Ultrasonographic Study of the Submandibular Gland for Botulinum Neurotoxin Injection.

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

Exploring facial overfilled syndrome from the perspective of anatomy and the mismatched delivery of fillers.

INTRODUCTION: Facial fillers and injectables have transformed the landscape of cosmetic procedures, offering rejuvenation possibilities. However, the emergence of "Facial Overfilled Syndrome (FOS)" presents a concerning trend attributed to excessive filler use and suboptimal injection techniques. Understanding the interplay between facial aging and augmentation techniques is crucial in addressing and preventing FOS. MATERIAL AND METHODS: Facial overfilled syndrome is characterized by the excessive use of fillers, resulting in a distorted and heavy appearance. It manifests in various forms, including 'flowerhorn' foreheads, 'sunset' eyes, 'chipmunk' cheeks, 'witch' chins, and 'pillow' faces. The syndrome arises from attempts to combat anatomical aging with dramatic filler treatments, causing rapid volume changes and skin tightening. Skeletal structures and soft tissue distribution across different ethnicities play a significant role in FOS development. RESULTS: Understanding the aging process across facial tissues is essential, as fillers cannot entirely reverse aging manifestations. Tailored assessment and treatment plans should precede filler injections, involving muscle assessment, observation of facial movements during injection, and ultrasound imaging of fat layers. Attention should be given to filler pressure and migration risks, particularly in areas with elevated pressure. Additionally, alternative approaches like energy-based devices and polymer reinforcement of facial ligaments should be considered to minimize filler use. Ethnic variations in facial anatomy require careful consideration to avoid overcorrection. CONCLUSION: FOS predominantly affects individuals of East Asian descent due to specific facial characteristics. Prevention strategies involve minimizing filler use, addressing underlying bone changes, and considering ethnic and gender differences in facial anatomy. Recent MRI and ultrasound studies challenge the notion of filler breakdown, emphasizing the importance of filler selection and injection techniques. Education, individualized treatments, and a holistic understanding of facial anatomy are key to preventing and managing FOS and ensuring natural and harmonious facial aesthetics.

Polynucleotides HPT for Asian Skin Regeneration and Rejuvenation.

Introduction: Even lightly compromised skin may impact self-esteem and social behaviour. After intradermal infiltration, natural-origin Polynucleotides High Purification Technology (PN HPT) promote new collagen and extracellular matrix production, translating into a physiological correction of the ageing skin. The study aimed to explore the benefits of intradermal PN HPT on the four perceptual skin quality categories "Skin Tone Evenness", "Skin Surface Evenness", "Skin Firmness", and "Skin Glow" in a representative sample of 30 Asian subjects (mean age 40.2± 11.4 years old). Methods: Study protocol: three intradermal injections of a PN HPT-based Class III CE-marked medical device at T0 (baseline assessment and first treatment session), T1 (four weeks after baseline), and T2 (eight weeks after baseline), with efficacy and safety evaluations at T1, T2, T3 (four months after baseline) and T4 (six months after baseline). Quantitative and qualitative assessments: 3D skin analysis system QuantifiCare and Global Aesthetic Improvement Scale (GAIS, Investigator and Patient subscales). Results: PN HPT treatment led to a meaningful and statistically significant improvement of the skin surface, firmness, pigmentation, and radiance, with no early- or late-onset adverse events and benefits persisting up to the sixth-month visit in all subjects. At T4, 33% and 43% of treated subjects felt "Much Improved" and "Very Much Improved" (optimal result); 56% and 44% of treated subjects felt "Satisfied" or "Very Satisfied". At T4, the mean Investigator GAIS scores were 3.33 out of 5.0 for the "Skin Tone Evenness" skin quality perceptual category, 3.46 for the "Skin Surface Evenness" category, 3.61 for "Skin Firmness", and 3.45 per for the radiance determinant of the "Skin Glow" category. Conclusion: Intradermal treatment with the PN HPT-based medical device led to a meaningful improvement of the skin surface, firmness, pigmentation, and radiance with complete safety. The aesthetic benefits persisted up to the sixth-month visit in all subjects.

Observation on cadavers and through ultrasonography using a 2 mm needle length for intradermal injections.

BACKGROUND: An intradermal injection is a medical procedure that involves administering a small amount of medication or substance into the dermal layer of the skin. This research focused on identifying the most suitable injection needle for precise intradermal administration of skin boosters. METHODS: The study involved conducting intradermal injections on four cadavers and participants using a 2 mm length, 34-gauge needle (N-Finders, Inc., South Korea). During the cadaveric study, the polynucleotide prefilled syringe was dyed green, and an anatomist performed dissections, removing only the skin layer. Ultrasonographic observations were carried out to ensure accurate intradermal injection placement. RESULTS: In all four cadavers, the facial injections at the anterior cheek region were precisely administered intradermally at a 30-degree injection angle. However, the 90-degree injection was found just below the dermal layer upon skin layer removal. DISCUSSION: The findings suggest that using a 2 mm needle length allows for easy and convenient intradermal injections.

Development and Validation of a Targeted Treatment for Brain Tumors Using a Multi-Drug Loaded, Relapse-Resistant Polymeric Theranostic.

This study aimed to develop a multifunctional polymer platform that could address the issue of treatment resistance when using conventional chemotherapeutics to treat glioblastoma (GBM). An antibody-conjugated, multi-drug loaded hyperbranched polymer was developed that provided a platform to evaluate the role of targeted nanomedicine treatments in overcoming resistant GBM by addressing the various complications with current clinically administered formulations. The polymer was synthesized via reversible addition fragmentation chain transfer polymerization and included the clinical first-line alkylating agent temozolomide (TMZ) which was incorporated as a polymerizable monomer, poly (ethylene glycol) (PEG) units to impart biocompatibility and enable conjugation with αPEG-αEphA2 bispecific antibody (αEphA2 BsAb) for tumor targeting, and hydrazide moieties for attachment of a secondary drug which allows exploration of synergistic therapies. To overcome the resistance to TMZ, the O6 alkylguanine DNA alkyltransferase (AGT, DNA repair protein) inhibitor, dialdehyde O6 benzylguanine (DABG) was subsequently conjugated to the polymer via an acid labile hydrazone linker to facilitate controlled release under conditions encountered within the tumor microenvironment. The prolonged degradation half-life (4-5 h) of the polymer conjugated TMZ in vitro offered a potential avenue to overcome the inability to deliver these drugs in combination at therapeutic doses. Although only 20% of DABG could be released within the studied timeframe (192 h) under conditions mimicking the acidic nature of the tumor environment, cytotoxicity evaluation using cell assays confirmed the improved therapeutic efficacy toward resistant GBM cells after attaching DABG to the polymer delivery vehicle. Of note, when the polymeric delivery vehicle was specifically targeted to receptors (Ephrin A2) on the surface of the GBM cells using our in-house developed EphA2 specific BsAb, the dual-drug-loaded polymer exhibited an improved therapeutic effect on TMZ-resistant cells compared to the free drug combination. Both in vitro and in vivo targeting studies showed high uptake of the construct to GBM tumors with an upregulated EphA2 receptor (T98G and U251) compared to a tumor that had low expression (U87MG), where a dual tumor xenograft model was used to demonstrate the enhanced accumulation in tumor tissue in vivo. Despite the synthetic challenges of developing systems to effectively deliver controlled doses of TMZ and DABG, these studies highlight the potential benefit of this formulation for delivering multi-drug combinations to resistant GBM tumor cells and offer a platform for future optimization in therapeutic studies.

Implementing leading practices in regional-level primary care workforce planning: Lessons learned in Toronto.

Investment in capacity for implementation of leading practices in regional-level health workforce planning is essential to support equitable distribution of resources and deployment of a health workforce that can meet local needs. Ontario Health Toronto and the Canadian Health Workforce Network (CHWN) co-developed and operationalized an integrated workforce planning process to support evidence-based primary care workforce decision-making for the Toronto region. The resultant planning toolkit incorporates planning processes centred around engagement with stakeholders, including environmental scanning tools and a quantitative planning model. The outputs of the planning process include estimates of population need and workforce capacity and address challenges specific to Toronto, such as patient mobility, anticipated rapid population growth, and physician retirement. We highlight important challenges and key considerations in the development and operationalization of workforce planning processes, particularly at the regional level.

Insights on Skin Quality and Clinical Practice Trends in Asia Pacific and a Practical Guide to Good Skin Quality from the Inside Out.

Objective: We sought to examine the current skin quality trends and gaps in clinical practice in the Asia Pacific region and develop a practical guide to improve skin quality. Methods: Medical practitioners from 11 countries in the Asia Pacific region completed an online survey on current trends in skin quality treatment. A panel of 12 leading experts convened for a virtual meeting to develop a practical guide for skin quality improvement. Results: A total of 153 practitioners completed the survey. The four most common skin quality issues were uneven skin tone, skin surface unevenness, skin laxity, and sebaceous gland hyperactivity and enlarged pores. Most practitioners reported using a combination of treatment modalities for each skin quality issue. It was also observed that each treatment modality could be used to treat several skin quality issues. A multimodal approach targeting different interrelated issues across the tissue planes was recommended for balanced results. The panel developed a practical guide for the appropriate combinations and sequence of treatments, and created treatment protocols for specific skin quality outcome goals. The guide employed an "inside-out" approach, treating the deeper tissue planes prior to the superficial layers to achieve harmonious results. Limitations: Future studies are needed to support the recommended treatment protocols for skin quality improvement. Conclusion: These findings provide valuable insights on current skin quality trends and gaps in clinical practice. The practical guide provides a framework for practitioners to customize their treatment plan according to each patient's needs.

Current Practices in Hyaluronic Acid Dermal Filler Treatment in Asia Pacific and Practical Approaches to Achieving Safe and Natural-Looking Results.

Complications such as delayed inflammatory reactions (DIRs) and unnatural outcomes can sometimes arise from hyaluronic acid (HA) dermal filler treatments and can be challenging to address. Given the popularity of HA dermal fillers for aesthetic procedures, there is a need for preventive strategies to minimize these complications. Two hundred practitioners from 10 regions in Asia Pacific who administer HA fillers completed a survey on prevention of DIRs and unnatural outcomes. Thirteen global experts convened to evaluate the current practices and propose practical approaches for safe and appropriate use of HA dermal fillers. From the survey, the top three measures used to reduce the risk of DIRs included choosing an appropriate HA filler, aseptic technique, and patient selection. Key strategies employed to achieve natural-looking outcomes were treatment customization, understanding the rheological properties and behavior of different HA fillers, and being conservative in treatment approach. The panel developed a concise reference guide aimed at minimizing the risk of DIRs while achieving natural aesthetic outcomes. Five practical considerations were recommended: patient assessment and individualization of treatment plan, choice of an appropriate HA filler, adequate knowledge of facial anatomy, strict adherence to aseptic methods, and proper injection technique. The panel highlighted the need for education efforts to increase awareness of differential immunogenicity between HA fillers and to improve understanding on the importance of preserving aesthetic individuality for optimal results. These practical insights from the global experts support practitioners in optimizing safety and quality of aesthetic treatment with HA fillers.

A review of combined treatments for melasma involving energy-based devices and proposed pathogenesis-oriented combinations.

BACKGROUND: Melasma is an acquired disorder of hyperpigmentation, affecting a million individuals worldwide. Energy-based devices (EBDs) employed to treat melasma include various types of lasers, intense pulsed light (IPL), and radiofrequency (RF). Recent studies have attempted to address recalcitrant and recurring melasma by combining energy-based devices with topical or oral medications. OBJECTIVE: This article reviews EBDs-based augmented treatment for melasma and suggests practical pathogenesis-oriented treatment regimens. Treatment algorithms are proposed to address various components of melasma. METHODS: A systematic PubMed search was conducted acquiring information from various studies on combination treatments of melasma involving EBDs. RESULTS: The 286 retrieved articles were filtered by title to contain at least one type of energy-based modality such as laser, IPL, or RF along with at least one other treatment method. Based on their subject matter, combinations were further categorized into the subheadings: laser plus medication, laser plus laser, and IPL- and RF-containing treatment methods. CONCLUSION: There are many energy-based combination treatments that have been explored for mitigation of melasma including laser therapy with medication, multi-laser therapies, IPL, RF, and microneedling devices. Melasma is an exceedingly difficult condition to treat, however, choosing the appropriate tailor-made treatment combination can improve the final outcome.

The aryl hydrocarbon receptor: A diagnostic and therapeutic target in glioma.

Glioblastoma multiforme (GBM) is a deadly disease; 5-year survival rates have shown little improvement over the past 30 years. In vivo positron emission tomography (PET) imaging is an important method of identifying potential diagnostic and therapeutic molecular targets non-invasively. The aryl hydrocarbon receptor (AhR) is a transcription factor that regulates multiple genes involved in immune response modulation and tumorigenesis. The AhR is an attractive potential drug target and studies have shown that its activation by small molecules can modulate innate and adaptive immunity beneficially and prevent AhR-mediated tumour promotion in several cancer types. In this review, we provide an overview of the role of the AhR in glioma tumorigenesis and highlight its potential as an emerging biomarker for glioma therapies targeting the tumour immune response and PET diagnostics.

Pan-Asian Consensus on Calcium Hydroxyapatite for Skin Biostimulation, Contouring, and Combination Treatments.

BACKGROUND: Several usage guidelines for calcium hydroxylapatite (CaHA), a dermal filler material, exist for non-Asian patients, making it necessary to determine whether their findings and consensuses are applicable to Asian patients who have distinct anatomies, cultural preferences, and aesthetic requests. OBJECTIVE: We sought to develop a Pan-Asian consensus on CaHA use in skin biostimulation, contouring, and combination treatments for face and body indications. METHODS: A survey on CaHA usage for contouring and biostimulation indications in Asian patients was conducted, followed by discussions to establish consensus statements and topics for examination. RESULTS: Several aspects of facial shaping and contouring or skin biostimulation with CaHA were agreed on, including that dilution is not a key consideration, that microfocused ultrasound with visualisation precedes CaHA in same day or session treatments, and that cannulas should be used. Among the many agreements on interventions in specific facial and body areas, there were also disagreements due to the diverse Asian patient presentations, requests, and access to tools or products; for example, CaHA should be placed in the interfascial layer for temple contouring, CaHA should not be injected directly into the infraorbital area for safety, and diluted CaHA should be injected subdermally for nonfacial or whole-face biostimulation and contouring. CONCLUSION: Our disagreements highlight the diversity of Asian facial morphotypes and desired aesthetic outcomes and underscore the need for customized aesthetic strategies to accommodate the heterogeneity of Asian anatomies, cultural preferences, and aesthetic ideals. Establishing consensus statements on critical aspects of Asian patient considerations, efficacy and safety, is crucial. This document provides strategic guidance on the use of classic, diluted CaHA for biostimulation or undiluted Radiesse®(+) (Merz Pharma GmbH & Co. KGaA, Frankfurt, Germany) for lifting and contouring to ensure consistent CaHA delivery for successful patient outcomes.

Consensus on the Use of Hyaluronic Acid Fillers from the Cohesive Polydensified Matrix Range: Best Practice in Specific Facial Indications.

BACKGROUND: As the treatment indications for the Cohesive Polydensified Matrix® hyaluronic acid (CPM-HA) portfolio continue to expand and diversify, injectors new to the range or those who are expanding the treatments they offer may be unsure of the optimal product and injection technique for specific facial areas. Each product in the CPM-HA portfolio has been intentionally designed to provide the best physical properties for a specific indication and target tissue. This document has been developed to provide a comprehensive, one-stop reference for clinicians using the portfolio. METHODS: An international panel of experts in the field of aesthetic medicine convened to develop guidelines on effective and safe injection technique when performing treatments with the CPM-HA range of soft-tissue fillers. RESULTS: Consensus members considered treatment indications in the upper, middle and lower face. Landmark deficiencies and anatomical considerations are described for each indication and consensus recommendations provided on the optimal product, injection depth and treatment technique. This is supplemented by the experts advice on avoidance of complications. Throughout, an evidence-based approach to selection of products and injection techniques is provided. The result is a fully tailored approach to a range of indications covering the full portfolio of CPM-HA products, including the newest addition for skin revitalization. CONCLUSION: The recommendations in this consensus document are provided to assist clinicians in the selection of CPM-HA products, administration techniques and depths of injection with the aim of providing seamless and natural treatment results, enhanced safety and patient satisfaction.

Synthesis, isolation and characterisation of fluorinated-benzimidazoisoquinoline regioisomers.

A pair of novel fluorinated-benzimidazoisoquinoline regioisomers was synthesised and isolated. Initial structural characterisation and identification employed 1D proton, 1D carbon, correlated spectroscopy (COSY), heteronuclear single quantum coherence (HSQC), and heteronuclear multiple bond correlation (HMBC) nuclear magnetic resonance spectroscopy and mass spectrometry. However, the fluorinated regioisomers could not be differentiated using nuclear magnetic resonance (NMR) alone. Density functional theory calculations and single-crystal X-ray diffraction experiments were used to completely characterise and identify the compounds.

Conductive polypyrrole-encapsulated silk fibroin fibers for cardiac tissue engineering.

Polypyrrole (PPy) has been utilized in smart scaffolds to improve the functionality of the engineered cardiac tissue. Compared to the commonly used aqueous coating, here, PPy was blended into silk fibroin (SF) solution to electrospin conductive PPy-encapsulated SF nanofibers. Combinations of various SF concentrations (5%, 7%, and 12%) and different PPy-to-SF ratios (15:85, 30:70, and 40:60) were compared. PPy reduced the fiber diameter (0.431 ± 0.060 µm), better-mimicking the myocardium fibrils. Conductive mats with 7% SF showed the closest mechanical properties (1.437 ± 0.044 MPa) to the native myocardium; meanwhile, a PPy-to-SF ratio of 15:85 exhibited sufficient electrical conductivity for cardiomyocytes (CMs). In vitro studies using three different types of CM demonstrated that the hybrid mats support CM contraction. Primary neonatal rat CMs on the mat with a PPy-to-SF ratio of 15:85 were elongated and orientated anisotropically with locally organized sarcomeric striations. By contrast, human-induced pluripotent stem cell derived-CMs on the mat with a PPy-to-SF ratio of 30:70 exhibited the strongest contractions. Contraction synchrony was further improved by external stimulation. Taken together, these findings indicated the great potential of the PPy-encapsulated SF electrospun mat for cardiac tissue engineering.

Customized Treatment Using Microfocused Ultrasound with Visualization for Optimized Patient Outcomes: A Review of Skin-tightening Energy Technologies and a Pan-Asian Adaptation of the Expert Panel's Gold Standard Consensus.

BACKGROUND: Noninvasive facial-rejuvenation devices, such as nonablative radiofrequency (RF) and laser-assisted technology, are increasingly replacing higher-risk surgeries for face and body skin laxity. OBJECTIVE: We sought to review published information on noninvasive energy device safety and efficacy in aesthetic skin tightening, compare these with our experiences in Asian patients, and disseminate a consensus for optimizing microfocused ultrasound with visualization (MFU-V) in Asian patients. METHODS: A broad, nonexhaustive, nonsystematic literature search of published studies indexed in PubMed was performed to compare selected energy technologies to MFU-V for noninvasive face and body skin tightening, in particular, among Asian patients. This was supplemented with internal documents to provide evidence and support arguments if no peer-reviewed data were available. RESULTS: We highlighted the differences between devices and platforms and identified factors requiring attention and caution. Due to the increase in new devices lacking strong supporting clinical evidence of both safety and efficacy in Asia, it is necessary to convene physicians with substantial experience in MFU-V and devise a consensus on Asian patient selection, treatment planning, and customization. CONCLUSION: Many platforms duplicate or claim similar technologies, efficacy, or safety without significant peer-reviewed scientific or clinical evidence. We showed that MFU-V satisfies this clinical imperative. Further, the patented DeepSEE® technology allows users to noninvasively "see" through the skin to ensure treatment precision, facilitate optimal skin lifting and tightening, and enhance patient comfort and safety. Therefore, we believe that MFU-V is the gold standard for nonsurgical lifting and skin tightening.

Skin Quality - A Holistic 360° View: Consensus Results.

INTRODUCTION: Skin quality is an important component of human attractiveness. To date, there are no standardized criteria for good skin quality. To establish a consensus for good skin quality parameters and measurement and treatment options, a virtual skin quality advisory board consisting of a global panel of highly experienced aesthetic dermatologists/aesthetic physicians was convened. METHODS: A total of 10 dermatologists/aesthetic physicians served on the advisory board. A modified version of the Delphi method was used to arrive at consensus. Members accessed an online platform to review statements on skin quality criteria from their peers, including treatment and measurement options, and voted to indicate whether they agreed or disagreed. Statements that did not have agreement were modified and the members voted again. Consensus was defined as: strong consensus = greater than 95% agreement; consensus = 75% to 95% agreement; majority consent = 50% to 75% agreement; no consensus = less than 50% agreement. RESULTS: There was strong consensus that good skin quality is defined as healthy, youthful in appearance (appearing younger than a person's chronological age), undamaged skin and that skin quality can be described across all ethnicities by four emergent perceptual categories (EPCs): skin tone evenness, skin surface evenness, skin firmness, and skin glow. The EPCs can be affected by multiple tissue layers (ie, skin surface quality can stem from and be impacted by deep structures or tissues). This means that topical approaches may not be sufficient. Instead, improving skin quality EPCs can require a multilayer treatment strategy. CONCLUSION: This global advisory board established strong consensus that skin quality can be described by four EPCs, which can help clinicians determine the appropriate treatment option(s) and the tissue or skin layer(s) to address. Skin quality is important to human health and wellbeing and patients' perception for the need for aesthetic treatment.

A New Simplified Visual Assessment Tool Describing Facial Morphotypes Observed and Desired in Asian Populations.

OBJECTIVE: A group of established aesthetic physicians sought to develop treatment guidelines for assessing Asian face morphologies that reflect accurate and current beauty standards across Asia. DESIGN: Physicians completed surveys, debated, and voted on their clinical strategies and developed an alternative simplified visual tool of assessment (SVAT) that discerns between country variations in genetic and ideal morphotypes. SETTING: Electronic and paper surveys were followed by consensus debates and voting. PARTICIPANTS: Established aesthetic physicians practicing regularly on Asian patients. MEAUSUREMENTS: A clinically applicable SVAT was developed, which considered facial index, mid-face projection, upper and lower face shape, submalar contour, nose length and dorsal height, eye shape and brow shape, proportion of lips-to-lower face and ratio of upper-to-lower lip, and chin shape. RESULTS: For facial shape change, physicians always assessed the horizontal thirds, facial symmetry, and lip-chin complex profile, and also analyzed overall face shapes and Ogee curves. Criteria for creating oval-shaped faces was also defined and included treating indications, such as loss of angularity and bilateral masseter muscle hypertrophy, narrow jawlines, and longer and wider foreheads. Critical differences and similarities in country-specific aesthetic preferences, treatment requests, and considerations or strategies were uncovered, including the inadequacy of assessing overall peripheral facial shapes. CONCLUSION: This consensus establishes the assessment and treatment criteria for achieving ideal shapes for Asian patients. Specific descriptors are affected by variations; therefore, we present the visual criteria for Asian facial morphotypes. We hope that physicians new to treating Asian patients can use this clinical information to improve their practice.

Serum chymase levels correlate with severe dengue warning signs and clinical fluid accumulation in hospitalized pediatric patients.

Dengue induces a spectrum of severity in humans from the milder dengue fever to severe disease, or dengue hemorrhagic fever (DHF). Chymase is a candidate biomarker that may aid dengue prognosis. This prospective study aimed to identify whether warning signs of severe dengue, including hypovolemia and fluid accumulation, were associated with elevated chymase. Serum chymase levels were quantified prospectively and longitudinally in hospitalized pediatric dengue patients in Sri Lanka. Warning signs were determined based on daily clinical assessments, laboratory tests and ultrasound findings. Chymase was significantly elevated during the acute phase of disease in DHF or Severe dengue, defined by either the 1997 or 2009 WHO diagnosis guidelines, and persisted longer in the most severe patients. Chymase levels were higher in patients with narrow pulse pressure and clinical warning signs such as severe leakage, fluid accumulation, pleural effusion, gall-bladder wall thickening and rapid haematocrit rise concurrent with thrombocytopenia. No association between chymase and liver enlargement was observed. This study confirms that serum chymase levels are associated with DHF/Severe dengue disease in hospitalized pediatric patients. Chymase levels correlate with warning signs of vascular dysfunction highlighting the possible functional role of chymase in vascular leakage during dengue.

Delayed Inflammatory Reactions to Hyaluronic Acid Fillers: A Literature Review and Proposed Treatment Algorithm.

BACKGROUND AND OBJECTIVES: There is a wide diversity of opinions regarding the management of delayed inflammatory reactions (DIRs) secondary to hyaluronic acid (HA)-based fillers. The plethora of approaches has led the authors to conduct a review regarding management and treatment of DIRs as well as establish therapeutic guidelines for this purpose. MATERIALS AND METHODS: A review of the literature was performed through databases such as PubMed using keywords including HA-fillers and complications, delayed HA filler sequelae and therapy, soft tissue and dermal filler reactions and management. Additionally, a survey comprised of questions regarding the management and treatment of DIRs was sent to 18 physicians highly experienced with soft-tissue filler injections in 10 countries. Their answers and recommendations were analyzed and debated amongst these panelists. RESULTS: Sixteen panelists favored antibiotic therapy as first-line treatment for DIRs, specifically dual antibiotic therapy consisting of a fluoroquinolone along with a tetracycline or macrolide for a period of 3-6 weeks. The majority refrained from the use of intralesional (IL) or systemic steroids except in the case of disfiguring or recalcitrant reactions. IL hyaluronidase was recommended by 13 panelists; however, some preferred a watchful waiting approach for a period of 48 hours to 2 weeks prior to IL hyaluronidase, and in cases where antibiotics did not lead to improvement. CONCLUSION: A consensus was reached and summarized to propose a clear, easy-to-follow, stepwise algorithm for the treatment of DIRs.

Maternal immunity and antibodies to dengue virus promote infection and Zika virus-induced microcephaly in fetuses.

Zika virus (ZIKV), an emergent flaviviral pathogen, has been linked to microcephaly in neonates. Although the risk is greatest during the first trimester of pregnancy in humans, timing alone cannot explain why maternal ZIKV infection leads to severe microcephaly in some fetuses, but not others. The antigenic similarities between ZIKV and dengue virus (DENV), combined with high levels of DENV immunity among ZIKV target populations in recent outbreaks, suggest that anti-DENV maternal antibodies could promote ZIKV-induced microcephaly. We demonstrated maternal-to-fetal ZIKV transmission, fetal infection, and disproportionate microcephaly in immunocompetent mice. We show that DENV-specific antibodies in ZIKV-infected pregnant mice enhance vertical ZIKV transmission and result in a severe microcephaly-like syndrome, which was dependent on the neonatal Fc receptor, FcRN. This novel immune-mediated mechanism of vertical transmission of viral infection is of special concern because ZIKV epidemic regions are also endemic to DENV.