Updating the Fitzpatrick Classification: The Skin Color and Ethnicity Scale.

BACKGROUND: There has been a significant increase in submissions to scientific journals addressing a broad spectrum of medical and surgical conditions in subjects grouped under the classification of "Skin of Color." Authors, reviewers, and editors have struggled with accurate terminology. OBJECTIVE: To update the Fitzpatrick scale to make it more accurate in stratifying various shades of skin color. MATERIALS AND METHODS: A thorough literature review was performed using PubMed and Embase to assess existing skin color scales, and an extensive internet search was conducted using makeup foundation ranges as a starting point for skin tone matching. RESULTS: The research resulted in a consensus that Fitzpatrick types 4 and 5 ratings were the most confusing in that these included a broad range of skin types with different responses to solar radiation, lasers, surgery, and cosmetic products. The authors reached a consensus that subdividing skin types 4 and 5 into "A" and "B" better defined them. The new scale that resulted was labeled the SCE scale (for Skin Color Ethnicity). CONCLUSION: This new updated SCE scale should assist authors in better reporting scientific data in skin of color.

Breast Ductal Carcinoma in Situ: Precursor to Invasive Breast Cancer.

This Editorial introduces this month's special Breast Ductal Carcinoma in Situ Theme Issue, a series of reviews intended to highlight the relationship of ductal carcinoma in situ as a precursor to breast cancer and emphasize the need for appropriate treatment in hopes of minimizing the progression to invasive disease.

Update on Nonfacial Fat Transplantation.

BACKGROUND: Fat transplantation is becoming increasingly popular for off-face rejuvenation. OBJECTIVE: To provide an update in the literature of current knowledge and emerging concepts in the use of fat transplantation for nonfacial applications. MATERIALS AND METHODS: This update includes the potential benefits and risks of using fat transfer techniques on the body. RESULTS: The current literature and author experiences are provided to help understand this growing field of aesthetic procedures. CONCLUSIONS: The use of nonfacial fat transplantation is increasing and will become a larger part of aesthetic practices.

A randomized, controlled multicenter study evaluating focused ultrasound treatment for fat reduction in the flanks.

INTRODUCTION: Energy-based cosmetic devices offer an in-office treatment option, with minimal downtime, to non-invasively remove unwanted fat. We evaluated focused, pulsed ultrasound treatment to randomized flanks, compared to corresponding non-treated contralateral flanks. MATERIAL AND METHODS: Subjects were enrolled at three sites for a series of focused ultrasound treatments to a single flank, with the contralateral flank remaining untreated throughout the study. Success criteria included measureable fat thickness reduction on ultrasound imaging in the treated areas at 16 weeks after the final treatment session, and correct identification of the post-treatment photo and treated flank in at least 80% of evaluated images, as assessed by two blinded evaluators. RESULTS: The post-treatment flank photo and treated flank side were correctly identified in 82% and 93% of cases, respectively. All study subjects demonstrated significant fat reduction in their treated area, as measured by ultrasound and skin caliper. Subjects expressed a high satisfaction from treatment outcomes. There were no complications with treatment. CONCLUSION: A series of three ultrasound treatments resulted in significant fat reduction in treated flanks. Although treatment results are more modest than with liposuction, non-invasive ultrasound treatment may provide an attractive alternative for patients seeking an in-office, nonsurgical procedure for fat reduction.

Next-Generation Breast Cancer Omics.

This Editorial highlights the reviews in the Breast Cancer Theme Issue that features topics related to next-generation breast cancer omics.

Discerning Clinical Responses in Breast Cancer Based On Molecular Signatures.

Breast cancer represents a heterogeneous collection of diseases with disparate clinical behaviors, responses to treatment, and patient outcomes, despite common histopathological features at diagnosis. Examination of molecular signatures of breast cancer (based on complex gene expression patterns) enabled identification of several intrinsic molecular subtypes: luminal A, luminal B, human epidermal growth factor receptor 2 enriched, and basal like. The intrinsic subtypes are associated with measures of clinical aggressiveness, but do not perfectly predict patient outcomes. Several molecular signatures have been developed for prediction and prognostication of breast cancer outcomes. This review describes the molecular classification of breast cancer and the use of predictive/prognostic molecular signatures for guiding treatment decisions in breast cancer patients.

A Multicenter Controlled Study to Evaluate Multiple Treatments With Nonthermal Focused Ultrasound for Noninvasive Fat Reduction.

BACKGROUND: Demand for nonsurgical esthetic body procedures has led to the development of noninvasive techniques for reducing localized subcutaneous adipose tissue. OBJECTIVE: This study assessed multiple treatments with nonthermal focused ultrasound for noninvasive abdominal treatment of excess fat deposits. MATERIALS AND METHODS: Subjects were randomly assigned to Group 1 for a 4-week control phase before undergoing 3 abdominal fat reduction treatments, at 2-week intervals, or to Group 2 for immediate treatment. Weight, abdominal circumference, tolerability to treatment, subject satisfaction, and adverse events were recorded. RESULTS: Weight remained stable in the 126 participants. Mean reduction in midline circumference was 2.5 ± 2.1 cm in the Group 1 and 3.5 ± 2.7 cm in the Group 2 at Week 22. The effect of multiple treatments was cumulative with a steady decrease in abdominal circumferences during the study. Erythema was observed in 28% of treatments but was mild and transient in nature. Subjects tolerated the treatments well and were satisfied with treatment outcome. CONCLUSION: The study demonstrated the efficacy and safety of multiple nonthermal focused ultrasound treatments of excess abdominal fat deposits. Although the remodeling effect is minor compared with traditional surgical procedures, successive focused ultrasound treatments significantly reduced treatment area circumference, while avoiding invasive techniques and their associated disadvantages.

Safety of IncobotulinumtoxinA in the Treatment of Facial Lines: Results From a Pooled Analysis of Randomized, Prospective, Controlled Clinical Studies.

BACKGROUND: The safety and efficacy of incobotulinumtoxinA in aesthetics has been established in multiple studies. Although individual studies have been reported, a combined assessment of incobotulinumtoxinA safety across studies is not available. OBJECTIVE: To assess the frequency of adverse events (AEs) across prospective incobotulinumtoxinA studies in aesthetics. MATERIALS AND METHODS: Safety data were assessed from 9 placebo-controlled or active-controlled single-dose studies on glabellar frown lines (GFL), crow's feet (CF), and upper facial lines (UFL). Analyses by treatment cycle included 4 repeat-dose studies on GFL and UFL. RESULTS: One thousand three hundred seventy-seven subjects received incobotulinumtoxinA (GFL, n = 1,189; CF, n = 83; UFL, n = 105) in single-dose studies (placebo-controlled studies: incobotulinumtoxinA, n = 866; placebo, n = 395). Over 1,000 subjects received incobotulinumtoxinA in repeat-dose studies (GFL, n = 880; UFL, n = 290). In placebo-controlled single-dose studies, incidences of treatment-related AEs ranged from 5.4% (GFL) to 22.9% (UFL). The most frequent treatment-related AE in single-dose studies was headache (GFL, 4.8%; UFL, 11.4%). In repeat-dose studies, incidence of AEs was highest during cycle 1 (GFL, 8.9%; UFL, 17.2%) and decreased across treatment cycles. No serious treatment-related AEs were observed. CONCLUSION: Results confirm the favorable safety and tolerability of incobotulinumtoxinA. The frequency of treatment-related AEs was low and may decrease with subsequent treatments.

A Multicenter Pivotal Study to Evaluate Tissue Stabilized-Guided Subcision Using the Cellfina Device for the Treatment of Cellulite With 3-Year Follow-Up.

BACKGROUND: Cellulite is a common female cosmetic concern for which no single treatment option had been proven effective over the long term. A novel tissue stabilized-guided subsicion system (TS-GS system) has demonstrated significant reduction in the appearance of cellulite after treatment. OBJECTIVE: The objective of this extended follow-up period was to assess the effectiveness of TS-GS out to 3 years after initial treatment. PATIENTS AND METHODS: After completing an open-label, multicenter, pivotal study, 45 subjects were followed for an extended period of up to 3 years after receiving a single treatment using the TS-GS system. Treatment areas were photographed prior to the procedure and at multiple time points post-treatment throughout the 3 years. In this open-label study, subjects served as their own controls. Effectiveness was assessed based on blinded independent physician panel assessments of improvement from baseline using a cellulite severity scale. Subject aesthetic improvement and patient-reported satisfaction were also collected. RESULTS: The results of this trial supported Food and Drug Administration clearance of the device for the long-term reduction in the appearance of cellulite following TS-GS. CONCLUSION: These data further demonstrate the safety and efficacy of this treatment with no reduction in treatment benefits out to 3 years.

Forehead Line Treatment With OnabotulinumtoxinA in Subjects With Forehead and Glabellar Facial Rhytids: A Phase 3 Study.

BACKGROUND: Effacement of horizontal forehead lines (FHL) with onabotulinumtoxinA has not been investigated in prospective Phase 3 studies. OBJECTIVE: To evaluate safety and efficacy of onabotulinumtoxinA treatment of FHL together with glabellar lines (GL). MATERIALS AND METHODS: A 12-month, Phase 3 study randomized subjects with moderate-to-severe FHL and GL to onabotulinumtoxinA 40 U or placebo, distributed between the frontalis (20 U) and glabellar complex (20 U). After Day 180, subjects could receive up to 2 additional open-label onabotulinumtoxinA treatments. Efficacy was assessed using the Facial Wrinkle Scale (FWS) and Facial Line Outcomes questionnaire. RESULTS: The intent-to-treat (ITT) population included 391 subjects, and the modified ITT (mITT) population (subjects with psychological impact) included 254 subjects. After 30 days, onabotulinumtoxinA significantly improved the investigator- and subject-assessed appearance of FHL severity by at least 2 FWS grades in 61.4% of ITT subjects versus 0% of placebo subjects (p < .0001). In the mITT population, 94.8% of onabotulinumtoxinA subjects and 1.7% of placebo subjects achieved investigator- and subject-assessed FWS ratings of none/mild (p = .0003). Patient-reported outcomes were consistent with FWS ratings. OnabotulinumtoxinA was well tolerated. CONCLUSION: OnabotulinumtoxinA 40 U distributed between the frontalis and glabellar complex was safe and effective for treatment of moderate-to-severe FHL.

Alkyl pyrazine synthesis via an open heated bath with variable sugars, ammonia, and various amino acids.

BACKGROUND: Semi-quantitative characteristics of headspace volatile pyrazines which constituted around 1% by weight of the final product have been previously described. The influence of reactant concentration, reaction temperature, and reaction time on both the yield of total alkyl pyrazines and the distribution pattern of specific identified pyrazines has not been reported. RESULTS: The optimum synthetic conditions were 5 mol L-1 NH4 OH, 2 mol L-1 rhamnose, 0.5 mol L-1 leucine at 110°C for 2 h. The greatest total amount of pyrazines obtained was 17 280 µg of extracted product which translated into 31% 2,6-dimethyl pyrazine, 17% 2-methyl pyrazine, 15% 2-ethyl-6-methyl pyrazine, and 16% 2-isoamyl-6-methyl pyrazine. CONCLUSION: The yield of synthesized pyrazines increased at higher temperatures. Quantitative total and specific pyrazine results as opposed to analysis of only headspace volatiles are more representative of pyrazine synthesis. © 2016 Society of Chemical Industry.

Dysregulation of the epigenome in human breast cancer: contributions of gene-specific DNA hypermethylation to breast cancer pathobiology and targeting the breast cancer methylome for improved therapy.

Triple-negative breast cancers (including basal-like and claudin-low molecular subtypes) represent 20% to 25% of all breast cancers, but disproportionately contribute to breast cancer-associated death. We have identified a novel fundamental biological property of triple-negative breast cancers: most triple-negative breast cancers express aberrant DNA hypermethylation due to overexpression of DNA methyltransferase 3b (and hyperactivity of the DNA methyltransferase enzymes). DNA methyltransferase 3b overexpression occurs secondary to loss of miRNA-mediated post-transcriptional regulation. The resulting hyperactivity of DNA methyltransferase 3b produces concurrent DNA methylation-dependent silencing of numerous critical gene targets (including tumor suppressors and pro-apoptotic genes) and resistance to cytotoxic chemotherapy. This observation presents new opportunities for development of innovative treatment strategies on the basis of the epigenome as a novel therapeutic target in triple-negative breast cancers. Epigenetic therapy represents a new principle in cancer treatment in which restoration of critical molecular pathways occurs secondary to reexpression of silenced genes that encode negative mediators of cancer cell growth.

Investigating the Role of Helicobacter pylori PriA Protein.

BACKGROUND: In bacteria, PriA protein, a conserved DEXH-type DNA helicase, plays a central role in replication restart at stalled replication forks. Its unique DNA binding property allows it to recognize and stabilize stalled forks and the structures derived from them. PriA plays a very critical role in replication fork stabilization and DNA repair in E. coli and N. gonorrhoeae. In our in vivo expression technology screen, priA gene was induced in vivo when Helicobacter pylori infects mouse stomach. MATERIALS AND METHODS: We decided to elucidate the role of H. pylori PriA protein in survival in mouse stomach, survival in gastric epithelial cells and macrophage cells, DNA repair, acid stress, and oxidative stress. RESULTS: The priA null mutant strain was unable to colonize mice stomach mucosa after long-term infections. Mouse colonization was observed after 1 week of infection, but the levels were much lower than the wild-type HpSS1 strain. PriA protein was found to be important for intracellular survival of epithelial cell-/macrophage cell-ingested H. pylori. Also, a priA null mutant was more sensitive to DNA-damaging agents and was much more sensitive to acid and oxidative stress as compared to the wild-type strain. CONCLUSIONS: These data suggest that the PriA protein is needed for survival and persistence of H. pylori in mice stomach mucosa.

A reporter mouse reveals lineage-specific and heterogeneous expression of IRF8 during lymphoid and myeloid cell differentiation.

The IFN regulatory factor family member 8 (IRF8) regulates differentiation of lymphoid and myeloid lineage cells by promoting or suppressing lineage-specific genes. How IRF8 promotes hematopoietic progenitors to commit to one lineage while preventing the development of alternative lineages is not known. In this study, we report an IRF8-EGFP fusion protein reporter mouse that revealed previously unrecognized patterns of IRF8 expression. Differentiation of hematopoietic stem cells into oligopotent progenitors is associated with progressive increases in IRF8-EGFP expression. However, significant induction of IRF8-EGFP is found in granulocyte-myeloid progenitors and the common lymphoid progenitors but not the megakaryocytic-erythroid progenitors. Surprisingly, IRF8-EGFP identifies three subsets of the seemingly homogeneous granulocyte-myeloid progenitors with an intermediate level of expression of EGFP defining bipotent progenitors that differentiation into either EGFP(hi) monocytic progenitors or EGFP(lo) granulocytic progenitors. Also surprisingly, IRF8-EGFP revealed a highly heterogeneous pre-pro-B population with a fluorescence intensity ranging from background to 4 orders above background. Interestingly, IRF8-EGFP readily distinguishes true B cell committed (EGFP(int)) from those that are noncommitted. Moreover, dendritic cell progenitors expressed extremely high levels of IRF8-EGFP. Taken together, the IRF8-EGFP reporter revealed previously unrecognized subsets with distinct developmental potentials in phenotypically well-defined oligopotent progenitors, providing new insights into the dynamic heterogeneity of developing hematopoietic progenitors.

Bimatoprost 0.03% for the Treatment of Eyebrow Hypotrichosis.

BACKGROUND: Eyebrow loss may have substantial negative functional and social consequences. OBJECTIVE: Evaluate the safety and efficacy of bimatoprost 0.03% in subjects with eyebrow hypotrichosis. METHODS: This multicenter, double-masked study randomized adult females or males with eyebrow hypotrichosis to receive bimatoprost 0.03% twice (BID) or once daily (QD) or vehicle BID for 7 months. Primary endpoint was overall eyebrow fullness at Month 7. Secondary endpoints included eyebrow fullness (mm), darkness (intensity units), and subject satisfaction with treatment. Safety was also assessed. RESULTS: At Month 7, the proportion of subjects with improvement was significantly higher in bimatoprost groups versus vehicle (both, p < .001). Improvements occurred in both bimatoprost groups versus vehicle after Month 1 and continued through follow-up; eyebrow fullness and darkness improved as early as Months 2 and 1, respectively (both, p < .001). Greater satisfaction was reported with bimatoprost versus vehicle at Month 2 and all subsequent time points. Overall, 38.1%, 42.4%, and 35.5% of subjects in the bimatoprost BID, QD, and vehicle groups, respectively, experienced ≥1 treatment-emergent adverse event (TEAE). Most frequent TEAEs were similar across groups. No skin or iris hyperpigmentation or conjunctival hyperemia occurred. CONCLUSION: Bimatoprost 0.03% BID and QD is safe, well tolerated, and effective for eyebrow hypotrichosis.