The complexity of transferring genetic information.

The Central Dogma has been a useful conceptualization of the transfer of genetic information, and our understanding of the detailed mechanisms involved in that transfer continues to evolve. Here, we speak to several scientists about their research, how it influences our understanding of information transfer, and questions for the future.

Who Gets Sick From COVID-19? Sociodemographic Correlates of Severe Adult Health Outcomes During Alpha- and Delta-Variant Predominant Periods: September 2020-November 2021.

BACKGROUND: Because COVID-19 case data do not capture most SARS-CoV-2 infections, the actual risk of severe disease and death per infection is unknown. Integrating sociodemographic data into analysis can show consequential health disparities. METHODS: Data were merged from September 2020 to November 2021 from 6 national surveillance systems in matched geographic areas and analyzed to estimate numbers of COVID-19-associated cases, emergency department visits, and deaths per 100 000 infections. Relative risks of outcomes per infection were compared by sociodemographic factors in a data set including 1490 counties from 50 states and the District of Columbia, covering 71% of the US population. RESULTS: Per infection with SARS-CoV-2, COVID-19-related morbidity and mortality were higher among non-Hispanic American Indian and Alaska Native persons, non-Hispanic Black persons, and Hispanic or Latino persons vs non-Hispanic White persons; males vs females; older people vs younger; residents in more socially vulnerable counties vs less; those in large central metro areas vs rural; and people in the South vs the Northeast. DISCUSSION: Meaningful disparities in COVID-19 morbidity and mortality per infection were associated with sociodemography and geography. Addressing these disparities could have helped prevent the loss of tens of thousands of lives.

Effectiveness of Community-Engaged Research Strategies in Increasing COVID-19 Vaccinations in Targeted Communities: The Community Engagement Alliance (CEAL) Regional Teams.

Objectives. To explore a key outcome of interest for the Community Engagement Alliance (CEAL) Regional Teams by examining COVID-19 vaccinations over time in US counties where CEAL teams operated and comparing them to demographically similar counties in the same state. Methods. Our evaluation used a nonequivalent control group design. Each county where a CEAL team operated was matched to a unique non-CEAL county in the same state. Components of the Centers for Disease Control and Prevention's Social Vulnerability Index were used as the matching criteria. COVID-19 vaccinations (county-level percentage of residents aged 18 years or older who are fully vaccinated) for CEAL and matched counties were analyzed over time. Results. The mean percentage of vaccinated adults was significantly higher in CEAL counties than in matched non-CEAL counties. Sensitivity analyses confirmed conclusions did not change depending on the CEAL cohort or closeness of matches. Conclusions. Our findings support CEAL team efforts to increase COVID-19 vaccinations in target communities and employ community-engaged research more broadly within public health contexts. (Am J Public Health. 2024;114(S1):S124-S127. https://doi.org/10.2105/AJPH.2023.307517).

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.

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.

Cellular Senescence in Human Skin Aging: Leveraging Senotherapeutics.

BACKGROUND: As the largest organ in the human body, the skin is continuously exposed to intrinsic and extrinsic stimuli that impact its functionality and morphology with aging. Skin aging entails dysregulation of skin cells and loss, fragmentation, or fragility of extracellular matrix fibers that are manifested macroscopically by wrinkling, laxity, and pigmentary abnormalities. Age-related skin changes are the focus of many surgical and nonsurgical treatments aimed at improving overall skin appearance and health. SUMMARY: As a hallmark of aging, cellular senescence, an essentially irreversible cell cycle arrest with apoptosis resistance and a secretory phenotype, manifests across skin layers by affecting epidermal and dermal cells. Knowledge of skin-specific senescent cells, such as melanocytes (epidermal aging) and fibroblasts (dermal aging), will promote our understanding of age-related skin changes and how to optimize patient outcomes in esthetic procedures. KEY MESSAGES: This review provides an overview of skin aging in the context of cellular senescence and discusses senolytic intervention strategies to selectively target skin senescent cells that contribute to premature skin aging.

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.

Predictive Models of Long-Term Outcome in Patients with Moderate to Severe Traumatic Brain Injury are Biased Toward Mortality Prediction.

BACKGROUND: The prognostication of long-term functional outcomes remains challenging in patients with traumatic brain injury (TBI). Our aim was to demonstrate that intensive care unit (ICU) variables are not efficient to predict 6-month functional outcome in survivors with moderate to severe TBI (msTBI) but are mostly associated with mortality, which leads to a mortality bias for models predicting a composite outcome of mortality and severe disability. METHODS: We analyzed the data from the multicenter randomized controlled Continuous Hyperosmolar Therapy in Traumatic Brain-Injured Patients trial and developed predictive models using machine learning methods and baseline characteristics and predictors collected during ICU stay. We compared our models' predictions of 6-month binary Glasgow Outcome Scale extended (GOS-E) score in all patients with msTBI (unfavorable GOS-E 1-4 vs. favorable GOS-E 5-8) with mortality (GOS-E 1 vs. GOS-E 2-8) and binary functional outcome in survivors with msTBI (severe disability GOS-E 2-4 vs. moderate to no disability GOS-E 5-8). We investigated the link between ICU variables and long-term functional outcomes in survivors with msTBI using predictive modeling and factor analysis of mixed data and validated our hypotheses on the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model. RESULTS: Based on data from 370 patients with msTBI and classically used ICU variables, the prediction of the 6-month outcome in survivors was inefficient (mean area under the receiver operating characteristic 0.52). Using factor analysis of mixed data graph, we demonstrated that high-variance ICU variables were not associated with outcome in survivors with msTBI (p = 0.15 for dimension 1, p = 0.53 for dimension 2) but mostly with mortality (p < 0.001 for dimension 1), leading to a mortality bias for models predicting a composite outcome of mortality and severe disability. We finally identified this mortality bias in the IMPACT model. CONCLUSIONS: We demonstrated using machine learning-based predictive models that classically used ICU variables are strongly associated with mortality but not with 6-month outcome in survivors with msTBI, leading to a mortality bias when predicting a composite outcome of mortality and severe disability.

Twelve tips for designing and implementing an academic coaching program.

Coaching has become increasingly popular as a mechanism to support learning across the health professions education (HPE) continuum. While there is a growing body of literature in this area, there is minimal guidance related to the design and implementation of academic coaching in health professional courses. This paper seeks to contribute to this literature by presenting guidance for academic developers who are considering introducing academic coaching into a health professional course. The 12 tips are based on the authors' collective experiences of designing and implementing academic coaching in university medical courses in Australia and the UK. Although focused on medical education, this paper is intended to have applicability across the health professions, and potentially across university and postgraduate training contexts. Together, the tips offer a strategic and operational framework to guide the design and implementation of academic coaching initiatives in health professions education.

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.

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 .

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 .

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 .

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.

BACKGROUND: Vision loss secondary to aesthetic filler treatment is a rare but disastrous complication. OBJECTIVES: The aim 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. METHODS: 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 are based on the number of cases with data available. RESULTS: 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%). Stroke-like 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 three most common treatments were subcutaneous hyaluronidase at or near the filler site (70.1%), systemic steroids (57.3%), and intra-arterial thrombolytic therapy (56.0%). No treatments were significantly associated with visual improvement (p > .05). CONCLUSIONS: Although blindness and stroke from fillers is a rare complication, practitioners who inject filler should have a thorough knowledge of prevention and management strategies.

Multidecadal mangrove forest change in Macajalar Bay, Northern Mindanao, Philippines (1950-2020) using remote sensing and geographic information systems.

The mangrove forest in Macajalar Bay is regarded as an important coastal ecosystem since it provides numerous ecosystem services. Despite their importance, the clearing of mangroves has been rampant and has reached critical rates. Addressing this problem and further advancing its conservation require accurate mangrove mapping. However, current spatial information related to mangroves is sparse and insufficient to understand the historical change dynamics. In this study, the synergy of 1950 vegetation maps and Landsat images was explored to provide multidecadal monitoring of mangrove forest change dynamics in Macajalar Bay, Philippines. Vegetation maps containing the 1950 mangrove extent and Landsat images were used as input data to monitor the rates of loss over 70 years. In 2020, the mangrove forest cover was estimated to be 201.73 ha, equivalent to only 61.99% of the 325.43 ha that was estimated in 1950. Between 1950 and 2020, net mangrove loss in Macajalar Bay totaled 324.29 ha. The highest clearing rates occurred between 1950 and 1990 when it recorded a total of 258.51 ha, averaging 6.46 ha/year. The original mangrove forest that existed in 1950 only represents 8.56% of the 2020 extent, suggesting that much of the old-growth mangrove had been cleared before 2000 and the existing mangrove forest is mainly composed of secondary mangrove forest stands. Across Macajalar Bay, intensified clearing that happened between 1950 and 1990 has been driven by large-scale aquaculture developments. Mangrove gains on the other hand were evident and have increased the total extent by 79.84 ha since 2000 as a result of several afforestation programs. However, approximately half of these gains that were observed since 2010 exhibited low canopy cover. As of writing, approximately 85% of the 2020 mangrove forest stands fall outside the 1950 original mangrove extent. Examining the viability of the original mangrove forest for mangrove reforestation together with promoting site-species matching, and biophysical assessment are necessary undertakings to advance current mangrove conservation initiatives in Macajalar Bay.

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.

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.

SARS-CoV-2 DNA Vaccine INO-4800 Induces Durable Immune Responses Capable of Being Boosted in a Phase 1 Open-Label Trial.

BACKGROUND: Additional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines that are safe and effective as primary vaccines and boosters remain urgently needed to combat the coronavirus disease 2019 (COVID-19) pandemic. We describe safety and durability of immune responses following 2 primary doses and a homologous booster dose of an investigational DNA vaccine (INO-4800) targeting full-length spike antigen. METHODS: Three dosage strengths of INO-4800 (0.5 mg, 1.0 mg, and 2.0 mg) were evaluated in 120 age-stratified healthy adults. Intradermal injection of INO-4800 followed by electroporation at 0 and 4 weeks preceded an optional booster 6-10.5 months after the second dose. RESULTS: INO-4800 appeared well tolerated with no treatment-related serious adverse events. Most adverse events were mild and did not increase in frequency with age and subsequent dosing. A durable antibody response was observed 6 months following the second dose; a homologous booster dose significantly increased immune responses. Cytokine-producing T cells and activated CD8+ T cells with lytic potential were significantly increased in the 2.0-mg dose group. CONCLUSIONS: INO-4800 was well tolerated in a 2-dose primary series and homologous booster in all adults, including elderly participants. These results support further development of INO-4800 for use as primary vaccine and booster. CLINICAL TRIALS REGISTRATION: NCT04336410.