Chronic postoperative Roseomonas endophthalmitis

We report one case with chronic postoperative endophthalmitis caused by Roseomonas species. Roseomonas spp. induced chronic endophthalmitis, which might result in misdiagnosis and delayed treatment and causes ocular damage and severe visual loss. This report is the first one related to a case with postoperative endophthalmitis secondary to Roseomonas infection.     

Tissue-engineered polyethylene oxide/chitosan scaffolds as potential substitutes for articular cartilage

Applications of composite scaffolds comprising polyethylene oxide (PEO) and chitosan to the culture of bovine knee chondrocytes (BKC) were investigated. Here, PEO and chitosan with various weight ratios were crosslinked, refrigerated at -80 degrees C, and lyophilized. Pore surfaces of the PEO/chitosan scaffolds were chemically modified by human fibronectin for accelerating BKC adhesion and growth. The results revealed that the range of pore diameters was between 200 and 400 mum. A high content of PEO in scaffolds generated high porosity, moisture content, physical ductility, biodegradation rate, and BKC viability, as well as low Young's and compression moduli. High levels of PEO, human fibronectin, and extracellular calcium were favorable to the BKC culture, as indicated by the enhanced amounts of BKC, glycosaminoglycans, and collagen. However, a high concentration of medium potassium caused detrimental influences on the proliferation of BKC and the secretion of extracellular matrices. The present PEO/chitosan scaffolds showed enhancements in biomedical characteristics for the formation of tissue-engineered cartilage toward clinical prosthesis.     

A systems analysis of the chemosensitivity of breast cancer cells to the polyamine analogue PG-11047

Background

When this trial was initiated, the combined measles, mumps and rubella (MMR) vaccine was licensed for subcutaneous administration in all European countries and for intramuscular administration in some countries, whereas varicella vaccine was licensed only for subcutaneous administration. This study evaluated the intramuscular administration of an MMR vaccine (M-M-RvaxPro^®) and a varicella vaccine (VARIVAX^®) compared with the subcutaneous route.

Methods

An open-label randomised trial was performed in France and Germany. Healthy children, aged 12 to18 months, received single injections of M-M-RvaxPro and VARIVAX concomitantly at separate injection sites. Both vaccines were administered either intramuscularly (IM group, n = 374) or subcutaneously (SC group, n = 378). Immunogenicity was assessed before vaccination and 42 days after vaccination. Injection-site erythema, swelling and pain were recorded from days 0 to 4 after vaccination. Body temperature was monitored daily between 0 and 42 days after vaccination. Other adverse events were recorded up to 42 days after vaccination and serious adverse events until the second study visit.

Results

Antibody response rates at day 42 in the per-protocol set of children initially seronegative to measles, mumps, rubella or varicella were similar between the IM and SC groups for all four antigens. Response rates were 94 to 96% for measles, 98% for both mumps and rubella and 86 to 88% for varicella. For children initially seronegative to varicella, 99% achieved the seroconversion threshold (antibody concentrations of ≥ 1.25 gpELISA units/ml). Erythema and swelling were the most frequently reported injection-site reactions for both vaccines. Most injection-site reactions were of mild intensity or small size (≤ 2.5 cm). There was a trend for lower rates of injection-site erythema and swelling in the IM group. The incidence and nature of systemic adverse events were comparable for the two routes of administration, except varicella-like rashes, which were less frequent in the IM group.

Conclusion

The immunogenicities of M-M-RvaxPro and VARIVAX administered by the intramuscular route were comparable with those following subcutaneous administration, and the tolerability of the two vaccines was comparable regardless of administration route. Integration of both administration routes in the current European indications for the two vaccines will now allow physicians in Europe to choose their preferred administration route in routine clinical practice.

Trial registration

ClinicalTrials.gov NCT00432523     

Immune and non-immune functions of the (not so) neonatal Fc receptor,FcRn

Careful regulation of the body’s immunoglobulin-G (IgG) and albumin concentrations is necessitated by the importance of their respective functions. As such, the neonatal Fc receptor (FcRn) which, as a single receptor, is capable of regulating both of these molecules, has become an important focus of investigation. In addition to these essential protection functions, FcRn possesses a host of other functions that are equally as critical. During the very first stages of life, FcRn mediates the passive transfer of IgG from mother to offspring both before and after birth. In the adult, FcRn regulates the persistence of both IgG and albumin in the serum as well as the movement of IgG, and any bound cargo, between different compartments of the body. This shuttling allows for the movement not only of monomeric ligand but also of antigen/antibody complexes from one cell type to another in such a way as to facilitate the efficient initiation of immune responses towards opsonized pathogens. As such, FcRn continues to play the role of an immunological sensor throughout adult life, particularly in regions such as the gut which are exposed to a large number of infectious antigens. Increasing appreciation for the contributions of FcRn to both homeostatic and pathological states is generating an intense interest in the potential for therapeutic modulation of FcRn binding. A greater understanding of FcRn’s pleiotropic roles is thus imperative for a variety of therapeutic purposes.     

Efficient Calculation of Empirical <Emphasis Type="Italic">P</Emphasis>-values for Genome-Wide Linkage Analysis Through Weighted Permutation

Linkage analysis in multivariate or longitudinal context presents both statistical and computational challenges. The permutation test can be used to avoid some of the statistical challenges, but it substantially adds to the computational burden. Utilizing the distributional dependencies between (defined as the proportion of alleles at a locus that are identical by descent (IBD) for a pairs of relatives, at a given locus) and the permutation test we report a new method of efficient permutation. In summary, the distribution of for a sample of relatives at locus x is estimated as a weighted mixture of drawn from a pool of ‘representative’ distributions observed at other loci. This weighting scheme is then used to sample from the distribution of the permutation tests at the representative loci to obtain an empirical P-value at locus x (which is asymptotically distributed as the permutation test at loci x). This weighted mixture approach greatly reduces the number of permutation tests required for genome-wide scanning, making it suitable for use in multivariate and other computationally intensive linkage analyses. In addition, because the distribution of is a property of the genotypic data for a given sample and is independent of the phenotypic data, the weighting scheme can be applied to any phenotype (or combination of phenotypes) collected from that sample. We demonstrate the validity of this approach through simulation. Edited by David Allison.     

An Interaction of Oxytocin Receptors with Metabotropic Glutamate Receptors in Hypothalamic Astrocytes

Hypothalamic astrocytes play a critical role in the regulation and support of many different neuroendocrine events, and are affected by oestradiol. Both nuclear and membrane oestrogen receptors (ERs) are expressed in astrocytes. Upon oestradiol activation, membrane‐associated ER signals through the type 1a metabotropic glutamate receptor (mGluR1a) to induce an increase of free cytoplasmic calcium concentration ([Ca²⁺]_i). Because the expression of oxytocin receptors (OTRs) is modulated by oestradiol, we tested whether oestradiol also influences oxytocin signalling. Oxytocin at 1, 10, and 100 nm induced a [Ca²⁺]_i flux measured as a change in relative fluorescence [ΔF Ca²⁺ = 330 ± 17 relative fluorescent units (RFU), ΔF Ca²⁺ = 331 ± 22 RFU, and ΔF Ca²⁺ = 347 ± 13 RFU, respectively] in primary cultures of female post‐pubertal hypothalamic astrocytes. Interestingly, OTRs interacted with mGluRs. The mGluR1a antagonist, LY 367385 (20 nm ), blocked the oxytocin (1 nm )‐induced [Ca²⁺]_i flux (ΔF Ca²⁺ = 344 ± 19 versus 127 ± 11 RFU, P < 0.001). Conversely, the mGluR1a receptor agonist, (RS)‐3,5‐dihydroxyphenyl‐glycine (100 nm ), increased the oxytocin (1 nm )‐induced [Ca²⁺]_i response (ΔF Ca²⁺ = 670 ± 31 RFU) compared to either compound alone (P < 0.001). Because both oxytocin and oestradiol rapidly signal through the mGluR1a, we treated hypothalamic astrocytes sequentially with oxytocin and oestradiol to determine whether stimulation with one hormone affected the subsequent [Ca²⁺]_i response to the second hormone. Oestradiol treatment did not change the subsequent [Ca²⁺]_i flux to oxytocin (P > 0.05) and previous oxytocin exposure did not affect the [Ca²⁺]_i response to oestradiol (P > 0.05). Furthermore, simultaneous oestradiol and oxytocin stimulation failed to yield a synergistic [Ca²⁺]_i response. These results suggest that the OTR signals through the mGluR1a to release Ca²⁺ from intracellular stores and rapid, nongenomic oestradiol stimulation does not influence OTR signalling in astrocytes.     

Sensory Acquisition in the Cerebellum: An fMRI Study of Cerebrocerebellar Interaction During Visual Duration Discrimination

It has been suggested that the cerebellum participates in diverse neuropsychological functions by adjusting the sensory information acquired for the connected brain regions to support its processing capabilities. Nevertheless, the knowledge of how the cerebellum is modulated by the sensory information is far from clear. Function magnetic resonance imaging was exploited to investigate how the cerebellum activity and cerebrocerebellum interaction can be affected by the interaction between visual size and duration information during visual duration discrimination. The present findings support the sensory acquisition hypothesis that the cerebellum, together with extensive cortical networks, yields higher activation with incongruent sensory information to cope with increasing cortical computational demand. Furthermore, comprehensive intracerebellum connections are engaged in tasks with congruent sensory information for saving cortical computation with integrated sensory information.     

The Role of Non-invasive Ventilation and Factors Predicting Extubation Outcome in Myasthenic Crisis

Introduction  Myasthenic crisis is a great threat to patients with myasthenia gravis. Usage of non-invasive ventilation (NIV) to prevent intubation and timing of extubating of patients in myasthenic crisis are important issues though not well documented. Methods  To explore the factors predicting NIV success and extubation outcome in myasthenic crisis, we reviewed the records of 41 episodes of myasthenia crisis. Results  NIV was applied to 14 episodes of myasthenic crisis and eight (57.1%) of them were successfully prevented from intubation. An Acute Physiology and Chronic Health Evaluation (APACHE) II score of <6 and a serum bicarbonate level of <30 mmol/l were independent predictors of NIV success. For patients undergoing invasive mechanical ventilation, extubation failure was observed in 13 (39.4%) of 33 episodes, and the most common cause was sputum impaction due to a poor cough strength (61.5%). A maximal expiratory pressure (Pemax) of ≥40 cmH₂O was a good predictor of extubation success. Extubation failure led to poorer outcomes. Conclusions  NIV may be applied to those patients with a low APACHE II score and a lesser degree of metabolic compensation for respiratory acidosis. For patients undergoing invasive mechanical ventilation, extubation failure is associated with significant in-hospital morbidity in myasthenic crisis. Adequate levels of Pemax and cough strength correlate significantly with extubation success.