Amino acid substitutions within the heptad repeat domain 1 of murine coronavirus spike protein restrict viral antigen spread in the central nervous system.

Targeted recombination was carried out to select mouse hepatitis viruses (MHVs) in a defined genetic background, containing an MHV-JHM spike gene encoding either three heptad repeat 1 (HR1) substitutions (Q1067H, Q1094H, and L1114R) or L1114R alone. The recombinant virus, which expresses spike with the three substitutions, was nonfusogenic at neutral pH. Its replication was significantly inhibited by lysosomotropic agents, and it was highly neuroattenuated in vivo. In contrast, the recombinant expressing spike with L1114R alone mediated cell-to-cell fusion at neutral pH and replicated efficiently despite the presence of lysosomotropic agents; however, it still caused only subclinical morbidity and no mortality in animals. Thus, both recombinant viruses were highly attenuated and expressed viral antigen which was restricted to the olfactory bulbs and was markedly absent from other regions of the brains at 5 days postinfection. These data demonstrate that amino acid substitutions, in particular L1114R, within HR1 of the JHM spike reduced the ability of MHV to spread in the central nervous system. Furthermore, the requirements for low pH for fusion and viral entry are not prerequisites for the highly attenuated phenotype

Elementary Administrators\u27 Exploring the Factors that Promote or Inhibit Reading Achievement

The purpose of this study was to explore the factors that promote or inhibit the reading achievement of elementary children. The participants for this study were administrators who were employed at eleven Title I schools in North Carolina. The study used a qualitative design and collected data by phone interviews with elementary administrators. Several recurring themes and patterns surfaced from the data gathered from the eleven participants. However, the overarching themes that promoted reading achievement were (a) family support, (b) early literacy exposure, and (c) teacher effectiveness and expectations. The reoccurring themes that inhibited reading achievement were (a) lack of early literacy exposure, (b) lack of family support, and (c) lack of teacher and parental expectations

Data Management Plans: Stages, Components, and Activities

Data management strategies have become increasingly important as new computer technologies allow for larger and more complex data sets to be analyzed easily. As a consequence, data management has become a specialty requiring specific skills and knowledge. Many new investigators have no formal training in management of data sets. This paper describes common basic strategies critical to the management of data as applied to a data set from a longitudinal study. The stages of data management are identified. Moreover, key components and strategies, at each stage are described

Patterns of Risk of Depressive Symptoms Among HIV-Positive Women in the Southeastern United States

Depressive symptoms are a common response to HIV disease, and women appear to be at particularly high risk. The authors report results from a crosssectional analysis of data collected from 280 rural women with HIV/AIDS in the Southeastern United States aimed at identifying risk factors of depressive symptoms. Stress theory provided a framework for identification of potential risk factors. Descriptive statistics, measures of association, and regression analyses were used to systematically identify patterns of risk. The final regression model included 22 factors that accounted for 69% of the variance in depressive symptoms. The majority of variance in depressive symptoms was accounted for by only six variables: the frequency of HIV symptoms, recent experiences of sadness/hopelessness, the availability of social support, and the use of three coping strategies: living positively with HIV, isolation/withdrawal, and denial/avoidance. The results suggest a number of intervention strategies for use with rural women with HIV/AIDS

Innate immune activation in neonatal tracheal aspirates suggests endotoxin-driven inflammation

Background:: Tracheal aspirates (TAs) from critically ill neonates accumulate bacterial endotoxin and demonstrate mobilization of endotoxin-binding proteins, but the potential bioactivity of endotoxin in TAs is unknown. We characterized innate immune activation in TAs of mechanically ventilated neonates. Methods: Innate immune activation in TAs of mechanically ventilated neonates was characterized using a targeted 84-gene quantitative real-time (qRT) PCR array. Protein expression of cytokines was confirmed by multiplex assay. Expression and localization of the endotoxin-inducible antimicrobial protein Calgranulin C (S100A12) was assessed by flow cytometry. Endotoxin levels were measured in TA supernatants using the Limulus amoebocyte lysate assay. Results:: Analyses by qRT-PCR demonstrated expression of pattern recognition receptors, Toll-like receptor-nuclear factor κB and inflammasome pathways, cytokines/chemokines and their receptors, and anti-infective proteins in TA cells. Endotoxin positivity increased with postnatal age. As compared with endotoxin-negative TAs, endotoxin-positive TAs demonstrated significantly greater tumor necrosis factor (TNF), interleukin (IL)-6, IL-10, and serpin peptidase inhibitor, clade E, member 1 (SERPINE1) mRNA, and IL-10, TNF, and IL-1β protein. Expression of S100A12 protein was localized to TA neutrophils. Conclusion:: Correlation of endotoxin with TA inflammatory responses suggests endotoxin bioactivity and the possibility that endotoxin antagonists could mitigate pulmonary inflammation and its sequelae in this vulnerable population

A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO)

Rationale Mandibular advancement devices (MADs) are used to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS) but evidence is lacking regarding their clinical and cost-effectiveness in less severe disease. Objectives To compare clinical- and cost-effectiveness of a range of MADs against no treatment in mild to moderate OSAHS. Measurements and methods This open-label, randomised, controlled, crossover trial was undertaken at a UK sleep centre. Adults with Apnoea-Hypopnoea Index (AHI) 5–<30/h and Epworth Sleepiness Scale (ESS) score ≥9 underwent 6 weeks of treatment with three nonadjustable MADs: self-moulded (SleepPro 1; SP1); semi-bespoke (SleepPro 2; SP2); fully-bespoke MAD (bMAD); and 4 weeks no treatment. Primary outcome was AHI scored by a polysomnographer blinded to treatment. Secondary outcomes included ESS, quality of life, resource use and cost. Main results 90 patients were randomised and 83 were analysed. All devices reduced AHI compared with no treatment by 26% (95% CI 11% to 38%, p=0.001) for SP1, 33% (95% CI 24% to 41%) for SP2 and 36% (95% CI 24% to 45%, p<0.001) for bMAD. ESS was 1.51 (95% CI 0.73 to 2.29, p<0.001, SP1) to 2.37 (95% CI 1.53 to 3.22, p<0.001, bMAD) lower than no treatment (p<0.001 for all). Compliance was lower for SP1, which was the least preferred treatment at trial exit. All devices were cost-effective compared with no treatment at a £20 000/quality-adjusted life year (QALY) threshold. SP2 was the most cost-effective up to £39 800/QALY. Conclusions Non-adjustable MADs achieve clinically important improvements in mild to moderate OSAHS and are cost-effective

Type Ia Supernova Properties as a Function of the Distance to the Host Galaxy in the SDSS-II SN Survey

We use type-Ia supernovae (SNe Ia) discovered by the SDSS-II SN Survey to search for dependencies between SN Ia properties and the projected distance to the host galaxy center, using the distance as a proxy for local galaxy properties (local star-formation rate, local metallicity, etc.). The sample consists of almost 200 spectroscopically or photometrically confirmed SNe Ia at redshifts below 0.25. The sample is split into two groups depending on the morphology of the host galaxy. We fit light-curves using both MLCS2k2 and SALT2, and determine color (AV, c) and light-curve shape (delta, x1) parameters for each SN Ia, as well as its residual in the Hubble diagram. We then correlate these parameters with both the physical and the normalized distances to the center of the host galaxy and look for trends in the mean values and scatters of these parameters with increasing distance. The most significant (at the 4-sigma level) finding is that the average fitted AV from MLCS2k2 and c from SALT2 decrease with the projected distance for SNe Ia in spiral galaxies. We also find indications that SNe in elliptical galaxies tend to have narrower light-curves if they explode at larger distances, although this may be due to selection effects in our sample. We do not find strong correlations between the residuals of the distance moduli with respect to the Hubble flow and the galactocentric distances, which indicates a limited correlation between SN magnitudes after standardization and local host metallicity.Comment: Accepted for publication in The Astrophysical Journal (33 pages, 5 figures, 8 tables

Recent Food Shortage Is Associated with Leprosy Disease in Bangladesh: A Case-Control Study

Although intensive control programs reduced the prevalence of leprosy worldwide, new cases of this infectious disease are still detected in several of the poorest areas of the world. Therefore the disease is known as a disease of poverty. To be able to control the disease it is important to know which aspects of poverty play a role in transmission and acquiring clinical signs of disease. In this study socio-economic circumstances of recently diagnosed leprosy patients were compared with those of a control population in the poverty stricken northwest area of Bangladesh where leprosy is common. A recent period of food shortage was the only socio-economic factor that was found related to leprosy disease in this study and not poverty as such. Food shortage is seasonal and poverty related in northwest Bangladesh, while malnutrition is known to lower immunity and make people more vulnerable to infectious diseases. Therefore it was concluded that malnutrition as an aspect of poverty played an important role in the development of the clinical signs of leprosy. We therefore recommend that nutritional support for high risk groups should be included in leprosy control programmes to reduce risk of disease in areas where leprosy is common