Deadly Carousel or Difficult Interpretation of New Diagnostic Tools for Whipple's Disease: Case Report and Review of the Literature

Abstract : Whipple's disease is a rare systemic disorder classically presenting with weight loss, arthralgias, and diarrhea, which was first described in 1907. The causative bacterium Tropheryma whipplei, is a fastidious organism not growing on conventional media. Before the introduction of polymerase chain reaction (PCR)-based methods, the diagnostic gold standard was histological detection of diastase-resistant periodic acid Schiff (PAS)-positive macrophages or electron microscopy. As in the present case, contradictory results between the former and new diagnostic methods may obscure the correct diagnosis. We critically summarize the performance of the different diagnostic methods and discuss their impact on the clinical management of patients with suspected Whipple's diseas

Body Image Dissatisfaction Among Third, Fourth, and Fifth Grade Children

Body image dissatisfaction has become increasingly more prevalent among the preadolescent population over recent years. This study examines the level of body image dissatisfaction among 261 third, fourth, and fifth grade girls and boys. A pictorial scale was used to assess how the participants viewed their current body shape, their ideal body shape, and what they believed to be the ideal body shape of the opposite gender. Overall results indicated that 50.6% of the children surveyed were dissatisfied with their current body shape, 41.8% wanted to be thinner, while 8.8% wanted to be larger. Fifty percent of the girls were dissatisfied with their current body shape, with 45.1% wishing to be thinner. Boys showed similar trends, with 48.9% dissatisfied and 38.9% wishing to be thinner. A greater percentage of boys wanted to be larger than their current body shape (12.3%) compared to girls (4.9%). A significant difference was found between genders regarding the difference between scores of their current self and ideal self, where girls selected a smaller ideal body shape than the boys. An encouraging finding was that the level of body dissatisfaction decreased from third grade to fifth grade among both genders. Girls, however, still wished to be thinner over time. Boys, on the other hand, indicated a preference for a somewhat larger body shape over time. These results indicate that body image dissatisfaction exists prior to adolescence among this sample of children. Prevention strategies and education are encouraged among this age group

An exploration of concepts of community through a case study of UK university web production

The paper explores the inter-relation and differences between the concepts of occupational community, community of practice, online community and social network. It uses as a case study illustration the domain of UK university web site production and specifically a listserv for those involved in it. Different latent occupational communities are explored, and the potential for the listserv to help realize these as an active sense of community is considered. The listserv is not (for most participants) a tight knit community of practice, indeed it fails many criteria for an online community. It is perhaps best conceived as a loose knit network of practice, valued for information, implicit support and for the maintenance of weak ties. Through the analysis the case for using strict definitions of the theoretical concepts is made

Bioactivity in silica/poly(γ-glutamic acid) sol–gel hybrids through calcium chelation

Bioactive glasses and inorganic/organic hybrids have great potential as biomedical implant materials. Sol–gel hybrids with interpenetrating networks of silica and biodegradable polymers can combine the bioactive properties of a glass with the toughness of a polymer. However, traditional calcium sources such as calcium nitrate and calcium chloride are unsuitable for hybrids. In this study calcium was incorporated by chelation to the polymer component. The calcium salt form of poly(γ-glutamic acid) (γCaPGA) was synthesized for use as both a calcium source and as the biodegradable toughening component of the hybrids. Hybrids of 40 wt.% γCaPGA were successfully formed and had fine scale integration of Ca and Si ions, according to secondary ion mass spectrometry imaging, indicating a homogeneous distribution of organic and inorganic components. 29Si magic angle spinning nuclear magnetic resonance data demonstrated that the network connectivity was unaltered with changing polymer molecular weight, as there was no perturbation to the overall Si speciation and silica network formation. Upon immersion in simulated body fluid a hydroxycarbonate apatite surface layer formed on the hybrids within 1 week. The polymer molecular weight (Mw 30–120 kDa) affected the mechanical properties of the resulting hybrids, but all hybrids had large strains to failure, >26%, and compressive strengths, in excess of 300 MPa. The large strain to failure values showed that γCaPGA hybrids exhibited non-brittle behaviour whilst also incorporating calcium. Thus calcium incorporation by chelation to the polymer component is justified as a novel approach in hybrids for biomedical materials

Considerations for a European animal welfare standard to evaluate adverse phenotypes in teleost fish

No abstract available

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

Endothelial alpha-parvin controls integrity of developing vasculature and is required for maintenance of cell-cell junctions

RATIONALE: Angiogenesis and vessel integrity depend on the adhesion of endothelial cells (EC) to the extracellular matrix (ECM) and to adjacent ECs. The focal adhesion protein alpha-parvin (alpha-pv) is essential for vascular development. However, the role of alpha-pv in ECs in vivo is not known. OBJECTIVE: To determine the function of alpha-pv in ECs during vascular development in vivo and the underlying mechanisms. METHODS AND RESULTS: We deleted the alpha-pv gene specifically in ECs of mice to study its role in angiogenesis and vascular development. Here we show that endothelial-specific deletion of alpha-pv in mice results in late embryonic lethality associated with hemorrhages and reduced vascular density. Postnatal induced EC-specific deletion of alpha-pv leads to retinal hypovascularization due to reduced vessel sprouting and excessive vessel regression. In the absence of alpha-pv, blood vessels display impaired VE-cadherin junction morphology. In vitro, alpha-pv deficient ECs show reduced stable adherens junctions, decreased monolayer formation and impaired motility, associated with reduced formation of integrin-mediated cell-ECM adhesion structures and an altered actin cytoskeleton. CONCLUSIONS: Endothelial alpha-pv is essential for vessel sprouting and for vessel stability

Lithium storage mechanisms in purpurin based organic lithium ion battery electrodes

Current lithium batteries operate on inorganic insertion compounds to power a diverse range of applications, but recently there is a surging demand to develop environmentally friendly green electrode materials. To develop sustainable and eco-friendly lithium ion batteries, we report reversible lithium ion storage properties of a naturally occurring and abundant organic compound purpurin, which is non-toxic and derived from the plant madder. The carbonyl/hydroxyl groups present in purpurin molecules act as redox centers and reacts electrochemically with Li-ions during the charge/discharge process. The mechanism of lithiation of purpurin is fully elucidated using NMR, UV and FTIR spectral studies. The formation of the most favored six membered binding core of lithium ion with carbonyl groups of purpurin and hydroxyl groups at C-1 and C-4 positions respectively facilitated lithiation process, whereas hydroxyl group at C-2 position remains unaltered

Biogenetically-Inspired Total Synthesis of Epidithiodiketopiperazines and Related Alkaloids

Natural products chemistry has historically been the prime arena for the discovery of new chemical transformations and the fountain of insights into key biological processes. It remains a fervent incubator of progress in the fields of chemistry and biology and an exchange mediating the flow of ideas between these allied fields of science. It is with this ethos that our group has taken an interest in and pursued the synthesis of a complex family of natural products termed the dimeric epipolythiodiketopiperazine (ETP) alkaloids. We present here an Account of the highly complex target molecules to which we pegged our ambitions, our systematic and relentless efforts toward those goals, the chemistry we developed in their pursuit, and the insight we have gained for their translational potential as potent anticancer molecules.National Institute of General Medical Sciences (U.S.) (Grant GM089732)Amgen Inc