Practice patterns regarding combination treatments and laser and energy based devices: A survey of American Society for Laser Medicine and Surgery Members.

OBJECTIVE: The use of laser and energy-based devices (LEBD) has grown exponentially in recent years, and variations in common practices exist. Our study sought to evaluate the current practice paradigms of leaders in the field of LEBD with regard to antimicrobial prophylaxis, adjuvant topical treatments, use of laser procedures in pregnancy, and combination of procedures. METHODS: Anonymous surveys were distributed to leading dermatologists in American Society for Laser Medicine & Surgery (ASLMS) via email. RESULTS: Surveys were distributed to 65 ASLMS members; 37 submitted responses. Routine antiviral prophylaxis is used by 76% for fractional ablative procedures of the face, but only 27% for fractional non-ablative procedures. Routine antifungal prophylaxis was used by a minority (16%) for ablative procedures, whereas antibacterial prophylaxis was used by 68%, with varying antibiotics. Wide variations exist in skin preparation and topicals used post-laser treatment. Most respondents feel comfortable combining same-day LEBD and botulinum toxin injections, specifically vascular or Q-switched/picosecond lasers. Most respondents avoid performing LEBD during pregnancy. CONCLUSIONS: Expert consensus in a rapidly growing field sheds light on common, reliable practices. However, even at the expert level, variations exist. Further high-quality research is needed to standardize and update guidelines.

Differences Between Children and Adults With Hidradenitis Suppurativa.

IMPORTANCE: Up to 50% of patients may have hidradenitis suppurativa (HS) onset between age 10 and 21 years. To our knowledge, little is known about how adolescents with HS utilize health care during their journey to receiving a diagnosis. OBJECTIVE: To assess the clinical characteristics and health care utilization patterns of pediatric vs adult patients with HS. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included adult and pediatric patients with HS claims from the MarketScan medical claims database during the study period, January 1, 2012, to December 31, 2016. The data were analyzed between March 1 and March 31, 2021. EXPOSURES: Clinical characteristics and health care utilization patterns of pediatric vs adult patients with HS. MAIN OUTCOMES AND MEASURES: Health care utilization patterns were examined and included concurrent diagnoses, outpatient care by discipline, and emergency/urgent care and inpatient claims. RESULTS: This study included 8727 members, comprising 1094 pediatric (155 male [14.2%] and 939 female patients [85.8%]; mean [SD] age, 14.3 [2.47] years) and 7633 adult patients (1748 men [22.9%] and 5885 women [77.1%]; mean [SD] age, 37.2 [12.99] years). Pediatric patients were likely to see pediatricians, dermatologists, emergency department (ED) staff, and family physicians before diagnosis and commonly received diagnoses of folliculitis and comedones. Pediatric patients with HS had high rates of comorbid skin and general medical conditions, including acne vulgaris (558 [51.0%]), acne conglobata (503 [45.9%]), obesity (369 [33.7%]), and anxiety disorders (367 [33.6%]). A higher percentage of pediatric than adult patients had HS-specific claims for services rendered by emergency and urgent care physicians (35.6% vs 28.2%; P < .001; and 18.1% vs 13.4%; P < .001; respectively). However, adult patients were more likely to have inpatient stays (2.38% vs 4.22%; P = .002). Pediatric patients had 2.24 ED claims per person, while adults had 3.5 claims per person. The mean cost per ED claim was similar between groups ($413.27 vs $682.54; P = .18). The largest component of the total 5-year disease-specific cost was the cost of inpatient visits for pediatric and adult patients with HS. CONCLUSIONS AND RELEVANCE: This cohort study suggests that pediatric patients utilize high-cost ED care when HS can often be treated as an outpatient. These data suggest that there are opportunities to improve recognition of HS in pediatric patients by nondermatologists and dermatologists.

Prevalence and Impact of Dietary Avoidance among Individuals with Hidradenitis Suppurativa.

BACKGROUND: People with hidradenitis suppurativa (HS) are interested in dietary alterations to manage the condition. However, there are few data on the prevalence of this or the impact on HS activity. The objective of this study was to investigate the prevalence and impact of dietary alterations made by people with HS. METHODS: A cross-sectional survey was sent to people with HS through multiple sources. Participants reported food alterations in the prior 6 months. -Results: Overall, 242 complete surveys were included in this analysis; the mean age was 35.8 years, and most (87.5%) were women. The majority (75.8%, n = 182) altered at least one food from their diet. Within this group, 154 (84.6%) made changes to multiple food groups. The top 5 food groups that were altered were gluten (48.8%), dairy (44.2%), refined sugars (40.0%), tomatoes (36.7%), and alcohol (37.1%). Smoking was eliminated in 27.5% of participants. Some participants (30.9%) reported the change made the HS "much better." CONCLUSIONS: Dietary alteration to manage HS was common among participants in this study. Some people reported improvement in HS activity, but some noted worsening. Additional research is needed to evaluate the efficacy of dietary alteration to manage HS and to better understand the underlying pathomechanisms.

Select α-arrestins control cell-surface abundance of the mammalian Kir2.1 potassium channel in a yeast model.

Protein composition at the plasma membrane is tightly regulated, with rapid protein internalization and selective targeting to the cell surface occurring in response to environmental changes. For example, ion channels are dynamically relocalized to or from the plasma membrane in response to physiological alterations, allowing cells and organisms to maintain osmotic and salt homeostasis. To identify additional factors that regulate the selective trafficking of a specific ion channel, we used a yeast model for a mammalian potassium channel, the K+ inward rectifying channel Kir2.1. Kir2.1 maintains potassium homeostasis in heart muscle cells, and Kir2.1 defects lead to human disease. By examining the ability of Kir2.1 to rescue the growth of yeast cells lacking endogenous potassium channels, we discovered that specific α-arrestins regulate Kir2.1 localization. Specifically, we found that the Ldb19/Art1, Aly1/Art6, and Aly2/Art3 α-arrestin adaptor proteins promote Kir2.1 trafficking to the cell surface, increase Kir2.1 activity at the plasma membrane, and raise intracellular potassium levels. To better quantify the intracellular and cell-surface populations of Kir2.1, we created fluorogen-activating protein fusions and for the first time used this technique to measure the cell-surface residency of a plasma membrane protein in yeast. Our experiments revealed that two α-arrestin effectors also control Kir2.1 localization. In particular, both the Rsp5 ubiquitin ligase and the protein phosphatase calcineurin facilitated the α-arrestin-mediated trafficking of Kir2.1. Together, our findings implicate α-arrestins in regulating an additional class of plasma membrane proteins and establish a new tool for dissecting the trafficking itinerary of any membrane protein in yeast.

Malachite green mediates homodimerization of antibody VL domains to form a fluorescent ternary complex with singular symmetric interfaces.

We report that a symmetric small-molecule ligand mediates the assembly of antibody light chain variable domains (VLs) into a correspondent symmetric ternary complex with novel interfaces. The L5* fluorogen activating protein is a VL domain that binds malachite green (MG) dye to activate intense fluorescence. Crystallography of liganded L5* reveals a 2:1 protein:ligand complex with inclusive C2 symmetry, where MG is almost entirely encapsulated between an antiparallel arrangement of the two VL domains. Unliganded L5* VL domains crystallize as a similar antiparallel VL/VL homodimer. The complementarity-determining regions are spatially oriented to form novel VL/VL and VL/ligand interfaces that tightly constrain a propeller conformer of MG. Binding equilibrium analysis suggests highly cooperative assembly to form a very stable VL/MG/VL complex, such that MG behaves as a strong chemical inducer of dimerization. Fusion of two VL domains into a single protein tightens MG binding over 1000-fold to low picomolar affinity without altering the large binding enthalpy, suggesting that bonding interactions with ligand and restriction of domain movements make independent contributions to binding. Fluorescence activation of a symmetrical fluorogen provides a selection mechanism for the isolation and directed evolution of ternary complexes where unnatural symmetric binding interfaces are favored over canonical antibody interfaces. As exemplified by L5*, these self-reporting complexes may be useful as modulators of protein association or as high-affinity protein tags and capture reagents.

Histone deacetylases RPD3 and HOS2 regulate the transcriptional activation of DNA damage-inducible genes.

DNA microarray and genetic studies of Saccharomyces cerevisiae have demonstrated that histone deacetylases (HDACs) are required for transcriptional activation and repression, but the mechanism by which they activate transcription remains poorly understood. We show that two HDACs, RPD3 and HOS2, are required for the activation of DNA damage-inducible genes RNR3 and HUG1. Using mutants specific for the Rpd3L complex, we show that the complex is responsible for regulating RNR3. Furthermore, unlike what was described for the GAL genes, Rpd3L regulates the activation of RNR3 by deacetylating nucleosomes at the promoter, not at the open reading frame. Rpd3 is recruited to the upstream repression sequence of RNR3, which surprisingly does not require Tup1 or Crt1. Chromatin remodeling and TFIID recruitment are largely unaffected in the Deltarpd3/Deltahos2 mutant, but the recruitment of RNA polymerase II is strongly reduced, arguing that Rpd3 and Hos2 regulate later stages in the assembly of the preinitiation complex or facilitate multiple rounds of polymerase recruitment. Furthermore, the histone H4 acetyltransferase Esa1 is required for the activation of RNR3 and HUG1. Thus, reduced or unregulated constitutive histone H4 acetylation is detrimental to promoter activity, suggesting that HDAC-dependent mechanisms are in place to reset promoters to allow high levels of transcription.