Sunscreen Use for Photoprotection in Skin of Color: A Literature Review.

BACKGROUND: To understand the prevalence and types of publications addressing darker skin types within the existing evidence base for sunscreen use.  Evidence Review: PubMed was searched from 1988, the time point at which the first skin of color (SOC) article was identified, through December 2022 using PubMed's Medical Subject Headings terms and keyword searches in title and abstract, with and without terms for SOC and ethnicity. Identified articles were reviewed for relevance, de-duplicated, and categorized; results are summarized. FINDINGS: Of the 5927 articles on sunscreen overall, only 314 (5.3%) articles addressed SOC, with the majority published since 2007 and representing only 4% to 7% of total publications annually except in 2022 when the proportion of SOC articles was 23.5%. Of the articles on SOC, many reported sunscreen knowledge and patient behaviors (29%), but very few reported clinical trials (5%). The 3 conditions most often discussed were melasma, post-inflammatory hyperpigmentation, and dyschromia. South Asian ethnicities (India, Pakistan, Bangladesh) had the highest representation within the literature, followed by Hispanics. CONCLUSIONS AND RELEVANCE: Although it was assumed there would be fewer papers discussing the use of sunscreen in darker skin types, the scale of the disparity revealed by this study is stark. The increase in a number of articles in 2022 suggests an increasing focus on SOC, but further discussion of the issues presented here will help the SOC community address gaps in the evidence base and better inform discussions on sunscreen and photoprotection between clinicians and patients.J Drugs Dermatol. 2024;23(7):575-577.  doi:10.36849/JDD.8250.

Remodeling of facial soft tissue induced by simultaneous application of HIFES and synchronized radiofrequency provides nonsurgical lift of facial soft tissues.

BACKGROUND: The application of radiofrequency (RF) and HIFES on the body provides improvement in skeletal muscle tissue, reduction in fatty tissue, reorganization of connective tissue, and skin texture improvement. However, overall facial appearance relies on both skin and underlying structures, specifically muscles and connective tissue which have to be treated as one unit to achieve proper care while preserving fatty layers that define youth facial appearance. AIMS: The aim of this study is to find whether the effect of novel RF + HIFES is safe and can induce the lifting of soft tissue and overall improvement in facial appearance. METHODS: In this study, 21 subjects were enrolled. The therapy was administered in four 20-min treatments on the forehead and cheeks. Photographs were evaluated by a Global Aesthetic Improvement Score (GAIS) and linear measurements of facial tissue lifting at 1- and 3-month follow-ups. Volumetric changes in the cheek area were investigated as well. The patients' satisfaction, safety, and comfort were documented throughout the study. RESULTS: The data indicated improvement in overall facial appearance, and 23% of average lifting was found in brows (p = 3.14 × 10-12 ) and cheeks (p = 6.00 × 10-15 ). The assessment of digital photographs showed an improvement in 100% of patients at 3-month follow-up. The treatments were safe, accompanied by high therapy comfort and subject satisfaction of 98%. CONCLUSIONS: The treatment by simultaneous RF and HIFES technology produces significant changes to the overall facial appearance, characterized by the lifting of facial tissues.

Self-perception of natural outcome, appearance, and emotional well-being after OnabotulinumtoxinA treatment for upper facial lines: Post hoc analysis across age and gender.

BACKGROUND: OnabotulinumtoxinA (onabotA) is indicated for upper facial lines (UFL). Fear of unnatural-looking outcomes is a frequently reported treatment barrier. AIMS: Examine patient-reported outcomes (PROs) after onabotA treatment for UFL. METHODS: A post hoc analysis was conducted on two 12-month pivotal studies of onabotA for forehead and glabellar lines (20 U each), with/without treatment of crow's feet lines (±24 U). This analysis used PROs from the Facial Line Satisfaction Questionnaire: Items 4 (natural look), 5 (treatment effect), 11 (met expectations), and Impact Domain (appearance and psychological impact). The analysis included 458 neurotoxin-naive adults achieving a ≥2-grade improvement in forehead line (FHL) severity on the Facial Wrinkle Scale at Day 30 (primary endpoint). [Corrections made on 28 December 2023, after first online publication: 'UFL' in the previous sentence has been corrected to 'forehead line (FHL)' in this version.] Data were further stratified into millennials and men. RESULTS: At Day 30, 90.5% of all participants, 94.6% of millennials, and 85.7% of men were satisfied with receiving a natural look. Millennials had higher odds of being satisfied with natural outcomes at Day 30. This measure remained > 80% for all groups throughout the 12 months. Additionally, ≥80% were satisfied with the treatment effect, and >90% reported results met expectations. At Day 30, ≥50% reported positive impacts on self-perceived appearance and psychological well-being, but millennials had higher, and men had lower odds of reporting these improvements. CONCLUSIONS: Participants achieving a ≥2-grade improvement in FHL severity after onabotA reported high satisfaction with natural outcomes and the treatment effect, with improved self-perceived appearance and psychological well-being. [Corrections made on 28 December 2023, after first online publication: 'UFL' in the previous sentence has been corrected to 'FHL' in this version.] These results may help aesthetic providers and patients address fears regarding unnatural results with onabotA.

Clinical Trials in Facial Plastic and Reconstructive Surgery.

Many facial plastic and reconstructive surgery providers are interested in incorporating clinical trials into their own practice. Clinical trials in facial plastics have made key contributions to current practices. Clinical trials range from investigating the safety and efficacy of Juvederm filler to reducing pain associated with injecting Juvederm. This article summarizes landmark clinical trials in facial plastic and reconstructive surgery and provides a framework for providers to get involved in clinical trials.

Laboratory evaluation of occupational exposure to hand-arm vibration (HAV) during grounds maintenance equipment operations.

INTRODUCTION AND OBJECTIVE: About 2.5 million workers in the USA are exposed to hand-arm vibration (HAV) from power tools. The aims of the study were to evaluate occupational exposure to HAV during grounds maintenance equipment operations and the effect of general work gloves on vibration magnitude under controlled laboratory conditions. MATERIAL AND METHODS: A simulation of grass trimmer, backpack blower, and chainsaw operations was conducted by two participants to measure vibration total value (ahv) using vibration dosimeters wearing gloves. ahv was also measured on the bare hands during grass trimmer and backpack blower operations. RESULTS: ahv of the gloved hand was 3.5-5.8, 1.1-2.0, and 3.0-3.6 m/s2 during the grass trimmer, backpack blower, and chainsaw operations, respectively. ahv of the bare hand was 4.5-7.2 and 1.2-2.3 m/s2 for the grass trimmer and blower operations, respectively. CONCLUSIONS: The highest HAV exposure was observed during the grass trimmer operation which showed higher vibration attenuation of the gloves.

Infraorbital Hollow Rejuvenation: Considerations, Complications, and the Contributions of Midface Volumization.

Infraorbital hollows are one of the most common target areas for facial aesthetic treatment; however, they are often perceived to be challenging to treat due to the complex anatomy of the periorbital area, concurrent deformities, and risk of complications. Treatment options include surgical (eg, lower eyelid blepharoplasty with fat transposition or injections) and nonsurgical approaches (eg, fillers). Among these approaches, filler injections have become common practice because they are minimally invasive and provide long-term patient satisfaction. In particular, hyaluronic acid (HA) fillers have been shown to be safe and effective for infraorbital hollow rejuvenation. This review provides an overview of infraorbital hollows, including periorbital anatomy, etiology, clinical assessment, and overlapping deformities, such as malar mounds, festoons, and dark circles under the eyes. Patient and HA filler product selection, injection techniques, as well as potential adverse events, such as bruising/swelling, lower eyelid and malar edema, and vascular occlusions, are discussed. This review also highlights the importance of midfacial volumization to improve outcomes in the infraorbital region and in the overall aesthetic appearance. By selecting appropriate patients and attaining proficiency in periorbital anatomy and infraorbital hollow rejuvenation techniques, clinicians can safely and successfully perform HA filler injections that result in high patient satisfaction.

Expert Recommendations on the Use of Hyaluronic Acid Filler for Tear Trough Rejuvenation.

Restylane® Lidocaine is one of the most widely used hyaluronic acid (HA) fillers to replace lost or displaced volume during tear trough correction. Patient goals for tear trough correction include looking less tired or removing dark circles and this may be achieved by administering HA filler into the infraorbital region to correct the lower eyelid relative to the volume deficit, thereby smoothing the transition from the lower eyelid to the cheek. To achieve patient satisfaction and consistent results with Restylane, optimal application is essential; however, clinical guidance based on experience is limited. This paper reflects the recommendations of an interdisciplinary expert panel for the use of Restylane in correcting tear trough deformity, including patient selection, dosing, injection technique, and post-treatment care. Recommendations were discussed and agreed as a consensus, according to cross-sectional expertise and clinical experience. J Drugs Dermatol. 2022;21(4):387-392. doi:10.36849/JDD.6597.

Racial and Ethnic Differences in Self-Assessed Facial Aging in Women: Results From a Multinational Study.

BACKGROUND: Racial/ethnic variations in skin structure and function may contribute to differential manifestations of facial aging in various races/ethnicities. OBJECTIVE: To examine self-assessed differences in facial aging in women by race/ethnicity and Fitzpatrick skin phototypes. METHODS: Women aged 18 to 75 years in the United States, Canada, the United Kingdom, and Australia compared their features against photonumeric rating scales depicting degrees of severity for 10 facial aging characteristics. Impact of race/ethnicity (black, Hispanic, Asian, and Caucasian) and skin phototypes on severity was assessed. RESULTS: In total, 3,267 women completed the study. Black women reported the least severe facial aging; Caucasian women reported the most severe facial aging, with Asian and Hispanic women falling between these groups. Similarly, women with a skin phototype V/VI reported lesser aging severity than women with phototypes I through IV. More than 30% of black women did not report the presence of moderate/severe aging of facial areas until 60 to 79 years; most Hispanics and Asians did not report moderate/severe facial aging until 50 to 69 years and Caucasians, 40 to 59 years. CONCLUSION: In this diverse sample, black women reported less severe aging of facial features compared with Hispanic, Asian, and Caucasian women. These results were supported by Fitzpatrick skin phototype analyses.

Understanding the Female African American Facial Aesthetic Patient

BACKGROUND: The patient populations seeking facial aesthetic treatments is expanding in terms of racial, ethnic, and cultural diversity. While treatment of facial aging patterns among white women is well-documented, far less information describes the aesthetic needs of the African American patient. OBJECTIVE: An online study was conducted to survey facial aesthetic concerns and treatment priorities among US-based population of African American women. MATERIALS AND METHODS: A total of 401 female African American participants ages 30 to 65 years reported their attitudes toward facial aging, current facial conditions, most bothersome facial areas and areas most/least likely to be treated first, awareness of treatment options and their consideration rates, and motives and barriers factoring into consideration of injectable treatments. RESULTS: Uneven skin tone/color (57%) and dark circles under the eyes (48%) were the most frequently-reported facial concerns. Other common bothersome facial areas affected by signs of aging were the submental area, periorbital area, forehead lines, and chin. Similarly, areas given greater priority with respect to future treatment included the periorbital area, submental area, and forehead lines. With advancing age, priorities heightened for the mid and lower facial areas, which included the nasolabial folds, chin, and oral commissures. Although the majority of participants would consider injectables, cost, and safety/side effects were cited as frequent concerns. CONCLUSION: For African American women, concerns about facial aging may be less about fine lines and wrinkles caused by increasing skin laxity, and more about pigmentary concerns and shifts in underlying soft tissue volume. J Drugs Dermatol. 2019;18(9):858-866.

Myths and Knowledge Gaps in the Aesthetic Treatment of Patients With Skin of Color

Background: Misperceptions about facial aesthetic treatments in individuals with skin of color (SOC) may influence treatment selection. Objective: We aimed to identify knowledge gaps and myths concerning facial aesthetic treatment in individuals with SOC. Methods: A PubMed search identified articles concerning patients with SOC receiving facial aesthetic treatments. The experience of experts in aesthetic treatment of patients with SOC was also considered. Results: Knowledge gaps included not seeking injectable filler treatment of lips, risk of developing keloids with injectable filler treatment, risk of hyperpigmentation precluding surgical procedures and nonsurgical injectable filler treatment, melasma being a minor cosmetic concern with limited treatments, and racial/ethnic groups being homogeneous with respect to facial characteristics and aesthetic concerns. Dispelled myths included perceptions that: individuals with SOC do not need sunscreen; dermal fillers and neuromodulators are not necessary or useful for patients with darker skin; laser treatments cannot be used on darker skin; facial products are unnecessary; and only medical providers with SOC can understand how to treat patients with SOC. Conclusions: Knowledge gaps and myths concerning facial aesthetic treatment in individuals with SOC exist. These patients may undergo various facial aesthetic procedures safely and effectively, as long as nuances in treatment approaches are recognized. J Drugs Dermatol. 2019;18(7):616-622.

Complete Genome Sequence of Bacillus thuringiensis Bacteriophage Smudge.

Smudge, a bacteriophage enriched from soil using Bacillus thuringiensis DSM-350 as the host, had its complete genome sequenced. Smudge is a myovirus with a genome consisting of 292 genes and was identified as belonging to the C1 cluster of Bacillus phages.

Rapid onset of response and patient-reported outcomes after onabotulinumtoxinA treatment of moderate-to-severe glabellar lines.

INTRODUCTION: no previously published botulinum toxin type A cosmetic trials included both physician and subject measures of onset. OBJECTIVE: determine physician- and subject-reported onset of onabotulinumtoxinA. METHODS: Two-center open-label, 14-day study in toxin-naive female patients with moderate-to-severe glabellar lines (GL) treated with 20-U onabotulinumtoxinA. Onset endpoint was categorical (physician assessed: days 2, 3, 4, 7 and 14; subject: 14-day diary). Subjects rated improvements in GL severity and completed the Facial Line Outcomes (FLO) and Self-Perception of Age (SPA) questionnaires. RESULTS: nearly half, 48 percent (n=45) of subjects, reported onset by day 1. Subject- and physician-reported onset rates, respectively, were 77 percent and 87 percent (day 2), 93 percent and 91 percent (day 3), 98 percent and 100 percent (day 4), and 100 percent thereafter. At all time points, FLO and SPA improved (P=0.008 and P=0.01, respectively). No serious adverse events occurred. CONCLUSION: onabotulinumtoxinA provides rapid onset (one to two days) based on physician and subject assessment.

A multi-center, double-blind, randomized controlled study of the safety and effectiveness of Juvéderm injectable gel with and without lidocaine.

INTRODUCTION: Pain is a common patient complaint during dermal filler injections. The primary objective of this study was to compare a new formulation of Juvéderm((R)) injectable gel with lidocaine (denoted as JUV + L) to commercially-available Juvéderm((R)) injectable gel without lidocaine (denoted as JUV) with respect to procedural pain scores in subjects desiring nasolabial fold (NLF) correction. METHODS: Subjects received randomized treatment with the lidocaine filler in one NLF and the filler without lidocaine in the other NLF. Investigators determined the appropriate formulation (Ultra or Ultra Plus) and volume of material to inject but were blinded as to which syringe contained lidocaine. Subjects rated procedural pain (pain during injection) using an 11-point scale within 30 min after receiving treatment in both NLFs and compared procedural pain between right and left NLFs using a 5-point scale. NLF severity was rated by both subjects and investigators before and 2 weeks after treatment. RESULTS: The mean difference on the procedural pain scale was 3.4 (P < 0.0001), and 93% of subjects found JUV + L to be less or slightly less painful than JUV. Improvement in NLF severity was comparable for both products. Common treatment site reactions (CTRs) of pain and tenderness were considerably less frequent for JUV + L than JUV while all other CTRs showed no statistically significant differences. CONCLUSION: The dermal filler formulated with lidocaine is effective in reducing procedural pain during correction of facial wrinkles and folds while maintaining a similar safety and effectiveness profile to the filler without lidocaine.

Six-month safety results of calcium hydroxylapatite for treatment of nasolabial folds in Fitzpatrick skin types IV to VI.

BACKGROUND: Recently, the cosmetic market has seen an increase in the options for treatment for people with dark skin. OBJECTIVES: This study evaluates the use of calcium hydroxylapatite (CaHA), a dermal filler indicated for the correction of moderate to severe facial wrinkles and folds, including the nasolabial folds (NLFs) in individuals with dark skin. METHODS: This open-label, nonrandomized, prospective, five-center trial enrolled 100 patients aged 18 and older with Fitzpatrick skin types IV to VI. CaHA was injected subdermally with a 25- to 27-gauge needle. Participants received a range of 0.6 to 2.8 mL of CaHA and returned at 3 and 6 months to be assessed for keloid formation, hypertrophic scarring, and hyper- or hypopigmentation. If necessary, each subject was offered a touch-up at the conclusion of the 6-month visit. RESULTS: No reports of keloid formation, hypertrophic scarring, hypo- or hyperpigmentation, or other clinically significant adverse events were recorded. CONCLUSIONS: People with dark skin injected subdermally with CaHA do not show signs of keloid formation, hypertrophic scarring, or hyper- or hypopigmentation. Because of this safety feature, as well as other characteristics of the product already shown in clinical literature, CaHA is an attractive dermal filler in this population.

The polarity-establishment component Bem1p interacts with the exocyst complex through the Sec15p subunit.

Spatial regulation of the secretory machinery is essential for the formation of a new bud in Saccharomyces cerevisiae. Yet, the mechanisms underlying cross-talk between the secretory and the cell-polarity-establishment machineries have not been fully elucidated. Here, we report that Sec15p, a subunit of the exocyst complex, might provide one line of communication. Not only is Sec15p an effector of the rab protein Sec4p, the master regulator of post-Golgi trafficking, but it also interacts with components of the polarity-establishment machinery. We have demonstrated a direct physical interaction between Sec15p and Bem1p, a protein involved in the Cdc42p-mediated polarity-establishment pathway, confirming a prior two-hybrid study. When this interaction is compromised, as in the case of cells lacking the N-terminal 138 residues of Bem1p, including the first Src-homology 3 (SH3) domain, the localization of green fluorescent protein (GFP)-tagged Sec15 is affected, especially in the early stage of bud growth. In addition, Sec15-1p, which is defective in Bem1p binding, mislocalizes along with Sec8p, another exocyst subunit. Overall, our evidence suggests that the interaction of Sec15p with Bem1p is important for Sec15p localization at the early stage of bud growth and, through this interaction, Sec15p might play a crucial role in integrating the signals between Sec4p and the components of the early-polarity-establishment machinery. This, in turn, helps to coordinate the secretory pathway and polarized bud growth.

Lysyl oxidase in development, aging and pathologies of the skin.

Lysyl oxidase (LOX) is a copper- and lysyl-tyrosyl cofactor containing amine oxidase that has been known to play a critical role in the catalysis of lysine-derived crosslinks in extracellular matrix (ECM) proteins in the dermis. Changes in the composition and crosslinked state of the ECM and alterations in LOX synthesis and activity are known to be associated with aging and a range of acquired and heritable skin disorders. It has been assumed until recently that the LOX-related changes in the skin are mediated through the catalytic activity of LOX. However, work by several laboratories over the last few years has shown that LOX is a multifunctional protein. In this review we discuss the regulation of expression, localization and activation of LOX in the normal developing and adult skin, and alterations in LOX expression and activity associated with skin aging and senescence, and in pathological conditions, including wound healing, fibrosis, hypertrophic scarring, keloids, scleroderma, and diabetic skin. We further evaluate the role of LOX in skin ECM changes associated with the normal aging process and with these pathological states. In addition to collagen and elastin cross-linkages, regulatory and activation mechanisms and cell type specific LOX interactions may contribute to a range of novel intra- and extracellular LOX functions that appear critical determinants of the cellular microenvironment in the normal skin and in these skin disorders.

Analysis of ABCC6 (MRP6) in normal human tissues.

To determine the tissue distribution of the ABC transporter ABCC6 in normal human tissues, we analyzed tissue arrays for the presence of ABCC6 mRNA by in situ hybridization and ABCC6 protein by immunohistochemistry using the polyclonal antibody HB-6. We detected ABCC6 mRNA and protein in various epithelial cells of exocrine and endocrine tissues, such as acinar cells in the pancreas, mucosal cells of the intestine and follicular epithelial cells of the thyroid. We obtained a very strong immunostaining for enteroendocrine G cells in the stomach. In addition, ABCC6 mRNA and protein were present in most neurons of the brain, in alveolar macrophages in the lungs and lymphocytes in the lymph node. Immunohistochemisty using the monoclonal antibody M6II-31 confirmed the widespread tissue distribution of ABCC6. The physiological substrate(s) of ABCC6 are yet unknown, but we suggest that ABCC6 fulfills multiple functions in different tissues. The strong immunostaining for ABCC6 in G cells suggests that it plays an important role in these endocrine cells.

The tissue distribution of murine Abcc6 (Mrp6) during embryogenesis indicates that the presence of Abcc6 in elastic tissues is not required for elastic fiber assembly.

Mutations in the gene coding for the ABC transporter, ABCC6, in humans cause Pseudoxanthoma elasticum, which is characterized by the deposition of aberrant elastic fibers. To investigate whether the presence of ABCC6 in tissues synthesizing elastin is required for elastin deposition and elastic fiber assembly, we have compared the steady-state levels and tissue distribution of Abcc6 and tropoelastin mRNAs during mouse embryogenesis. Whereas tropoelastin mRNA levels rose during embryogenesis and were the highest in neonatal mice, Abcc6 mRNA levels remained constantly low throughout embryogenesis. In some tissues, both Abcc6 and tropoelastin mRNA were detected. However, Abcc6 mRNA and protein were not detected in neonatal aorta and arteries, which produce large amounts of elastin indicating that the presence of Abcc6 in elastic tissues is not required for elastic fiber assembly.

Phase I and initial phase II results from a trial investigating weekly docetaxel and carboplatin given neoadjuvantly and then concurrently with concomitant boost radiotherapy for locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: The current Phase I/II study assessed induction docetaxel/carboplatin given weekly for 4 weeks, followed by weekly docetaxel/carboplatin and concomitant boost radiotherapy (CB-XRT) for locally advanced head and neck squamous cell carcinoma. METHODS: Twenty patients with Stage III or IV (M0) disease of the oropharynx, supraglottic larynx, or hypopharynx were enrolled. Patients initially received docetaxel 20 mg/m2 and carboplatin area under the curve (AUC) 2 weekly x 4. Patients with stable (SD) or responding disease subsequently received dose-escalated docetaxel (10-20 mg/m2 in sequential patient cohorts) and carboplatin AUC 1 weekly x 5 with CB-XRT (1.8 gray [Gy] every day x 15 days, followed by 1.8/1.5 Gy twice per day x 13 days). RESULTS: All patients were evaluable, and 15 patients (5 patients with Stage III disease, 10 patients with Stage IV disease) completed all planned therapy. The target docetaxel dose level of 20 mg/m(2) weekly with radiotherapy was achieved with no dose-limiting toxicities. The most frequent maximum toxicities during chemoradiotherapy were Grade 3 mucositis, dysphagia, and/or pain. Primary site responses after induction included 4 patients with partial responses, 11 patients with SD, and 5 patients with disease progression. Fifteen patients (75%) continued to receive chemoradiotherapy, with 14 patients attaining a complete response (CR). Overall, a clinicopathologic neck CR after chemoradiotherapy was achieved in 9 of 10 patients. One patient had persistent primary disease and underwent salvage surgery, whereas another died of unrelated causes before neck assessment. Thirteen patients remain free of any disease event, with a median follow-up of 15 months (range, 3-29 months). CONCLUSIONS: This regimen was feasible, safe, and particularly well tolerated. Early Phase II outcomes revealed promising activity in patients completing all treatment. Initial induction response results suggested that further investigation of this regimen with more aggressive induction therapy is warranted.

Vesicles carry most exocyst subunits to exocytic sites marked by the remaining two subunits, Sec3p and Exo70p.

Exocytosis in the budding yeast Saccharomyces cerevisiae occurs at discrete domains of the plasma membrane. The protein complex that tethers incoming vesicles to sites of secretion is known as the exocyst. We have used photobleaching recovery experiments to characterize the dynamic behavior of the eight subunits that make up the exocyst. One subset (Sec5p, Sec6p, Sec8p, Sec10p, Sec15p, and Exo84p) exhibits mobility similar to that of the vesicle-bound Rab family protein Sec4p, whereas Sec3p and Exo70p exhibit substantially more stability. Disruption of actin assembly abolishes the ability of the first subset of subunits to recover after photobleaching, whereas Sec3p and Exo70p are resistant. Immunogold electron microscopy and epifluorescence video microscopy indicate that all exocyst subunits, except for Sec3p, are associated with secretory vesicles as they arrive at exocytic sites. Assembly of the exocyst occurs when the first subset of subunits, delivered on vesicles, joins Sec3p and Exo70p on the plasma membrane. Exocyst assembly serves to both target and tether vesicles to sites of exocytosis.