Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

Let us not neglect the impact of organizational culture on increasing diversity within medical schools.

Peer reviewedPublisher PD

Impact of Age and Body Site on Adult Female Skin Surface pH

Background: pH is known as an important parameter in epidermal barrier function and homeostasis. Aim: The impact of age and body site on skin surface pH (pH(SS)) of women was evaluated in vivo. Methods: Time domain dual lifetime referencing with luminescent sensor foils was used for pH(SS) measurements. pH(SS) was measured on the forehead, the temple, and the volar forearm of adult females (n = 97, 52.87 +/- 18.58 years, 20-97 years). Every single measurement contained 2,500 pH values due to the luminescence imaging technique used. Results: pH(SS) slightly increases with age on all three investigated body sites. There are no significant differences in pH(SS) between the three investigated body sites. Conclusion: Adult pH(SS) on the forehead, the temple and the volar forearm increases slightly with age. This knowledge is crucial for adapting medical skin care products. Copyright (C) 2012 S. Karger AG, Base

Flavor in Minimal Conformal Technicolor

We construct a complete, realistic, and natural UV completion of minimal conformal technicolor that explains the origin of quark and lepton masses and mixing angles. As in "bosonic technicolor", we embed conformal technicolor in a supersymmetric theory, with supersymmetry broken at a high scale. The exchange of heavy scalar doublets generates higher-dimension interactions between technifermions and quarks and leptons that give rise to quark and lepton masses at the TeV scale. Obtaining a sufficiently large top quark mass requires strong dynamics at the supersymmetry breaking scale in both the top and technicolor sectors. This is natural if the theory above the supersymmetry breaking also has strong conformal dynamics. We present two models in which the strong top dynamics is realized in different ways. In both models, constraints from flavor-changing effects can be easily satisfied. The effective theory below the supersymmetry breaking scale is minimal conformal technicolor with an additional light technicolor gaugino. We argue that this light gaugino is a general consequence of conformal technicolor embedded into a supersymmetric theory. If the gaugino has mass below the TeV scale it will give rise to an additional pseudo Nambu-Goldstone boson that is observable at the LHC.Comment: 37 pages; references adde

Strategy-Focused Agile Transformation: A Case Study

Strategic agility enables an organisation to sense and seize opportunities, manage uncertainty and adapt to changes. This paper presents one case study of a traditional charitable organisation taking a strategy-focused approach to agile transformation. Interview data was collected over a 13-month period through interviews at different stages and with different members of the transformation team and Heads of Department. This case study illustrates the challenges faced in such a transformation, and shows that strategic agility requires different time horizons to co-exist: a future vision, a medium term set of objectives and a short term performance monitoring perspective

Minimal Conformal Technicolor and Precision Electroweak Tests

We study the minimal model of conformal technicolor, an SU(2) gauge theory near a strongly coupled conformal fixed point, with conformal symmetry softly broken by technifermion mass terms. Conformal symmetry breaking triggers chiral symmetry breaking in the pattern SU(4) -> Sp(4), which gives rise to a pseudo-Nambu-Goldstone boson that can act as a composite Higgs boson. The top quark is elementary, and the top and electroweak gauge loop contributions to the Higgs mass are cut off entirely by Higgs compositeness. In particular, the model requires no top partners and no "little Higgs" mechanism. A nontrivial vacuum alignment results from the interplay of the top loop and technifermion mass terms. The composite Higgs mass is completely determined by the top loop, in the sense that m_h/m_t is independent of the vacuum alignment and is computable by a strong-coupling calculation. There is an additional composite pseudoscalar A with mass larger than m_h and suppressed direct production at LHC. We discuss the electroweak fit in this model in detail. Corrections to Z -> bb and the T parameter from the top sector are suppressed by the enhanced Sp(4) custodial symmetry. Even assuming that the strong contribution to the S parameter is positive and usuppressed, a good electroweak fit can be obtained for v/f ~ 0.25, where v and f are the electroweak and chiral symmetry breaking scales respectively. This requires fine tuning at the 10% level.Comment: 34 pages, 4 figures; v2: updated precision electroweak fi

Prognostic value of hematogenous dissemination and biological profile of the tumor in early breast cancer patients: A prospective observational study

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate the incidence and prognostic value of disseminated tumor cells in bone marrow of breast carcinoma patients with early disease, and to analyze this finding in relation to lymph node involvement, determined by sentinel lymph node (SLN) biopsy analysis, and to prognostic factors of interest.</p> <p>Methods</p> <p>104 patients with operable (T < 3 cm) breast cancer and clinically- and sonographically-negative axillary lymph nodes were scheduled for SLN biopsy. Bone marrow aspirates were collected before the start of surgery from both iliac crests, and mononuclear cell layers were separated by density centrifugation (Lymphoprep). Slide preparations were then examined for the presence of disseminated tumor cells by immunocytochemistry with anti-cytokeratin antibodies (A45-B/B3). Lymphoscintigraphy was performed 2 hours after intratumor administration of 2 mCi (74 MBq) of 99mTc colloidal albumin. The SLN was evaluated for the presence of tumor cells by hematoxylin-eosin staining and, when negative, by immunocytochemistry using anti-cytokeratin antibody (CAM 5.2). Survival analyses and comparative analyses were performed on the results of bone marrow determinations, SLN biopsy, and known prognostic factors, including breast cancer subtypes according to the simplified classification based on ER, PR and HER2.</p> <p>Results</p> <p>Lymph node and hematogenous dissemination occur in one-third of patients with early-stage breast cancer, although not necessarily simultaneously. In our study, disseminated tumor cells were identified in 22% of bone marrow aspirates, whereas 28% of patients had axillary lymph node involvement. Simultaneous lymph node and bone marrow involvement was found in only 5 patients (nonsignificant). In the survival study (60 months), a higher, although nonsignificant rate of disease-related events (13%) was seen in patients with disseminated tumor cells in bone marrow, and a significant association of events was documented with the known, more aggressive tumor subtypes: triple negative receptor status (21%) and positive ERBB2 status (29%).</p> <p>Conclusions</p> <p>Tumor cell detection in bone marrow can be considered a valid prognostic parameter in patients with early disease. However, the classic prognostic factors remain highly relevant, and the newer breast cancer subtypes are also useful for this purpose.</p

Fair play:Perceived fairness in crowdsourcing competitions and the customer relationship-related consequences

TeleRehab enables the rehabilitation services to be delivered in distance by providing information exchange between patient with disabilities and the clinical professionals. The readiness step in any adoption of healthcare services should always be one of the requirements for a successful implementation of an innovation. However, little scholarly has been undertaken to study its influence on TeleRehab and the various barrier factors that influence its adoption. This research explores the barrier factors that influence the readiness of healthcare institution to adopt TeleRehab. This paper presents a semi-structured interview involving 23 clinical professionals of a case study on the issues of TeleRehab readiness in one rehabilitation centre in Malaysia. By applying thematic analysis, the study uncovers seven barriers that affect the TeleRehab readiness. This includes barriers of no urgency to change, less awareness, less involvement in planning, not enough exposure on e-Healthcare knowledge, resistance to change, low usage of hardware and software, and less connectivity. The study contributes to both TeleRehab management and technology readiness research in hospitals

Infliximab: 12 years of experience

Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are immune-mediated conditions that share an inflammatory mechanism fuelled by excessive cytokines, particularly TNF. Control of inflammation and rapid suppression of cytokines are important in treating these diseases. With this understanding and the corresponding advent of TNF inhibitors, RA patients, AS patients and PsA patients have found more choices than ever before and have greater hope of sustained relief. As a widely used TNF inhibitor, infliximab has a deep and established record of efficacy and safety data. Extensive evidence - from randomised controlled clinical trials, large registries and postmarketing surveillance studies - shows that infliximab effectively treats the signs and symptoms, provides rapid and prolonged suppression of inflammation, prevents radiologically observable disease progression and offers an acceptable safety profile in RA, AS and PsA. In very recent studies, investigators have observed drug-free remission in some patients. Additionally, infliximab may interfere with rapidly progressing disease in RA by early addition to methotrexate in patients with signs of an aggressive course. Finally, infliximab has been shown to reduce PsA clinical manifestations such as nail involvement. With our current understanding, substantial data and increasing confidence regarding use in practice, infliximab can be considered a well-known drug in our continued campaign against inflammatory rheumatic diseases

Collective Dynamics of Gene Expression in Cell Populations

The phenotypic state of the cell is commonly thought to be determined by the set of expressed genes. However, given the apparent complexity of genetic networks, it remains open what processes stabilize a particular phenotypic state. Moreover, it is not clear how unique is the mapping between the vector of expressed genes and the cell's phenotypic state. To gain insight on these issues, we study here the expression dynamics of metabolically essential genes in twin cell populations. We show that two yeast cell populations derived from a single steady-state mother population and exhibiting a similar growth phenotype in response to an environmental challenge, displayed diverse expression patterns of essential genes. The observed diversity in the mean expression between populations could not result from stochastic cell-to-cell variability, which would be averaged out in our large cell populations. Remarkably, within a population, sets of expressed genes exhibited coherent dynamics over many generations. Thus, the emerging gene expression patterns resulted from collective population dynamics. It suggests that in a wide range of biological contexts, gene expression reflects a self-organization process coupled to population-environment dynamics