A phase 3 multicenter, prospective, open-label efficacy and safety study of immune globulin (human) 10% caprylate/chromatography purified in patients with myasthenia gravis exacerbations

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission. Exacerbations may involve increasing bulbar weakness and/or sudden respiratory failure, both of which can be critically disabling. Management of MG exacerbations includes plasma exchange and intravenous immunoglobulin (IVIG); they are equally effective, but patients experience fewer side effects with IVIG. The objective of this study was to assess the efficacy and safety of immune globulin caprylate/chromatography purified (IGIV-C) in subjects with MG exacerbations. Methods: This prospective, open-label, non-controlled 28-day clinical trial was conducted in adults with MG Foundation of America class IVb or V status. Subjects received IGIV-C 2 g/kg over 2 consecutive days (1 g/kg/day) and were assessed for efficacy/safety on Days 7, 14, 21, and 28. The primary efficacy endpoint was the change from Baseline in quantitative MG (QMG) score to Day 14. Secondary endpoints of clinical response, Baseline to Day 14, included at least a 3-point decrease in QMG and MG Composite and a 2-point decrease in MG-activities of daily living (MG-ADL). Results: Forty-nine subjects enrolled. The change in QMG score at Day 14 was significant (p < 0.001) in the Evaluable (-6.4, n = 43) and Safety (-6.7, n = 49) populations. Among evaluable subjects, Day 14 response rates were 77, 86, and 88% for QMG, MG Composite, and MG-ADL, respectively. IGIV-C showed good tolerability with no serious adverse events. Conclusions: The results of this study show that IGIV-C was effective, safe, and well tolerated in the treatment of MG exacerbations

Comparing the hierarchy of keywords in on-line news portals

The tagging of on-line content with informative keywords is a widespread phenomenon from scientific article repositories through blogs to on-line news portals. In most of the cases, the tags on a given item are free words chosen by the authors independently. Therefore, relations among keywords in a collection of news items is unknown. However, in most cases the topics and concepts described by these keywords are forming a latent hierarchy, with the more general topics and categories at the top, and more specialised ones at the bottom. Here we apply a recent, cooccurrence-based tag hierarchy extraction method to sets of keywords obtained from four different on-line news portals. The resulting hierarchies show substantial differences not just in the topics rendered as important (being at the top of the hierarchy) or of less interest (categorised low in the hierarchy), but also in the underlying network structure. This reveals discrepancies between the plausible keyword association frameworks in the studied news portals

Modelling for Taenia solium control strategies beyond 2020

The cestode Taenia solium is responsible for a considerable cross-sectoral health and economic burden due to human neurocysticercosis and porcine cysticercosis. The 2012 World Health Organization (WHO) roadmap for neglected tropical diseases called for the development of a validated strategy for control of T. solium; however, such a strategy is not yet available. In 2019, WHO launched a global consultation aimed at refining the post-2020 targets for control of T. solium for a new roadmap for neglected tropical diseases. In response, two groups working on taeniasis and cysticercosis mathematical models (cystiSim and EPICYST models), together with a range of other stakeholders organized a workshop to provide technical input to the WHO consultation and develop a research plan to support efforts to achieve the post-2020 targets. The workshop led to the formation of a collaboration, CystiTeam, which aims to tackle the population biology, transmission dynamics, epidemiology and control of T. solium through mathematical modelling approaches. In this paper, we outline developments in T. solium control and in particular the use of modelling to help achieve post-2020 targets for control of T. solium. We discuss the steps involved in improving confidence in the predictive capacities of existing mathematical and computational models on T. solium transmission, including model comparison, refinement, calibration and validation. Expanding the CystiTeam partnership to other research groups and stakeholders, particularly those operating in different geographical and endemic areas, will enhance the prospects of improving the applicability of T. solium transmission models to inform taeniasis and cysticercosis control strategies

Erasmus Language students in a British University – a case study

Students’ assessment of their academic experience is actively sought by Higher Education institutions, as evidenced in the National Student Survey introduced in 2005. Erasmus students, despite their growing numbers, tend to be excluded from these satisfaction surveys, even though they, too, are primary customers of a University. This study aims to present results from bespoke questionnaires and semi-structured interviews with a sample of Erasmus students studying languages in a British University. These methods allow us insight into the experience of these students and their assessment as a primary customer, with a focus on language learning and teaching, university facilities and student support. It investigates to what extent these factors influence their levels of satisfaction and what costs of adaptation if any, they encounter. Although excellent levels of satisfaction were found, some costs affect their experience. They relate to difficulties in adapting to a learning methodology based on a low number of hours and independent learning and to a guidance and support system seen as too stifling. The results portray this cohort’s British University as a well-equipped and well-meaning but ultimately overbearing institution, which may indicate that minimising costs can eliminate some sources of dissatisfaction

Water dispersible microbicidal cellulose acetate phthalate film

BACKGROUND: Cellulose acetate phthalate (CAP) has been used for several decades in the pharmaceutical industry for enteric film coating of oral tablets and capsules. Micronized CAP, available commercially as "Aquateric" and containing additional ingredients required for micronization, used for tablet coating from water dispersions, was shown to adsorb and inactivate the human immunodeficiency virus (HIV-1), herpesviruses (HSV) and other sexually transmitted disease (STD) pathogens. Earlier studies indicate that a gel formulation of micronized CAP has a potential as a topical microbicide for prevention of STDs including the acquired immunodeficiency syndrome (AIDS). The objective of endeavors described here was to develop a water dispersible CAP film amenable to inexpensive industrial mass production. METHODS: CAP and hydroxypropyl cellulose (HPC) were dissolved in different organic solvent mixtures, poured into dishes, and the solvents evaporated. Graded quantities of a resulting selected film were mixed for 5 min at 37°C with HIV-1, HSV and other STD pathogens, respectively. Residual infectivity of the treated viruses and bacteria was determined. RESULTS: The prerequisites for producing CAP films which are soft, flexible and dispersible in water, resulting in smooth gels, are combining CAP with HPC (other cellulose derivatives are unsuitable), and casting from organic solvent mixtures containing ≈50 to ≈65% ethanol (EtOH). The films are ≈100 µ thick and have a textured surface with alternating protrusions and depressions revealed by scanning electron microscopy. The films, before complete conversion into a gel, rapidly inactivated HIV-1 and HSV and reduced the infectivity of non-viral STD pathogens >1,000-fold. CONCLUSIONS: Soft pliable CAP-HPC composite films can be generated by casting from organic solvent mixtures containing EtOH. The films rapidly reduce the infectivity of several STD pathogens, including HIV-1. They are converted into gels and thus do not have to be removed following application and use. In addition to their potential as topical microbicides, the films have promise for mucosal delivery of pharmaceuticals other than CAP

Biological Activity of CXCL8 Forms Generated by Alternative Cleavage of the Signal Peptide or by Aminopeptidase-Mediated Truncation

Posttranslational modification of chemokines is one of the mechanisms that regulate leukocyte migration during inflammation. Multiple natural NH(2)-terminally truncated forms of the major human neutrophil attractant interleukin-8 or CXCL8 have been identified. Although differential activity was reported for some CXCL8 forms, no biological data are available for others.status: publishe

Lectin-like bacteriocins from pseudomonas spp. utilise D-rhamnose containing lipopolysaccharide as a cellular receptor

Lectin-like bacteriocins consist of tandem monocot mannose-binding domains and display a genus-specific killing activity. Here we show that pyocin L1, a novel member of this family from Pseudomonas aeruginosa, targets susceptible strains of this species through recognition of the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide that is predominantly a homopolymer of d-rhamnose. Structural and biophysical analyses show that recognition of CPA occurs through the C-terminal carbohydrate-binding domain of pyocin L1 and that this interaction is a prerequisite for bactericidal activity. Further to this, we show that the previously described lectin-like bacteriocin putidacin L1 shows a similar carbohydrate-binding specificity, indicating that oligosaccharides containing d-rhamnose and not d-mannose, as was previously thought, are the physiologically relevant ligands for this group of bacteriocins. The widespread inclusion of d-rhamnose in the lipopolysaccharide of members of the genus Pseudomonas explains the unusual genus-specific activity of the lectin-like bacteriocins