Why simulation can be efficient: on the preconditions of efficient learning in complex technology based practices

Background  

It is important to demonstrate learning outcomes of simulation in technology based practices, such as in advanced health care. Although many studies show skills improvement and self-reported change to practice, there are few studies demonstrating patient outcome and societal efficiency.     

Peptide phage libraries can be an efficient tool for identifying antibody ligands for polyclonal antisera.

We have examined the potential of isolating ligands for polyclonal antibodies from a nanopeptide phage library. The library was screened with a rabbit polyclonal antiserum raised against a synthetic peptide (ALWFRNHFVFGGGTKVT). Following screening, the positive phages were tested in an ELISA for their reactivity with the antiserum. Phages that showed positive reactivity with the antiserum compared with a normal rabbit serum were selected and their displayed peptides were determined. Among the 36 random positive clones, 31 clones carried the sequence AVFGGGTKL, PFFGGGSRA or APTGGSKRT that have a significant homology to the immunizing peptide. Five positive phages displayed the ATNIFIEGT sequence, which has no obvious linear homology with either the other selected peptides or with the peptide used for immunization. In contrast to the control peptide, the immunizing peptide inhibited binding of the antiserum to the peptide-displaying phages in a dose-dependent manner, thus demonstrating the specificity of the interaction. Furthermore, the rabbit B cell response to the peptide was found to be limited and focused on its C-terminal. Taken together, our data demonstrate the potential of random peptide phage libraries for defining epitopes for polyclonal antisera as well as for investigation of the nature of B cell responses to any given antigen.     

Diabetes drugs in the fight against Alzheimer's disease

Alzheimer’s disease (AD) is the most prevalent form of dementia, particularly in old age subjects. Hyperinsulinemia and insulin resistance, which are known as pathophysiological features of Type 2 Diabetes Mellitus (T2DM), have also been demonstrated to have a significant impact on cognitive impairment. Studies have shown that an altered insulin pathway may interact with amyloid-β protein deposition and tau protein phosphorylation, both leading factors for AD development. Drugs used for T2DM treatment from insulin and metformin through dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists may represent a promising approach to fight AD. With this review from animal to human studies, we aim at responding to the reasons why drugs for diabetes may represent potential treatments for AD.     

Understanding h-prune biology in the fight against cancer

The h-prune protein is a member of the DHH protein superfamily, and its overexpression in breast, colorectal and gastric cancers correlates with depth of invasion and degree of lymph-node metastasis. Taken together with the observation that h-prune is highly expressed in metastatic breast cancer, this suggests that h-prune can be used as a marker for the identification of subsets of cancer patients with highly aggressive tumours. H-prune possesses a phosphodiesterase (cAMP-PDE) activity, and inhibition of PDE activity with dipyridamole suppresses cell motility. H-prune interacts with nm23-H1, GSK-3β and gelsolin. Although a correlation between an h-prune PDE activity and cellular motility has been shown, GSK-3β does not affect the PDE activity of h-prune. Inhibition of the interactions between h-prune and GSK-3β and nm23-H1 additively suppresses the migration of colon cancer and breast cancer cells, thus suggesting that h-prune regulates cell motility by two different means of action: through its PDE activity and in its interactions with protein partners. Therefore, the identification of highly specific inhibitors of h-prune should be useful in the development of drugs to treat cancer metastasis.     

The airway epithelium: soldier in the fight against respiratory viruses

The airway epithelium acts as a frontline defense against respiratory viruses, not only as a physical barrier and through the mucociliary apparatus but also through its immunological functions. It initiates multiple innate and adaptive immune mechanisms which are crucial for efficient antiviral responses. The interaction between respiratory viruses and airway epithelial cells results in production of antiviral substances, including type I and III interferons, lactoferrin, β-defensins, and nitric oxide, and also in production of cytokines and chemokines, which recruit inflammatory cells and influence adaptive immunity. These defense mechanisms usually result in rapid virus clearance. However, respiratory viruses elaborate strategies to evade antiviral mechanisms and immune responses. They may disrupt epithelial integrity through cytotoxic effects, increasing paracellular permeability and damaging epithelial repair mechanisms. In addition, they can interfere with immune responses by blocking interferon pathways and by subverting protective inflammatory responses toward detrimental ones. Finally, by inducing overt mucus secretion and mucostasis and by paving the way for bacterial infections, they favor lung damage and further impair host antiviral mechanisms.     

Superoxide production by human eosinophils can be inhibited in an agonist-selective manner

This paper focuses on eosinophil activation and its selective inhibition. Superoxide anion (O ₂ ^– ) production by human eosinophils, an indicator of their activation, was induced by a variety of activators. Several compounds which are known to inhibit protein kinase C (staurosporine, K252a, sphingosine) inhibited O ₂ ^– production induced by phorbol ester (PMA) but failed to inhibit O ₂ ^– production induced by IgG coupled to Sepharose beads. Inhibition of O ₂ ^– production by other agents (plasma-activated zymosan, fMLP, and leukotriene B₄ (LTB₄), was intermediate. By contrast, wortmannin, a compound which has been previously reported to inhibit O ₂ ^– production in neutrophils via a protein kinase-independent pathway, potently inhibited O ₂ ^– production in eosinophils which had been activated by IgG and by Platelet-Activating Factor but was virtually inactive against PMA-induced O ₂ ^– production. Taken together, the results indicate that, as a minimum, there must be two pathways of induction of O ₂ ^– production in eosinophils. Moreover, the intermediate levels of inhibition in cells which had been activated with serum-activated zymosan, FMLP, and LTB₄ suggest that these agents may either be acting via both of these pathways or that yet other pathways may exist.     

Dysplasia can be a pain in the gut

In the gastrointestinal tract, the term 'dysplasia' is used to refer to non-invasive neoplastic epithelium. Although we recognise adenomas of the gut as dysplastic, we don't use the term 'dysplasia' in reporting them. The use of the term 'dysplasia' for pre-invasive epithelium gradually came to replace other terms in studies attempting to identify epithelial changes that were cancer precursors in surveillance biopsies of patients with chronic colitides. The two-tier system of classification, dividing dysplasias into low-grade or high-grade lesions is conceptually straightforward; however, difficulties exist in the distinction of regenerative epithelium from low-grade dysplasia, of low-grade from high-grade dysplasia, and in identifying superficially invasive carcinoma in a dysplastic mucosa. The category 'indefinite for dysplasia' is an honest recognition of the difficulties in distinguishing reactive or regenerative epithelium from low-grade dysplasia, since these epithelia share many cytological features. In surveillance biopsies in ulcerative colitis and Barrett's mucosa, for each epithelial category from non-dysplastic through indefinite, low-grade and high-grade dysplasia, there are specific management recommendations that vary from no change in surveillance to increased surveillance to definitive therapy that is often a major resection. The recommendation for referral of high-grade dysplasias to consultants reflects the concern pathologists have about making such clinically significant diagnoses with limited experience. Pathologists should use the accepted terminology, share cases to expand their experience, and seek consultation in selected cases. This paper follows the evolution of the dysplasia concept, details the difficult areas of diagnosis, and discusses the importance of interaction between clinicians and pathologists in dealing with dysplasias.     

A consensus envelope protein domain III can induce neutralizing antibody responses against serotype 2 of dengue virus in non-human primates

We have previously demonstrated that vaccination with a subunit dengue vaccine containing a consensus envelope domain III with aluminum phosphate elicits neutralizing antibodies against all four serotypes of dengue virus in mice. In this study, we evaluated the immunogenicity of the subunit dengue vaccine in non-human primates. After vaccination, monkeys that received the subunit vaccine with aluminum phosphate developed a significantly strong and long-lasting antibody response. A specific T cell response with cytokine production was also induced, and this correlated with the antibody response. Additionally, neutralizing antibodies against serotype 2 were detected in two of three monkeys. The increase in serotype-2-specific antibody titers and avidity observed in these two monkeys suggested that a serotype-2-biased antibody response occurs. These data provide evidence that a protective neutralizing antibody response was successfully elicited in non-human primates by the dengue subunit vaccine with aluminum phosphate adjuvant.     

Layered double hydroxide as an efficient drug reservoir for folate derivatives

Folic acid derivatives such as folinic acid and methotrexate (MTX) have been successfully hybridized with layered double hydroxide (LDH) by ion-exchange reaction. The X-ray diffraction patterns and spectroscopic analyses indicate that these molecules intercalated into the hydroxide interlayer space are stabilized in the tilted longitudinal monolayer mode by electrostatic interaction. No significant changes in their structural and functional properties are found in the hybrids. The cellular uptake test of MTX-LDH hybrid is carried out in the fibroblast (human tendon) and SaOS-2 cell line (Osteosarcoma, human) by in vitro MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide) assay. The initial proliferation of SaOS-2 cell is more strongly suppressed by treatment with MTX-LDH hybrid than with MTX alone. This study clearly shows that LDH not only plays a role as a biocompatible-delivery matrix for drugs but also facilitates a significant increase in the delivery efficiency.     

Early efforts of blacks in the fight against heart disease and stroke

This article highlighted the early efforts of some individuals whose vision and dedication helped to set the stage for later progress in the fight against heart disease, who forged links to those who eagerly took up the cause of creating an appropriate place for minority participation in the specialty of cardiovascular diseases, and to contribute to efforts to establish programs for the reduction of morbidity and mortality and for prevention in African Americans. This is only one view of what was an exciting period of fitful progress and controversy. Dr Wilson reviewed the still deplorable state of affairs in regard to minorities and the medical profession in 1986, stating: A meaningful role for minorities will not exist until there is access to academic postgraduate training programs that will lead to faculty positions and research opportunities for minorities to serve as role models for future students. The Association of Academic Minority Physicians was established to foster greater progress in this regard across disciplines. Again, while much has been accomplished, including Donald Wilson's becoming the first African-American dean of a nonminority medical school, much remains to be done as we approach the end of the 20th century.