Risk-stratified seroprevalence of SARS coronavirus in children residing in a district with point-source outbreak compared to a low-risk area.

1. SARS coronavirus has low transmissibility at the community level. 2. Subclinical SARS coronavirus infection is rare in children.published_or_final_versio

Access to the next wave of biologic therapies (Abatacept and Tocilizumab) for the treatment of rheumatoid arthritis in England and Wales: Addressing treatment outside the current NICE guidance

Patients in England and Wales with rheumatoid arthritis (RA) receive treatment from the National Health Service (NHS) with therapies approved by the European Medicines Agency (EMA), under guidance from the National Institute for Health and Clinical Excellence (NICE). This document overviews the current NICE guidelines for the treatment of RA and identifies scenarios when such guidance may not represent the optimum management strategy for individual patients. Specifically, we consider the use of tocilizumab or abatacept as the most appropriate treatments for some patients. In such scenarios, it may be possible for the clinician to secure access to the required therapy through an application procedure known as an ‘individual funding request’, the process of which is described in detail here. At present, it is unclear the extent to which the proposed reform of the NHS will affect the role of NICE in providing guidance and setting standards of care. Until the full impact of the proposed changes are realized, individual funding requests will remain a valuable way of securing the optimal treatment for all patients suffering from RA

Thoracic CT findings of novel influenza A (H1N1) infection in immunocompromised patients

The goal of this study is to describe the spectrum of initial and follow-up CT findings of novel influenza A (H1N1) infection in a series of immunocompromised patients. Eight immunocompromised patients with documented novel influenza A (H1N1) had CT imaging at our institution between May 2009 and August 2009. A total of 20 CTs (initial and follow-up) were reviewed for the presence, severity, and distribution of the following: ground glass opacity, consolidation, interlobular septal thickening, mosaic perfusion, airway wall thickening, airway dilatation, nodules, cysts, pleural effusion, pericardial effusion, lymphadenopathy, and air trapping. The most common findings were airway thickening/dilatation, peribronchial ground glass opacity, centrilobular nodules, and tree-in-bud opacities. Peripheral consolidation involving the lower lobes was also a common pattern. Findings frequently involved all lobes and were closely associated with either large or small airways. Two patients presented with atypical CT findings including focal lobar consolidation and patchy lower lobe consolidation with soft tissue centrilobular nodules. Most survivors showed near complete resolution of findings within 35 days. CT scans in immunocompromised patients with novel influenza H1N1 commonly show a strong airway predominance of findings or peripheral areas of consolidation involving the lower lobes. A subset of patients with novel influenza A (H1N1) will show findings not typical of viral infection

Expression of interleukin 6 (IL-6) correlates with oestrogen receptor in human breast carcinoma

Multifunctional cytokines play important and only partially defined roles in mammary tumour development and progression. Normal human mammary epithelial cells constitutively produce interleukin 6 (IL-6), IL-8 and a non-secreted form of tumour necrosis factor. Transformation of mammary epithelial cells by different oncogenes is frequently associated with alterations of cytokine/growth factor production and responsiveness. In the present study we analysed the expression of IL-6 in 149 cases of invasive breast carcinoma and the data have been correlated with clinico-pathological variables including tumour size, histological grade, nodal status, and oestrogen and progesterone receptors, Ki67 and p53, protein expression. Though the majority of breast carcinomas expressed at least low levels of immunoreactive IL-6, we found that expression of this cytokine was inversely associated with histological tumour grade (P = 0.0017), but not with tumour size and nodal status. Ki67 positivity was inversely correlated with IL-6 expression (P = 0.027). Among biological parameters analysed, a direct association was found between the percentage of IL-6-positive cells and that of oestrogen (P = 0.00005) and progesterone (P = 0.025) receptor-positive cells. No correlation was observed between IL-6 and p53 protein expression. These data indicate that down regulation of IL-6 is associated with highly malignant mammary carcinomas. It will be of interest to evaluate whether alterations of cytokines that are constitutively produced by mammary cells are also associated with high-grade tumours

Predicting RNA secondary structure by the comparative approach: how to select the homologous sequences

<p>Abstract</p> <p>Background</p> <p>The secondary structure of an RNA must be known before the relationship between its structure and function can be determined. One way to predict the secondary structure of an RNA is to identify covarying residues that maintain the pairings (Watson-Crick, Wobble and non-canonical pairings). This "comparative approach" consists of identifying mutations from homologous sequence alignments. The sequences must covary enough for compensatory mutations to be revealed, but comparison is difficult if they are too different. Thus the choice of homologous sequences is critical. While many possible combinations of homologous sequences may be used for prediction, only a few will give good structure predictions. This can be due to poor quality alignment in stems or to the variability of certain sequences. This problem of sequence selection is currently unsolved.</p> <p>Results</p> <p>This paper describes an algorithm, <it>SSCA</it>, which measures the suitability of sequences for the comparative approach. It is based on evolutionary models with structure constraints, particularly those on sequence variations and stem alignment. We propose three models, based on different constraints on sequence alignments. We show the results of the <it>SSCA </it>algorithm for predicting the secondary structure of several RNAs. <it>SSCA </it>enabled us to choose sets of homologous sequences that gave better predictions than arbitrarily chosen sets of homologous sequences.</p> <p>Conclusion</p> <p><it>SSCA </it>is an algorithm for selecting combinations of RNA homologous sequences suitable for secondary structure predictions with the comparative approach.</p

Is the diurnal variation in muscle force output detected/detectable when multi-joint movements are analysed using the musclelab force-velocity encoder?

We have investigated the magnitude of diurnal variation in back squat and bench press performance using the MuscleLab force velocity transducer. Thirty resistance-trained males (mean ± SD: age 21.7 ± 1.4 years; body mass 80.5 ± 4.5 kg; height 1.79 ± 0.06 m) underwent two sessions at different times of day: morning (M, 07:30 h) and evening (E, 17:30 h). Each session included a period when rectal temperature (Trec) was measured at rest, a 5-min standardized 150 W warm-up on a cycle ergometer, then defined programme of bench press (at 20, 40 and 60 kg) and back squat (at 30, 50 and 70 kg) exercises. A linear encoder was attached to an Olympic bar used for the exercises and average force (AF), peak velocity (PV) and time-to-peak velocity (tPV) were measured (MuscleLab software; MuscleLab Technology, Langesund, Norway) during the concentric phase of the movements. Values for Trec at rest were higher in the evening compared to morning values (0.48°C, P < 0.0005). Daily variations were apparent for both bench press and back squat performance for AF (1.9 and 2.5%), PV (8.3 and 12.7%) and tPV (-16.6 and -9.8%; where a negative number indicates a decrease in the variable from morning to evening). There was a main effect for load where AF and tPV increased and PV decreased from the lightest load to the heaviest for both bench press and back squat (47.1 and 80.2%; 31.7 and 57.7%; -42.1 and -73.9%; P < 0.0005 where a negative number indicates a decrease in the variable with increasing load). An interaction was found only for tPV, such that the tPV occurs earlier in the evening than the morning at the highest loads (60 and 70 kg) for both bench press and back squat, respectively (mean difference of 0.32 and 0.62 s). In summary, diurnal variation in back squat and bench press was shown; and the tPV in complex multi-joint movements occurs earlier during the concentric phase of exercise when back squat or bench press is performed in the evening compared to the morning. This difference can be detected using a low cost, portable and widely available commercial instrument and enables translation of past laboratory/tightly controlled experimental research in to main-stream coaching practice

Inflammation and tissue repair markers distinguish the nodular sclerosis and mixed cellularity subtypes of classical Hodgkin's lymphoma

Background: Classical Hodgkin's lymphoma (cHL), although a malignant disease, has many features in common with an inflammatory condition. The aim of this study was to establish the molecular characteristics of the two most common cHL subtypes, nodular sclerosis (NS) and mixed cellularity (MC), based on molecular profiling and immunohistochemistry, with special reference to the inflammatory microenvironment. Methods: We analysed 44 gene expression profiles of cHL whole tumour tissues, 25 cases of NS and 19 cases of MC, using Affymetrix chip technology and immunohistochemistry. Results: In the NS subtype, 152 genes showed a significantly higher expression, including genes involved in extracellular matrix (ECM) remodelling and ECM deposition similar to wound healing. Among these were SPARC, CTSK and COLI. Immunohistochemistry revealed that the NS-related genes were mainly expressed by macrophages and fibroblasts. Fifty-three genes had a higher expression in the MC subtype, including several inflammation-related genes, such as C1Qα, C1Qβ and CXCL9. In MC tissues, the C1Q subunits were mainly expressed by infiltrating macrophages. Conclusions and interpretations: We suggest that the identified subtype-specific genes could reflect different phases of wound healing. Our study underlines the potential function of infiltrating macrophages in shaping the cHL tumour microenvironment