Ultrasonographic analysis of facial skin thickness in relation to age, site, sex, and body mass index.

BACKGROUND: Numerous nonsurgical but invasive cosmetic procedures are performed blindly in the dermis or subcutaneous fat layer of the facial skin. OBJECTIVES: To measure the numerical skin thickness of the facial areas where dermatological procedures are performed by applying ultrasound techniques, and to make it possible to estimate the skin thickness by investigating the influence of several individual constitutional factors such as age, sex, and body mass index (BMI), so that these variables can be applied to estimate skin thickness. MATERIALS AND METHODS: Skin thickness was measured at eight different facial points using an ultrasound machine (Affiniti 50; Philips Inc.). Demographic data were gathered using questionnaires. Manual BMI was calculated from the weight and height of each participant, and individual BMI measurements were performed using a body composition analyzer. RESULTS: In terms of whole skin thickness, the thickest point was the mouth corner, and the thinnest point was the lateral forehead. The thickest point in the epidermis was the chin, and the thinnest point was the nasolabial fold. The thickest point in the dermis was the corner of the mouth, and the thinnest was the lateral forehead. Full skin thickness and dermal thickness were mostly lower in females. Skin thickness was not significantly correlated with BMI. CONCLUSION: The skin thickness at different points on the face was variable, and realistic data about skin thickness can be obtained by in vivo ultrasonographic analysis of the skin.

Dynamic thermal imaging for pigmented basal cell carcinoma and seborrheic keratosis.

BACKGROUND: Clinical differentiation between pigmented basal cell carcinoma (BCC) and seborrheic keratosis (SK) can sometimes be difficult. Noninvasive diagnostic technologies, such as thermal imaging, can be helpful in these situations. This study explored the use of dynamic thermal imaging (DTI), which records thermal images after the application of external thermal stimuli (heat or cold) for the differential diagnosis of pigmented BCC and SK. MATERIALS AND METHODS: Twenty-two patients with pigmented BCC and 15 patients with SK participated in this study. Dynamic thermal images of lesions (pigmented BCC or SK) and control sites (contralateral normal skin) were recorded after the heat and cold stimuli. Temperature changes in the region of interest (ROI) are plotted as a thermal response graph. After fitting an exponential equation to each thermal response graph, the rate constants were compared between groups (pigmented BCC versus control, SK versus control). RESULTS: The thermal response graphs revealed that the average temperature of pigmented BCC showed faster thermal recovery to baseline than the control site. There was a significant difference in the rate constants of the fitted exponential equations between the pigmented BCCs and the control sites (p<.001). However, we did not find a significantly different thermal recovery pattern between SK lesions and control sites. CONCLUSIONS: DTI can be used as a diagnostic tool for distinguishing pigmented BCC from SK by comparing thermal recovery patterns between target lesions (pigmented BCC or SK) and the control site.

Dynamic thermal imaging on actinic keratosis patients: A preliminary study.

BACKGROUND: Diagnosis of actinic keratosis (AK) based only on clinical findings can be misleading, and histopathological diagnosis results in scars. Dynamic thermal imaging is a potential non-invasive tool for the diagnosis of AK. This imaging technique quantifies the infrared (IR) radiation emitted by a subject after exposure to external thermal stimuli, such as heat or cold. METHODS: Twenty-six histopathologically confirmed AK patients participated in the study. We compared the dynamic thermal images of AK lesions and normal skin (control sites). Temperature changes were plotted as a thermal response graph. After fitting exponential curves to the thermal response graph, the curve was converted to a logarithmic form. RESULTS: Comparison of the early thermal response graphs of lesions and control sites showed faster thermal recovery of AK lesions. There was a significant difference in the gradient component of the calculated logarithmic equation between the AK lesions and control sites (P < 0.001). CONCLUSION: Dynamic thermal imaging can be used as an auxiliary diagnostic tool for AK.

Application of dynamic thermal imaging in a photocarcinogenesis mouse model.

INTRODUCTION: In clinical practice and experimental settings, cutaneous premalignant and malignant lesions are commonly diagnosed by histopathological biopsy. However, this technique is invasive and results in functional or cosmetic defects. Dynamic thermal imaging is a non-invasive technique that quantifies the infra-red (IR) radiation emitted by a subject after the introduction of external thermal stimuli (such as heat or cold). METHODS: Forty hairless albino (Crl:SKH1-hr) mice were randomised to the control group or the experimental group. The experimental group was regularly irradiated with artificial ultraviolet. Clinical photographs, immunohistochemical staining and dynamic thermal imaging results of both groups were obtained. RESULTS: As photocarcinogenesis proceeded, faster thermal recovery to basal temperature after heat stimuli was significant on dynamic thermal imaging. With histopathological correlations, it was possible to differentiate normal, premalignant and malignant cutaneous lesions according to thermal imaging results. CD 31 staining analysis showed that increased vasculature was the key change responsible for different thermal imaging results among photocarcinogenesis steps. CONCLUSIONS: Dynamic thermal imaging is useful to differentiate normal, premalignant and malignant cutaneous lesions. Increased vasculature is the key change responsible for different thermal imaging results.

Quantitative method for measuring therapeutic efficacy of the 308 nm excimer laser for vitiligo.

BACKGROUND: There are several available treatments for vitiligo, but measurement of their therapeutic efficacy is not standardized and is somewhat arbitrary based largely on the global impression of the overall response. The purpose of this study was to develop a quantitative method for evaluating the treatment response of vitiligo measuring changes in area using digital image analysis. We applied this parametric model to the evaluation of efficacy of the 308 nm excimer laser. METHODS: This study was a retrospective study, designed as a before and after trial with a single arm. A total of 18 patients were enrolled who had been treated with a 308 nm excimer laser as monotherapy twice a week for 20 sessions. The repigmentation percentage was calculated by measuring changes in area before and after treatment using digital image analysis and graded on a five-point ordinal scale [global assessment scale (GAS)]. GAS was also measured by physician and patient for comparison with our estimates. Additional GASs were also measured by four different evaluators for inter-rater variability. RESULTS: The mean repigmentation percentage after treatment was 45.3% (range, 0.7-100%). The changes in area after treatment were statistically significant (P < 0.05). A substantial agreement of outcomes was observed between physicians and digital image analysis (κ(w) = 0.78), but lower agreement was observed between patients and digital image analysis (κ(w) = 0.49). The inter-rater variability for GAS was substantially low (Krippendorff's α = 79.3%). CONCLUSION: Measurement of changes in area using digital image analysis could be used as a quantitative method in evaluating efficacy of treatment for vitiligo. Because vitiligo lesions can occur in any location with various shapes and sizes, digital image analysis would be a more objective method for measuring treatment response than a GAS.

The efficacy of stereoimage optical topometry to evaluate depressed acne scar treatment using cultured autologous fibroblast injection.

BACKGROUND: Despite the use of several evaluation methods, the lack of a true consensus scale hinders standardization of evaluation and treatment of depressed acne scars. OBJECTIVE: To investigate the usefulness of a stereoimage optical topometer (SOT) system in evaluating the efficacy of autologous cultured fibroblast injection for depressed acne scars and to compare the results with those obtained using a visual grading system. MATERIALS AND METHODS: Twenty-two patients with depressed acne scars were included. Three doses of cultured autologous fibroblast (2 × 10(7) cell/mL) injections were given at 2-week intervals. Efficacy was evaluated at 2, 4, 12, and 16 weeks using a visual grading system and a SOT. RESULTS: After autologous fibroblast injection, the lesions evaluated using the visual grading and SOT systems steadily improved. Visual grading and SOT variables obtained showed a similar tendency, although an interrater reliability test of the visual grading system correlated poorly. CONCLUSIONS: A three-dimensional morphologic study can be a useful and reliable method of evaluating the severity of acne scars. We were able to more objectively and quantitatively evaluate acne scar severity through combined analysis using visual grading and SOT systems.

Pep-1 Peptide-modified liposomal carriers for intracellular delivery of gold nanoparticles.

A Pep-1 peptide-modified liposomal (Pep1-Lipo) carrier system was investigated to increase the intracellular delivery of gold nanoparticles (Au NPs). Au NPs with a mean diameter of 13 nm were successfully encapsulated into the inner aqueous compartment of the novel carrier using an ethanol injection technique, reserving the distinctive optical characteristics of the surface plasmon resonance peak around 530 nm. The Au NP-loaded liposomal carrier was physically characterized as 150-170 nm in size and 45 mV in zeta potential. Dark field microscopic observation demonstrated that in vitro cellular association and/or translocation of the nanoprobes into the cells was increased by Pep1-Lipo carriers compared to bare Au NPs. In conclusion, this novel liposomal formulation is a promising platform for the intracellular delivery of metallic nanoprobes including Au NPs.

Effect of pedunculagin investigated by non-invasive evaluation on atopic-like dermatitis in NC/Nga mice.

BACKGROUND/PURPOSE: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder that is becoming increasingly prevalent. Experimental animal models have been an indispensable tool for studying its pathological mechanisms and for in vivo testing of novel therapeutic approaches. AD-like lesions can be induced experimentally in NC/Nga mice. Pedunculagin, an ellagitannin purified from the Manchurian alder, Alnus hirsuta var. microphylla, Betulaceae, is a novel immunomodulator. To evaluate the effect of pedunculagin for AD-like lesions in NC/Nga mice, using clinical and non-invasive methods. METHODS: AD-like lesions were induced in NC/Nga mice using 2,4,6-trinitrochlorobenzene (TNCB). A cream containing 0.1% or 0.5% pedunculagin was applied to the positive treatment group, and the base cream without pedunculagin was applied to the negative treatment group. The control group did not receive any kind of topical agents. We evaluated the therapeutic efficacy of pedunculagin for AD by statistical evaluation of the clinical severity score using non-invasive biomedical engineering tools before treatment, and 1 day, 3 days, 1 week, 2 weeks and 4 weeks afterwards. RESULTS: An AD-like skin rash was successfully induced using TNCB in NC/Nga mice. The group receiving higher concentrations of pedunculagin showed faster and greater improvement. CONCLUSION: Our results suggest that remedies made from natural materials like pedunculagin are now showing promise for medical applications, and many new studies are expected to explore this potential.

Highly sensitive immunoassay of lung cancer marker carcinoembryonic antigen using surface-enhanced Raman scattering of hollow gold nanospheres.

A quick and reproducible surface-enhanced Raman scattering (SERS)-based immunoassay technique, using hollow gold nanospheres (HGNs) and magnetic beads, has been developed. Here, HGNs show strong enhancement effects from individual particles because hot spots can be localized on the pinholes in the hollow particle structure. Thus, HGNs can be used for highly reproducible immunoanalysis of cancer markers. Magnetic beads were used as supporting substrates for the formation of the immunocomplex. This SERS-based immunoassay technique overcomes the problem of slow immunoreaction caused by the diffusion-limited kinetics on a solid substrate because all of the reactions occur in solution. For the validation of our SERS immunoassay, a well-known lung cancer marker, carcinoembryonic antigen (CEA), was used as a target marker. According to our experimental results, the limit of detection (LOD) was determined to be 1-10 pg/mL, this value being about 100-1000 times more sensitive than the LOD of enzyme-linked immunosorbent assay. Furthermore, the assay time took less than 1 h, including washing and optical detection steps.

Intravital imaging in zebrafish using quantum dots.

BACKGROUND/AIMS: Fluorescent quantum dots (QDs) are powerful multipurpose interfaces of nanotechnology providing long-term and multicolor imaging of cellular and molecular interactions. The application of QDs in living organisms is just beginning to be explored, and zebrafish embryos may be suitable vertebrate model organisms for intravital imaging with QDs. To investigate their potential in skin research, we used QDs as microangiography contrast agents and attempted to visualize the cardiovascular system in zebrafish. We also attempted to find the pathway relationship between the cardiovascular system and the nerve network using QDs together with the transgenic zebrafish line. METHOD: Quantum Dot QD605, which reveals green color under the fluorescent microscope, was used as a microangiography contrast agent. The olig2-Dsred transgenic zebrafish line, which expresses motor neurons in red color, was used together with QDs. Images of QD605-injected embryos were recorded with a digital camera. RESULTS: Combining the green fluorescence of QD605 and the red fluorescence of olig2-Dsred transgenic zebrafish, we could obtain detailed images manifesting the spatial relationship between the vascular and the nervous system of zebrafish CONCLUSION: QDs could easily be used as a bright microangiography agent in living embryos. Our image of the vascular and motor nervous system in zebrafish showed a similar pattern of trajectory overall. However, their segmented repetitive networks along the dorsoventral axis were not completely overlapped.

Rapid DNA hybridization analysis using a PDMS microfluidic sensor and a molecular beacon.

A rapid DNA analysis has been developed based on a fluorescence intensity change of a molecular beacon in a PDMS microfluidic channel. Recently, we reported a new analytical method of DNA hybridization involving a PDMS microfluidic sensor using fluorescence energy transfer (FRET). However, there are some limitations in its application to real DNA samples because the target DNA must be labelled with a suitable fluorescent dye. To resolve this problem, we have developed a new DNA microfluidic sensor using a molecular beacon. By monitoring the change in the restored fluorescence intensity along the channel length, it is possible to rapidly detect any hybridization of the molecular beacon to the target DNA. In this case, the target DNA does not need to be labelled. Our experimental results demonstrate that this microfluidic sensor using a molecular beacon is a promising diagnostic tool for rapid DNA hybridization analysis.

Updated view on epidemiology and clinical aspects of pilomatricoma in adults.

BACKGROUND: Clinically, pilomatricoma offers potential for a wide spectrum of differential diagnoses. It typically occurs in pediatric patients with the head being the most common location. A second peak of clinical presentation occurs in adults at age 50-65 years, suggesting a bimodal pattern of occurrence. OBJECTIVE: To investigate the clinical and epidemiological features of pilomatricoma in adults over 20 years old, as it is a common and frequently misdiagnosed tumor. METHODS: This was a retrospective study of pilomatricomas surgically removed at a tertiary hospital between January 1994 and December 2014. A search of the all-pathological database of patients aged over 20 years old with a pathological diagnosis of pilomatricoma was carried out. RESULTS: The clinical preoperative diagnosis of pilomatricoma was made in 34.0% of cases. Tumor location showed a predilection to the head and neck. Of the reported concomitant neoplasm, a majority had accompanying skin tumors. CONCLUSION: We conclude that clinical features in adults were similar to those of children. This study outlines clinical presentations that should help to guide differential diagnoses. Additionally, because of similarities between the distribution and depth of vellus hair follicles and pilomatricomas, it is probable that vellus hair bulbs may be the origin of this tumor.

Fast and sensitive analysis of DNA hybridization in a PDMS micro-fluidic channel using fluorescence resonance energy transfer.

Fluorescence resonance energy transfer has been used to illustrate its applicability to the sensitive detection of DNA hybridization reactions in a PDMS microfluidic channel.

Molecular Phenotyping Small (Asian) versus Large (Western) Plaque Psoriasis Shows Common Activation of IL-17 Pathway Genes but Different Regulatory Gene Sets.

Psoriasis is present in all racial groups, but in varying frequencies and severity. Considering that small plaque psoriasis is specific to the Asian population and severe psoriasis is more predominant in the Western population, we defined Asian small and intermediate plaque psoriasis as psoriasis subtypes and compared their molecular signatures with the classic subtype of Western large plaque psoriasis. Two different characteristics of psoriatic spreading-vertical growth and radial expansion-were contrasted between subtypes, and genomic data were correlated to histologic and clinical measurements. Compared with Western large plaque psoriasis, Asian small plaque psoriasis revealed limited psoriasis spreading, but IL-17A and IL-17-regulated proinflammatory cytokines were highly expressed. Paradoxically, IL-17A and IL-17-regulated proinflammatory cytokines were lower in Western large plaque psoriasis, whereas T cells and dendritic cells in total psoriatic skin area were exponentially increased. Negative immune regulators, such as CD69 and FAS, were decreased in both Western large plaque psoriasis and psoriasis with accompanying arthritis or obesity, and their expression was correlated with psoriasis severity index. Based on the disease subtype comparisons, we propose that dysregulation of T-cell expansion enabled by downregulation of immune negative regulators is the main mechanism for development of large plaque psoriasis subtypes.

Conversion of mouse fibroblasts into cardiomyocyte-like cells using small molecule treatments.

The possibility of controlling cell fates by overexpressing specific transcription factors has led to numerous studies in stem cell research. Small molecules can be used, instead of transcription factors, to induce the de-differentiation of somatic cells or to induce pluripotent cells (iPSCs). Here we reported that combinations of small molecules could convert mouse fibroblasts into cardiomyocyte-like cell without requiring transcription factor expression. Treatment with specific combinations of small molecules that are enhancer for iPSC induction converted mouse fibroblasts into spontaneously contracting, cardiac troponin T-positive, cardiomyocyte-like cells. We specifically identified five small molecules that can induce mouse fibroblasts to form these cardiomyocyte-like cells. These cells are similar to primary cardiomyocytes in terms of marker gene expression, epigenetic status of cardiac-specific genes, and subcellular structure. Our findings indicate that lineage conversion can be induced not only by transcription factors, but also by small molecules.

Objective interpretation of severity of SLS induced edema by stereoimaging.

BACKGROUND: In the evaluation of the severity of skin inflammations, visual scoring system is widely being used as a subjective method. However, it is well known that interobserver variations occur even between the interpretations of experienced dermatologists. OBJECTIVE: To develop a new objective and quantitative method for the evaluation of skin surface contours and for the assessment of severity in SLS-induced edema, a new investigatory tool based on the concept of "stereoimaging" was studied. Differences between binocular images were used by a stereoimage optical topometer (SOT) system capable of calculating skin surface topographic information, which was then used to produce a three-dimensional image. METHODS: We compared the results obtained by SOT with a visual scoring system after applying sodium lauryl sulfate (SLS) to skin. The degree of edema was assessed qualitatively by visual scoring (0: none, 1: mild edema, 2: moderate edema, 3: severe edema). To quantify the severity, five three-dimensional parameters (S(a), S(z), SL, SA and SV) were used in the SOT analysis. RESULTS: The means of these five parameters increased significantly in visual grade 1+ compared to visual grade 0 and the means of the five parameters decreased significantly and proportionally as the visual grades increased from 1+ to 3+. A highly significant correlation was found to exist between the visual scoring results and the five SOT parameters. CONCLUSION: SOT can be used to evaluate the severity of SLS-induced edema objectively and can be extensively applied to evaluate the degree of severity in other inflammatory skin conditions.

Trichorhinophalangeal syndrome type I--clinical, microscopic, and molecular features.

Trichorhinophalangeal syndrome type I (TRPS I) is an autosomal dominant malformation syndrome characterized by a triad of hair alteration, craniofacial and skeletal abnormalities. TRPS1 gene was first identified in 2000 and mapped on chromosome 8q23.3. A 39-year-old female patient with short stature (149 cm) visited for fine sparse and slow-growing hair with receded medio-occipital hairline of roughly triangular shape since infancy. A typical pear-shaped nose and elongated philtrum were noticeable. In addition, she reported deviation of middle phalanges, bilateral coxa varus in both hips and brachydactyly on bilateral fourth digits. Mutation analysis identified a transition of cytosine to thymine at position 1630 (exon 4), which results in amino acid change R544X and a premature stop of translation. There is no established treatment. But through careful evaluation of suspicious cases to identify potential mutation carriers, the patient can receive information about the disease and genetic counseling.