"Filler-Associated Acute Stroke Syndrome": Classification, Predictive Modelling of Hyaluronidase Efficacy, and Updated Case Review on Neurological and Visual Complications.

INTRODUCTION: The rising use of soft tissue fillers for aesthetic procedures has seen an increase in complications, including vascular occlusions and neurological symptoms that resemble stroke. This study synthesizes information on central nervous system (CNS) complications post-filler injections and evaluates the effectiveness of hyaluronidase (HYAL) treatment. METHODS: A thorough search of multiple databases, including PubMed, EMBASE, Scopus, Web of Science, Google Scholar, and Cochrane, focused on publications from January 2014 to January 2024. Criteria for inclusion covered reviews and case reports that documented CNS complications related to soft tissue fillers. Advanced statistical and computational techniques, including logistic regression, machine learning, and Bayesian analysis, were utilized to dissect the factors influencing therapeutic outcomes. RESULTS: The analysis integrated findings from 20 reviews and systematic analyses, with 379 cases reported since 2018. Hyaluronic acid (HA) was the most commonly used filler, particularly in nasal region injections. The average age of patients was 38, with a notable increase in case reports in 2020. Initial presentation data revealed that 60.9% of patients experienced no light perception, while ptosis and ophthalmoplegia were present in 54.3 and 42.7% of cases, respectively. The statistical and machine learning analyses did not establish a significant linkage between the HYAL dosage and patient recovery; however, the injection site emerged as a critical determinant. CONCLUSION: The study concludes that HYAL treatment, while vital for managing complications, varies in effectiveness based on the injection site and the timing of administration. The non-Newtonian characteristics of HA fillers may also affect the incidence of complications. The findings advocate for tailored treatment strategies incorporating individual patient variables, emphasizing prompt and precise intervention to mitigate the adverse effects of soft tissue fillers. LEVEL OF EVIDENCE III: 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 ."

A Systematic Review on the Reinforcement Loop in Aesthetic Medicine and Surgery: The Interplay of Social Media, Self-Perception, and Repeat Procedures.

INTRODUCTION: This systematic review delves into the impact of social media on self-perception and the escalating interest in clinical aesthetic procedures, proposing that social media significantly influences beauty standards and increases demand for aesthetic enhancements. METHOD: Following PRISMA guidelines, a mixed-method analysis of 34 articles was conducted, sourced from various databases, focusing on social media's psychological effects on clinical aesthetics decisions. The studies encompassed a broad spectrum, including qualitative, quantitative, and mixed methodologies, reflecting diverse geographical and cultural perspectives. RESULTS: The quantitative analysis demonstrated a strong positive correlation between social media usage and the consideration of aesthetic procedures (r=0.45, p<0.001), indicating a significant impact. Specific findings included a large effect size (Cohen's d=0.8) for the relationship between time spent on social media and the desire for aesthetic enhancements. Individuals spending more than 3 hours per day on social media platforms were twice as likely to consider aesthetic procedures compared to those with less usage, with a 95% confidence interval indicating robustness in these findings. CONCLUSION: Confirming the reinforcing effect of social media on aesthetic decision-making, this study highlights the complex interplay between digital media exposure, altered self-perception, and the increased inclination towards aesthetic procedures. It suggests a critical need for practitioners to carefully navigate the digital influence on patient's desires, reinforcing the significance of understanding psychological motivations and societal pressures in clinical aesthetics. This comprehensive analysis offers pivotal insights for clinical practice and ongoing research into social media's role in contemporary beauty standards. LEVEL OF EVIDENCE III: 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 .

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.

Implementing a Food Prescription Program during COVID-19: Benefits and Barriers.

Food prescription programs (Food Rx) have the potential to improve management of diet-related chronic diseases or underlying conditions such as type 2 diabetes (T2D), hypertension, and high body mass index (BMI) among food-insecure patients. The purpose of this study was to examine the effectiveness of a Food Rx program implemented in two community-based clinics in Florida. Data were collected through researcher-administered surveys (food insecurity, demographics, and socio-economic variables) and biometric data (HbA1c, blood pressure, and BMI). Key results include the following: (1) Hispanic patients are more likely to utilize the program than their Black and White counterparts (p < 0.001); (2) older patients (≥50 years) have a higher food redemption rate when compared to younger patients (36-49.9 years); (3) food redemption rate is negatively associated with food security scores indicating improvements in food security status over time (r2 = -0.184, p = 0.036); (4) diabetic patients with higher baseline HbA1c (>9%) have significant reductions in glycated hemoglobin (p = 0.011) over time as compared to patients with lower baseline values (<7%); and (5) patients enrolled in the program for at least 6 months have a significant reduction in systolic blood pressure (p = 0.051). Changes in BMI were not significantly associated with redemption rates. This study is significant as it offers insights into the potential benefits and challenges of implementing Food Rx programs to address diet-related chronic diseases among underserved populations.

Developing Consensus-Based Guidelines for Case Reporting in Aesthetic Medicine: Enhancing Transparency and Standardization.

Clinical case reporting plays a vital role in sharing detailed patient narratives, providing insights into rare conditions, innovative treatments, and unexpected outcomes. However, existing reporting guidelines in aesthetic medicine fail to capture the specific nuances of procedures and outcomes in this field. The authors' objectives were to develop comprehensive guidelines for Case REporting in Aesthetic Medicine (CREAM). The study employed a 3-phase consensus process, including a literature review, expert interviews, and a consensus meeting. A diverse group of 10 expert participants (plastic surgeons, dermatologists, noncore specialists, evidence-based medicine expert, and research scientist) in Phase I and 30 experienced aesthetic practitioners in Phase II contributed to the research. Statistical analysis was conducted to assess agreement levels among participants and explore associations and variations within the data. The participants represented various specialties, genders, LGBTQ+ identities, and ethnic backgrounds. The research resulted in the development of the CREAM guidelines, consisting of a 16-item checklist. The guidelines covered essential aspects of case reporting, such as patient and practice information, procedure details, clinical assessment and outcomes, adverse events, and ethical considerations. Statistical analysis indicated a high level of consensus among participants, as well as significant associations between checklist items. CREAM guidelines represent a step toward enhancing transparency and standardization in case reporting in aesthetic medicine. Adhering to these guidelines will allow authors to contribute to a robust evidence base, prioritize patient safety, and drive advancements aesthetic medicine.

Prebiotic Synthesis of Aspartate Using Life's Metabolism as a Guide.

A protometabolic approach to the origins of life assumes that the conserved biochemistry of metabolism has direct continuity with prebiotic chemistry. One of the most important amino acids in modern biology is aspartic acid, serving as a nodal metabolite for the synthesis of many other essential biomolecules. Aspartate's prebiotic synthesis is complicated by the instability of its precursor, oxaloacetate. In this paper, we show that the use of the biologically relevant cofactor pyridoxamine, supported by metal ion catalysis, is sufficiently fast to offset oxaloacetate's degradation. Cu2+-catalysed transamination of oxaloacetate by pyridoxamine achieves around a 5% yield within 1 h, and can operate across a broad range of pH, temperature, and pressure. In addition, the synthesis of the downstream product ß-alanine may also take place in the same reaction system at very low yields, directly mimicking an archaeal synthesis route. Amino group transfer supported by pyridoxal is shown to take place from aspartate to alanine, but the reverse reaction (alanine to aspartate) shows a poor yield. Overall, our results show that the nodal metabolite aspartate and related amino acids can indeed be synthesised via protometabolic pathways that foreshadow modern metabolism in the presence of the simple cofactor pyridoxamine and metal ions.

Single vs replicate Real-Time PCR SARS-CoV-2 testing: Lessons learned for effective pandemic management.

Coronavirus Disease 19 (COVID-19) caused by the SARS-CoV-2 virus remains a global pandemic having a serious impact on national economies and healthcare infrastructure. Accurate infection detection protocols are key to policy guidance and decision making. In this pilot study, we compared single versus replicate PCR testing for effective and accurate SARS-CoV-2 infection detection. One-Step Real-Time RT-PCR was employed for the detection of SARS-CoV-2 RNA isolated from individual nasopharyngeal swabs. A total of 10,014 swabs, sampled from the general public (hospital admissions, A&E, elective surgeries, cancer patients, care home residents and healthcare staff), were tested using standard replicate testing. Our analysis demonstrates that approximately 19% of SARS-CoV-2 infected individuals would have been reported as false negative if single sample Real-Time PCR testing was used. Therefore, two replicate tests can substantially decrease the risk of false negative reporting and reduce hospital and community infection rates. As the number of variants of concern increases, we believe that replicate testing is an essential consideration for effective SARS-CoV-2 infection detection and prevention of further outbreaks. A strategic approach limiting the number of missed infections is crucial in controlling the rise of new SARS-CoV-2 variants as well as the management of future pandemics.

Is there a role for stem cell therapy in erectile dysfunction secondary to cavernous nerve injury? Network meta-analysis from animal studies and human trials.

Introduction: We carried out systematic review and network meta-analysis to investigate the role of stem cell therapy (SCT) in the management of erectile dysfunction (ED) secondary to cavernous nerve injury in rats and post-radical prostatectomy (RP) in humans. Patients and Methods: The protocol was registered with PROSPERO database. We searched studies analyzing the efficacy of SCT for ED due to bilateral cavernous nerve injury (BCNI) in rats using Healthcare Databases Advanced Search (HDAS) Export software (MEDLINE, EMBASE, Scopus) from inception to September 2020. The outcome measurements, for 29 animal studies, were intracavernosal pressure (ICP), ICP/MAP (mean arterial pressure) ratio, and histological/molecular changes. All three available human trials evaluating SCT in post-RP ED were assessed for International Index for Erectile Function (IIEF) Score and Erection Hardness Score (EHS). Results: For ICP measurement, animal studies were divided into adipose-derived stem cells (ADSCs) subgroup and bone marrow-derived stem cells (BMSCs) subgroup. Pooled analysis of these studies showed a beneficial effect of SCT in improving erectile function in rats with BCNI using network meta-analysis (95% confidence interval, CI; p < 0.001). There was an increase in ICP/MAP ratio in stem cell groups (including co-intervention) compared with control BCNI group. Histological and molecular evaluation of penile tissue revealed an increase in neuronal nitric oxide synthase (nNOS), smooth muscle content, and anti-apoptotic activity. Human trials revealed improved IIEF (70-150% from baseline at 6 months) and EHS (80-200% from baseline). Conclusion: Our results confirm that SCT does improve the erectile function in rats having cavernous nerve injury. Similarly, early human results have shown promising results. PROSPERO registration ID: CRD42020201343.

Auricular reconstruction: where are we now? A critical literature review.

PURPOSE: Deformities of the external ear can affect psychosocial well-being and hearing. Current gold-standard reconstructive treatment is autologous costal cartilage grafting despite the vast morbidity profile. Tissue engineering using stem cells and 3D printing can create patient-specific reconstructed auricles with superior cosmetic outcomes and reduced morbidity. This review critically analyses recent and breakthrough research in the field of regenerative medicine for the pinna, considering gaps in current literature and suggesting further steps to identify whether this could be the new gold-standard. METHODS: A literature review was conducted. PubMed (MEDLINE) and Cochrane databases were searched using key terms regenerative medicine, tissue engineering, 3D printing, biofabrication, auricular reconstruction, auricular cartilage, chondrocyte, outer ear and pinna. Studies in which tissue-engineered auricles were implanted into animal or human subjects were included. Exclusion criteria included articles not in English and not published within the last ten years. Titles, abstracts and full texts were screened. Reference searching was conducted and significant breakthrough studies included. RESULTS: 8 studies, 6 animal and 2 human, were selected for inclusion. Strengths and weaknesses of each are discussed. Common limitations include a lack of human studies, small sample sizes and short follow-up times. CONCLUSION: Regenerative medicine holds significant potential to improve auricular reconstruction. To date there are no large multi-centred human studies in which tissue-engineered auricles have been implanted. However, recent human studies suggest promising results, raising the ever-growing possibility that tissue engineering is the future of auricular reconstruction. We aim to continue developing knowledge in this field.

Ubiquitination of Histone H2B by Proteasome Subunit RPT6 Controls Histone Methylation Chromatin Dynamics During Memory Formation.

BACKGROUND: Posttranslational histone modifications play a critical role in the regulation of gene transcription underlying synaptic plasticity and memory formation. One such epigenetic change is histone ubiquitination, a process that is mediated by the ubiquitin-proteasome system in a manner similar to that by which proteins are normally targeted for degradation. However, histone ubiquitination mechanisms are poorly understood in the brain and in learning. In this article, we describe a new role for the ubiquitin-proteasome system in histone crosstalk, showing that learning-induced monoubiquitination of histone H2B (H2Bubi) is required for increases in the transcriptionally active H3 lysine 4 trimethylation (H3K4me3) mark at learning-related genes in the hippocampus. METHODS: Using a series of molecular, biochemical, electrophysiological, and behavioral experiments, we interrogated the effects of short interfering RNA-mediated knockdown and CRISPR (clustered regularly interspaced short palindromic repeats)-mediated upregulation of ubiquitin ligases, deubiquitinating enzymes and histone methyltransferases in the rat dorsal hippocampus during memory consolidation. RESULTS: We show that H2Bubi recruits H3K4me3 through a process that is dependent on the 19S proteasome subunit RPT6 and that a loss of H2Bubi in the hippocampus prevents learning-induced increases in H3K4me3, gene transcription, synaptic plasticity, and memory formation. Furthermore, we show that CRISPR-dCas9-mediated increases in H2Bubi promote H3K4me3 and memory formation under weak training conditions and that promoting histone methylation does not rescue memory impairments resulting from loss of H2Bubi. CONCLUSIONS: These results suggest that H2B ubiquitination regulates histone crosstalk in learning by way of nonproteolytic proteasome function, demonstrating a novel mechanism by which histone modifications are coordinated in response to learning.

Update on the role of emerging stem cell technology in head and neck medicine.

Head and neck surgery is a broad discipline that involves the management of complex conditions such as burns, skin cancer, head and neck cancer, congenital abnormalities, and facial rejuvenation. For patients with cancer, surgery, radiotherapy, and chemotherapy are often the main modes of treatment. Many patients require follow-up reconstructive surgery, and the use of stem cells offers novel treatments that could aid recovery. Laryngeal, tracheal, and neuronal tissues are frequently damaged by surgery in the head and neck and these tissues have little intrinsic regenerative ability. Pluripotent embryonic stem cells retain the ability to differentiate into a wide variety of cells meaning that large tissue defects can be reduced by stimulating new cell growth. Research has demonstrated potential benefits of using stem cells in facial rejuvenation procedures and the management of burns sequelae. The advancements made in the use of adult progenitor stem cells as a possible source for pluripotent stem cells (induced pluripotent stem cells) mean that ethical considerations around the use of embryological tissue can be minimized, allowing for more research to take place. Currently, the evidence base for the use of stem cells in head and neck surgery is limited, but it has now been proven that stem cells can act as a source for lost or damaged tissue in the head and neck. With continuous advancements being made in the fields of tissue engineering, it is likely that stem cells will play a major role in head and neck surgery in the future.

The Significance of Metal Coordination in Imidazole-Functionalized Metal-Organic Frameworks for Carbon Dioxide Utilization.

The grafting of imidazole species onto coordinatively unsaturated sites within metal-organic framework MIL-101(Cr) enables enhanced CO2 capture in close proximity to catalytic sites. The subsequent combination of CO2 and epoxide binding sites, as shown through theoretical findings, significantly improves the rate of cyclic carbonate formation, producing a highly active CO2 utilization catalyst. An array of spectroscopic investigations, in combination with theoretical calculations reveal the nature of the active sites and associated catalytic mechanism which validates the careful design of the hybrid MIL-101(Cr).

The SETD6 Methyltransferase Plays an Essential Role in Hippocampus-Dependent Memory Formation.

BACKGROUND: Epigenetic mechanisms are critical for hippocampus-dependent memory formation. Building on previous studies that implicate the N-lysine methyltransferase SETD6 in the activation of nuclear factor-κB RELA (also known as transcription factor p65) as an epigenetic recruiter, we hypothesized that SETD6 is a key player in the epigenetic control of long-term memory. METHODS: Using a series of molecular, biochemical, imaging, electrophysiological, and behavioral experiments, we interrogated the effects of short interfering RNA-mediated knockdown of Setd6 in the rat dorsal hippocampus during memory consolidation. RESULTS: Our findings demonstrate that SETD6 is necessary for memory-related nuclear factor-κB RELA methylation at lysine 310 and associated increases in H3K9me2 (histone H3 lysine 9 dimethylation) in the dorsal hippocampus and that SETD6 knockdown interferes with memory consolidation, alters gene expression patterns, and disrupts spine morphology. CONCLUSIONS: Together, these findings suggest that SETD6 plays a critical role in memory formation and may act as an upstream initiator of H3K9me2 changes in the hippocampus during memory consolidation.

The Unexamined Calling.

Philosophy and philosophical assumptions are crucial to our work as physicians and investigators; however, training in philosophy remains poorly represented among medical students and their educators. In this brief essay, I argue the case that philosophical assumptions concerning knowledge and the scientific method are relevant for medical practice and research, concluding with a call for greater attention to philosophy in pre-medical and medical education.

PGRMC2 is an intracellular haem chaperone critical for adipocyte function.

Haem is an essential prosthetic group of numerous proteins and a central signalling molecule in many physiologic processes1,2. The chemical reactivity of haem means that a network of intracellular chaperone proteins is required to avert the cytotoxic effects of free haem, but the constituents of such trafficking pathways are unknown3,4. Haem synthesis is completed in mitochondria, with ferrochelatase adding iron to protoporphyrin IX. How this vital but highly reactive metabolite is delivered from mitochondria to haemoproteins throughout the cell remains poorly defined3,4. Here we show that progesterone receptor membrane component 2 (PGRMC2) is required for delivery of labile, or signalling haem, to the nucleus. Deletion of PGMRC2 in brown fat, which has a high demand for haem, reduced labile haem in the nucleus and increased stability of the haem-responsive transcriptional repressors Rev-Erbα and BACH1. Ensuing alterations in gene expression caused severe mitochondrial defects that rendered adipose-specific PGRMC2-null mice unable to activate adaptive thermogenesis and prone to greater metabolic deterioration when fed a high-fat diet. By contrast, obese-diabetic mice treated with a small-molecule PGRMC2 activator showed substantial improvement of diabetic features. These studies uncover a role for PGRMC2 in intracellular haem transport, reveal the influence of adipose tissue haem dynamics on physiology and suggest that modulation of PGRMC2 may revert obesity-linked defects in adipocytes.

O-GlcNAc and EZH2-mediated epigenetic regulation of gene expression during consolidation of fear memories.

O-GlcNAcylation of serine/threonine residues on target proteins occurs dynamically in postmitotic neurons of the hippocampus and may serve to control both the stability and activity of target proteins. Remarkably, the addition and removal of the O-GlcNAc posttranslational modifications are catalyzed by a pair of enzymes, the O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). More than thousands of proteins are modified by O-GlcNAcylation including epigenetic modifying enzymes. A critical target of OGT is the polycomb repressive complex 2 (PRC2) containing the histone lysine methyltransferase EZH2 that mediates trimethylation of lysine 27 on histone H3 (H3K27me3). However, whether OGT and PRC2 activity in the hippocampus couple to regulate gene transcription mechanisms during memory consolidation remains unknown. Here, we found increases in OGT expression and global O-GlcNAcylation levels in dorsal area CA1 of the hippocampus during memory consolidation. Additionally, we observed that OGT exerts control over epigenetic regulation via EZH2-H3K27me3 during memory consolidation. Blocking O-GlcNAc signaling via RNAi within dorsal area CA1 led to the global and site-specific loss of activity-dependent epigenetic plasticity at genes regulated by H3K27me3 and impairment of hippocampus-dependent memory. Together, these findings illustrate a unique epigenetic role of OGT via regulation of histone methylation mediated by EZH2 during memory consolidation of fear conditioned memories.