Spot diagnosis: An ominous rash in a newborn

Purpura fulminans (PF) is an ominous cutaneous condition usually associated with meningococcemia. PF in the newborn is rarely reported. We report the case of a female preterm infant with extensive PF due to group B streptococcus (GBS) septicemia. She developed multi-organ system failure despite neonatal intensive care support and succumbed 9 days later. GBS, sensitive to penicillin, was isolated from the blood cultures of the mother and the infant. Invasive early GBS infection is common in the newborn and is empirically treated with prompt institution of intravenous antibiotics. PF associated with GBS is a rare cutaneous sign that must not be missed. Mortality remains high despite aggressive treatment and ICU support

Recent advances in the compound-oriented and pattern-oriented approaches to the quality control of herbal medicines

The current approaches to the quality control of herbal medicines are either compound-oriented or pattern-oriented, the former targeting specific components with some known chemical properties and the latter targeting all detectable components. The marker approach uses specific chemical compounds with known molecular structures, while the multi-compound approach uses both chemical compounds with known structures and those with partial chemical information e.g. retention times, mass spectra and ultraviolet spectra. Apart from chromatographic techniques, new techniques such as oscillating and electrochemistry fingerprints have been developed for quality control. Chemometric resolution methods are widely used for component deconvolution and data comparison. Pattern recognition techniques are used for authentication of herbal medicines

Identification of QTL genes for BMD variation using both linkage and gene-based association approaches

Low bone mineral density (BMD) is a risk factor for osteoporotic fracture with a high heritability. Previous large scale linkage study in Northern Chinese has identified four significant quantitative trait loci (QTL) for BMD variation on chromosome 2q24, 5q21, 7p21 and 13q21. We performed a replication study of these four QTL in 1,459 Southern Chinese from 306 pedigrees. Successful replication was observed on chromosome 5q21 for femoral neck BMD with a LOD score of 1.38 (nominal p value = 0.006). We have previously identified this locus in a genome scan meta-analysis of BMD variation in a white population. Subsequent QTL-wide gene-based association analysis in 800 subjects with extreme BMD identified CAST and ERAP1 as novel BMD candidate genes (empirical p value of 0.032 and 0.014, respectively). The associations were independently replicated in a Northern European population (empirical p value of 0.01 and 0.004 for CAST and ERAP1, respectively). These findings provide further evidence that 5q21 is a BMD QTL, and CAST and ERAP1 may be associated with femoral neck BMD variation

How students cope with part-time study

This study provides a qualitative test and illustration of a model of how students cope with the demands of part-time study. The model shows that students who are successful in finding the time to complete the requirements of part-time courses do so by adopting three mechanisms; sacrifice, support and the negotiation of arrangements. All three mechanisms operate in four domains, namely work, family, social lives and the self. The mechanisms and domains were related together in a three by four matrix. Data to verify and illuminate the model were gathered by the researchers through an on-line forum discussion on the topic of coping with part-time study. The researchers themselves were studying part-time in a course called Adult Education and Professional Development. Analysis of the data showed that the work domain was very important but little adaptation was possible. The family was seen as the most important domain and all three mechanisms were used. Time was commonly found for part-time study by sacrificing social lives. The self-domain was interpreted as important in establishing motivation and self-determination

Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Dijet Resonance Search with Weak Supervision Using root S=13 TeV pp Collisions in the ATLAS Detector

This Letter describes a search for narrowly resonant new physics using a machine-learning anomaly detection procedure that does not rely on signal simulations for developing the analysis selection. Weakly supervised learning is used to train classifiers directly on data to enhance potential signals. The targeted topology is dijet events and the features used for machine learning are the masses of the two jets. The resulting analysis is essentially a three-dimensional search A → BC, for mA ∼ OðTeVÞ, mB; mC ∼ Oð100 GeVÞ and B, C are reconstructed as large-radius jets, without paying a penalty associated with a large trials factor in the scan of the masses of the two jets. The full run 2 ffiffi s p ¼ 13 TeV pp collision dataset of 139 fb−1 recorded by the ATLAS detector at the Large Hadron Collider is used for the search. There is no significant evidence of a localized excess in the dijet invariant mass spectrum between 1.8 and 8.2 TeV. Cross-section limits for narrow-width A, B, and C particles vary with mA, mB, and mC. For example, when mA ¼ 3 TeV and mB ≳ 200 GeV, a production cross section between 1 and 5 fb is excluded at 95% confidence level, depending on mC. For certain masses, these limits are up to 10 times more sensitive than those obtained by the inclusive dijet search. These results are complementary to the dedicated searches for the case that B and C are standard model boson

The morphological plasticity of Retiral ganglion cells during development and regeneration: a luciferyellow intracellular injection study

published_or_final_versionAnatomyDoctoralDoctor of Philosoph

Effects of visual or light deprivation on the morphology, and the elimination of the transient features during development, of Type I retinal ganglion cells in hamsters

Intracellular injection of Lucifer Yellow (LY) was used to study the detailed morphology of the normal, visually deprived, and light-deprived superior colliculus projecting Type I retinal ganglion cells (RGCs) in hamsters. The soma size of the normal Type I cells ranged from 337 to 583 μm2 with a mean of 436 μm2. Two to six primary dendrites were observed in these cells. The mean dendritic field diameter was 495 μm and ranged from 309 to 702 μm. The dendritic field diameter of this population of cells exhibited an eccentricity dependence. Quantitative comparisons between the normal and visually deprived or light-deprived Type I RGCs indicated that the morphology of these three groups of cells were similar to each other in terms of the soma size, dendritic field diameter, branching pattern, and total length of the dendrites. During the normal development of cats and hamsters, several transient features, such as exuberant dendritic spines and intraretinal axonal branches, have been observed in the developing RGCs. The complete elimination of these transient features occurs at about 3 and 2 weeks after the opening of the eyes in cats and hamsters, respectively. In the present study, the hypothesis whether visual experience or light stimulation is required for the elimination of these transient features during development was examined. After studying a total of 115 mature Type I RGCs, which included cells from the normal, visually deprived, and light deprived animals, no transient feature was observed. We conclude that visual or light deprivation has no effect on the morphological development of superior colliculus projecting Type I RGCs in hamsters, and the elimination of the transient features on the Type I RGCs during development does not depend on visual experience or light stimulation.link_to_subscribed_fulltex