Craniofacial dysmorphology in Down syndrome is caused by increased dosage of Dyrk1a and at least three other genes.

Down syndrome (DS), trisomy of human chromosome 21 (Hsa21), occurs in 1 in 800 live births and is the most common human aneuploidy. DS results in multiple phenotypes, including craniofacial dysmorphology, which is characterised by midfacial hypoplasia, brachycephaly and micrognathia. The genetic and developmental causes of this are poorly understood. Using morphometric analysis of the Dp1Tyb mouse model of DS and an associated mouse genetic mapping panel, we demonstrate that four Hsa21-orthologous regions of mouse chromosome 16 contain dosage-sensitive genes that cause the DS craniofacial phenotype, and identify one of these causative genes as Dyrk1a. We show that the earliest and most severe defects in Dp1Tyb skulls are in bones of neural crest (NC) origin, and that mineralisation of the Dp1Tyb skull base synchondroses is aberrant. Furthermore, we show that increased dosage of Dyrk1a results in decreased NC cell proliferation and a decrease in size and cellularity of the NC-derived frontal bone primordia. Thus, DS craniofacial dysmorphology is caused by an increased dosage of Dyrk1a and at least three other genes.

Resolving morphogenesis into quantifiable cell behaviours.

Morphogenesis is extremely diverse, but its systematic quantification to determine the physical mechanisms that produce different phenotypes is possible by quantifying the underlying cell behaviours. These are limited and definable: they consist of cell proliferation, orientation of cell division, cell rearrangement, directional matrix production, cell addition/subtraction and cell size/shape change. Although minor variations in these categories are possible, in sum they capture all possible morphogenetic behaviours. This article summarises these processes, discusses their measurement, and highlights some salient examples.

Early perturbation of Wnt signaling reveals patterning and invagination-evagination control points in molar tooth development.

Tooth formation requires complex signaling interactions both within the oral epithelium and between the epithelium and the underlying mesenchyme. Previous studies of the Wnt/ß-catenin pathway have shown that tooth formation is partly inhibited in loss-of-function mutants, and gain-of-function mutants have perturbed tooth morphology. However, the stage at which Wnt signaling is first important in tooth formation remains unclear. Here, using an Fgf8-promoter-driven, and therefore early, deletion of ß-catenin in mouse molar epithelium, we found that loss of Wnt/ß-catenin signaling completely deletes the molar tooth, demonstrating that this pathway is central to the earliest stages of tooth formation. Early expression of a dominant-active ß-catenin protein also perturbs tooth formation, producing a large domed evagination at early stages and supernumerary teeth later on. The early evaginations are associated with premature mesenchymal condensation marker, and are reduced by inhibition of condensation-associated collagen synthesis. We propose that invagination versus evagination morphogenesis is regulated by the relative timing of epithelial versus mesenchymal cell convergence regulated by canonical Wnt signaling. Together, these studies reveal new aspects of Wnt/ß-catenin signaling in tooth formation and in epithelial morphogenesis more broadly.

A landmark-free morphometrics pipeline for high-resolution phenotyping: application to a mouse model of Down syndrome.

Characterising phenotypes often requires quantification of anatomical shape. Quantitative shape comparison (morphometrics) traditionally uses manually located landmarks and is limited by landmark number and operator accuracy. Here, we apply a landmark-free method to characterise the craniofacial skeletal phenotype of the Dp1Tyb mouse model of Down syndrome and a population of the Diversity Outbred (DO) mouse model, comparing it with a landmark-based approach. We identified cranial dysmorphologies in Dp1Tyb mice, especially smaller size and brachycephaly (front-back shortening), homologous to the human phenotype. Shape variation in the DO mice was partly attributable to allometry (size-dependent shape variation) and sexual dimorphism. The landmark-free method performed as well as, or better than, the landmark-based method but was less labour-intensive, required less user training and, uniquely, enabled fine mapping of local differences as planar expansion or shrinkage. Its higher resolution pinpointed reductions in interior mid-snout structures and occipital bones in both the models that were not otherwise apparent. We propose that this landmark-free pipeline could make morphometrics widely accessible beyond its traditional niches in zoology and palaeontology, especially in characterising developmental mutant phenotypes.

Higher Responder Rates Observed With Live Participant Assessment Versus Photographic Assessment After VYC-20L Hyaluronic Acid Treatment for Chin Augmentation.

BACKGROUND: In an evaluator-blinded, randomized controlled trial, the hyaluronic acid soft-tissue filler VYC-20L injectable gel was safe and effective for correcting volume deficits and retrusion in the chin. OBJECTIVES: The objective of this subanalysis was to compare responder rates obtained with photographic vs live assessments. METHODS: Participants were randomized 3:1 to VYC-20L treatment or a 6-month, no-treatment control period followed by optional treatment. Responder rates (≥1-point improvement from baseline on the validated Allergan Chin Retrusion Scale [ACRS]) obtained with photographic assessments and live assessments at Month 6 were compared. Prespecified subgroup analyses compared responder rates by baseline ACRS severity, filler volume, cannula usage, and investigation site. RESULTS: VYC-20L was effective for chin augmentation as evaluated with both live and photographic assessments. The ACRS responder rates at Month 6 were 91.8% with live assessments and 56.3% with photographic assessments. Consistently higher response rates were observed by live vs photographic assessment regardless of baseline ACRS severity, filler volume, cannula usage, and investigation site. CONCLUSIONS: Live assessment of ACRS response after VYC-20L treatment resulted in higher responder rates than photographic assessment, supporting the use of live assessment for this indication to approximate real-world clinical practice.

Increasing Precision When Targeting the Depressor Anguli Oris (DAO) Muscle With Neuromodulators - An Ultrasound-Based Investigation.

BACKGROUND: Neuromodulator treatments of the perioral region are increasingly popular and aim to modulate the position of the modiolus. The predominantly targeted muscle is the depressor anguli oris (DAO) which allows for the modiolus to reposition cranially once temporarily relaxed. OBJECTIVES: To identify the precise anatomic position of the DAO in relation to the Marionette Line for increasing precision and reducing adverse events during neuromodulator treatments. METHODS: A total of n = 80 DAO muscles were investigated in n = 40 healthy, toxin naïve volunteers (11 males, 29 females) having a mean age of 48.15 (15) years and a mean body mass index of 24.07 (3.7) kg/m2. The location of the DAO in relation to the labiomandibular sulcus (LMS), its depth, extent, and thickness were investigated with high frequency ultrasound imaging. RESULTS: The skin surface projection of the LMS separates the DAO into medial and lateral portions. The distance between skin surface and muscle surface was on average 4.4 mm with males having a greater distance (p < 0.001) and higher BMI being an important influencing factor for a greater distance (p < 0.001). The thickness of the DAO was on average 3.5 mm with a range of 2.8-4.8 mm and with females having thinner muscles when compared to men (p < 0.001). The most favorable injection depth was calculated to be 6.1 mm for intra-muscular product placement. CONCLUSIONS: Understanding the perioral anatomy and the influence of age, sex, and BMI will potentially allow the injectors to increase efficacy and duration of neuromodulator treatments while expertly managing adverse events.

A Multicenter, Randomized, Evaluator-Blinded Study to Examine the Safety and Effectiveness of Hyaluronic Acid Filler in the Correction of Infraorbital Hollows.

BACKGROUND: Hyaluronic acid injections are increasingly used for correction of infraorbital hollows (IOHs). OBJECTIVES: Examination of effectiveness (IOH correction) and safety of Restylane® EyelightTM hyaluronic acid (HAEYE, Galderma, Uppsala, Sweden) injections. METHODS: Subjects with moderate/severe IOHs, assessed using the Galderma infraorbital hollows scale (GIHS), were randomized to HAEYE injections (via needle/cannula) (Day 1+optional Month-1 touch up) or no-treatment control. Primary endpoint was blinded evaluator-reported Month-3 response, defined as ≥1-point GIHS improvement from baseline (both sides, concurrently). Other endpoints examined investigator-reported aesthetic improvement (GAIS), subject-reported satisfaction (FACE-Q™ satisfaction with outcome; satisfaction questionnaire), and adverse events. RESULTS: Overall, 333 subjects were randomized. Month 3 GIHS responder rate was significantly higher with HA-EYE (87.4%) versus control (17.7%; p<0.001), and comparable between HA-EYE-needle and HA-EYE-cannula groups (p=0.967). HAEYE GAIS responder rate was 87.5-97.7% (Months 3-12). Mean FACE-Q Rasch-transformed scores were 64.3-73.5 (HAEYE) versus 14.1-16.2 (control) through Month 12. Subjects reported looking younger (≥71%) and less tired (≥79%) with reduced under-eye shadows (≥76%) and recovered within 3-5 hours, post-treatment. Efficacy was maintained through Month 12 (63.5% GIHS responders) and through Month 18, after Month-12 retreatment (80.3% GIHS responders; 99.4% GAIS responders; FACE-Q scores: 72.5-72.8). Forty subjects (12.7%) reported typically mild adverse events (4.9% HAEYE-needle; 20.9% HAEYE-cannula). CONCLUSION: HAEYE treatment was effective in correcting moderate/severe IOHs at the primary endpoint (Month 3). Efficacy was sustained through Month 12 after first treatment for 63.5% and through Month 18 for 80.3% (after one retreatment) with needle or cannula administration. Safety outcomes were reassuring.

Perturbation analysis of a multi-morphogen Turing reaction-diffusion stripe patterning system reveals key regulatory interactions.

Periodic patterning is widespread in development and can be modelled by reaction-diffusion (RD) processes. However, minimal two-component RD descriptions are vastly simpler than the multi-molecular events that actually occur and are often hard to relate to real interactions measured experimentally. Addressing these issues, we investigated the periodic striped patterning of the rugae (transverse ridges) in the mammalian oral palate, focusing on multiple previously implicated pathways: FGF, Hh, Wnt and BMP. For each, we experimentally identified spatial patterns of activity and distinct responses of the system to inhibition. Through numerical and analytical approaches, we were able to constrain substantially the number of network structures consistent with the data. Determination of the dynamics of pattern appearance further revealed its initiation by 'activators' FGF and Wnt, and 'inhibitor' Hh, whereas BMP and mesenchyme-specific-FGF signalling were incorporated once stripes were formed. This further limited the number of possible networks. Experimental constraint thus limited the number of possible minimal networks to 154, just 0.004% of the number of possible diffusion-driven instability networks. Together, these studies articulate the principles of multi-morphogen RD patterning and demonstrate the utility of perturbation analysis for constraining RD systems.This article has an associated 'The people behind the papers' interview.

Pervasive cortical and white matter anomalies in a mouse model for CHARGE syndrome.

CHARGE (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth, Genital anomalies and Ear abnormalities) syndrome is a disorder caused by mutations in the gene encoding CHD7, an ATP dependent chromatin remodelling factor, and is characterised by a diverse array of congenital anomalies. These include a range of neuroanatomical comorbidities which likely underlie the varied neurodevelopmental disorders associated with CHARGE syndrome, which include intellectual disability, motor coordination deficits, executive dysfunction, and autism spectrum disorder. Cranial imaging studies are challenging in CHARGE syndrome patients, but high-throughput magnetic resonance imaging (MRI) techniques in mouse models allow for the unbiased identification of neuroanatomical defects. Here, we present a comprehensive neuroanatomical survey of a Chd7 haploinsufficient mouse model of CHARGE syndrome. Our study uncovered widespread brain hypoplasia and reductions in white matter volume across the brain. The severity of hypoplasia appeared more pronounced in posterior areas of the neocortex compared to anterior regions. We also perform the first assessment of white matter tract integrity in this model through diffusion tensor imaging (DTI) to assess the potential functional consequences of widespread reductions in myelin, which suggested the presence of white matter integrity defects. To determine if white matter alterations correspond to cellular changes, we quantified oligodendrocyte lineage cells in the postnatal corpus callosum, uncovering reduced numbers of mature oligodendrocytes. Together, these results present a range of promising avenues of focus for future cranial imaging studies in CHARGE syndrome patients.

The perception of lip aesthetics in the context of facial proportions-An eye-tracking-based analysis.

BACKGROUND: Minimally invasive lip volumizing and contouring soft tissue filler procedures are frequently requested by both female and male aesthetic patients. Guidance on how to achieve the most beautiful outcome is inconsistent. OBJECTIVE: To investigate what the most beautiful proportions are in relation to vermillion thickness, the distance of the upper and lower lip in relation to nose and chin, and relation to the bigonial distance. METHODS: This study included a total of n = 101 volunteers (52 females, 49 males, 100% Caucasian) who inspected frontal images of modified facial proportions and answered a related questionnaire showcasing the same images. Image presentation followed a randomized sequence both for the eye tracking and for the survey component of this study but was equal for all observers. RESULTS: The most attractive vertical position of lips was the 1:2 ratio in which the distance between lips and chin is double the length as the distance between lips and nose. For the ratio between the width of the lips and the bigonial distance, it was the 1:2.5 ratio, whereas for the thickness of the upper lip vermilion in relation to the upper lip ergotrid it was the 1:3/1:2 (male/female) ratio and for the lower lip vermilion and lower lip ergotrid it was the 1:4 ratio for both genders. CONCLUSION: The results of this eye tracking and survey-based investigation revealed that instead of one single universal ratio, multiple facial proportions exist that are perceived as most attractive/masculine/feminine. Regarding the perception of facial aesthetics, it appears there is a distinction between attractiveness and masculinity/femininity: the most attractive male/female face is not necessarily the most masculine or feminine.

Impact of Glabellar Injection Technique With DaxibotulinumtoxinA for Injection on Brow Position.

BACKGROUND: Precise injection technique is vital for avoiding suboptimal eyebrow position when treating glabellar lines with botulinum toxin type A. OBJECTIVES: The aim of this study was to evaluate the impact of glabellar injection technique on eyebrow position in patients treated with DaxibotulinumtoxinA for Injection (DAXI). METHODS: This retrospective post hoc analysis involved 60 adults who received a single treatment with DAXI 40 U to the glabella and had standardized facial photography. Median vertical and horizontal displacement of the brows (at rest) at baseline and 2 weeks after glabellar injection were measured. Brow position outcomes were evaluated by an oculoplastic surgeon and expert anatomist. Investigators were interviewed to ascertain individual injection techniques. RESULTS: Precise injection location and depth, and median resting brow position following treatment varied between investigators. Positive brow outcomes were achieved with deep DAXI injections into the medial corrugator, superficial lateral corrugator injections placed between the midpupil and lateral limbus, and deep midline procerus injections. Glabellar injection technique that more precisely targeted the corrugator muscles resulted in longer glabellar line treatment duration compared to a less targeted technique. Medial corrugator injections above the medial brow; lateral corrugator injections administered deeply or more medially, toward the medial third of the brow; and procerus injections superior to the inferomedial brow tended to be associated with suboptimal outcomes that were more apparent during dynamic expression. CONCLUSIONS: Aesthetically pleasing brow outcomes and greater duration of efficacy can be achieved with an injection pattern that precisely treats the anatomic location of the corrugator supercilii and procerus muscles, avoiding the frontalis.

Multicenter Pivotal Study Demonstrates Safety and Efficacy of a New Cellulite Procedure: 3-Month Results.

BACKGROUND: Cellulite is an aesthetic condition affecting the appearance of skin in certain body regions and is associated with body dissatisfaction, psychosocial stress, and decreased quality of life. Previous studies established the safety and feasibility of a novel, minimally invasive device to identify and release septa responsible for cellulite depressions: targeted verifiable subcision (TVS). OBJECTIVES: The objective of this single-arm, open-label, multicenter study was to evaluate the safety and efficacy of TVS for reducing the appearance of moderate to severe cellulite in adult women. METHODS: Adult women aged 21 to 55 years and a BMI < 30 kg/m2 with moderate or severe cellulite on the buttocks and/or thighs were eligible to enroll at 9 sites. Endpoint data included results from 4 of the postprocedural follow-up visits at 24 hours, 7 days, 30 days, and 90 days. The primary endpoints were a mean ≥1 point reduction in the Cellulite Severity Scale at 90 days and no related serious adverse events at 30 days. RESULTS: Seventy-four female participants with a mean BMI of 24.8 ±â€…2.7 and age of 41.4 ±â€…7.4 years received this single procedure. The mean improvement in Cellulite Severity Scale (N = 68) was 1.5 ±â€…0.9 (P < 0.0001). There were no device-related serious adverse events at 30 days. CONCLUSIONS: TVS for selectively identifying and verifiably releasing septa responsible for cellulite depressions is an effective and safe means to improve the appearance of moderate to severe cellulite in adult women.

Multicenter Pivotal Study Demonstrates Safety and Efficacy of a New Cellulite Procedure: Final Results at 12 Months.

BACKGROUND: Safety and efficacy endpoints for the single-arm, multicenter, open-label pivotal study, CONtrolled Focal Fibrous Band Release Method (CONFFIRM) [NCT04743635] assessing targeted verifiable subcision (TVS) for the treatment of cellulite were met at 3 months postprocedure and have been published. Final, 12-month data describing durability of treatment effect and safety are presented here for the first time. OBJECTIVES: The authors sought to evaluate safety and efficacy out to 12 months of initial treatment for a single TVS procedure performed employing the Avéli device (Revelle Aesthetics, Inc.; Mountain View, CA) to treat cellulite on the buttock and thigh areas of adult females. METHODS: Effectiveness was determined by 3 independent physicians employing the Cellulite Severity Scale and Global Aesthetic Improvement Scale to assess improvement of baseline photographs when compared with 3-, 6- and 12-month posttreatment photographs. Blinded participant-reported outcomes and safety evaluations were also performed at all postprocedure time points. RESULTS: Clinically significant improvement in primary endpoint Cellulite Severity Scale scores were sustained out to 1 year, improving by 1.50 (P < .0001) at 3 months, 1.54 points at 6 months, and 1.48 points at 12 months. Adverse events were mild and mostly resolved by the 12-month visit. CONCLUSIONS: A single TVS treatment has durable efficacy and safety in reducing cellulite on the buttocks and thighs of women with moderate to severe cellulite out to 12 months posttreatment.

A Pilot Study of the Safety and Effectiveness of a Novel Device in Subjects With Axillary Hyperhidrosis.

BACKGROUND: One-third of U.S. adults are bothered by excessive sweating and 5% suffer from hyperhidrosis, both of which negatively affect quality-of-life (QoL). A single-use disposable patch using the novel targeted alkali thermolysis (TAT) technology is being developed to address this condition. OBJECTIVE: Assess the efficacy and safety of the TAT patch for the treatment of excessive sweating using a randomized, double-blind, sham-controlled study design. MATERIALS AND METHODS: Adults with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 ( n = 16) were treated with an active or sham patch for up to 3 minutes (as established in a previous unpublished feasibility study) and evaluated weekly for 6 weeks post-treatment. The primary effectiveness measure was improved HDSS at Week-4. RESULTS: The study met its objective. For the primary efficacy measure, 83% of TAT-treated subjects reported HDSS scores of 1 or 2 at Week-4 versus 0% of sham-treated subjects ( p = .0032). Furthermore, 67% of TAT-treated subjects had a 2-point improvement in HDSS scores versus 0% of sham-treated subjects ( p = .0123). Quality-of-life improvement correlated with HDSS. The TAT patch seemed to be well-tolerated; one transient moderate adverse event that resolved without sequelae was reported. CONCLUSION: The TAT patch successfully demonstrated efficacy and was well-tolerated.

Aging of the Neck Decoded: New Insights for Minimally Invasive Treatments.

BACKGROUND: Many signs of aging manifest in the neck region, including platysmal bands, excess skin, horizontal neck lines and decreasing contour of the neck. While the clinical signs of an aged neck are well-known, data determining the underlying aging process are limited. OBJECTIVE: To decode aging of the neck. MATERIALS AND METHODS: This prospective study investigated elasticity and firmness of skin, muscle activity and skin displacement upon muscular contraction in the neck in 77 young-, middle- and old-age individuals. Objective outcome measures, including 3-dimensional imaging, cutometry and surface electromyography, were utilized for all assessments. RESULTS: Mean firmness of skin decreased significantly from young to old individuals (0.37 ± 0.13 mm, 0.30 ± 0.12 mm and 0.26 ± 0.12 mm in young, middle and old subjects, respectively; p < 0.001). Gross elasticity decreased significantly from 75.1 ± 13.0% in young subjects, to 64.53 ± 15.7% in middle-aged subjects and 55.79 ± 13.0% in old subjects (p < 0.001). The mean y-axis skin displacement increased from 2.48 ± 4.33 mm in young subjects, to 3.11 ± 4.49 mm in middle-aged subjects and 3.61 ± 5.38 mm in old subjects (p = 0.006). The mean signal-to-noise ratio decreased significantly from 16.74 ± 5.77 µV in young subjects, to 14.41 ± 4.86 µV in middle-aged subjects and to 12.23 ± 5.99 µV in old subjects (p < 0.001). CONCLUSION: This study provides insights into the interplay between skin elasticity, muscular activity and the reflected movement of the skin of the neck. Appreciation of these age-related changes lays the fundament for aesthetic treatments in this delicate region. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Use of a Novel Artificial Intelligence Platform for the Evaluation of Rhytids.

BACKGROUND: Artificial intelligence (AI) platforms are increasingly being utilized in various healthcare applications. There are few platforms that provide quantifiable assessments of dermatologic or aesthetic conditions by employing industry established scales. OBJECTIVES: The authors sought to report the results of a pilot study that evaluated the utilization and functionality of an AI engine to measure and monitor rhytids (fine lines). For this study, glabellar frown lines were employed as the clinical model. METHODS: Seventy-one patients were enrolled and monitored remotely employing current high-quality mobile phone cameras over a 14-day period. The patients were prompted to take photographs employing this platform at preset intervals, and these photographs were then rated by the AI platform and qualified raters experienced in the field of facial aesthetics. RESULTS: The AI platform had concordance with 2 qualified raters of 46% to 68%, and the inter-rater concordance between 2 rates ranged from 44% to 66%. The intra-rater concordance for the raters was between 57% and 84%, whereas the AI platform had a 100% concordance with itself. The participant and investigator satisfaction ratings of the platform were high on multiple dimensions of the platform. CONCLUSIONS: This AI platform evaluated photos on a comparable level of accuracy as the qualified raters, and it evaluated more consistently than the qualified raters. This platform may have high utility in clinical research and development, including the management of clinical trials, and efficient management of patient care at the clinical practices.

Real-Time Ultrasound Imaging of the Tear Trough: Lessons Learned From Functional Anatomy.

BACKGROUND: The tear trough is one of the most challenging facial regions for soft-tissue filler injections. A thorough understanding of the underlying facial, muscular, and vascular anatomy is crucial to perform safe and effective tear trough injectable treatments. OBJECTIVES: The authors sought to evaluate the location and function of the angular vein in the tear trough in 3 different facial expressions: repose, smiling, and max. orbicularis oculi contraction. METHODS: Twenty study participants with a mean age of 48.3 years and mean BMI of 24.5 kg/m2 were investigated via functional ultrasound imaging. The diameter of the angular vein and the velocity and direction of venous blood flow were analyzed in repose, smiling, and during max. orbicularis oculi contraction. RESULTS: The angular vein was identified in 100% of the cases to travel inside the orbicularis oculi muscle (intra-muscular course) within the tear trough, whereas the angular artery was not identified in this location. The distance between the angular vein and the inferior orbital rim was (lateral to medial): 4.6 mm, 4.5 mm, 3.9 mm, and 3.8 mm. The caudally directed blood flow was in repose 10.2 cm/s and was 7.3 cm/s at max. orbicularis oculi muscle contraction; however, no blood flow was detectable during smiling. CONCLUSIONS: The diameter and the venous blood flow of the angular vein varied between the 3 tested facial expressions. Based on these anatomical findings, the deep injection approach to the tear trough is recommended due to the intramuscular course of the angular vein.

Facial Soft Tissue Repositioning With Neuromodulators: Lessons Learned From Facial Biomechanics.

BACKGROUND: Neuromodulators have proven efficacy in reducing facial rhytides and have also been reported to improve jawline contour and the appearance of platysmal bands. Lifting effects of the tail of the eyebrow are expected outcomes when targeting the lateral periorbital region, underscoring the versatility of neuromodulator treatments. OBJECTIVES: The aim of this study was to analyze the clinical effectiveness of a novel neuromodulator-based injection algorithm with regards to its ability to reposition the middle and lower facial soft tissues. METHODS: Seventy-five study participants (8 males, 67 females) with a mean [standard deviation] age of 37.5 [8.5] years were injected with neuromodulators in the subdermal plane of the mandibular soft tissues following a standardized algorithm. Live rating of clinical appearance was performed, as well as volume change and skin vector displacement measured by 3-dimensional imaging at baseline, Day 14, and Day 30. RESULTS: Three-dimensional volume analysis revealed an increase in midfacial volume by 0.46 mL, and a decrease of the lower facial volume by 0.30 mL compared with baseline. Additionally, an improvement of midfacial fullness (by 0.13) and jawline contour (by 0.44) was reported on clinical rating scales at Day 30 compared with baseline. CONCLUSIONS: Facial soft tissues can be repositioned during the 30-day follow-up period following a neuromodulator treatment; this was reflected through an increase in midfacial volume as well as through a decrease in lower facial volume. The novel injection algorithm presented can provide a safe and effective option for patients desiring improvement of midfacial fullness and jawline contour with neuromodulator treatment alone.

Skin Tightening With Hyperdilute CaHA: Dilution Practices and Practical Guidance for Clinical Practice.

BACKGROUND: Over the past several years, hyperdilute calcium hydroxylapatite (CaHA) has emerged as an effective modality for improving skin quality and managing laxity in the face, arms, hands, neck, décolletage, upper arms, abdomen, buttocks, and upper legs, as well as for treating cellulite and striae. Whereas undiluted CaHA is used to provide volume, hyperdilute CaHA is distributed across a much larger surface area in a more superficial plane to stimulate neocollagenesis and elastin formation over time. The absence of lymphocytic infiltrates and predominance of type 1 collagen in the tissue response to CaHA make hyperdilute CaHA a valuable tool for nonsurgical skin tightening. OBJECTIVES: The aim of this study was to provide practical step-by-step guidance on patient selection, dilution practices, and optimal injection technique to facilitate incorporation of the technique into clinical practice. METHODS: Over the course of 3 regional meetings in the United States, 12 expert physician injectors participated in live webinars as part of a continuing medical education program. RESULTS: The practical guidance in this manuscript is based upon the most frequently requested information by audience members and the information considered critical for success by the authors. CONCLUSIONS: The minimally invasive nature of filler injection results in little downtime, making this treatment particularly appealing. The recommendations presented are consistent with previously published consensus guidelines on hyperdilute CaHA but are intended to serve as "how-to" guidance based on the experience of expert injectors who have successfully treated the face and body.

Computational biology: Turing's lessons in simplicity.

Biophysical modeling of development started with Alan Turing. His two-morphogen reaction-diffusion model was a radical but powerful simplification. Despite its apparent limitations, the model captured real developmental processes that only recently have been validated at the molecular level in many systems. The precision and robustness of reaction-diffusion patterning, despite boundary condition-dependence, remain active areas of investigation in developmental biology.