Predictive modelling of Immunogenicity to Botulinumtoxin A Treatments for Glabellar Lines.

INTRODUCTION: Botulinum toxin A (BoNT-A), derived from Clostridium botulinum, is widely used in medical and aesthetic treatments. Its clinical application extends from managing chronic conditions like cervical dystonia and migraine to reducing facial wrinkles. Despite its efficacy, a significant challenge associated with BoNT-A therapy is immunogenicity, where the immune system produces neutralising antibodies (NAbs) against BoNT-A, reducing its effectiveness over time. This issue is critical for patients requiring repeated treatments. The study aims to compare FDA-approved BoNT-A products, examining the factors influencing NAbs development using advanced machine learning techniques. METHOD: This research analysed data from randomised controlled trials (RCTs) involving five main BoNT-A products. The study selected trials based on detailed immunogenic responses to these treatments, particularly for glabellar lines. Machine learning models, including logistic regression, random forest classifiers, and Bayesian logistic regression, were employed to assess how treatment specifics and BoNT-A product types affect the development of NAbs. RESULTS: Analysis of 14 studies with 8,190 participants revealed that dosage and treatment frequency are key factors influencing the risk of NAbs development. Among BoNT-A products, IncobotulinumtoxinA shows the lowest, and AbobotulinumtoxinA the highest likelihood of inducing NAbs. The study's machine learning and logistic regression findings indicated that treatment planning must consider these variables to minimise immunogenicity. CONCLUSION: The study underscores the importance of understanding BoNT-A immunogenicity in clinical practice. By identifying the main predictors of NAbs development and differentiating the immunogenic potential of BoNT-A products, the research provides insights for clinicians in optimising treatment strategies. It highlights the need for careful treatment customisation to reduce immunogenic risks, advocating for further research into the mechanisms of BoNT-A immunogenicity.

Regenerative Aesthetics: A Genuine Frontier or Just a Facet of Regenerative Medicine: A Systematic Review.

BACKGROUND: Regenerative aesthetics claims to enhance cosmetic outcomes through advanced biological interventions like Stem cell and Exosome therapy, Polydeoxyribonucleotide (PDRN), Photobiomodulation, bioactive peptides and treatment for cellular senescence yet lacks substantial scientific and regulatory validation. OBJECTIVE: To evaluate the scientific and clinical foundations of regenerative medicine techniques in non-surgical aesthetics and assess the legitimacy of regenerative aesthetics as a medical specialty. METHODS: A systematic review was conducted according to PRISMA guidelines, searching databases including PubMed, Scopus, and Web of Science for studies published in the last ten years. We included 19 studies, comprising 14 randomized controlled trials (RCTs) and 5 prospective studies, focusing on interventions that purportedly use regenerative medicine principles in aesthetic applications. RESULTS: The review highlights a prevalent gap in molecular and clinical evidence supporting the efficacy and safety of regenerative aesthetics. Despite the robust design of the included RCTs and prospective studies, there remains a significant lack of consistent, high-quality evidence proving the effectiveness of these interventions. Issues such as inadequate reporting, unclear molecular mechanisms, and absence of long-term safety data were common. CONCLUSION: The field of regenerative aesthetics lacks the necessary scientific rigour and regulatory compliance to be recognized as a legitimate medical specialty. This review underscores the need for stringent scientific validation and regulatory oversight to ensure patient safety and treatment efficacy before these techniques can be recommended for clinical use. LEVEL OF EVIDENCE II: 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 .

Immunogenicity of Botulinum Toxin A: Insights.

BACKGROUND: Botulinum toxin A (BoNT-A) is widely used in treating dystonia and spasticity to managing chronic migraine and cosmetic applications. However, its immunogenic potential presents challenges, such as the development of neutralizing antibodies that lead to diminished therapeutic efficacy over time, known as secondary nonresponse. OBJECTIVE: This review aims to bridge the knowledge gap regarding the immunogenic mechanisms of BoNT-A and to explore effective management strategies to mitigate these immune responses. MATERIALS AND METHODS: The authors conducted a systematic search in databases including PubMed, Embase, and Web of Science, using keywords related to BoNT-A's immunogenicity. The selection process refined 157 initial articles down to 23 relevant studies, which underwent analysis to investigate the underlying mechanisms of immunogenicity and the factors influencing it. RESULTS: The analysis revealed that both the neurotoxin component and the neurotoxin-associated proteins could elicit an immune response. However, only antibodies against the core toxin influence therapeutic outcomes. Various patient-specific factors such as genetic predispositions and prior immune experiences, along with treatment-related factors such as dosage and frequency, play crucial roles in shaping these responses. CONCLUSION: Understanding the specific immunogenic triggers and responses to BoNT-A is critical for optimizing treatment protocols and improving patient outcomes.

Intradermal Botulinum Toxin A on Skin Quality and Facial Rejuvenation: A Systematic Review and Meta-analysis.

Background: Botulinum toxin A (BTxA) has gained popularity as a nonsurgical aesthetic treatment for skin rejuvenation. However, previous studies on intradermal BTxA have shown inconsistent results. This systematic review and meta-analysis with trial sequential analysis aimed to assess the efficacy and safety of intradermal BTxA for facial rejuvenation. Methods: Following PRISMA guidelines, a comprehensive search was conducted in various databases from January 2008 to March 2023. Outcome measures included sebum production, pore size, skin hydration, skin texture, erythema index, facial wrinkles, and facelift. Eligible studies included human-based clinical trials and prospective cohort studies published in English, focusing on healthy populations requiring facial rejuvenation. Two authors independently screened the titles and abstracts, followed by a full-text review to determine study eligibility. Data extraction and quality assessment were performed by two authors using predefined criteria. Results: Ten studies met the inclusion criteria, including five randomized controlled trials and five prospective cohort studies with 153 participants. Studies revealed positive effects of intradermal BTxA on various outcome measures related to facial rejuvenation. These effects included improvements in sebum production, pore size, erythema index, facial wrinkles, skin texture and elasticity, and overall facelift but not skin hydration. All failed to reach the required information size in the trial sequential analysis. Conclusions: Findings suggest positive outcomes in multiple attributes of skin quality and facial rejuvenation. However, more high-quality research is needed to establish definitive conclusions. These findings contribute to the evidence base for nonsurgical aesthetic treatments, emphasizing the importance of ongoing research in this field.

Integrating Psychological Insights into Aesthetic Medicine: A Cross-Generational Analysis of Patient Archetypes (IMPACT Study).

BACKGROUND: Aesthetic medicine has evolved significantly, accommodating diverse demographics and motivations influenced by societal shifts and technological advancements. The IMPACT (integrative multigenerational psychological analysis for cosmetic treatment) study refines patient archetypes, integrating psychological theories to tailor treatments, especially for younger demographics and LGBTQIA + communities. METHODS: This cross-sectional study utilized a comprehensive, validated survey with a Cronbach's alpha of 0.89 and a Content Validity Index (CVI) of 0.92, distributed across a globally diverse, generationally stratified sample. Techniques like regression analysis, ANOVA, Bayesian modelling, and factor analysis were employed to analyse the data, focusing on developing nuanced patient archetypes. RESULTS: Among 5645 participants, 5340 complete responses highlighted significant generational differences in aesthetic preferences. Millennials showed a strong preference for non-invasive procedures (ß = 0.65, p < 0.001). ANOVA results confirmed significant variances across generations [F (3, 5118) = 157.6, p < 0.001], with post-hoc analyses delineating specific inter-group differences. Bayesian modelling provided insights into the probability of non-invasive preferences among younger cohorts at over 92% certainty. Factor analysis revealed key dimensions such as 'Generational Influence' and 'Technological Adoption,' which helped in defining archetypes including Dynamic Self-Identity, Digital Native, Stability Seeker, Classic Conservatism, and Holistic Health, collectively explaining up to 78% of the variance in responses. CONCLUSION: The IMPACT study underscores the influence of generational identity and digital exposure on aesthetic preferences, advocating for personalized, archetype-based treatment approaches. This aligns with enhancing patient satisfaction and treatment outcomes, promoting an adaptive aesthetic medicine practice that meets the evolving needs of modern patients. 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 .

Exosomes Exposed: Overview Systematic Review on Evidence Versus Expectation in Aesthetic and Regenerative Medicine.

INTRODUCTION: Exosomes, diminutive extracellular vesicles, are integral to intercellular communication, harbouring potential for applications in regenerative medicine and aesthetic interventions. The field, however, grapples with the complexities of harmonising exosome characterisation protocols and safeguarding therapeutic integrity. METHODOLOGY: In this scholarly overview, systematic adherence to the Cochrane Collaboration and Preferred Reporting Items for Overviews of Reviews guidelines was observed, scrutinising the congruence of exosome-related therapies with the Minimal Information for Studies of Extracellular Vesicles standards delineated by the International Society for Extracellular Vesicles, alongside criteria set forth by the International Society for Cell Therapy and the International Society for Stem Cell Research. A meticulous search strategy spanning databases such as PubMed, Scopus, Web of Science, EMBASE, and Cochrane database was employed to encapsulate studies pertinent to the isolation, characterisation, and functional assessment of exosomes. RESULTS: The initial search yielded 225 articles, of which 17 systematic reviews were selected based on predefined criteria, encompassing 556 primary studies. Notwithstanding the acknowledged therapeutic promise of exosome modalities, the synthesis illuminated a prevalent deficiency in adherence to established reporting and experimental benchmarks, notably in exosome source characterisation and bioactive constituent delineation. A critical appraisal employing the AMSTAR-2 tool underscored a pervasive shortfall in methodological rigour. CONCLUSION: This review accentuates the imperative for stringent methodological standardisation within exosome research to fortify the validity and reproducibility of empirical findings. Amidst the burgeoning therapeutic optimism, the discipline must rectify methodological disparities and comply with regulatory mandates, ensuring the ethically sound and scientifically robust advancement of exosome-based therapeutic modalities. 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 .

Generational Exploration on Aesthetic Medicine Products: Influence of Social Media, Reviews, and Brand Identity-GEMS Bond Survey.

INTRODUCTION: The study investigates the impact of social media reviews and brand identity on consumer preferences in the non-surgical aesthetics products across different generations. It highlights the evolving landscape of aesthetic medicine and surgery, driven by technological advancements and a cultural shift towards individual well-being. The research aims to explore the interplay between generational preferences, the influence of social media, and the role of brand identity in shaping consumer decisions. METHODS: A cross-sectional study design was employed, with a sample size of > 5000 participants stratified across various generational cohorts. The study utilized an online questionnaire to capture both quantitative and qualitative insights into consumer behaviour, with statistical analysis performed to identify patterns and relationships. RESULTS: Analysis of 5850 responses revealed distinct generational preferences and behaviours. Social media engagement varied significantly across generations, with younger cohorts placing a higher emphasis on online reviews. The study also found that brand identity's influence is diminishing in decision-making processes, with consumers increasingly relying on peer reviews and social media content. CONCLUSION: The findings highlight a pivotal shift in the non-surgical aesthetics consumer market, emphasizing the growing importance of social media and peer reviews over traditional brand identities. Importantly, the study underscores the critical need for integrating patient safety and evidence-based practice within marketing strategies. As consumer preferences evolve towards valuing transparency and authenticity, non-surgical aesthetics providers must prioritize these elements, ensuring that their services are not only appealing but also grounded in safety and scientific validity. 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 ."

Update on Blindness From Filler: Review of Prognostic Factors, Management Approaches, and a Century of Published Cases.

Vision loss secondary to aesthetic filler treatment is a rare but disastrous complication. The aim of this review was to update the published cases of blindness after filler injection that have occurred since our group published reviews of 98 cases in 2015 and an additional 48 cases in 2019. A literature review was performed to identify all cases of visual complications caused by filler injection published between September 2018 and March 2023. The cases were analyzed independently and in combination with previously reviewed cases. Analyses were based on the number of cases with data available. A total of 365 new cases of partial or complete vision loss after filler injection were identified. The sites that were highest risk were the nose (40.6%), forehead (27.7%), and glabella (19.0%). The filler injected was hyaluronic acid in 79.6% of cases. The most common associated signs were ptosis (56.2%), ophthalmoplegia (44.1%), pain (31.2%), and skin changes (73.2%). Strokelike features were seen in 19.2% of cases. Of the cases reporting visual outcomes (318), 6.0% experienced complete vision recovery, 25.8% had partial improvement in visual acuity, and 68.2% had no vision recovery. Partially preserved visual acuity at onset was a significant predictor of visual improvement (P < .001). The 3 most common treatments were subcutaneous hyaluronidase at or near the filler site (70.1%), systemic steroids (57.3%), and intraarterial thrombolytic therapy (56.0%). No treatments were significantly associated with visual improvement (P > .05). Although blindness and stroke from fillers is a rare complication, practitioners who inject filler should have a thorough knowledge of prevention and management strategies.

2020 design and methods of the Population Assessment of Tobacco and Health (PATH) study during the COVID-19 pandemic.

The Population Assessment of Tobacco and Health (PATH) Study is a nationally representative, longitudinal study of the US population on tobacco use and its effects on health, collecting data annually since 2013. The COVID-19 pandemic interrupted in-person survey data collections around the world. In the USA, this included a PATH Study data collection focused on youth (13-17) and young adults (18-19) as well as other US surveys on tobacco use. Given that it was necessary to pause data collection and considering that tobacco-use behaviours could be expected to change along with pandemic-related changes in the social environment, the original design for the 2020 PATH Study data collection for youth and young adults was modified. Also, the PATH Study Adult Telephone Survey was developed to address the need for adult tobacco use monitoring in this unprecedented time. This article describes the modifications made to the 2020 PATH Study design and protocol to provide nationally representative data for youth and adults after the onset of the COVID-19 pandemic as well as the implications of these modifications for researchers.

Embracing Spectrum: Celebrating LGBTQIA+ Journeys in Aesthetic Medicine: A Kaleidoscope of Identity.

PURPOSE: This synaptic systemised review critically examines the provision of aesthetic medical care to LGBTQIA+ (lesbian, gay, bisexual, transgender, queer or questioning, intersex, asexual, and more) individuals, assessing both the clinical practices and the educational frameworks that guide interactions with LGBTQIA+ patients in aesthetic settings. METHODS: Following PRISMA-S guidelines, a comprehensive review was conducted, initially identifying 159 potentially relevant articles. Upon stringent full-text review, 33 studies met the inclusion criteria and were subject to an in-depth thematic analysis. The scope encompassed qualitative studies, quantitative analyses, and a cross section of interdisciplinary research, predominantly from Western settings. RESULTS: The analysis distilled four principal themes: the imperative of identity affirmation in aesthetic interventions, substantial barriers to inclusive and empathetic care, the critical need for patient empowerment, and the existing deficiencies within medical education regarding LGBTQIA+ care. These themes highlight a complex interplay between the clinical aspirations of LGBTQIA+ individuals and the current capacity of aesthetic medicine to cater to this diversity. CONCLUSIONS: There is a pressing need for a paradigmatic shift towards more inclusive, competent, and sensitive aesthetic medical care for LGBTQIA+ patients. It underscores the necessity of reform in medical education and advocates for policy changes that promote a more equitable healthcare environment. This research serves as a call to action, emphasizing the ethical imperative to integrate comprehensive LGBTQIA+ care competencies into aesthetic medicine curricula and practice. 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.

Prevalence of hepatitis B and C infection and linkage to care among patients with Non-Communicable Diseases in three rural Rwandan districts: a retrospective cross-sectional study.

INTRODUCTION: Rwanda's Hepatitis C elimination campaign has relied on mass screening campaigns. An alternative "micro-elimination" strategy focused on specific populations, such as non-communicable disease (NCD) patients, could be a more efficient approach to identifying patients and linking them to care. METHODS: This retrospective cross-sectional study used routine data collected during a targeted screening campaign among NCD patients in Kirehe, Kayonza, and Burera districts of Rwanda and patients receiving oncology services from the Butaro District Hospital. The campaign used rapid diagnostic tests to screen for Hepatitis B surface antigen (HBsAg) and Hepatitis C antibody (anti-HCV). We reported prevalences and 95% confidence intervals for HBsAg and anti-HCV, assessed for associations between patients' clinical programs and hepatitis B and C, and reported cascade of care for the two diseases. RESULTS: Out of 7,603 NCD patients, 3398 (45.9%) self-reported a prior hepatitis screening. Prevalence of HBsAg was 2.0% (95% CI: 1.7%-2.3%) and anti-HCV was 6.7% (95% CI: 6.2%-7.3%). The prevalence of HBsAg was significantly higher among patients < 40 years (2.4%). Increased age was significantly associated with anti-HCV (12.0% among patients ≥ 70 years). Of the 148 individuals who screened positive for HbsAg, 123 had viral load results returned, 101 had detectable viral loads (median viral load: 451 UI/mL), and 12 were linked to care. Of the 507 individuals who screened positive for anti-HCV, 468 had their viral load results returned (median viral load: 1,130,000 UI/mL), 304 had detectable viral loads, and 230 were linked to care. CONCLUSION: Anti-HCV prevalence among Rwandan patients with NCD was high, likely due to their older age. NCD-HCV co-infected patients had high HCV viral loads and may be at risk of poor outcomes from hepatitis C. Hepatitis C micro-elimination campaigns among NCD patients are a feasible and acceptable strategy to enhance case detection in this high-prevalence population with elevated viral loads and may support linkage to care for hepatitis C among elderly populations.

Angiogenesis in Lung Cancer: Understanding the Roles of Growth Factors.

Research has shown the role of growth factors in lung cancer angiogenesis. Angiogenesis promotes lung cancer progression by stimulating tumor growth, enhancing tumor invasion, contributing to metastasis, and modifying immune system responses within the tumor microenvironment. As a result, new treatment techniques based on the anti-angiogenic characteristics of compounds have been developed. These compounds selectively block the growth factors themselves, their receptors, or the downstream signaling pathways activated by these growth factors. The EGF and VEGF families are the primary targets in this approach, and several studies are being conducted to propose anti-angiogenic drugs that are increasingly suitable for the treatment of lung cancer, either as monotherapy or as combined therapy. The efficacy of the results are encouraging, but caution must be placed on the higher risk of toxicity, outlining the importance of personalized follow-up in the management of these patients.

The sweet spot study-Developing e-liquid product standards for nicotine form and concentration to improve public health: Protocol for a randomized, double-blinded, crossover study.

OBJECTIVES: E-cigarettes pose significant risks to youth, but smokers may benefit from switching to e-cigarettes by reducing their exposure to toxicants, which creates a challenge for the Food and Drug Administration (FDA) in regulating e-cigarettes to protect population health. This study aims to develop e-liquid product standards for nicotine form and concentration that reduce the appeal of e-cigarettes to young people while keeping e-cigarettes available as a safer alternative for smokers. DESIGN AND PARTICIPANTS: A single-visit, double-blinded, randomized crossover design will be used to examine the effects of e-liquids with varying fractions of free-base nicotine (5%, 25%, 45%, 65%, 85%) among a sample of 66 young adult EC users and 66 older adult smokers, across ecologically valid total nicotine concentrations (20 mg or 50 mg/mL). INTERVENTIONS AND OUTCOMES: A 2-puff session will be conducted to test each of the 10 e-liquids in randomly assigned sequences, followed by a 10-minute washout period and participant ratings on appeal and sensory attributes such as throat hit and harshness, as well as behavioral intentions for continued use. Generalized linear mixed models will be used to determine a free-base nicotine level that has limited or no appeal to young adult e-cigarette users while remaining acceptable to smokers. CONCLUSIONS: This study will provide the FDA with scientific evidence regarding the effect of product standards that mandate a minimum threshold for the fraction of free-base nicotine. TRIAL REGISTRATION: The study is registered on clinicaltrials.gov under the identifier NCT05864586.

Evidence of compost contamination with per- and polyfluoroalkyl substances (PFAS) from "compostable" food serviceware.

Per- and polyfluoroalkyl substances (PFAS) have been used to waterproof and greaseproof food serviceware for decades. Health concerns about these compounds have drawn attention to the potential for contamination of the food system. Finished compost (n = 3) made from manure and food serviceware labeled "compostable" generated at a large fair was found to contain 12 or 13 of the 28 PFAS compounds sampled for, in concentrations ranging from 1.1 to 183 µg/kg (Σ28PFAS range = 209-455 µg/kg). Of note, perfluorooctanoic acid, a known carcinogen, was found at concentrations between 47.2 and 55.5 µg/kg. In contrast, fresh manure contained only perfluoroctanesulfonic acid at 3.7 µg/kg, and separated food waste from the fair composted with grass clippings and livestock bedding had no detectable PFAS in 2022, and Σ28PFAS = 9.6 µg/kg in 2019. Including compostable serviceware in compost likely contaminates the finished compost and threatens surrounding groundwater and surface waters, in addition to increasing potential crop uptake.

Update to the design and methods of the PATH Study, Wave 4 (2016-2017).

The Population Assessment of Tobacco and Health (PATH) Study is a nationally representative study of the US population on tobacco use and its effects on health, with four waves of data collection between 2013 and 2017. Prior work described the methods of the first three waves. In this paper, we describe the methods of Wave 4, during which a replenishment sample was added to the ongoing cohort. We describe the design and estimation methods of the continuing Wave 1 cohort (with four waves of data) and the Wave 4 cohort (the new cohort created at Wave 4). We provide survey quality metrics, including response rates for both cohorts and a panel conditioning analysis, and guidance on understanding the target populations for both cohorts.

Cytotoxicity of the methanol extracts and compounds of Brucea antidysenterica (Simaroubaceae) towards multifactorial drug-resistant human cancer cell lines.

BACKGROUND: Cancer remains a global health concern and constitutes an important barrier to increasing life expectancy. Malignant cells rapidly develop drug resistance leading to many clinical therapeutic failures. The importance of medicinal plants as an alternative to classical drug discovery to fight cancer is well known. Brucea antidysenterica is an African medicinal plant traditionally used to treat cancer, dysentery, malaria, diarrhea, stomach aches, helminthic infections, fever, and asthma. The present work was designed to identify the cytotoxic constituents of Brucea antidysenterica on a broad range of cancer cell lines and to demonstrate the mode of induction of apoptosis of the most active samples. METHODS: Seven phytochemicals were isolated from the leaves (BAL) and stem (BAS) extract of Brucea antidysenterica by column chromatography and structurally elucidated using spectroscopic techniques. The antiproliferative effects of the crude extracts and compounds against 9 human cancer cell lines were evaluated by the resazurin reduction assay (RRA). The activity in cell lines was assessed by the Caspase-Glo assay. The cell cycle distribution, apoptosis via propidium iodide (PI) staining, mitochondrial membrane potential (MMP) through 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, and the reactive oxygen species (ROS) via 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFH-DA) staining, were investigated by flow cytometry. RESULTS: Phytochemical studies of the botanicals (BAL and BAS) led to the isolation of seven compounds. BAL and its constituents 3, (3-(3-Methyl-1-oxo-2-butenyl))1H indole (1) and hydnocarpin (2), as well as the reference compound, doxorubicin, had antiproliferative activity against 9 cancer cell lines. The IC50 values varied from 17.42 µg/mL (against CCRF-CEM leukemia cells) to 38.70 µg/mL (against HCT116 p53-/- colon adenocarcinoma cells) for BAL, from 19.11 µM (against CCRF-CEM cells) to 47.50 µM (against MDA-MB-231-BCRP adenocarcinoma cells) for compound 1, and from 4.07 µM (against MDA-MB-231-pcDNA cells) to 11.44 µM (against HCT116 p53+/+ cells) for compound 2. Interestingly, hypersensitivity of resistant cancer cells to compound 2 was also observed. BAL and hydnocarpin induced apoptosis in CCRF-CEM cells mediated by caspase activation, the alteration of MMP, and increased ROS levels. CONCLUSION: BAL and its constituents, mostly compound 2, are potential antiproliferative products from Brucea antidysenterica. Other studies will be necessary in the perspective of the discovery of new antiproliferative agents to fight against resistance to anticancer drugs.

The Efficacy and Duration of Onabotulinum Toxin A in Improving Upper Facial Expression Lines With 64-Unit Dose Optimization: A Systematic Review and Meta-Analysis With Trial Sequential Analysis of the Randomized Controlled Trials.

BACKGROUND: Onabotulinumtoxin A (Onabot A) was the first treatment to be approved for aesthetic indications, namely glabellar lines (GLs), crow's feet lines (CFLs), and forehead lines (FHLs), with a cumulative dose of 64 U. OBJECTIVES: The aim of this study was to conduct a meta-analysis to combine the available data for approved doses for GLs, CFLs, and FHLs to explore the effect and duration of simultaneous treatment with Onabot A. METHODS: PubMed/MEDLINE, Embase, and other national clinical trial registries were searched for randomized controlled trials from January 2010 to July 2022. The meta-analysis, trial sequential analysis, and investigator-assessed time to return to nonresponder status in GLs, CFLs, and FHLs following Onabot A were plotted to elicit a cumulative dose-adjusted response curve based on Kaplan-Meier analysis with a log-rank test. RESULTS: Fourteen randomized controlled trials were eligible for quantitative analysis. A total of 8369 subjects were recruited across the trials. The meta-analysis results show that Onabot A is very effective in reducing moderate to severe GLs, CFLs, and FHLs. The cumulative Z-curve for GLs, CFLs, and FHLs also exceeds the required information size (RIS). Kaplan-Meier analysis with a log-rank test demonstrated that simultaneous treatment of GLs, CFLs, and FHLs requires 182 days (95% CI = 179, 215 days) (P < 0.00002) to return to nonresponder status. CONCLUSIONS: Treatment of the upper facial expression lines with Onabot A is effective, and the approved cumulative dose of 64 U gives longer-lasting effects.

Integrative Assessment for Optimizing Aesthetic Outcomes When Treating Glabellar Lines With Botulinum Toxin Type A: An Appreciation of the Role of the Frontalis.

Despite the perception that treatment of glabellar lines with botulinum toxin A is straightforward, the reality is that the glabellar region contains a number of interrelated muscles. To avoid adverse outcomes, practitioners need to appreciate how treatment of 1 facial muscle group influences the relative dominance of others. In particular, practitioners need to understand the independent role of the frontalis in eyebrow outcomes and the potential for negative outcomes if the lower frontalis is unintentionally weakened by botulinum toxin A treatment. In addition, practitioners must recognize how inter-individual variation in the depth, shape, and muscle fiber orientation among the upper facial muscles can affect outcomes. For optimal results, treatment of the glabellar complex requires a systematic and individualized approach based on anatomical principles of opposing muscle actions rather than a one-size-fits-all approach. This review provides the anatomical justification for the importance of an integrated assessment of the upper facial muscles and eyebrow position prior to glabellar treatment. In addition, a systematic and broad evaluation system is provided that can be employed by practitioners to more comprehensively assess the glabellar region in order to optimize outcomes and avoid negatively impacting resting brow position and dynamic brow movement.