Six3 demarcates the anterior-most developing brain region in bilaterian animals.

BACKGROUND: The heads of annelids (earthworms, polychaetes, and others) and arthropods (insects, myriapods, spiders, and others) and the arthropod-related onychophorans (velvet worms) show similar brain architecture and for this reason have long been considered homologous. However, this view is challenged by the 'new phylogeny' placing arthropods and annelids into distinct superphyla, Ecdysozoa and Lophotrochozoa, together with many other phyla lacking elaborate heads or brains. To compare the organisation of annelid and arthropod heads and brains at the molecular level, we investigated head regionalisation genes in various groups. Regionalisation genes subdivide developing animals into molecular regions and can be used to align head regions between remote animal phyla. RESULTS: We find that in the marine annelid Platynereis dumerilii, expression of the homeobox gene six3 defines the apical region of the larval body, peripherally overlapping the equatorial otx+ expression. The six3+ and otx+ regions thus define the developing head in anterior-to-posterior sequence. In another annelid, the earthworm Pristina, as well as in the onychophoran Euperipatoides, the centipede Strigamia and the insects Tribolium and Drosophila, a six3/optix+ region likewise demarcates the tip of the developing animal, followed by a more posterior otx/otd+ region. Identification of six3+ head neuroectoderm in Drosophila reveals that this region gives rise to median neurosecretory brain parts, as is also the case in annelids. In insects, onychophorans and Platynereis, the otx+ region instead harbours the eye anlagen, which thus occupy a more posterior position. CONCLUSIONS: These observations indicate that the annelid, onychophoran and arthropod head develops from a conserved anterior-posterior sequence of six3+ and otx+ regions. The six3+ anterior pole of the arthropod head and brain accordingly lies in an anterior-median embryonic region and, in consequence, the optic lobes do not represent the tip of the neuraxis. These results support the hypothesis that the last common ancestor of annelids and arthropods already possessed neurosecretory centres in the most anterior region of the brain. In light of its broad evolutionary conservation in protostomes and, as previously shown, in deuterostomes, the six3-otx head patterning system may be universal to bilaterian animals.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Solvent effects in permeation assessed in vivo by skin surface biopsy

BACKGROUND: Transdermal drug delivery has become an important means of drug administration. It presents numerous advantages but it is still limited by the small number of drugs with a suitable profile. The use of solvents that affect the skin barrier function is one of the classic strategies of penetration enhancement. Some of these solvents have well characterised actions on the stratum corneum, but the majority are still selected using empirical criteria. The objective of this work was to conduct a systematic study on the ability to affect skin permeation of solvents commonly used in transdermal formulations. An innovative methodology in this area was employed, consisting of the combination of skin surface biopsy with colorimetry. METHODS: The study compared in vivo differences in the permeation of a hydrophilic (methylene blue) and a lipophilic (Sudan III) dye, after treatment of the skin with different vehicles. Consecutive skin surface biopsies of each site were taken and the cumulative amounts of the dyes in the stripped stratum corneum were measured by reflectance colourimetry. RESULTS: Results indicate that the amount of methylene blue present in the stratum corneum varied significantly with different skin pre-treatments. Some solvents provided a 1.5 fold penetration enhancement but others decreased by almost half the permeation of the dye. The permeation of Sudan III was less significantly affected by solvent pre-treatment. CONCLUSIONS: This study has only superficially explored the potential of the combination of skin surface biopsy and colourimetry, but the encouraging results obtained confirm that the methodology can be extended to the study of more complex formulations

InternationaL cross-sectIonAl and longItudinal assessment on aSthma cONtrol in European adult patients : the LIAISON study protocol

The study is funded by Chiesi Farmaceutici S.p.A., Parma, ItalyPeer reviewedPublisher PD

Long term time variability of cosmic rays and possible relevance to the development of life on Earth

An analysis is made of the manner in which the cosmic ray intensity at Earth has varied over its existence and its possible relevance to both the origin and the evolution of life. Much of the analysis relates to the 'high energy' cosmic rays ($E>10^{14}eV;=0.1PeV$) and their variability due to the changing proximity of the solar system to supernova remnants which are generally believed to be responsible for most cosmic rays up to PeV energies. It is pointed out that, on a statistical basis, there will have been considerable variations in the likely 100 My between the Earth's biosphere reaching reasonable stability and the onset of very elementary life. Interestingly, there is the increasingly strong possibility that PeV cosmic rays are responsible for the initiation of terrestrial lightning strokes and the possibility arises of considerable increases in the frequency of lightnings and thereby the formation of some of the complex molecules which are the 'building blocks of life'. Attention is also given to the well known generation of the oxides of nitrogen by lightning strokes which are poisonous to animal life but helpful to plant growth; here, too, the violent swings of cosmic ray intensities may have had relevance to evolutionary changes. A particular variant of the cosmic ray acceleration model, put forward by us, predicts an increase in lightning rate in the past and this has been sought in Korean historical records. Finally, the time dependence of the overall cosmic ray intensity, which manifests itself mainly at sub-10 GeV energies, has been examined. The relevance of cosmic rays to the 'global electrical circuit' points to the importance of this concept.Comment: 18 pages, 5 figures, accepted by 'Surveys in Geophysics

Rapid Intradermal Delivery of Liquid Formulations Using a Hollow Microstructured Array

Purpose The purpose of this work is to demonstrate rapid intradermal delivery of up to 1.5 mL of formulation using a hollow microneedle delivery device designed for self-application. Methods 3M’s hollow Microstructured Transdermal System (hMTS) was applied to domestic swine to demonstrate delivery of a variety of formulations including small molecule salts and proteins. Blood samples were collected after delivery and analyzed via HPLC or ELISA to provide a PK profile for the delivered drug. Site evaluations were conducted post delivery to determine skin tolerability. Results Up to 1.5 mL of formulation was infused into swine at a max rate of approximately 0.25 mL/min. A red blotch, the size of the hMTS array, was observed immediately after patch removal, but had faded so as to be almost indistinguishable 10 min post-patch removal. One-mL deliveries of commercial formulations of naloxone hydrochloride and human growth hormone and a formulation of equine anti-tetanus toxin were completed in swine. With few notable differences, the resulting PK profiles were similar to those achieved following subcutaneous injection of these formulations. Conclusions 3M’s hMTS can provide rapid, intradermal delivery of 300–1,500 µL of liquid formulations of small molecules salts and proteins, compounds not typically compatible with passive transdermal delivery. KEY WORDS transdermal drug delivery. microneedles. intradermal. hollow microstructures. MT

Unconventional Transcriptional Response to Environmental Enrichment in a Mouse Model of Rett Syndrome

Background: Rett syndrome (RTT) is an X-linked postnatal neurodevelopmental disorder caused by mutations in the gene encoding methyl-CpG binding protein 2 (MeCP2) and one of the leading causes of mental retardation in females. RTT is characterized by psychomotor retardation, purposeless hand movements, autistic-like behavior and abnormal gait. We studied the effects of environmental enrichment (EE) on the phenotypic manifestations of a RTT mouse model that lacks MeCP2 (Mecp2 2/y). Principal Findings: We found that EE delayed and attenuated some neurological alterations presented by Mecp2 2/y mice and prevented the development of motor discoordination and anxiety-related abnormalities. To define the molecular correlate of this beneficial effect of EE, we analyzed the expression of several synaptic marker genes whose expression is increased by EE in several mouse models. Conclusions/Significance: We found that EE induced downregulation of several synaptic markers, suggesting that th

The study on the outsourcing of Taiwan's hospitals: a questionnaire survey research

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the outsourcing situation in Taiwanese hospitals and compares the differences in hospital ownership and in accreditation levels.</p> <p>Methods</p> <p>This research combined two kinds of methods: a questionnaire survey and the in-depth interview to two CEOs of the sample hospitals. One hospital is not-for-profit, while the other is a public hospital and the research samples are from the hospital data from Taiwan's 2005 to 2007 Department of Health qualifying lists of hospital accreditation. The returned questionnaires were analyzed with STATISTICA^®7.1 version software.</p> <p>Results</p> <p>The results for non-medical items showed medical waste and common trash both have the highest rate (94.6 percent) of being outsourced. The gift store (75 percent) and linen (73 percent) follow close behind, while the lowest rate of outsourcing is in utility maintenance (13.5 percent). For medical items, the highest rate of outsourcing is in the ambulance units (51.4 percent), while the hemodialysis center follows close behind with a rate of 50 percent. For departments of nutrition, pharmacy, and nursing however, the outsourcing rate is lower than 3 percent. This shows that Taiwan's hospitals are still conservative in their willingness to outsource for medical items. The results of the satisfaction paired t-test show that the non-medical items have a higher score than the medical items. The factor analysis showed the three significant factors in of non medical items' outsourcing are "performance", "finance", and "human resource". For medical items, the two factors are "operation" and satisfaction". To further exam the factor validity and reliability of the satisfaction model, a confirmative factor analysis (CFA) was conducted using structure equation modeling (SEM) method and found the model fitting well.</p> <p>Conclusion</p> <p>Hospitals, especially for public hospitals, can get benefits from outsourcing to revive the full-time-equivalent and human resource limitation.</p

Bayesian Wavelet Shrinkage of the Haar-Fisz Transformed Wavelet Periodogram.

It is increasingly being realised that many real world time series are not stationary and exhibit evolving second-order autocovariance or spectral structure. This article introduces a Bayesian approach for modelling the evolving wavelet spectrum of a locally stationary wavelet time series. Our new method works by combining the advantages of a Haar-Fisz transformed spectrum with a simple, but powerful, Bayesian wavelet shrinkage method. Our new method produces excellent and stable spectral estimates and this is demonstrated via simulated data and on differenced infant electrocardiogram data. A major additional benefit of the Bayesian paradigm is that we obtain rigorous and useful credible intervals of the evolving spectral structure. We show how the Bayesian credible intervals provide extra insight into the infant electrocardiogram data