HIC2 regulates isoform switching during maturation of the cardiovascular system.

Physiological changes during embryonic development are associated with changes in the isoform expression of both myocyte sarcomeric proteins and of erythrocyte haemoglobins. Cell type-specific isoform expression of these genes also occurs. Although these changes appear to be coordinated, it is unclear how changes in these disparate cell types may be linked. The transcription factor Hic2 is required for normal cardiac development and the mutant is embryonic lethal. Hic2 embryos exhibit precocious expression of the definitive-lineage haemoglobin Hbb-bt in circulating primitive erythrocytes and of foetal isoforms of cardiomyocyte genes (creatine kinase, Ckm, and eukaryotic elongation factor Eef1a2) as well as ectopic cardiac expression of fast-twitch skeletal muscle troponin isoforms. We propose that HIC2 regulates a switching event within both the contractile machinery of cardiomyocytes and the oxygen carrying systems during the developmental period where demands on cardiac loading change rapidly

Safety and efficacy of fluticasone propionate in the topical treatment of skin diseases

Fluticasone propionate - the first carbothioate corticosteroid - has been classified as a potent anti-inflammatory drug for dermatological use. It is available as 0.05% cream and 0.005% ointment formulations for the acute and maintenance treatment of patients with dermatological disorders such as atopic dermatitis, psoriasis and vitiligo. This glucocorticoid is characterized by high lipophilicity, high glucocorticoid receptor binding and activation, and a rapid metabolic turnover in skin. Although skin blanching following fluticasone propionate exceeds that of corticosteroids of medium strength, several clinical trials demonstrate a low potential for cutaneous and systemic side-effects, even in difficult-to-treat areas like the face, the eyelids and intertriginous areas. Even among paediatric patients with atopic dermatitis, fluticasone propionate proved to be safe and effective. These pharmacological and clinical properties are reflected by the high therapeutic index of this glucocorticoid

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

A Requirement for Zic2 in the Regulation of Nodal Expression Underlies the Establishment of Left-Sided Identity

ZIC2 mutation is known to cause holoprosencephaly (HPE). A subset of ZIC2 HPE probands harbour cardiovascular and visceral anomalies suggestive of laterality defects. 3D-imaging of novel mouse Zic2 mutants uncovers, in addition to HPE, laterality defects in lungs, heart, vasculature and viscera. A strong bias towards right isomerism indicates a failure to establish left identity in the lateral plate mesoderm (LPM), a phenotype that cannot be explained simply by the defective ciliogenesis previously noted in Zic2 mutants. Gene expression analysis showed that the left-determining NODAL-dependent signalling cascade fails to be activated in the LPM, and that the expression of Nodal at the node, which normally triggers this event, is itself defective in these embryos. Analysis of ChiP-seq data, in vitro transcriptional assays and mutagenesis reveals a requirement for a low-affinity ZIC2 binding site for the activation of the Nodal enhancer HBE, which is normally active in node precursor cells. These data show that ZIC2 is required for correct Nodal expression at the node and suggest a model in which ZIC2 acts at different levels to establish LR asymmetry, promoting both the production of the signal that induces left side identity and the morphogenesis of the cilia that bias its distribution

Working Memory Training Using Mental Calculation Impacts Regional Gray Matter of the Frontal and Parietal Regions

Training working memory (WM) improves performance on untrained cognitive tasks and alters functional activity. However, WM training's effects on gray matter morphology and a wide range of cognitive tasks are still unknown. We investigated this issue using voxel-based morphometry (VBM), various psychological measures, such as non-trained WM tasks and a creativity task, and intensive adaptive training of WM using mental calculations (IATWMMC), all of which are typical WM tasks. IATWMMC was associated with reduced regional gray matter volume in the bilateral fronto-parietal regions and the left superior temporal gyrus. It improved verbal letter span and complex arithmetic ability, but deteriorated creativity. These results confirm the training-induced plasticity in psychological mechanisms and the plasticity of gray matter structures in regions that have been assumed to be under strong genetic control

Breastfeeding and weaning practices among Hong Kong mothers: a prospective study

<p>Abstract</p> <p>Background</p> <p>Breastfeeding provides optimal and complete nutrition for newborn babies. Although new mothers in Hong Kong are increasingly choosing to breastfeed their babies, rates of exclusive breastfeeding are low and duration remains short. The purpose of this study was to describe the breastfeeding and weaning practices of Hong Kong mothers over the infant's first year of life to determine the factors associated with early cessation.</p> <p>Methods</p> <p>A cohort of 1417 mother-infant pairs was recruited from the obstetric units of four public hospitals in Hong Kong in the immediate post-partum period and followed prospectively for 12 months or until weaned. We used descriptive statistics to describe breastfeeding and weaning practices and multiple logistic regression to investigate the relationship between maternal characteristics and breastfeeding cessation.</p> <p>Results</p> <p>At 1 month, 3 months, 6 months and 12 months only 63%, 37.3%, 26.9%, and 12.5% of the infants respectively, were still receiving any breast milk; approximately one-half of breastfeeding mothers were exclusively breastfeeding. Younger mothers, those with a longer duration of residence in Hong Kong, and those returning to work postpartum were more likely to wean before 1 month. Mothers with higher education, previous breastfeeding experience, who were breastfed themselves and those who were planning to exclusively breastfeed and whose husbands preferred breastfeeding were more likely to continue breastfeeding beyond 1 month. The introduction of infant formula before 1 month and returning to work postpartum were predictive of weaning before 3 months.</p> <p>Conclusions</p> <p>Breastfeeding promotion programs have been successful in achieving high rates of breastfeeding initiation but the focus must now shift to helping new mothers exclusively breastfeed and sustain breastfeeding for longer.</p

Evidence-Based Management of Hand Eczema

Hand eczema is a common skin disease with a wide variation in morphology and a complex etiology based on endogenous and exogenous factors.The diagnosis of hand eczema is based on patient history, exposure assessment, physical examination, and the results of patch testing. Management of hand eczema starts with education of the patient on the etiology of the disease, and the needed changes in behavior regarding skin care and preventive measures, and avoidance of relevant exposure factors. In many cases, medical treatment is needed for successful management of the disease; use of medication can only be successful with proper education and avoidance of relevant exposure