Routine application of ex vivo confocal laser scanning microscopy with digital staining for examination of surgical margins in basal cell carcinomas.

BACKGROUND AND OBJECTIVES: Ex vivo confocal laser scanning microscopy (CLSM) allows histologic examination of native tissue based on tissue reflection and nuclear fluorescence staining. The newly introduced digital staining process almost perfectly mimics conventional hematoxylin and eosin (HE) slides. The aim was to evaluate the new method in clinical routine, with regard to quality of findings and time requirements, in the examination of surgical margins of basal cell carcinomas. PATIENTS AND METHODS: 78 patients with 101 basal cell carcinomas were prospectively enrolled. Surgery was performed either with complete margin control (n = 60) or as elliptical excision (n = 41). Immediately after excision specimens were scanned with CLSM and then routinely processed by conventional histopathology. Blinded evaluation of images and slides was performed by a dermatopathologist. RESULTS: Basal cell carcinomas were excellently recognizable by CLSM directly after excision, and the use of digital staining did not require any adjustment of the examiner's visualization preferences. CLSM images showed a sensitivity of 73.6 % and a specificity of 96.5 % compared to conventional HE stained slides. Erroneous findings were often due to limited assessment potential in cases where the epidermis could not be fully visualized. CONCLUSIONS: CLSM with digital HE staining is very well suited to diagnose basal cell carcinomas and their incision margins even under routine conditions and thus represents a tissue-saving alternative to rapid cryostat sectioning.

Universal and language-specific sublexical cues in speech perception: a novel electroencephalography-lesion approach.

SEE CAPPA DOI101093/BRAIN/AWW090 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE : The phonological structure of speech supports the highly automatic mapping of sound to meaning. While it is uncontroversial that phonotactic knowledge acts upon lexical access, it is unclear at what stage these combinatorial rules, governing phonological well-formedness in a given language, shape speech comprehension. Moreover few studies have investigated the neuronal network affording this important step in speech comprehension. Therefore we asked 70 participants-half of whom suffered from a chronic left hemispheric lesion-to listen to 252 different monosyllabic pseudowords. The material models universal preferences of phonotactic well-formedness by including naturally spoken pseudowords and digitally reversed exemplars. The latter partially violate phonological structure of all human speech and are rich in universally dispreferred phoneme sequences while preserving basic auditory parameters. Language-specific constraints were modelled in that half of the naturally spoken pseudowords complied with the phonotactics of the native language of the monolingual participants (German) while the other half did not. To ensure universal well-formedness and naturalness, the latter stimuli comply with Slovak phonotactics and all stimuli were produced by an early bilingual speaker. To maximally attenuate lexico-semantic influences, transparent pseudowords were avoided and participants had to detect immediate repetitions, a task orthogonal to the contrasts of interest. The results show that phonological 'well-formedness' modulates implicit processing of speech at different levels: universally dispreferred phonological structure elicits early, medium and late latency differences in the evoked potential. On the contrary, the language-specific phonotactic contrast selectively modulates a medium latency component of the event-related potentials around 400 ms. Using a novel event-related potential-lesion approach allowed us to furthermore supply first evidence that implicit processing of these different phonotactic levels relies on partially separable brain areas in the left hemisphere: contrasting forward to reversed speech the approach delineated an area comprising supramarginal and angular gyri. Conversely, the contrast between legal versus illegal phonotactics consistently projected to anterior and middle portions of the middle temporal and superior temporal gyri. Our data support the notion that phonological structure acts on different stages of phonologically and lexically driven steps of speech comprehension. In the context of previous work we propose context-dependent sensitivity to different levels of phonotactic well-formedness.

Reduced Serum Levels of Bone Formation Marker P1NP in Psoriasis.

Psoriasis is a chronic inflammatory disease of the skin and joints. More recent data emphasize an association with dysregulated glucose and fatty acid metabolism, obesity, elevated blood pressure and cardiac disease, summarized as metabolic syndrome. TNF-α and IL-17, central players in the pathogenesis of psoriasis, are known to impair bone formation. Therefore, the relation between psoriasis and bone metabolism parameters was investigated. Two serum markers of either bone formation-N-terminal propeptide of type I procollagen (P1NP) or bone resorption-C-terminal telopeptide of type I collagen (CTX-I)-were analyzed in a cohort of patients with psoriasis vulgaris. In patients with psoriasis, P1NP serum levels were reduced compared to gender-, age-, and body mass index-matched healthy controls. CTX-I levels were indistinguishable between patients with psoriasis and controls. Consistently, induction of psoriasis-like skin inflammation in mice decreases bone volume and activity of osteoblasts. Moreover, efficient anti-psoriatic treatment improved psoriasis severity, but did not reverse decreased P1NP level suggesting that independent of efficient skin treatment psoriasis did affect bone metabolism and might favor the development of osteoporosis. Taken together, evidence is provided that bone metabolism might be affected by psoriatic inflammation, which may have consequences for future patient counseling and disease monitoring.