operant responding for food as a reinforcer. Further, we assessed mGluR5 KO, Het and WT mice across a battery of cocaine locomotor, place preference and anxiety related tests. Although KO mice showed expected differences in some locomotor and anxiety measures, Het mice either exhibited no phenotype or an intermediate one. In total, these data demonstrate a key role for mGluR5 in OSS, indicating an important role for this receptor in reinforcement-based behavior

Transcription analysis on response of swine lung to H1N1 swine influenza virus

<p>Abstract</p> <p>Background</p> <p>As a mild, highly contagious, respiratory disease, swine influenza always damages the innate immune systems, and increases susceptibility to secondary infections which results in considerable morbidity and mortality in pigs. Nevertheless, the systematical host response of pigs to swine influenza virus infection remains largely unknown. To explore it, a time-course gene expression profiling was performed for comprehensive analysis of the global host response induced by H1N1 swine influenza virus in pigs.</p> <p>Results</p> <p>At the early stage of H1N1 swine virus infection, pigs were suffering mild respiratory symptoms and pathological changes. A total of 268 porcine genes showing differential expression (DE) after inoculation were identified to compare with the controls on day 3 post infection (PID) (Fold change ≥ 2, p < 0.05). The DE genes were involved in many vital functional classes, mainly including signal transduction, immune response, inflammatory response, cell adhesion and cell-cell signalling. Noticeably, the genes associated with immune and inflammatory response showed highly overexpressed. Through the pathway analysis, the significant pathways mainly concerned with Cell adhesion molecules, Cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway and MAPK signaling pathway, suggesting that the host took different strategies to activate these pathways so as to prevent virus infections at the early stage. However, on PID 7, the predominant function classes of DE genes included signal transduction, metabolism, transcription, development and transport. Furthermore, the most significant pathways switched to PPAR signaling pathway and complement and coagulation cascades, showing that the host might start to repair excessive tissue damage by anti-inflammatory functions. These results on PID 7 demonstrated beneficial turnover for host to prevent excessive inflammatory damage and recover the normal state by activating these clusters of genes.</p> <p>Conclusions</p> <p>This study shows how the target organ responds to H1N1 swine influenza virus infection in pigs. The observed gene expression profile could help to screen the potential host agents for reducing the prevalence of swine influenza virus and further understand the molecular pathogenesis associated with H1N1 infection in pigs.</p

Mycoplasma genitalium: An Emerging Cause of Sexually Transmitted Disease in Women

Mycoplasma genitalium is an emerging sexually transmitted pathogen implicated in urethritis in men and several inflammatory reproductive tract syndromes in women including cervicitis, pelvic inflammatory disease (PID), and infertility. This comprehensive review critically examines epidemiologic studies of M. genitalium infections in women with the goal of assessing the associations with reproductive tract disease and enhancing awareness of this emerging pathogen. Over 27,000 women from 48 published reports have been screened for M. genitalium urogenital infection in high- or low-risk populations worldwide with an overall prevalence of 7.3% and 2.0%, respectively. M. genitalium was present in the general population at rates between those of Chlamydia trachomatis and Neisseria gonorrhoeae. Considering more than 20 studies of lower tract inflammation, M. genitalium has been positively associated with urethritis, vaginal discharge, and microscopic signs of cervicitis and/or mucopurulent cervical discharge in seven of 14 studies. A consistent case definition of cervicitis is lacking and will be required for comprehensive understanding of these associations. Importantly, evidence for M. genitalium PID and infertility are quite convincing and indicate that a significant proportion of upper tract inflammation may be attributed to this elusive pathogen. Collectively, M. genitalium is highly prevalent in high- and low-risk populations, and should be considered an etiologic agent of select reproductive tract disease syndromes in women

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

Health behaviour modelling for prenatal diagnosis in Australia: a geodemographic framework for health service utilisation and policy development

BACKGROUND: Despite the wide availability of prenatal screening and diagnosis, a number of studies have reported no decrease in the rate of babies born with Down syndrome. The objective of this study was to investigate the geodemographic characteristics of women who have prenatal diagnosis in Victoria, Australia, by applying a novel consumer behaviour modelling technique in the analysis of health data. METHODS: A descriptive analysis of data on all prenatal diagnostic tests, births (1998 and 2002) and births of babies with Down syndrome (1998 to 2002) was undertaken using a Geographic Information System and socioeconomic lifestyle segmentation classifications. RESULTS: Most metropolitan women in Victoria have average or above State average levels of uptake of prenatal diagnosis. Inner city women residing in high socioeconomic lifestyle segments who have high rates of prenatal diagnosis spend 20% more on specialist physician's fees when compared to those whose rates are average. Rates of prenatal diagnosis are generally low amongst women in rural Victoria, with the lowest rates observed in farming districts. Reasons for this are likely to be a combination of lack of access to services (remoteness) and individual opportunity (lack of transportation, low levels of support and income). However, there are additional reasons for low uptake rates in farming areas that could not be explained by the behaviour modelling. These may relate to women's attitudes and choices. CONCLUSION: A lack of statewide geodemographic consistency in uptake of prenatal diagnosis implies that there is a need to target health professionals and pregnant women in specific areas to ensure there is increased equity of access to services and that all pregnant women can make informed choices that are best for them. Equally as important is appropriate health service provision for families of children with Down syndrome. Our findings show that these potential interventions are particularly relevant in rural areas. Classifying data to lifestyle segments allowed for practical comparisons of the geodemographic characteristics of women having prenatal diagnosis in Australia at a population level. This methodology may in future be a feasible and cost-effective tool for service planners and policy developers

Smoking among pregnant women in Cantabria (Spain): trend and determinants of smoking cessation

<p>Abstract</p> <p>Background</p> <p>Cantabria (Spain) has one of the highest prevalence of smoking among women of the European Union. The objectives are to assess the trend of smoking during pregnancy in a five-year period and the determinants of smoking cessation during pregnancy in Cantabria.</p> <p>Methods</p> <p>A 1/6 random sample of all women delivering at the reference hospital of the region for the period 1998–2002 was drawn, 1559 women. Information was obtained from personal interview, clinical chart, and prenatal care records. In the analysis relative risks and 95% confidence intervals were estimated. Multivariable analysis was carried out using stepwise logistic regression.</p> <p>Results</p> <p>Smoking prior to pregnancy decreased from 53.6% in 1998 to 39.4% in 2002. A decrease in smoking cessation among women smoking at the beginning of pregnancy was observed, from 37.3% in 1998 to 20.6% in 2002. The mean number of cigarettes/day (cig/d) before pregnancy remained constant, around 16 cig/d, whereas a slight trend to increase over time was seen, from 7.7 to 8.9 cig/d. In univariate analysis two variables favoured significantly smoking cessation, although they were not included in the stepwise logistic regression analysis, a higher education level and to be married. The logistic regression model included five significant predictors (also significant in univariate analysis): intensity of smoking, number of previous pregnancies, partner's smoking status, calendar year of study period (these four variables favoured smoking continuation), and adequate prenatal care (which increased smoking cessation).</p> <p>Conclusion</p> <p>The frequency of smoking among pregnant women is very high in Cantabria. As smoking cessation rate has decreased over time, a change in prenatal care programme on smoking counseling is needed. Several determinants of smoking cessation, such as smoking before pregnancy and partner's smoking, should be also addressed by community programmes.</p

Prevalence, prenatal screening and neonatal features in children with Down syndrome: a registry-based national study

BACKGROUND: Down syndrome (DS) is one of the most common chromosomal abnormalities among newborns. In recent years advances in perinatal and neonatal care have improved chance of survival for the children with DS. The objective of this Registry-Based study was to get more accurate data of DS prevalence with evaluation of antenatal screening, neonatal and maternal features among total births in Croatia from 2009 to 2012. ----- METHODS: We used retrospectively collected data for DS newborns from the medical birth database and perinatal mortality database for the period of 2009-2012. Differences between DS and the referent population for each year in quantitative measures were assessed with the independent t-test. Other differences in nominal and categorical values were analyzed with the chi-square test. ----- RESULTS: The total prevalence for DS in the period of 2009-2012 was 7.01 per 10,000 births, while the live-birth prevalence was 6.49 per 10,000 births. The significant differences (p < 0.05) between the DS and reference populations for each year were noticed for birth weight and length, gestational age, mother age, Apgar score of ≥6 after 5 min and breastfeeding. Among newborns with DS, there were 64 (53.33 %) males and 56 (46.67 %) females versus 88,587 (51.76 %) males and 82,553 (48.23 %) females in the reference population. In the DS group compared to the reference population the mean birth weight was 2845 grams versus 3467 grams in males and 2834 grams versus 3329 grams in females, respectively, with a mean birth length of 47 cm versus 50 cm for both genders. The mean gestational age of the DS births was 37 weeks and the mean age of the mothers was 32.6 years, versus 39 weeks and 29.1 years, respectively, in the reference population. Only 68.3 % of children with DS were breastfed from birth, compared with 94.72 % of children in the reference population. ----- CONCLUSIONS: The significant differences for neonatal and maternal features between DS and the referent population were found similar to other studies. The total prevalence of DS in Croatia in the period of 2009-2012 was lower than the previously estimated prevalence based on EUROCAT data. The establishment of a new national registry of congenital malformations covering 99 % of all births in Croatia is necessary to improve the health and prosperity of children, adolescents and adults with DS in Croatia