Comparative Efficacy of Radiofrequency and Pulsed Dye Laser in the Treatment of Rosacea.

BACKGROUND: Laser and light-based therapies have been used successfully in the treatment of rosacea; however, evidence is lacking regarding the efficacy of radiofrequency (RF). OBJECTIVE: This study evaluated the efficacy of RF in the treatment of rosacea compared with pulsed dye laser (PDL). METHODS: Thirty patients with rosacea (erythematotelangiectatic rosacea [ETR], n = 20; papulopustular rosacea [PPR], n = 10) were enrolled in a randomized, controlled, split-face study. The patients were treated with RF on one side and PDL on the other side. Each treatment consisted of 3 sessions at 4-week intervals and followed up until 4 weeks after the last treatment. Efficacy was assessed by rosacea severity score, erythema index, lesion counts, physician's subjective evaluation, and patient's satisfaction. RESULTS: Radiofrequency and PDL resulted in significant improvement in severity scores and erythema and 70% of the patients receiving RF treatment showed a clinical improvement of >50%. No significant difference was noted between RF and PDL treatment in ETR. However, RF treatment led to a significantly greater decrease in papulopustular lesion count and rosacea severity score in PPR compared with PDL treatment. CONCLUSION: RF therapy was effective in the treatment of rosacea. It should be considered an alternative therapeutic option, especially in PPR.

Adiponectin corrects premature cellular senescence and normalizes antimicrobial peptide levels in senescent keratinocytes.

Stress-induced premature senescence or aging causes dysfunction in the human somatic system. Adiponectin (Acrp30) plays a role in functional recovery, especially with adenosine 3',5'-monophosphate (AMP)-activated protein kinase (AMPK) and silent mating type information regulation 2 homolog 1 (SIRT1). Acrp30 stimulation reduced the premature senescence positive ratio induced by hydrogen peroxide (H2O2) and restituted human ß-defensin 2 (hBD-2) levels in senescent keratinocytes. Acrp30 recovered AMPK activity in senescent keratinocytes and increased SIRT1 deacetylation activity. As a result, FoxO1 and FoxO3 transcription activity was recovered. Additionally, Acrp30 stimulation suppresses NFκB p65, which induces abnormal expression of hBD-2 induced by H2O2. In the present study, we have shown that Acrp30 reduces premature senescence and recovers cellular function in keratinocytes. These results suggest a role for Acrp30 as an anti-aging agent to improve impaired skin immune barriers.

Teacher-Student Relationship and Peer Disliking and Liking Across Grades 1-4.

Between-child and within-child effects of teacher-student warmth and conflict on children's peer-nominated disliking and liking across Grades 1-4 (ages 6-10) were investigated in a sample of 746 ethnically diverse and academically at-risk children in Texas. Multilevel modeling controlled for time-invariant between-child differences while modeling the effect of time-varying teacher-student relationship (TSR) warmth and conflict on children's peer relatedness. Teachers reported on warmth and conflict. Peers reported on liking and disliking. Above between-child effects of average levels of teacher warmth and conflict on initial level and rate of change in liking and disliking and classroom teacher support, year-to-year changes in TSR conflict and warmth predicted intraindividual change in children's peer disliking but not peer liking.

Effects of Extracurricular Participation During Middle School on Academic Motivation and Achievement at Grade 9.

We investigated the effect of participating in two domains of extracurricular activities (sports and performance arts/clubs) in Grades 7 and 8 on Grade 9 academic motivation and letter grades, above baseline performance. Participants were 483 students (55% male; 33% Euro-American, 25% African American, and 39% Latino). Propensity score weighting controlled for potential confounders in all analyses. Delayed (Grade 8 only) and continuous participation (Grades 7 and 8) in sports predicted competence beliefs and valuing education; delayed and continuous participation in performance arts/clubs predicted teacher-rated engagement and letter grades. Benefits of participation were similar across gender and ethnicity; however, Latino youth were least likely to participate in extracurricular activities. Implications for reducing ethnic and income disparities in educational attainment are discussed.

Inhibitory effect of cucurbitacin B on imiquimod-induced skin inflammation.

Psoriasis is a common skin disease, of which pathogenesis involves the increase of inflammatory reaction in epidermal cells. In an attempt to find therapeutics for psoriasis, we found that cucurbitacin B has an inhibitory potential on imiquimod-induced inflammation of keratinocytes. Cucurbitacin B significantly inhibited imiquimod-induced expression of crucial psoriatic cytokines, such as IL-8 and CCL20, via down-regulation of NF-κB and STAT3 signaling pathway in human keratinocytes. In addition, keratinocyte proliferation was markedly inhibited by cucurbitacin B. The potential beneficial effect of cucurbitacin B on psoriasis was further validated in imiquimod-induced psoriasiform dermatitis of experimental animal. Topical application of cucurbitacin B resulted in significant reduction of epidermal hyperplasia and inflammatory cytokines production, and ameliorated the psoriatic symptom. Taken together, these results suggest that cucurbitacin B may be a potential candidate for the treatment of psoriasis.

A low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminium garnet laser for the treatment of café-au-lait macules.

BACKGROUND: Café-au-lait macules (CALMs) are a common pigmentary disorder. Although a variety of laser modalities have been used to treat CALMs, their efficacies vary and dyspigmentation may develop. OBJECTIVE: We evaluated the clinical efficacy and safety of a low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminium garnet (Nd:YAG) laser for the treatment of CALMs. METHODS: In a preliminary investigation, 6 patients underwent a split-lesion comparative study with 532- and 1064-nm Q-switched Nd:YAG laser treatment. In total, 32 patients with 39 CALMs were enrolled in a subsequent prospective trial to evaluate the treatment with a low-fluence 1064-nm Q-switched Nd:YAG laser. RESULTS: In the preliminary study, the 1064-nm treatment group had a more favorable response and a shorter recovery time. In a subsequent prospective trial of a 1064-nm laser, 74.4% of the lesions showed a clinical response with clearance of ≥50.0%. The treatment regimen was well tolerated; 15.4% of patients experienced adverse events. LIMITATIONS: The study participants were followed for 6 months, and there were no relevant treatment controls in the prospective trial group. CONCLUSION: Low-fluence 1064-nm Q-switched Nd:YAG laser therapy afforded good clinical improvement for treating CALMs.

Inhibitory role of Id1 on TGF-ß-induced collagen expression in human dermal fibroblasts.

Inhibitor of DNA binding 1 (Id1) is a basic helix-loop-helix (bHLH) protein that has a variety of functional roles in cellular events including differentiation, cell cycle and cancer development. In addition, it has been demonstrated that Id1 is related with TGF-ß and Smad signaling in various biological conditions. In this study, we investigated the effect of Id1 on TGF-ß-induced collagen expression in human dermal fibroblasts. When Id1-b isoform was overexpressed, TGF-ß-induced collagen expression was markedly inhibited. Consistent with this result, Id1-b significantly inhibited TGF-ß-induced collagen gel contraction. In addition, Id1-b inhibited TGF-ß-induced phosphorylation of Smad2 and Smad3. Finally, immunohistochemistry showed that Id1 expression was decreased in fibrotic skin diseases while TGF-ß signaling was increased. Together, these results suggest that Id1 is an inhibitory regulator on TGF-ß-induced collagen expression in dermal fibroblasts.

Regional difference in sebum production by androgen susceptibility in human facial skin.

Androgens are important hormones that influence sebum production from the sebaceous glands. Human facial skin can be categorized as T- and U-zones, which are areas with high and low levels of sebum secretion, respectively. This study was performed to investigate whether there are topographical differences in androgen receptor (AR) expression related to regional variations in facial sebum secretion. The results of in vivo analysis indicated a statistically significant increase in AR expression in the sebaceous gland T-zones compared with the U-zones. In vitro experiments using human primary sebocytes also yielded similar results, with higher levels of AR protein and mRNA expression in T-zones. The results of this study suggested that differences in androgen susceptibility may be an important factor influencing regional differences in sebum production in human facial skin.

Glucocorticoid receptor enhances involucrin expression of keratinocyte in a ligand-independent manner.

In this study, we investigated the role of glucocorticoid receptor (GR) in epidermal keratinocytes. In adult normal human skin, GR was highly expressed in the upper layers of the epidermis. Consistent with normal skin, GR expression was increased after calcium treatment of HaCaT keratinocytes cultured in vitro, suggesting that GR is involved in keratinocyte differentiation process. Overexpression of GR using an adenovirus showed that expression of involucrin, an early differentiation marker of keratinocytes, was markedly increased due to GR overexpression. However, treatment with dexamethasone, a GR agonist, did not increase involucrin expression. Overexpression of GR led to phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinases (ERK) in the absence of glucocorticoid, suggesting that the GR effect on involucrin expression is related to activation of intracellular signaling cascades. This idea was supported by the fact that GR-mediated involucrin induction was abolished after treatment with JNK and ERK inhibitors. In addition, GR mutants lacking the ligand-binding domain increased involucrin expression concomitantly with increase of ERK phosphorylation. Together, these results suggest that GR modulates involucrin expression of keratinocytes by regulating the intracellular signaling network in a ligand-independent manner.

Toenail onychomycosis treated with a fractional carbon-dioxide laser and topical antifungal cream.

BACKGROUND: Traditional pharmacotherapy for onychomycosis has low to moderate efficacy and may be associated with adverse reactions and medication interactions limiting its use in many patients. OBJECTIVE: We evaluated the clinical efficacy and safety of a fractional carbon-dioxide laser with topical antifungal therapy in the treatment of onychomycosis. METHODS: In all, 24 patients were treated with fractional carbon-dioxide laser therapy and a topical antifungal cream. The laser treatment consisted of 3 sessions at 4-week intervals. Efficacy was assessed based on the response rate from standardized photographs, a microscopic examination of subungual debris, and subjective evaluations. RESULTS: Among the patients, 92% showed a clinical response and 50% showed a complete response with a negative microscopic result. The factors that influenced a successful outcome were the type of onychomycosis and the thickness of the nail plate before treatment. The treatment regimen was well tolerated and there was no recurrence 3 months after the last treatment episode. LIMITATIONS: The study followed up only 24 patients and there were no relevant treatment controls. CONCLUSIONS: Fractional carbon-dioxide laser therapy, combined with a topical antifungal agent, was effective in the treatment of onychomycosis. It should be considered an alternative therapeutic option in patients for whom systemic antifungal agents are contraindicated.

Learning-related skills and academic achievement in academically at-risk first graders.

Using an academically at-risk, ethnically diverse sample of 744 first-grade children, this study tested a multi-method (i.e., child performance measures, teacher ratings, and peer ratings) measurement model of learning-related skills (i.e., effortful control [EC], behavioral self-regulation [BSR], and social competence [SC]), and their shared and unique contributions to children's reading and math achievement, above the effect of demographic variables. The hypothesized correlated factor measurement model demonstrated relatively good fit, with BSR and SC correlated highly with one another and moderately with EC. When entered in separate regression equations, EC and BSR each predicted children's reading and math achievement; SC only predicted reading achievement. When considered simultaneously, neither EC, BSR, nor SC contributed independently to reading achievement; however, EC had a direct effect on math achievement and an indirect effect on reading achievement via both BSR and SC. Implications for research and early intervention efforts are discussed.

Clinical significance of serum high-mobility group box 1 level in alopecia areata.

BACKGROUND: Alopecia areata (AA), a chronic, relapsing hair-loss disorder, is considered to be a T-cell-mediated autoimmune disease. High-mobility group box 1 (HMGB1), released by necrotic cells and in response to various inflammatory stimuli, is currently considered to be a significant target antigen in diverse autoimmune diseases. OBJECTIVE: We sought to investigate the clinical significance of serum HMGB1 levels in AA. METHODS: We compared levels of HMGB1 in scalp specimens from 7 patients with AA and 8 healthy control subjects and in blood samples from 45 patients with AA and 10 healthy control subjects. Moreover, we evaluated the correlation between HMGB1 level and clinical severity. RESULTS: Immunohistochemical staining of scalp tissues from patients with AA revealed higher HMGB1 levels than in healthy control subjects. In addition, serum HMGB1 levels in the AA group were generally higher, and showed concordance with the patients' clinical characteristics, including onset, hair-pull test results, and treatment response. LIMITATIONS: The number of patients and healthy control subjects evaluated was small. CONCLUSION: These results suggest that HMGB1 plays a significant role in the pathogenesis of AA, and that it is a promising predictor of prognosis and treatment response. Moreover, this study identifies a new potential therapeutic target for the treatment of AA.

S100A8 and S100A9 are messengers in the crosstalk between epidermis and dermis modulating a psoriatic milieu in human skin.

S100A8 and S100A9 are members of the S100A8 protein family that exist as homodimers and heterodimers in neutrophils, monocytes, and macrophages. Recent studies have shown the pivotal roles of S100A8 and S100A9 in the propagation of inflammation and keratinocyte proliferation in psoriasis. We found significant up-regulation of S100A8 and S100A9 secretion from keratinocytes in psoriatic lesions. To mimic the in vivo secretory conditions of S100A8 and S100A9 from psoriatic epidermal keratinocytes, we used the culture medium (CM) of S100A8 and S100A8/A9 adenovirus-transduced keratinocytes to investigate the functions of S100A8 and S100A9. We detected increased levels of various pro-inflammatory cytokines in the CM, including IL-8 and TNF-α, which are involved in aggravating psoriatic skin lesions, and IL-6 and members of the CXCL family of pro-angiogenic cytokines. The CM increased immune cell migration and increased angiogenesis in human umbilical vein endothelial cells. In conclusion, we found that the upregulated production of S100A8 and S100A9 by psoriatic epidermal keratinocytes activated adjacent keratinocytes to produce several cytokines. Moreover, S100A8 and S100A9 themselves function as pro-angiogenic and chemotactic factors, generating a psoriatic milieu in skin.

Autologous platelet-rich plasma: a potential therapeutic tool for promoting hair growth.

BACKGROUND: Recently, autologous platelet-rich plasma (PRP) has attracted attention in various medical fields, including plastic and orthopedic surgery and dermatology, for its ability to promote wound healing. PRP has been tested during facelift and hair transplantation to reduce swelling and pain and to increase hair density. OBJECTIVE: To investigate the effects of PRP on hair growth using in vivo and in vitro models. METHODS: PRP was prepared using the double-spin method and applied to dermal papilla (DP) cells. The proliferative effect of activated PRP on DP cells was measured. To understand the mechanisms of activated PRP on hair growth, we evaluated signaling pathways. In an in vivo study, mice received subcutaneous injections of activated PRP, and their results were compared with control mice. RESULTS: Activated PRP increased the proliferation of DP cells and stimulated extracellular signal-regulated kinase (ERK) and Akt signaling. Fibroblast growth factor 7 (FGF-7) and beta-catenin, which are potent stimuli for hair growth, were upregulated in DP cells. The injection of mice with activated PRP induced faster telogen-to-anagen transition than was seen on control mice. CONCLUSIONS: Although few studies tested the effects of activated PRP on hair growth, this research provides support for possible clinical application of autologous PRP and its secretory factors for promotion of hair growth.

Alteration of the ß-catenin pathway in spiradenoma.

BACKGROUND: Although skin carcinogenesis has been widely investigated, only limited information is available for epidermal tumors, while even less is known about other skin structures. Alterations in the ß-catenin pathway have been reported in several epidermal tumors, while little is known about in adnexal tumors. This study was performed to assess alterations in the ß-catenin pathway associated with adnexal tumors, and to investigate the mechanisms underlying these alterations. METHODS: ß-Catenin expression in 48 adnexal tumors (trichoepithelioma, trichofolliculoma, pilomatricoma, syringoma, eccrine poroma, spiradenoma, sebaceous hyperplasia and nevus sebaceus) was assessed using immunohistochemistry. The tumors showing intense nuclear reactivity for ß-catenin were further evaluated by immunohistochemistry for ß-catenin degradation complex such as adenomatosis polyposis coli (APC), Axin and glycogen synthase kinase 3ß (GSK-3ß). RESULTS: Intense nuclear immunoreactivity for ß-catenin was observed in pilomatricoma and spiradenoma. Among 12 eccrine spiradenomas, APC was downregulated in 2 (16.7%) cases, and Axin and GSK-3ß were downregulated in 11 (91.7%) and 10 (83.3%) cases, respectively. CONCLUSIONS: This is the first reported analysis of the role of alterations in the ß-catenin pathway in spiradenoma. We suggest that downregulation of Axin and GSK-3ß in the ß-catenin pathway may be an important signaling alteration in the development of spiradenoma.

Multiple miliary osteoma cutis: treatment with CO(2) laser and hook.

Miliary osteoma cutis refers to the variant of morphologically normal bone formation disorder in the dermis or subcutaneous tissue. The etiology of miliary osteoma cutis is still uncertain. But it may be due to osteoblastic metaplasia of mesenchymal elements. In our case, a healthy 55-year-old woman presented with multiple, skin-colored, non-tender, firm papules measuring 1 to 3 mm in diameter disseminated over the both cheeks for 3 years. We treated her with carbon dioxide (CO(2)) laser extraction with the hook through a small hole and patient had dramatic response to quick and simple treatment modality.

Activation of NLRP3 Inflammasome by Palmitic Acid in Human Sebocytes.

BACKGROUND: Sebocytes are the main cells involved in the pathogenesis of acne by producing lipids and inflammatory cytokines. Although palmitic acid (PA) has been suggested to induce an inflammatory reaction, its effect on sebocytes remains to be elucidated. OBJECTIVE: In the present study, we investigated whether PA promotes inflammasome-mediated inflammation of sebocytes both in vivo and in vitro. METHODS: We intradermally injected PA into the mice ears. And, we treated cultured human sebocytes with PA. Inflammasome-mediated inflammation was verified by immunohistochemistry, Western blot and ELISA. RESULTS: PA-treated mice developed an inflammatory response associated with increased interleukin (IL)-1ß expression in the sebaceous glands. When PA was added to cultured human sebocytes, caspase-1 activation and IL-1ß secretion were significantly enhanced. In addition, NLRP3 knockdown attenuated IL-1ß production by sebocytes stimulated with PA. PA-mediated inflammasome activation required reactive oxygen species. CONCLUSION: These findings indicate that PA activates the NLRP3 inflammasome before induction of an inflammatory response in sebocytes. Thus, PA may play a role in the inflammation of acne.

Primary splenic angiosarcoma: a rare entity often associated with rupture and hemoperitoneum.

Primary splenic angiosarcoma (PSA) is a rare neoplasm of vascular origin associated with aggressive behavior and poor prognosis. The clinical presentation is usually non-specific and is mostly characterized by a wasting disease with anemia and splenomegaly, mimicking a wide range of entities. The authors present the case of an 80-year-old woman with cardiovascular comorbidities with a 6-month history of weight loss, fatigue, weakness, pallor, and abdominal pain. The physical examination showed massive splenomegaly and pallor. After a thorough evaluation that ruled out lymphoproliferative diseases, the working diagnosis was a myelodysplastic disorder. A few days after discharge, she returned to the emergency room with severe abdominal pain, worsening fatigue, and a remarkable pallor. Point-of-care ultrasound showed free intraperitoneal fluid. Spleen rupture was confirmed by abdominal computed tomography (CT) scan, and an emergency laparotomy with splenectomy was performed. The postoperative period was uneventful, and the patient recovered in a few days. The histopathology confirmed the diagnosis of PSA and the patient was referred to an oncological center. Two months later staging CT demonstrated liver and peritoneal metastases, and despite the chemotherapy she died 6 months after the diagnosis.