Imaging denervation in motor neuron disease for future clinical trials: a longitudinal cohort study

A key area-of-need in motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) translational research is a tool to objectively track disease progression over short timescales, to reduce duration and cost of clinical trials. Previous studies have focused on the central nervous system

Canine respiratory coronavirus employs caveolin-1-mediated pathway for internalization to HRT-18G cells

Canine respiratory coronavirus (CRCoV), identified in 2003, is a member of the Coronaviridae family. The virus is a betacoronavirus and a close relative of human coronavirus OC43 and bovine coronavirus. Here, we examined entry of CRCoV into human rectal tumor cells (HRT-18G cell line) by analyzing co-localization of single virus particles with cellular markers in the presence or absence of chemical inhibitors of pathways potentially involved in virus entry. We also targeted these pathways using siRNA. The results show that the virus hijacks caveolin-dependent endocytosis to enter cells via endocytic internalization

Reliability and acceptability of the Multiple Sclerosis Quality of Life-29 questionnaire in an English-speaking cohort

Background: Multiple Sclerosis Quality-of-Life Questionnaire-54 (MSQoL-54) is a disease-specific instrument for assessing health-related quality of life (HRQoL). Due to the number of items, the time taken to complete it is long. A shorter 29-item version, Multiple Sclerosis Quality-of-Life Questionnaire-29 (MSQoL-29) is yet to be evaluated in English. Objective: To assess reliability and acceptability of English version of MSQoL-29. Methods: Among 100 participants with MS who first completed both MSQoL-54 and MSQoL-29, 91 completed MSQoL-29 after 4–8 weeks. We looked for internal consistency (Cronbach’s alpha), acceptability, reliability (intraclass correlation coefficients (ICCs)) and agreement (Bland–Altman plots). Results: ICCs were strongly positive between MSQoL-54 and MSQoL-29 (Physical Health Composite (PHC) –ICC = 0.914, confidence interval (CI) = 0.872–0.942; Mental Health Composite (MHC) – ICC = 0.875, CI = 0.814–0.916) and between the two MSQoL-29 (PHC – ICC = 0.970, CI = 0.955–0.980; MHC – ICC = 0.937, CI = 0.904–0.958). On Bland–Altman plots, the MSQoL-29 scores of 95% of participants during two visits were within the limits of agreement (LOAs). Time taken to complete MSQoL-29 was 7.2 ± 2.9 minutes and MSQoL-54 was 19.79 ± 5.4 minutes (p = 0.0001). Conclusion: MSQoL-29 has good test–retest reliability in English-speaking population and was quicker to complete

Synthesis, characterization, antimicrobial activity and LPS-interaction properties of SB041, a novel dendrimeric peptide with antimicrobial properties

Multimeric peptides offer several advantages with respect to their monomeric counterparts, as increased activity and greater stability to peptidases and proteases. SB041 is a novel antimicrobial peptide with dendrimeric structure; it is a tetramer of pyrEKKIRVRLSA linked by a lysine core, with an amino valeric acid chain. Here, we report on its synthesis, NMR characterization, antimicrobial activity, and LPS-interaction properties. The peptide was especially active against Gram-negative strains, with a potency comparable (on molar basis) to that of lipopeptides colistin and polymixin B, but it also displayed some activity against selected Gram-positive strains. Following these indications,weinvestigated the efficacy of SB041 in binding Escherichia coli and Pseudomonas aeruginosa LPS in vitro and counteracting its biological effects in RAW-BlueTM cells, derived from RAW 264.7 macrophages. SB041 strongly bound purified LPS, especially that of E. coli, as proved by fluorescent displacement assay, and readily penetrated into LPS monolayers. However, the killing activity of SB041 against E. coli was not inhibited by increasing concentrations of LPS added to the medium. Checking the SB041 effect on LPS-induced activation of pattern recognition receptors (PRRs) in Raw-Blue cells revealed that while the peptide gave a statistically significant decrease in PRRs stimulation when RAW-Blue cells were challenged with P. aeruginosa LPS, the same was not seen when E. coli LPS was used to activate innate immune defense-like responses. Thus, as previously seen for other antimicrobial peptides, also for SB041 binding to LPS did not translate necessarily into LPS-neutralizing activity, suggesting that SB041–LPS interactions must be of complex natur

Prevalent diagnosed HIV in England, Wales and Northern Ireland: adjusted totals 1996 to 2001 and extrapolations to 2004.

OBJECTIVE: To predict trends in diagnosed HIV prevalence by extrapolation to 2004 using data from the annual surveys of individuals receiving HIV-related care in England, Wales and Northern Ireland from 1996 to 2001. METHODS: Data from the annual surveys of prevalent HIV infections diagnosed (SOPHID) were adjusted for under-reporting and non-attendance and separately extrapolated for infections acquired homosexually, heterosexually and by other routes. The data were extrapolated using negative binomial and linear regression models based on the 1996 to 2001 annual surveys. RESULTS: The negative binomial model predicted an increase of 56% in diagnosed HIV prevalence in England, Wales and Northern Ireland between 2001 and 2004. The linear model predicted an increase of 25% for the same time period. The predicted increases are mostly driven by the large rise in the number of new diagnoses, in particular in individuals infected heterosexually. CONCLUSION: Increases in HIV prevalence in England, Wales and Northern Ireland have diverged from a linear trend. Negative binomial modelling of the data predicts that large rises in prevalence will continue during the early 2000s

No time to wait: how many HIV-infected homosexual men are diagnosed late and consequently die? (England and Wales, 1993-2002).

OBJECTIVES: To present national trends of the estimated number and proportion of late HIV diagnoses and short-term mortality following diagnosis among men who have had sex with men (MSM). To determine separately risk factors for late diagnosis and short-term mortality. METHODS: Analysis of national HIV/AIDS case reports of new diagnoses linked to CD4 cell counts from the CD4 Surveillance Scheme. Inverse probability weighting adjusted for individuals with no CD4 cell count at diagnosis. Outcomes were late diagnosis (CD4 cell count <200 x 10(6) cells/l at diagnosis) and short-term mortality (death within 1 year of diagnosis). RESULTS: Of 14,158 new diagnoses, 31% were estimated as late diagnoses. Despite a decreasing trend (P trend <0.01) an estimated 430 (25%) MSM were still diagnosed late in 2001. Late diagnosis disproportionately affected individuals diagnosed outside London, of non-white ethnicity, and of older age. There were 710 (5.0% of 14 158) deaths within a year of HIV diagnosis. Estimated short-term mortality was 14% for MSM diagnosed late and 1% for other MSM (adjusted odds ratio, 10.8; 95% confidence interval, 7.7-15.9). Short-term mortality declined concurrently with availability of highly active antiretroviral therapy and was independently associated with age and diagnosis outside London but not ethnicity. CONCLUSIONS: The continued late diagnosis of one in four MSM means these individuals lose the option to start therapy early, miss opportunities to prevent further transmission and are approximately 10 times more likely to die within a year of diagnosis. Early diagnosis of all MSM in 2001 could have reduced short-term mortality by 84% and all mortality in that year by 22%