Expression of therapeutic misconception amongst Egyptians: a qualitative pilot study

<p>Abstract</p> <p>Background</p> <p>Studies have shown that research participants fail to appreciate the difference between research and medical care, labeling such phenomenon as a "therapeutic misconception" (TM). Since research activity involving human participants is increasing in the Middle East, qualitative research investigating aspects of TM is warranted. Our objective was to assess for the existence of therapeutic misconception amongst Egyptians.</p> <p>Methods</p> <p><it>Study Tool: </it>We developed a semi-structured interview guide to elicit the knowledge, attitudes, and perspectives of Egyptians regarding medical research.</p> <p><it>Setting: </it>We recruited individuals from the outpatient settings (public and private) at Ain Shams University in Cairo, Egypt.</p> <p><it>Analysis: </it>Interviews were taped, transcribed, and translated. We analyzed the content of the transcribed text to identify the presence of a TM, defined in one of two ways: TM₁= inaccurate beliefs about how individualized care can be compromised by the procedures in the research and TM₂= inaccurate appraisal of benefit obtained from the research study.</p> <p>Results</p> <p>Our findings showed that a majority of participants (11/15) expressed inaccurate beliefs regarding the degree with which individualized care will be maintained in the research setting (TM₁) and a smaller number of participants (5/15) manifested an unreasonable belief in the likelihood of benefits to be obtained from a research study (TM₂). A total of 12 of the 15 participants were judged to have expressed a TM on either one of these bases.</p> <p>Conclusion</p> <p>The presence of TM is not uncommon amongst Egyptian individuals. We recommend further qualitative studies investigating aspects of TM involving a larger sample size distinguished by different types of illnesses and socio-economic variables, as well as those who have and have not participated in clinical research.</p

Illusionary Self-Motion Perception in Zebrafish

Zebrafish mutant belladonna (bel) carries a mutation in the lhx2 gene (encoding a Lim domain homeobox transcription factor) that results in a defect in retinotectal axon pathfinding, which can lead to uncrossed optic nerves failing to form an optic chiasm. Here, we report on a novel swimming behavior of the bel mutants, best described as looping. Together with two previously reported oculomotor instabilities that have been related to achiasmatic bel mutants, reversed optokinetic response (OKR) and congenital nystagmus (CN, involuntary conjugate oscillations of both eyes), looping opens a door to study the influence of visual input and eye movements on postural balance. Our result shows that looping correlates perfectly with reversed OKR and CN and is vision-dependent and contrast sensitive. CN precedes looping and the direction of the CN slow phase is predictive of the looping direction, but is absent during looping. Therefore, looping may be triggered by CN in bel. Moreover, looping in wild-type fish can also be evoked by whole-field motion, suggesting that looping in a bel mutant larvae is a result of self-motion perception. In contrary to previous hypotheses, our findings indicate that postural control in vertebrates relies on both direct visual input (afference signal) and eye-movement-related signals (efference copy or reafference signal)

Microanatomy of Adult Zebrafish Extraocular Muscles

Binocular vision requires intricate control of eye movement to align overlapping visual fields for fusion in the visual cortex, and each eye is controlled by 6 extraocular muscles (EOMs). Disorders of EOMs are an important cause of symptomatic vision loss. Importantly, EOMs represent specialized skeletal muscles with distinct gene expression profile and susceptibility to neuromuscular disorders. We aim to investigate and describe the anatomy of adult zebrafish extraocular muscles (EOMs) to enable comparison with human EOM anatomy and facilitate the use of zebrafish as a model for EOM research. Using differential interference contrast (DIC), epifluorescence microscopy, and precise sectioning techniques, we evaluate the anatomy of zebrafish EOM origin, muscle course, and insertion on the eye. Immunofluorescence is used to identify components of tendons, basement membrane and neuromuscular junctions (NMJs), and to analyze myofiber characteristics. We find that adult zebrafish EOM insertions on the globe parallel the organization of human EOMs, including the close proximity of specific EOM insertions to one another. However, analysis of EOM origins reveals important differences between human and zebrafish, such as the common rostral origin of both oblique muscles and the caudal origin of the lateral rectus muscles. Thrombospondin 4 marks the EOM tendons in regions that are highly innervated, and laminin marks the basement membrane, enabling evaluation of myofiber size and distribution. The NMJs appear to include both en plaque and en grappe synapses, while NMJ density is much higher in EOMs than in somatic muscles. In conclusion, zebrafish and human EOM anatomy are generally homologous, supporting the use of zebrafish for studying EOM biology. However, anatomic differences exist, revealing divergent evolutionary pressures

The impact of radiotherapy in the treatment of desmoid tumours. An international survey of 110 patients. A study of the Rare Cancer Network

PURPOSE: A multi-centre study to assess the value of combined surgical resection and radiotherapy for the treatment of desmoid tumours. PATIENTS AND METHODS: One hundred and ten patients from several European countries qualified for this study. Pathology slides of all patients were reviewed by an independent pathologist. Sixty-eight patients received post-operative radiotherapy and 42 surgery only. Median follow-up was 6 years (1 to 44). The progression-free survival time (PFS) and prognostic factors were analysed. RESULTS: The combined treatment with radiotherapy showed a significantly longer progression-free survival than surgical resection alone (p smaller than 0.001). Extremities could be preserved in all patients treated with combined surgery and radiotherapy for tumours located in the limb, whereas amputation was necessary for 23% of patients treated with surgery alone. A comparison of PFS for tumour locations proved the abdominal wall to be a positive prognostic factor and a localization in the extremities to be a negative prognostic factor. Additional irradiation, a fraction size larger than or equal to 2 Gy and a total dose larger than 50 Gy to the tumour were found to be positive prognostic factors with a significantly lower risk for a recurrence in the univariate analysis. This analysis revealed radiotherapy at recurrence as a significantly worse prognostic factor compared with adjuvant radiotherapy. The addition of radiotherapy to the treatment concept was a positive prognostic factor in the multivariate analysis. CONCLUSION: Postoperative radiotherapy significantly improved the PFS compared to surgery alone. Therefore it should always be considered after a non-radical tumour resection and should be given preferably in an adjuvant setting. It is effective in limb preservation and for preserving the function of joints in situations where surgery alone would result in deficits, which is especially important in young patients

Mutations in Zebrafish lrp2 Result in Adult-Onset Ocular Pathogenesis That Models Myopia and Other Risk Factors for Glaucoma

The glaucomas comprise a genetically complex group of retinal neuropathies that typically occur late in life and are characterized by progressive pathology of the optic nerve head and degeneration of retinal ganglion cells. In addition to age and family history, other significant risk factors for glaucoma include elevated intraocular pressure (IOP) and myopia. The complexity of glaucoma has made it difficult to model in animals, but also challenging to identify responsible genes. We have used zebrafish to identify a genetically complex, recessive mutant that shows risk factors for glaucoma including adult onset severe myopia, elevated IOP, and progressive retinal ganglion cell pathology. Positional cloning and analysis of a non-complementing allele indicated that non-sense mutations in low density lipoprotein receptor-related protein 2 (lrp2) underlie the mutant phenotype. Lrp2, previously named Megalin, functions as an endocytic receptor for a wide-variety of bioactive molecules including Sonic hedgehog, Bone morphogenic protein 4, retinol-binding protein, vitamin D-binding protein, and apolipoprotein E, among others. Detailed phenotype analyses indicated that as lrp2 mutant fish age, many individuals—but not all—develop high IOP and severe myopia with obviously enlarged eye globes. This results in retinal stretch and prolonged stress to retinal ganglion cells, which ultimately show signs of pathogenesis. Our studies implicate altered Lrp2-mediated homeostasis as important for myopia and other risk factors for glaucoma in humans and establish a new genetic model for further study of phenotypes associated with this disease

Phenylthiourea Specifically Reduces Zebrafish Eye Size

Phenylthiourea (PTU) is commonly used for inhibiting melanization of zebrafish embryos. In this study, the standard treatment with 0.2 mM PTU was demonstrated to specifically reduce eye size in larval fish starting at three days post-fertilization. This effect is likely the result of a reduction in retinal and lens size of PTU-treated eyes and is not related to melanization inhibition. This is because the eye size of tyr, a genetic mutant of tyrosinase whose activity is inhibited in PTU treatment, was not reduced. As PTU contains a thiocarbamide group which is presented in many goitrogens, suppressing thyroid hormone production is a possible mechanism by which PTU treatment may reduce eye size. Despite the fact that thyroxine level was found to be reduced in PTU-treated larvae, thyroid hormone supplements did not rescue the eye size reduction. Instead, treating embryos with six goitrogens, including inhibitors of thyroid peroxidase (TPO) and sodium-iodide symporter (NIS), suggested an alternative possibility. Specifically, three TPO inhibitors, including those that do not possess thiocarbamide, specifically reduced eye size; whereas none of the NIS inhibitors could elicit this effect. These observations indicate that TPO inhibition rather than a general suppression of thyroid hormone synthesis is likely the underlying cause of PTU-induced eye size reduction. Furthermore, the tissue-specific effect of PTU treatment might be mediated by an eye-specific TPO expression. Compared with treatment with other tyrosinase inhibitors or bleaching to remove melanization, PTU treatment remains the most effective approach. Thus, one should use caution when interpreting results that are obtained from PTU-treated embryos

Interaction between Axons and Specific Populations of Surrounding Cells Is Indispensable for Collateral Formation in the Mammillary System

An essential phenomenon during brain development is the extension of long collateral branches by axons. How the local cellular environment contributes to the initial sprouting of these branches in specific points of an axonal shaft remains unclear.The principal mammillary tract (pm) is a landmark axonal bundle connecting ventral diencephalon to brainstem (through the mammillotegmental tract, mtg). Late in development, the axons of the principal mammillary tract sprout collateral branches at a very specific point forming a large bundle whose target is the thalamus. Inspection of this model showed a number of distinct, identified cell populations originated in the dorsal and the ventral diencephalon and migrating during development to arrange themselves into several discrete groups around the branching point. Further analysis of this system in several mouse lines carrying mutant alleles of genes expressed in defined subpopulations (including Pax6, Foxb1, Lrp6 and Gbx2) together with the use of an unambiguous genetic marker of mammillary axons revealed: 1) a specific group of Pax6-expressing cells in close apposition with the prospective branching point is indispensable to elicit axonal branching in this system; and 2) cooperation of transcription factors Foxb1 and Pax6 to differentially regulate navigation and fasciculation of distinct branches of the principal mammillary tract.Our results define for the first time a model system where interaction of the axonal shaft with a specific group of surrounding cells is essential to promote branching. Additionally, we provide insight on the cooperative transcriptional regulation necessary to promote and organize an intricate axonal tree

A Multi-Component Model of the Developing Retinocollicular Pathway Incorporating Axonal and Synaptic Growth

During development, neurons extend axons to different brain areas and produce stereotypical patterns of connections. The mechanisms underlying this process have been intensively studied in the visual system, where retinal neurons form retinotopic maps in the thalamus and superior colliculus. The mechanisms active in map formation include molecular guidance cues, trophic factor release, spontaneous neural activity, spike-timing dependent plasticity (STDP), synapse creation and retraction, and axon growth, branching and retraction. To investigate how these mechanisms interact, a multi-component model of the developing retinocollicular pathway was produced based on phenomenological approximations of each of these mechanisms. Core assumptions of the model were that the probabilities of axonal branching and synaptic growth are highest where the combined influences of chemoaffinity and trophic factor cues are highest, and that activity-dependent release of trophic factors acts to stabilize synapses. Based on these behaviors, model axons produced morphologically realistic growth patterns and projected to retinotopically correct locations in the colliculus. Findings of the model include that STDP, gradient detection by axonal growth cones and lateral connectivity among collicular neurons were not necessary for refinement, and that the instructive cues for axonal growth appear to be mediated first by molecular guidance and then by neural activity. Although complex, the model appears to be insensitive to variations in how the component developmental mechanisms are implemented. Activity, molecular guidance and the growth and retraction of axons and synapses are common features of neural development, and the findings of this study may have relevance beyond organization in the retinocollicular pathway

Development of mandibular, hyoid and hypobranchial muscles in the zebrafish: homologies and evolution of these muscles within bony fishes and tetrapods

<p>Abstract</p> <p>Background</p> <p>During vertebrate head evolution, muscle changes accompanied radical modification of the skeleton. Recent studies have suggested that muscles and their innervation evolve less rapidly than cartilage. The freshwater teleostean zebrafish (<it>Danio rerio</it>) is the most studied actinopterygian model organism, and is sometimes taken to represent osteichthyans as a whole, which include bony fishes and tetrapods. Most work concerning zebrafish cranial muscles has focused on larval stages. We set out to describe the later development of zebrafish head muscles and compare muscle homologies across the Osteichthyes.</p> <p>Results</p> <p>We describe one new muscle and show that the number of mandibular, hyoid and hypobranchial muscles found in four day-old zebrafish larvae is similar to that found in the adult. However, the overall configuration and/or the number of divisions of these muscles change during development. For example, the undivided adductor mandibulae of early larvae gives rise to the adductor mandibulae sections A0, A1-OST, A2 and Aω, and the protractor hyoideus becomes divided into dorsal and ventral portions in adults. There is not always a correspondence between the ontogeny of these muscles in the zebrafish and their evolution within the Osteichthyes. All of the 13 mandibular, hyoid and hypobranchial muscles present in the adult zebrafish are found in at least some other living teleosts, and all except the protractor hyoideus are found in at least some extant non-teleost actinopterygians. Of these muscles, about a quarter (intermandibularis anterior, adductor mandibulae, sternohyoideus) are found in at least some living tetrapods, and a further quarter (levator arcus palatini, adductor arcus palatini, adductor operculi) in at least some extant sarcopterygian fish.</p> <p>Conclusion</p> <p>Although the zebrafish occupies a rather derived phylogenetic position within actinopterygians and even within teleosts, with respect to the mandibular, hyoid and hypobranchial muscles it seems justified to consider it an appropriate representative of these two groups. Among these muscles, the three with clear homologues in tetrapods and the further three identified in sarcopterygian fish are particularly appropriate for comparisons of results between the actinopterygian zebrafish and the sarcopterygians.</p

Understanding the retinal basis of vision across species

The vertebrate retina first evolved some 500 million years ago in ancestral marine chordates. Since then, the eyes of different species have been tuned to best support their unique visuoecological lifestyles. Visual specializations in eye designs, large-scale inhomogeneities across the retinal surface and local circuit motifs mean that all species' retinas are unique. Computational theories, such as the efficient coding hypothesis, have come a long way towards an explanation of the basic features of retinal organization and function; however, they cannot explain the full extent of retinal diversity within and across species. To build a truly general understanding of vertebrate vision and the retina's computational purpose, it is therefore important to more quantitatively relate different species' retinal functions to their specific natural environments and behavioural requirements. Ultimately, the goal of such efforts should be to build up to a more general theory of vision