An abnormality in glucocorticoid receptor expression differentiates steroid responders from nonresponders in keloid disease

Background: Glucocorticoids (GCs) are first-line treatment for keloid disease (KD) but are limited by high incidence of resistance, recurrence and undesirable sideeffects. Identifying patient responsiveness early could guide therapy. Methods: Nineteen patients with KD were recruited at week 0 (before treatment) and received intralesional steroids. At weeks 0, 2 and 4, noninvasive imaging and biopsies were performed. Responsiveness was determined by clinical response and a significant reduction in vascular perfusion following steroid treatment, using full-field laser perfusion imaging (FLPI). Responsiveness was also evaluated using (i) spectrophotometric intracutaneous analysis to quantify changes in collagen and melanin and (ii) histology to identify changes in epidermal thickness and glycosaminoglycan (GAG) expression. Biopsies were used to quantify changes in glucocorticoid receptor (GR) expression using quantitative reverse transcriptase polymerase chain reaction, immunoblotting and immunohistochemistry. Results: At week 2, the FLPI was used to separate patients into steroid responsive (n = 12) and nonresponsive groups (n = 7). All patients demonstrated a signifccant decrease in GAG at week 2 (P < 0 05). At week 4, responsive patients exhibited significant reduction in melanin, GAG, epidermal thickness (all P < 0 05) and a continued reduction in perfusion (P < 0 001) compared with nonresponders. Steroid-responsive patients had increased GR expression at baseline and showed autoregulation of GR compared with nonresponders, who showed no change in GR transcription or protein. Conclusions: This is the first demonstration that keloid response to steroids can be measured objectively using noninvasive imaging. FLPI is a potentially reliable tool to stratify KD responsiveness. Altered GR expression may be the mechanism gating therapeutic response

Morphological characterisation of unstained and intact tissue microarchitecture by x-ray computed micro- and nano-tomography

Characterisation and quantification of tissue structures is limited by sectioning-induced artefacts and by the difficulties of visualising and segmenting 3D volumes. Here we demonstrate that, even in the absence of X-ray contrast agents, X-ray computed microtomography (microCT) and nanotomography (nanoCT) can circumvent these problems by rapidly resolving compositionally discrete 3D tissue regions (such as the collagen-rich adventitia and elastin-rich lamellae in intact rat arteries) which in turn can be segmented due to their different X-ray opacities and morphologies. We then establish, using X-ray tomograms of both unpressurised and pressurised arteries that intra-luminal pressure not only increases lumen cross-sectional area and straightens medial elastic lamellae but also induces profound remodelling of the adventitial layer. Finally we apply microCT to another human organ (skin) to visualise the cell-rich epidermis and extracellular matrix-rich dermis and to show that conventional histological and immunohistochemical staining protocols are compatible with prior X-ray exposure. As a consequence we suggest that microCT could be combined with optical microscopy to characterise the 3D structure and composition of archival paraffin embedded biological materials and of mechanically stressed dynamic tissues such as the heart, lungs and tendons

Comparisons against baseline within randomised groups are often used and can be highly misleading

<p>Abstract</p> <p>Background</p> <p>In randomised trials, rather than comparing randomised groups directly some researchers carry out a significance test comparing a baseline with a final measurement separately in each group.</p> <p>Methods</p> <p>We give several examples where this has been done. We use simulation to demonstrate that the procedure is invalid and also show this algebraically.</p> <p>Results</p> <p>This approach is biased and invalid, producing conclusions which are, potentially, highly misleading. The actual alpha level of this procedure can be as high as 0.50 for two groups and 0.75 for three.</p> <p>Conclusions</p> <p>Randomised groups should be compared directly by two-sample methods and separate tests against baseline are highly misleading.</p

When my object becomes me:The mere ownership of an object elevates domain-specific self-efficacy

Past research on the mere ownership effect has shown that when people own an object, they perceive the owned objects more favorably than the comparable non-owned objects. The present research extends this idea, showing that when people own an object functional to the self, they perceive an increase in their self-efficacy. Three studies were conducted to demonstrate this new form of the mere ownership effect. In Study 1, participants reported an increase in their knowledge level by the mere ownership of reading materials (a reading package in Study 1a, and lecture notes in Study 1b). In Study 2, participants reported an increase in their resilience to sleepiness by merely owning a piece of chocolate that purportedly had a sleepiness-combating function. In Study 3, participants who merely owned a flower essence that is claimed to boost creativity reported having higher creativity efficacy. The findings provided insights on how associations with objects alter one\u27s self-perception