Poly-d,l-Lactic Acid Via Transdermal Microjet Drug Delivery for Treating Rosacea in Asian Patients.

BACKGROUND: Rosacea, a chronic inflammatory skin condition, is marked by enduring redness, visible blood vessels, and inflammatory eruptions in facial areas. Managing rosacea remains a persistent challenge for dermatologists, especially in cases unresponsive to conventional treatments. Injectable poly-d,l-lactic acid (PDLLA) has shown promise in treating erythema and telangiectasia associated with rosacea in addition to age-related concerns. Employing Mirajet, a laser-induced microjet system, for administering PDLLA is a novel and promising treatment for rosacea. AIMS: We aimed to evaluate the efficacy and safety of injectable PDLLA delivered via a needle-free microjet system for managing rosacea. METHODS: Four Korean women with persistent and refractory rosacea received five monthly sessions of PDLLA needle-free injections. Clinical assessments were conducted using the Clinician's Erythema Assessment and Patient's Self-Assessment (PSA) at baseline, 4 weeks post-treatment, and 22 weeks post-final treatment. Adverse events were monitored throughout the study period. RESULTS: At 4 weeks post-treatment, both Clinician's Erythema Assessment and PSA scores indicated significant improvements in erythema that were sustained up to the 22-week follow-up. Patients reported high satisfaction with resolution of redness and improved skin texture. Mild swelling, redness, and petechiae were observed post-treatment but resolved spontaneously. No product-related adverse events were noted during the study period. CONCLUSION: Injectable PDLLA delivered via laser-induced microjet injection demonstrated promising efficacy in improving rosacea symptoms and skin quality for up to 22 weeks without significant adverse effects. Larger randomized controlled trials are needed to confirm these findings and evaluate long-term safety and sustainability of outcomes.

Reverse and antegrade vector thread lifting techniques: Correcting nasolabial and marionette lines.

BACKGROUND: This study evaluates the efficacy of reverse and antegrade thread lifting vectors in conjunction with thread selection for correcting nasolabial folds and marionette lines, aiming to enhance treatment precision and effectiveness. METHODS: Three female patients aged 43, 48, and 53, presenting with primary concerns regarding nasolabial folds, underwent distinct treatment regimens utilizing various types of threads and vectors. Additionally, video demonstrations were recorded to showcase the procedural techniques employed in each case. RESULTS: The outcomes of the thread lifting procedures demonstrated significant improvements in the correction of the nasolabial fold and marionette line. CONCLUSION: Innovative thread insertion techniques involve entry points above the zygomatic arch and threading toward the temple hairline for lateral face lifting. These utilize barbs to pull skin and underlying tissues. The reversal technique involves inserting threads in a criss-cross pattern, forming a fibrous structure that may prolong the duration of results. Various thread combinations, considering factors such as composition, thickness, and barb size, provide customized procedures. This research introduces clinical applications, including temple area hairline lifting for nasolabial fold and marionette line correction, reverse vectors targeting nasolabial folds and marionette lines, and antegrade approaches from the lateral side.

Anatomical perspectives of brow-lifting using threads: Clinical cases with techniques.

INTRODUCTION: Tailoring surgical interventions to target age-related transformations is paramount. Many candidates seeking blepharoplasty commonly exhibit eyebrow ptosis, underscoring the necessity for surgeons to possess a comprehensive understanding of techniques for brow and forehead rejuvenation. METHODS: Various surgical techniques are available for eyebrow and forehead enhancement, contrasting the standardized approaches in upper and lower blepharoplasty. Thread lifting has gained popularity for forehead lifting, although a more precise term would be eyebrow lifting. The thread lifting methods using V and I techniques with floating-type threads (Secret Line, Hyundai Meditech., Inc., Wonju-si, Republic of Korea) are used. RESULTS: The natural aging process often causes the forehead and eyebrows to sag under the influence of gravity, leading to the appearance of heavy eyelids. Elevating the eyebrows can mitigate droopiness, enhance vision clarity, and rejuvenate the facial aesthetic. While non-surgical methods like Botulinum Toxin A can weaken muscles and potentially aid in brow elevation, their visible effects may be somewhat constrained. DISCUSSION: Surgical methods encompass endoscopic forehead lift, eyebrow lift techniques, and scalp excision-based forehead reduction surgery, each with specific advantages and drawbacks. Thread lifting bridges the gap between surgical and non-surgical modalities. Forehead areas often lack subcutaneous fat, requiring precise anatomical understanding for effective thread lifting. Cannula usage with partial tunneling ensures efficacy even in patients with strong adhesions. Presented cases showcase successful eyebrow lifting using cog threads, illustrating immediate and gradual post-procedure changes. CONCLUSION: Eyebrow thread lifting demands periodic procedures, offering subtler improvements than surgery. Anatomical knowledge is crucial, and the technique presents discomfort. Effects last about 6 months, requiring re-treatment as effects regress. Thread lifting, a middle ground between surgical and non-surgical methods, can rejuvenate brows with less downtime.

Exploring novel A2AAR antagonists: Design, synthesis, and evaluation of 2,6,9-trisubstituted purine derivatives as promising antifibrotic agents.

A series of 2,6,9-trisubstituted purine derivatives were designed and synthesized with diverse chemical moieties. Through a comprehensive biological evaluation, we identified 4-(6-(methylamino)-2-(phenylethynyl)-9H-purin-9-yl)phenol (6a) as a promising A2AAR antagonist with potent antifibrotic properties. Compound 6a demonstrated significant efficacy in inhibiting CRE promoter activity and in reducing the expression of fibrogenic marker proteins and downstream effectors of A2AAR activation, surpassing the A2AAR antagonist ZM241385 and initial screening hits, 9-benzyl-N-methyl-2-(phenylethynyl)-9H-purin-6-amine (5a) and 9-((benzyloxy)methyl)-N-methyl-2-(phenylethynyl)-9H-purin-6-amine (5j). Further validation revealed that compound 6a effectively inhibited fibrogenic marker proteins induced by A2AAR overexpression or TGF-ß1 treatment in hepatic stellate cells, alongside reducing PKA and CREB phosphorylation. These findings suggest that compound 6a exerts its antifibrotic action by modulating the cAMP/PKA/CREB pathway through A2AAR inhibition. Overall, our study provides valuable insights for the development of novel therapeutics that target hepatic fibrosis through A2AAR antagonism.

Sihler's staining of the anterior belly of digastric muscle for botulinum toxin injection.

PURPOSE: The anterior belly of the digastric muscle (ABDM) is the target of botulinum toxin injection; however, anatomical considerations related to the injection point are absent. This study used Sihler's staining to analyze the intramuscular nerve distribution of ABDM to identify the most effective botulinum toxin injection points. METHODS: We used 12 specimens from 6 embalmed cadavers in this study. The specimens were manually dissected to preserve the mylohyoid nerve and subjected to Sihler's staining. From the gnathion to and hyoid bone, the ABDM was divided into three equal parts, distinguishing the anterior, middle, and posterior thirds. RESULTS: Only a branch of the mylohyoid nerve entered the ABDM, and its entry point was located in the middle-third region in all cases. The nerve endings were concentrated in the middle third (100%), followed by the anterior third (58.3%) and were not observed in the posterior third. CONCLUSION: The landmarks used in this study (gnathion and hyoid bone) are easily palpable on the skin surface, allowing clinicians to target the most effective injection site (middle third of ABDM). These results provide scientific and anatomic evidence for injection points, and will aid in the management of ABDM injection procedures in clinical practice.

Comparison between botulinum toxin type A injection on masseter muscle only and additional injection on anterior belly of digastric muscle in sleep bruxism patients: A clinical trial.

OBJECTIVE: This study aims to evaluate the effects on bite force and muscle thickness of the botulinum toxin (BoNT) injection for patients with sleep bruxism (SB) by comparing injections into the masseter muscle only and both the masseter and the anterior belly of the digastric muscle (ABDM) in a clinical trial. METHODS: Twelve SB patients received BoNT-A injections using US-guided techniques into the masseter muscle only (Group A), while the remaining 12 SB patients received injections into both the masseter and ABDM (Group B). Bite force and muscle thickness were measured before injection, as well as 1 and 2 months after injection. RESULTS: The bite force and masseter muscle thickness decreased in both Group A and Group B before injection, and at 1 and 2 months after injection. However, there was no significant difference (p > .05, repeated measures analysis of variance) between the two groups, and there was also no significant difference in ABDM thickness (p > .05, repeated measures analysis of variance). CONCLUSION: This study is the first to assess the short-term effects of BoNT injected into ABDM for SB control. Results show no influence on SB reduction, suggesting the need for further research on BoNT's effectiveness in controlling intense ABDM contractions during sleep and assessing suprahyoid muscle potential impact on rhythmic masticatory muscle activity occurrence.

Sonoanatomy of injecting botulinum neurotoxin into the facial muscles.

INTRODUCTION: Ultrasonography (US) has become an essential tool for guiding botulinum neurotoxin (BoNT) injections in facial muscles, enhancing precision and safety. This narrative review explores the role of US in BoNT administration, particularly in complex anatomical regions, highlighting its impact on treatment customization, real-time visualization, and complication reduction. MATERIALS AND METHODS: A comprehensive literature search was conducted using PubMed, MEDLINE, Embase, and Cochrane Library for articles published from January 2018 to December 2023. Search terms included "Botulinum neurotoxin," "facial anatomy," "ultrasonography guided injection," and "facial muscle sonoanatomy." Studies focusing on US-guided BoNT injections in facial muscles were included. Data extraction and synthesis were performed independently by two reviewers, focusing on study design, ultrasonography techniques, outcomes, and conclusions. RESULTS: The review found that US guidance significantly enhances the precision of BoNT injections by providing real-time visualization of facial muscles and blood vessels, thereby reducing the risk of adverse events. US enables tailored injection strategies, ensuring symmetrical facial expressions and minimizing over-treatment. The technique also offers immediate feedback, allowing for on-the-spot adjustments to improve treatment efficacy and safety. However, the review identified limitations, including potential selection bias and variability in US techniques across different studies. CONCLUSION: US guidance for BoNT injections into facial muscles offers substantial benefits in terms of precision, safety, and treatment customization. Despite the identified limitations, the integration of US into clinical practice is poised to enhance patient outcomes in aesthetic and therapeutic procedures. Further research is needed to standardize US techniques and broaden the inclusivity of studies to validate these findings comprehensively.

Poly­d,l­lactic acid­enhanced atrophic scar treatment via transdermal microjet drug delivery in Asians.

BACKGROUND: Acne vulgaris often results in permanent scars, with atrophic scars being the most common type and posing a significant therapeutic challenge due to their prevalence and impact on patients' quality of life. Various treatment options exist, including the use of poly-d,l-lactic acid delivered via different methods. OBJECTIVE: This study aimed to assess the efficacy and safety of poly-d,l-lactic acid delivered via laser-assisted needle-free microjet injection for treating atrophic scars. METHODS: Five Korean participants with atrophic facial scars were recruited. Poly-d,l-lactic acid solution was administered via the Mirajet system in five sessions, with clinical assessments conducted at baseline, before each session, and at 12-week and 22-week follow-ups. Outcome measures included the Global Aesthetic Improvement Scale and patient satisfaction scores. RESULTS: Positive results were observed at the 12-week and 22-week follow-ups, with high patient satisfaction and improvements in atrophic scars and skin texture. Mild discomfort and transient side effects were reported, with no adverse events observed during the follow-up period. CONCLUSION: Poly-d,l-lactic acid delivered by a laser-assisted needle-free microjet injector was judged to be effective for improving atrophic the facial area. Further research, particularly through randomized controlled trials, is needed to validate these findings and assess the longer-term safety and sustainability of outcomes.

Spatiotemporal estimation of groundwater and surface water conditions by integrating deep learning and physics-based watershed models.

The impacts of climate change on hydrology underscore the urgency of understanding watershed hydrological patterns for sustainable water resource management. The conventional physics-based fully distributed hydrological models are limited due to computational demands, particularly in the case of large-scale watersheds. Deep learning (DL) offers a promising solution for handling large datasets and extracting intricate data relationships. Here, we propose a DL modeling framework, incorporating convolutional neural networks (CNNs) to efficiently replicate physics-based model outputs at high spatial resolution. The goal was to estimate groundwater head and surface water depth in the Sabgyo Stream Watershed, South Korea. The model datasets consisted of input variables, including elevation, land cover, soil type, evapotranspiration, rainfall, and initial hydrological conditions. The initial conditions and target data were obtained from the fully distributed hydrological model HydroGeoSphere (HGS), whereas the other inputs were actual measurements in the field. By optimizing the training sample size, input design, CNN structure, and hyperparameters, we found that CNNs with residual architectures (ResNets) yielded superior performance. The optimal DL model reduces computation time by 45 times compared to the HGS model for monthly hydrological estimations over five years (RMSE 2.35 and 0.29 m for groundwater and surface water, respectively). In addition, our DL framework explored the predictive capabilities of hydrological responses to future climate scenarios. Although the proposed model is cost-effective for hydrological simulations, further enhancements are needed to improve the accuracy of long-term predictions. Ultimately, the proposed DL framework has the potential to facilitate decision-making, particularly in large-scale and complex watersheds.

Effective improvement methods for striae distensae: A novel approach utilizing laser-induced micro-jet injectors with poly-d,l-lactic acid.

INTRODUCTION: Striae distensae (SD), or stretch marks, result from rapid stretching of the skin due to various factors. Conventional treatments often yield unsatisfactory results, leading to the exploration of alternative methods. Laser-induced microjet technology offers a promising approach for drug delivery to target areas. This study investigates the efficacy of using a microjet injector with poly-d,l-lactic acid for treating SD. METHODS: Four female participants with SD were treated with poly-d,l-lactic acid solution using a microjet injector over five sessions. Patients were assessed based on severity scales before and after treatment. Topical anesthetics were applied to minimize discomfort. Injection techniques were optimized to reduce side effects such as bleeding and pain. RESULTS: All patients showed significant improvement in SD appearance after 5-7 treatments. Assessment scales indicated positive outcomes both immediately after treatment and at the 32-week follow-up. Minimal side effects, primarily petechiae, were observed. DISCUSSION: Laser-induced microjet technology offers several advantages, including rapid drug delivery and mechanotransduction effects, promoting skin regeneration. Poly-d,l-lactic acid injections demonstrated effectiveness in treating SD, particularly when delivered via microjet injectors. Patients expressed high satisfaction due to the procedure's minimal invasiveness and quick recovery. CONCLUSION: Utilizing a needleless microjet injector with poly-d,l-lactic acid shows promise as a treatment for SD, typically requiring 5-7 sessions for optimal results. Mild petechiae may occur as a common side effect. This approach offers an effective and minimally invasive alternative for addressing this common cosmetic concern.

Ultrasonographic Study of the Submandibular Gland for Botulinum Neurotoxin Injection.

BACKGROUND: Hypertrophied submandibular glands provide a bulky contour to the lower face. Botulinum neurotoxin injection methods are commonly used for facial contouring; however, no studies have suggested injection points because of the lack of delicate anatomical information on the submandibular gland. OBJECTIVE: The aim of this study was to determine the optimal injection site for botulinum neurotoxin injections in the submandibular gland. MATERIALS AND METHODS: Anatomical considerations when injecting botulinum neurotoxin into the submandibular gland were determined using ultrasonography. The thickness of the submandibular gland, its depth from the skin surface, and the location of the vascular bundle were observed bilaterally in 42 participants. Two cadavers were dissected to measure the location of the submandibular gland corresponding to the ultrasonographic observation. RESULTS: The thickest part of the submandibular gland measured 11.12 ± 2.46 in width with a depth of 4.63 ± 0.76. At the point where it crosses the line of the lateral canthus, it measured 5.53 ± 1.83 in width and 8.73 ± 1.64 in depth. CONCLUSION: The authors suggest optimal injection sites based on external anatomical landmarks. These guidelines aim to maximize the effects of botulinum neurotoxin therapy by minimizing its deleterious effects, which can be useful in clinical settings.

Effects of high-intensity interval robot-assisted gait training on cardiopulmonary function and walking ability in chronic stroke survivors: A multicenter single-blind randomized controlled trial.

BACKGROUND: Chronic stroke can impair cardiopulmonary function, mobility, and daily activities. This study assessed the impact of robot-assisted gait training (RAGT) on such impairments. OBJECTIVE: To investigate the effects of robot-assisted gait training on cardiopulmonary function, walking ability, lower extremity function and strength, activities of daily living (ADLs), and blood test results among individuals with chronic stroke. METHODS: A multicenter, prospective, single-blinded, randomized controlled trial with 22 chronic stroke participants compared RAGT against a control exercise regimen. RAGT involved three days weekly sessions of high-intensity interval training for 8 weeks (24 sessions) with a Morning Walk® device. The control group also performed home exercises. (24 sessions) Measures included VO2max, Functional Ambulatory Category, 2-minute walk test, 10-meter walk test, Motricity Index-Lower, Korean version of the Fugl-Meyer Assessment Scale, Modified Barthel Index, Berg Balance Scale, muscle strength, InBody body composition, and blood tests (cholesterol, lipid, glucose). RESULTS: RAGT significantly improved VO2max, gait, balance, and lower limb strength compared with controls, with significant improvements in 2-minute walk test, 10-meter walk test, Motricity Index-Lower, and Fugl-Meyer Assessment outcomes. No changes were seen in muscle mass or blood markers. CONCLUSION: RAGT enhances cardiopulmonary function and ambulatory capacity in chronic stroke patients, underscoring its potential in stroke rehabilitation.

Thread Lifting Materials: A Review of Its Difference in Terms of Technical and Mechanical Perspective.

Thread lifting involves the use of slender materials, reminiscent of threads, for aesthetic procedures. These materials are distinct from traditional sutures and vary in composition, purpose, and performance. The introduction delves into the literal and material significance of threads, establishing the broad concept of thread lifting materials. The article revisits the evolution of thread lifting materials, emphasizing the preexistence of cog threads for tissue manipulation before their widespread adoption in plastic surgery. Observations regarding the efficacy and longevity of absorbable versus non-absorbable threads are discussed, stressing the efficiency of high-quality absorbable cog threads. The conclusion underlines the proliferation of thread lifting materials beyond PDO, highlighting the importance of considering multiple factors beyond duration when selecting threads for lifting procedures.

Basic concepts in facial and neck thread lifting procedures.

In this review article, our objective is to elucidate fundamental principles and offer practical illustrations concerning the procedures involved in facial and neck thread lifting. Moreover, we aim to explore associated concepts such as the fixing point, hanging point, and anchoring point terminologies, along with the elucidation of vectors. Additionally, we will provide anatomically oriented explanations of the lifting process required for each facial region using thread lifting methods like V, U, and I techniques using floating type threads (Secrete line, Hyundai Meditech., Inc., Wonjusi, Republic of Korea). Furthermore, our intention is to delve deeply into the concepts of tensile strength, anchoring strength, and holding strength, contextualizing their practical applications within this specific field.

Self-crossing hyaluronic acid filler with combination use of polydioxanone thread in minipig model.

INTRODUCTION: The advances of self-crossing hyaluronic acid (SC-HA) fillers combination use with polydioxanone thread in minipigs were examined for compatibility, effectiveness, and immune response. MATERIALS AND METHODS: A 12-week experiment was conducted using 6 minipigs (3 male and 3 female each) to evaluate the effects of SC-HA filler. The molecular weight of SC-HA filler was fixed at 200 kDa and alternative storage modulus of G80, G250, and G500 were examined. The procedure involved injecting SC-HA filler and polydioxanone threads into the skin tissue of anesthetized minipigs, and tissue sampling after 1 month (three minipigs), and 3 months (three minipigs) for histological staining and analysis. The immune reaction was observed during the experiment. RESULTS: The practitioner reported it was easy to inject the SC-HA filler in combination with polydioxanone threads. All four storage modulus of SC-HA fillers were injectable within the polydioxanone thread containing cannula. Also, during the procedure, there were no immune responses at the treated sites. The results of the histological tissue examination confirmed that there was no chemical interaction between SC-HA filler and the existing polydioxanone thread, and it was observed that SC-HA filler was more uniformly distributed within the tissue with lower storage modulus, resulting in a higher production of collagen in the surrounding filler. When combined with scaffold polydioxanone thread, the scaffold polydioxanone thread helped spread the filler evenly, resulting in a more evenly distributed collagen around the filler. CONCLUSION: Today, the combination therapy of filler and polydioxanone thread in one procedure is challenging due to the high viscosity of conventional fillers. However, this study confirmed that combination therapy of filler and polydioxanone thread is possible with SC-HA fillers. Additionally, it was found that polydioxanone thread does not seem to interfere with the crosslinking reaction of SC-HA filler, and if used with a higher pH of polydioxanone, it may enhance the cross-linking reaction and achieve a higher viscosity value. Finally, the study resulted in the idea of concrete as SC-HA filler and reinforcing rod for polydioxanone thread.

Depth of the subcutaneous tissue in the nose: Application to filler injection.

INTRODUCTION: The nasal region plays a pivotal role in both facial esthetics and functionality. The use of volumizing fillers has emerged as a potential means to enhance nasal appearance. Preliminary findings from cadaveric studies have highlighted potential risks associated with deeper needle injection, leading to cartilage damage and lateral migration of filler material. Understanding the subcutaneous tissue depth is crucial to prevent such complications and ensure safe filler placement guided by anatomical knowledge. METHODS: This study aimed to employ ultrasonographic assessment to precisely measure the depth of soft tissue in the nasal area. Fifty-two participants without prior nasal surgery or filler injections underwent detailed ultrasonographic evaluation, focusing on seven key anatomical points: Glabellar, Sellion, Rhinion, between Rhinion and Pronasal, Pronasal, between Pronasal and Subnasal, and Subnasal. RESULTS: The ultrasonographic observation revealed varying depths of subcutaneous tissue across these points: Glabellar (4.11 ± 0.79), Sellion (5.21 ± 0.97), Rhinion (2.02 ± 0.74), Rhinion to Pronasal midpoint (6.45 ± 3.1), Pronasal (9.5 ± 2.2), between Pronasal and Subnasal (8.8 ± 0.8), and Subnasal (8.5 ± 0.5). DISCUSSION: The discussion underscores the significance of understanding subcutaneous tissue depth in guiding needle length and approach angles during filler injections. This knowledge aids in achieving effective filling while ensuring safe placement within the subcutaneous tissue.