Soluble mediators in platelet concentrates modulate dendritic cell inflammatory responses in an experimental model of transfusion

The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose associated suppression of the production of DC IL-12, IL-6, IL-1a, tumor necrosis factor-a (TNF-a), and macrophage inflammatory protein (MIP)-1b and storage-associated suppression of the production of DC IL-10, TNF-a, and IL-8. For the overall inflammatory response, IL-6, TNF-a, MIP-1a, MIP-1b, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1b significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications.

Agreement between physiotherapists rating scapular posture in multiple planes in patients with neck pain: Reliability study

Objective Evaluation of scapular posture is an integral component of the clinical assessment of painful neck disorders. The aim of this study was to evaluate agreement between therapist judgements of scapula posture in multiple biomechanical planes in individuals with neck pain. Design Inter-therapist reliability study. Setting Research laboratory. Participants Fifteen participants with chronic neck pain. Main outcome measures Four physiotherapists recorded ratings of scapular orientation (relative to the thorax) in five different scapula postural planes (plane of scapula, sagittal plane, transverse plane, horizontal plane, and vertical plane) under four test conditions (at rest, and during three isometric shoulder conditions) in all participants. Inter-therapist reliability was expressed using both generalized and paired kappa coefficient. Results Following adjustment for expected agreement and the high prevalence of neutral ratings (81%), on average both the generalised kappa (0.37) as well as Cohen's Kappa for the two therapist pairs (0.45 and 0.42) demonstrated only slight to moderate inter-therapist reliability. Conclusions The findings suggest that ratings of scapular posture in individuals with neck pain by visual inspection has only slight to moderate reliability and should only be used in conjunction with other clinical tests when judging scapula function in these patients.

Reply to comment on 'Bi nanolines on Si(001): Registry with the substrate'

The registry of bismuth dimers, integral components of the bismuth nanoline on Si(001), is examined. In contrast to the currently accepted view, the bismuth dimers are found to be in registry with the two-dimensional lattice created by the silicon dimers. The consequences of this finding are briefly explored.

Staphylococcus epidermidis as a cause of bacteremia

Staphylococcus epidermidis is a biofilm-producing commensal organism found ubiquitously on human skin and mucous membranes, as well as on animals and in the environment. Biofilm formation enables this organism to evade the host immune system. Colonization of percutaneous devices or implanted medical devices allows bacteria access to the bloodstream. Isolation of this organism from blood cultures may represent either contamination during the blood collection procedure or true bacteremia. S. epidermidis bloodstream infections may be indolent compared with other bacteria. Isolation of S. epidermidis from a blood culture may present a management quandary for clinicians. Over-treatment may lead to patient harm and increases in healthcare costs. There are numerous reports indicating the difficulty of predicting clinical infection in patients with positive blood cultures with this organism. No reliable phenotypic or genotypic algorithms currently exist to predict the pathogenicity of a S. epidermidis bloodstream infection. This review will discuss the latest advances in identification methods, global population structure, pathogenicity, biofilm formation, antimicrobial resistance and clinical significance of the detection of S. epidermidis in blood cultures. Previous studies that have attempted to discriminate between invasive and contaminating strains of S. epidermidis in blood cultures will be analyzed.

The genetic associations of acute anterior uveitis and their overlap with the genetics of ankylosing spondylitis

Acute anterior uveitis (AAU) involves inflammation of the iris and ciliary body of the eye. It occurs both in isolation and as a complication of ankylosing spondylitis (AS). It is strongly associated with HLA-B*27, but previous studies have suggested that further genetic factors may confer additional risk. We sought to investigate this using the Illumina Exomechip microarray, to compare 1504 cases with AS and AAU, 1805 with AS but no AAU and 21 133 healthy controls. We also used a heterogeneity test to test the differences in effect size between AS with AAU and AS without AAU. In the analysis comparing AS+AAU+ cases versus controls, HLA-B*27 and HLA-A*02:01 were significantly associated with the presence of AAU (P<10−300 and P=6 × 10−8, respectively). Secondary independent association with PSORS1C3 (P=4.7 × 10−5) and TAP2 (P=1.1 × 10−5) were observed in the major histocompatibility complex. There was a new suggestive association with a low-frequency variant at zinc-finger protein 154 in the AS without AAU versus control analysis (zinc-finger protein 154 (ZNF154), P=2.2 × 10−6). Heterogeneity testing showed that rs30187 in ERAP1 has a larger effect on AAU compared with that in AS alone. These findings also suggest that variants in ERAP1 have a differential impact on the risk of AAU when compared with AS, and hence the genetic risk for AAU differs from AS.