Scientific Validation of Three-Dimensional Stereophotogrammetry Compared to the IGAIS Clinical Scale for Assessing Wrinkles and Scars after Laser Treatment

Measuring outcomes from treatments to the skin is either reliant upon patient’s subjective feedback or scale-based peer assessments. Three-Dimensional stereophotogrammetry intend to accurately quantify skin microtopography before and after treatments. The objective of this study is comparing the accuracy of stereophotogrammetry with a scale-based peer evaluation in assessing topographical changes to skin surface following laser treatment. A 3D stereophotogrammetry system photographed skin surface of 48 patients with facial wrinkles or scars before and three months after laser resurfacing, followed immediately by topical application of vitamin C. The software measured changes in skin roughness, wrinkle depth and scar volume. Images were presented to three observers, each independently scoring cutaneous improvement according to Investigator Global Aesthetic Improvement Scale (IGAIS). As for the results, a trend reflecting skin/scar improvement was reported by 3D SPM measurements and raters. The percentage of topographical change given by the raters matched 3D SPM findings. Agreement was highest when observers analysed 3D images. However, observers overestimated skin improvement in a nontreatment control whilst 3D SPM was precise in detecting absence of intervention. This study confirmed a direct correlation between the IGAIS clinical scale and 3D SPM and confirmed the efficacy and accuracy of the latter when assessing cutaneous microtopography alterations as a response to laser treatment

Kinetic analysis of novel mono- and multivalent VHH-fragments and their application for molecular imaging of brain tumours

Background and purpose:? The overexpression of epidermal growth factor receptor (EGFR) and its mutated variant EGFRvIII occurs in 50% of glioblastoma multiforme. We developed antibody fragments against EGFR/EGFRvIII for molecular imaging and/or therapeutic targeting applications. Experimental approach:? An anti\u2013EGFR/EGFRvIII llama single-domain antibody (EG2) and two higher valency format constructs, bivalent EG2-hFc and pentavalent V2C-EG2 sdAbs, were analysed in vitro for their binding affinities using surface plasmon resonance and cell binding studies, and in vivo using pharmacokinetic, biodistribution, optical imaging and fluorescent microscopy studies. Key results:? Kinetic binding analyses by surface plasmon resonance revealed intrinsic affinities of 55 nM and 97 nM for the monovalent EG2 to immobilized extracellular domains of EGFR and EGFRvIII, respectively, and a 10- to 600-fold increases in apparent affinities for the multivalent binders, V2C-EG2 and EG2-hFc, respectively. In vivo pharmacokinetic and biodistribution studies in mice revealed plasma half-lives for EG2, V2C-EG2 and EG2-hFc of 41 min, 80 min and 12.5 h, respectively, as well as a significantly higher retention of EG2-hFc compared to the other two constructs in EGFR/EGFRvIII-expressing orthotopic brain tumours, resulting in the highest signal in the tumour region in optical imaging studies. Time domain volumetric optical imaging fusion with high-resolution micro-computed tomography of microvascular brain network confirmed EG2-hFc selective accumulation/retention in anatomically defined tumour regions. Conclusions:? Single domain antibodies can be optimized for molecular imaging applications by methods that improve their apparent affinity and prolong plasma half-life and, at the same time, preserve their ability to penetrate tumour parenchyma.Peer reviewed: YesNRC publication: Ye

Supplementary Material for: Reduction of Inflammatory and Noninflammatory Lesions with Topical Tyrothricin 0.1% in the Treatment of Mild to Severe Acne Papulopustulosa: A Randomized Controlled Clinical Trial

<b><i>Background/Aims:</i></b> Antibiotic-induced drug resistance requires new approaches in topical acne treatment. Tyrothricin is known to produce no resistance. In this study, it was tested for the first time in topical acne treatment. The efficacy and tolerability of topical tyrothricin 0.1% was evaluated. <b><i>Methods:</i></b> A<b> </b>randomized, active comparator-controlled, exploratory, observer-blind clinical study was conducted in 24 patients with acne papulopustulosa. Randomization on a split-face was either tyrothricin versus clindamycin + benzoyl peroxide (BPO) (n = 12) or tyrothricin versus BPO 5% (n = 12). The main outcome was change in inflammatory and noninflammatory lesion counts. <b><i>Results:</i></b> The mean differences in inflammatory lesion counts from baseline were -12.3 (95% CI: -20.5 to -4.1) in clindamycin + BPO, -10.2 (95% CI: -15.3 to -5.0) in BPO 5%, and -7.7 (95% CI: -11.7 to -3.7) in tyrothricin. Tyrothricin reduced noninflammatory lesions (mean difference: -6.5 (95% CI: -11.6 to -1.4) and caused less product-related adverse events (n = 31) compared to BPO (n = 37) and clindamycin + BPO (n = 20). <b><i>Conclusion:</i></b> The results indicate that tyrothricin might be a candidate for treating acne and it seems to be more tolerable than both comparator treatments

Association between dynamic asymmetry of the newborn's head and intrauterine factors Associação entre a assimetria dinâmica da cabeça do recém-nascido e fatores intra-uterinos

A non-comparable, individual, observational and contemporary cross-sectional study in newborns was made to determine the dynamic lateralization in the head turning after release from the midline and its relationship with obstetric variables. From October to December of 2005, 320 newborns were admitted to the Adjacent Lodgings of the University Hospital of Santa Maria. From those, 89 were selected for assessment of the vestibular function since they have had previously fetal static control through ultrasound. Our results show that the right-sided head lateralization was significantly greater than the left-sided. The predominancy of the lateralization towards the right side also occurred in cephalic presentations and left-sided back, however these were not significant. Results corroborate with the existing literature and suggest an association between fetal static and vestibular function.<br>Com o objetivo determinar a lateralização dinâmica na prova da queda da cabeça e sua associação com variáveis obstétricas, foi realizado um estudo transversal no recém-nascido, não comparado, individual, observacional e contemporâneo. No período de outubro a dezembro de 2005, 320 recém-nascidos foram admitidos no Alojamento Conjunto do Hospital Universitário de Santa Maria, e destes 89 foram selecionados para avaliação da função vestibular, por terem feito controle da estática fetal através do ultrasom. Nossos resultados mostram que a lateralização da cabeça para a direita foi significativamente maior do que para esquerda. Também este predomínio da lateralização para a direita ocorreu nas apresentações cefálicas e com o dorso para esquerda, no entanto estes não foram significativos. Nossos resultados corroboram com a literatura existente, e sugerem uma associação entre a estática fetal e a função vestibular

mTORC1 promotes survival through translational control of Mcl-1

Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is a frequent occurrence in human cancers and a major promoter of chemotherapeutic resistance. Inhibition of one downstream target in this pathway, mTORC1, has shown potential to improve chemosensitivity. However, the mechanisms and genetic modifications that confer sensitivity to mTORC1 inhibitors remain unclear. Here, we demonstrate that loss of TSC2 in the Eμ-myc murine lymphoma model leads to mTORC1 activation and accelerated oncogenesis caused by a defective apoptotic program despite compromised AKT phosphorylation. Tumors from Tsc2+/−Eμ-Myc mice underwent rapid apoptosis upon blockade of mTORC1 by rapamycin. We identified myeloid cell leukemia sequence 1 (Mcl-1), a bcl-2 like family member, as a translationally regulated genetic determinant of mTORC1-dependent survival. Our results indicate that the extent by which rapamycin can modulate expression of Mcl-1 is an important feature of the rapamycin response