RNA aggregates harness the danger response for potent cancer immunotherapy.

Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became "hot" within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.

Identification and specification of the mouse skeletal stem cell.

How are skeletal tissues derived from skeletal stem cells? Here, we map bone, cartilage, and stromal development from a population of highly pure, postnatal skeletal stem cells (mouse skeletal stem cells, mSSCs) to their downstream progenitors of bone, cartilage, and stromal tissue. We then investigated the transcriptome of the stem/progenitor cells for unique gene-expression patterns that would indicate potential regulators of mSSC lineage commitment. We demonstrate that mSSC niche factors can be potent inducers of osteogenesis, and several specific combinations of recombinant mSSC niche factors can activate mSSC genetic programs in situ, even in nonskeletal tissues, resulting in de novo formation of cartilage or bone and bone marrow stroma. Inducing mSSC formation with soluble factors and subsequently regulating the mSSC niche to specify its differentiation toward bone, cartilage, or stromal cells could represent a paradigm shift in the therapeutic regeneration of skeletal tissues.

Utilization of Virtual Consultations in Facial Plastic Surgery during the COVID-19 Pandemic.

BACKGROUND: The coronavirus disease 2019 pandemic affected many aspects of medical practice, particularly surgical fields. The American College of Surgery initially recommended the cancellation of all elective procedures. As a result, virtual consultations (VCs; a form of telemedicine), became widely used in the field of facial plastic and reconstructive surgery. With more facial plastic and reconstructive surgeons (FPRS) conducting both in-person and virtual visits, it is imperative to understand how VCs are utilized in practice. METHODS: An electronic, anonymous survey was distributed to 1,282 electronic mail addresses in the 2018 American Academy of Facial Plastic and Reconstructive Surgery directory. The survey collected responses on various topics including demographic information and past, current, and future use of VCs. RESULTS: The survey yielded 84 responses. Most surgeons (66.7%) were 11+ years out of fellowship. There was a significant increase in the percentage of VCs scheduled after the pandemic than before (p = 0.03). FPRS most frequently responded that VCs should always be followed by an in-person visit (48.6%). A majority of FPRS (66.2%) believe that VCs have improved the delivery of health care in at least some cases. Almost all FPRS (86.5%) plan on using VCs after the pandemic. CONCLUSION: Since the pandemic, VCs are more frequently used by surgeons and are mostly utilized as an initial patient visit. A majority of FPRS believe that VCs have improved health care in at least some cases, and plan on using VCs after the pandemic.

YAP at the Crossroads of Biomechanics and Drug Resistance in Human Cancer.

Biomechanical forces are of fundamental importance in biology, diseases, and medicine. Mechanobiology is an emerging interdisciplinary field that studies how biological mechanisms are regulated by biomechanical forces and how physical principles can be leveraged to innovate new therapeutic strategies. This article reviews state-of-the-art mechanobiology knowledge about the yes-associated protein (YAP), a key mechanosensitive protein, and its roles in the development of drug resistance in human cancer. Specifically, the article discusses three topics: how YAP is mechanically regulated in living cells; the molecular mechanobiology mechanisms by which YAP, along with other functional pathways, influences drug resistance of cancer cells (particularly lung cancer cells); and finally, how the mechanical regulation of YAP can influence drug resistance and vice versa. By integrating these topics, we present a unified framework that has the potential to bring theoretical insights into the design of novel mechanomedicines and advance next-generation cancer therapies to suppress tumor progression and metastasis.

Factors mediating spaceflight-induced skeletal muscle atrophy.

Skeletal muscle atrophy is a well-known consequence of spaceflight. Because of the potential significant impact of muscle atrophy and muscle dysfunction on astronauts and their mission, a thorough understanding of the mechanisms of this atrophy and the development of effective countermeasures is critical. Spaceflight-induced muscle atrophy is similar to atrophy seen in many terrestrial conditions, and therefore our understanding of this form of atrophy may also contribute to the treatment of atrophy in humans on Earth. The unique environmental features humans encounter in space include the weightlessness of microgravity, space radiation, and the distinctive aspects of living in a spacecraft. The disuse and unloading of muscles in microgravity are likely the most significant factors that mediate spaceflight-induced muscle atrophy and have been extensively studied and reviewed. However, there are numerous other direct and indirect effects on skeletal muscle that may be contributing factors to the muscle atrophy and dysfunction seen as a result of spaceflight. This review offers a novel perspective on the issue of muscle atrophy in space by providing a comprehensive overview of the unique aspects of the spaceflight environment and the various ways in which they can lead to muscle atrophy. We systematically review the potential contributions of these different mechanisms of spaceflight-induced atrophy and include findings from both actual spaceflight and ground-based models of spaceflight in humans, animals, and in vitro studies.

Specific ZNF274 binding interference at SNORD116 activates the maternal transcripts in Prader-Willi syndrome neurons.

Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia, developmental delay and hyperphagia/obesity. This disorder is caused by the absence of paternally expressed gene products from chromosome 15q11-q13. We previously demonstrated that knocking out ZNF274, a Kruppel-associated box-A-domain zinc finger protein capable of recruiting epigenetic machinery to deposit the H3K9me3 repressive histone modification, can activate expression from the normally silent maternal allele of SNORD116 in neurons derived from PWS induced pluripotent stem cells (iPSCs). However, ZNF274 has many other targets in the genome in addition to SNORD116. Depleting ZNF274 will surely affect the expression of other important genes and disrupt other pathways. Here, we used CRISPR/Cas9 to delete ZNF274 binding sites at the SNORD116 locus to determine whether activation of the maternal copy of SNORD116 could be achieved without altering ZNF274 protein levels. We obtained similar activation of gene expression from the normally silenced maternal allele in neurons derived from PWS iPSCs, compared with ZNF274 knockout, demonstrating that ZNF274 is directly involved in the repression of SNORD116. These results suggest that interfering with ZNF274 binding at the maternal SNORD116 locus is a potential therapeutic strategy for PWS.

Telemedicine trends at a comprehensive cancer center during the first wave of the COVID-19 pandemic.

INTRODUCTION: This article reports on the effects of an early outbreak during the COVID-19 pandemic on visit volume and telehealth use by various specialists at a comprehensive cancer center. MATERIALS AND METHODS: The number of on-site and telehealth visits (THV) for medical and surgical specialties were obtained from scheduling software. RESULTS: Total visits were most drastically limited in April 2020 to a low point of 3139; THV made up 28% of all visits. For head and neck surgery, THV made up 54% and 30% of visits in April and May, respectively. Other specialties, such as psychiatry and palliative care, had higher levels of THV. For most specialties, the rebound in June through September did not make up for visits lost during the outbreak, and fiscal year  (FY) 2020 had a 9% loss from FY 2019 with 5786 fewer total annual visits across all specialties. CONCLUSIONS: While telemedicine was a helpful part of this cancer center's response to the initial COVID-19 surge, it was not able to replace the in-person services offered at the same center. The main strategy of physicians at this cancer center was to defer care, with telemedicine being an auxiliary response.

Radiology Implementation Considerations for Artificial Intelligence (AI) Applied to COVID-19, From the AJR Special Series on AI Applications.

Hundreds of imaging-based artificial intelligence (AI) models have been developed in response to the COVID-19 pandemic. AI systems that incorporate imaging have shown promise in primary detection, severity grading, and prognostication of outcomes in COVID-19, and have enabled integration of imaging with a broad range of additional clinical and epidemiologic data. However, systematic reviews of AI models applied to COVID-19 medical imaging have highlighted problems in the field, including methodologic issues and problems in real-world deployment. Clinical use of such models should be informed by both the promise and potential pitfalls of implementation. How does a practicing radiologist make sense of this complex topic, and what factors should be considered in the implementation of AI tools for imaging of COVID-19? This critical review aims to help the radiologist understand the nuances that impact the clinical deployment of AI for imaging of COVID-19. We review imaging use cases for AI models in COVID-19 (e.g., diagnosis, severity assessment, and prognostication) and explore considerations for AI model development and testing, deployment infrastructure, clinical user interfaces, quality control, and institutional review board and regulatory approvals, with a practical focus on what a radiologist should consider when implementing an AI tool for COVID-19.

Defining the impact of mutation accumulation on replicative lifespan in yeast using cancer-associated mutator phenotypes.

Mutations accumulate within somatic cells and have been proposed to contribute to aging. It is unclear what level of mutation burden may be required to consistently reduce cellular lifespan. Human cancers driven by a mutator phenotype represent an intriguing model to test this hypothesis, since they carry the highest mutation burdens of any human cell. However, it remains technically challenging to measure the replicative lifespan of individual mammalian cells. Here, we modeled the consequences of cancer-related mutator phenotypes on lifespan using yeast defective for mismatch repair (MMR) and/or leading strand (Polε) or lagging strand (Polδ) DNA polymerase proofreading. Only haploid mutator cells with significant lifetime mutation accumulation (MA) exhibited shorter lifespans. Diploid strains, derived by mating haploids of various genotypes, carried variable numbers of fixed mutations and a range of mutator phenotypes. Some diploid strains with fewer than two mutations per megabase displayed a 25% decrease in lifespan, suggesting that moderate numbers of random heterozygous mutations can increase mortality rate. As mutation rates and burdens climbed, lifespan steadily eroded. Strong diploid mutator phenotypes produced a form of genetic anticipation with regard to aging, where the longer a lineage persisted, the shorter lived cells became. Using MA lines, we established a relationship between mutation burden and lifespan, as well as population doubling time. Our observations define a threshold of random mutation burden that consistently decreases cellular longevity in diploid yeast cells. Many human cancers carry comparable mutation burdens, suggesting that while cancers appear immortal, individual cancer cells may suffer diminished lifespan due to accrued mutation burden.

The Potential Impact of COVID-19 on Aesthetic Fellowship Programs.

BACKGROUND: The COVID-19 pandemic has brought about immense change in health care. Surgical specialties in particular have had to make major adjustments because of the cancellation of nonemergent surgeries. Aesthetic surgery fellowships are uniquely affected because of the high number of elective cases and the length of the fellowship. The impact of the COVID-19 pandemic on current and upcoming aesthetic surgery fellows has not been studied. OBJECTIVE: The aim of this article was to study the potential impact of the COVID-19 pandemic on both American Society for Aesthetic Plastic Surgeons-endorsed and nonendorsed aesthetic fellowship programs. METHODS: A 23-question anonymous web-based survey was sent to aesthetic surgery fellowship directors with an active program in the United States. Surveys were collected from April 18, 2020, through May 14, 2020, with Qualtrics and then analyzed with Microsoft Excel. A 7-question follow-up survey was sent to directors, and a 23-question survey was sent to aesthetic surgery fellows. Data for these surveys were collected from June 6, 2020, through August 18, 2020. The surveys asked questions pertaining to adjustments and impact on current fellow training, as well as possible impact on fellows starting in 2020 and 2021. RESULTS: There was a 65.5% (19 of 29) response rate for the initial director survey, a 31% (9 of 29) rate for the director follow up survey, and a 28% (9 of 32) rate for the fellow-specific survey. All directors and fellows reported that the pandemic had some impact on aesthetic fellow training. A total of 5.3% of directors reported that they believe COVID-19 would have a "significant impact" on their fellows becoming well-trained aesthetic surgeons, whereas 66.7% of fellows reported that it will have a "mild impact." Predicted impact on future fellows was not as significant. CONCLUSION: Telemedicine, educational efforts, and standardization of guidelines can be increased to minimize loss of training due to COVID-19. Ongoing evaluation and shared experiences can assist fellowships in customizing programs to provide well-rounded education during the pandemic.

How businesses are working together to deliver NASA/JPL-designed ventilators to the world in the fight against COVID-19.

In response to the COVID-19 pandemic, NASA Jet Propulsion Laboratory (JPL) engineers had embarked on an ambitious project to design a reliable, easy-to-use, and low-cost ventilator that was made of readily available parts to address the unexpected global shortage of these lifesaving devices. After successfully designing and building the VITAL (Ventilator Intervention Technology Accessible Locally) ventilator in record time, FDA Emergency Use Authorization (EUA) was obtained and then the license to manufacture and sell these ventilators was made available to select companies through a competitive process. STARK Industries, LLC (STARK), located in Columbus, OH, USA, was one of only eight U.S. companies to be selected to receive this worldwide license. Motivated by its mission to improve human health and well-being through innovated medical technologies, STARK accepted the challenge of further developing the VITAL technology and manufacturing the ventilators in large quantities and making them available to those in need around the world. To this end, Spiritus Medical, Inc (Spiritus) was spun off from STARK to focus on the ventilator business. Through collaborative efforts with various corporate, academic, governmental, and non-profit partners, Spiritus was able to successfully begin manufacturing and selling its ventilators. Due to its low-cost nature and its straightforward design, this ventilator is ideal for use in developing countries where ventilators are in short supply and affordability is a major consideration. This is a story of how NASA's ingenuity, based on space-based know-how and experience, was used to rapidly design this innovative ventilator. And by forging partnerships with highly qualified and motivated partners such as STARK and Spiritus, NASA has succeeded in translating this work into technology that could potentially save thousands of lives in the fight against the COVID-19 pandemic.

Wounds Inhibit Tumor Growth In Vivo.

OBJECTIVE: The aim of this study was to determine the interaction of full thickness excisional wounds and tumors in vivo. SUMMARY OF BACKGROUND DATA: Tumors have been described as wounds that do not heal due to similarities in stromal composition. On the basis of observations of slowed tumor growth after ulceration, we hypothesized that full thickness excisional wounds would inhibit tumor progression in vivo. METHODS: To determine the interaction of tumors and wounds, we developed a tumor xenograft/allograft (human head and neck squamous cell carcinoma SAS/mouse breast carcinoma 4T1) wound mouse model. We examined tumor growth with varying temporospatial placement of tumors and wounds or ischemic flap. In addition, we developed a tumor/wound parabiosis model to understand the ability of tumors and wounds to recruit circulating progenitor cells. RESULTS: Tumor growth inhibition by full thickness excisional wounds was dose-dependent, maintained by sequential wounding, and relative to distance. This effect was recapitulated by placement of an ischemic flap directly adjacent to a xenograft tumor. Using a parabiosis model, we demonstrated that a healing wound was able to recruit significantly more circulating progenitor cells than a growing tumor. Tumor inhibition by wound was unaffected by presence of an immune response in an immunocompetent model using a mammary carcinoma. Utilizing functional proteomics, we identified 100 proteins differentially expressed in tumors and wounds. CONCLUSION: Full thickness excisional wounds have the ability to inhibit tumor growth in vivo. Further research may provide an exact mechanism for this remarkable finding and new advances in wound healing and tumor biology.

A SERS-Active Electrospun Polymer Mesh for Spatially Localized pH Measurements of the Cellular Microenvironment.

Extracellular pH (pHe) is an important chemical factor in many cellular processes and disease pathologies. The routine sampling of pHe in vitro could lead to innovative advances in therapeutics. To this end, we have fabricated a novel gold-coated polymer mesh, which facilitates the real-time measurement of pHe via surface-enhanced Raman scattering (SERS). In this proof of concept study, we apply our SERS sensor to measure metabolically induced changes in the pHe of carcinoma-derived cell line HepG2/C3A. We demonstrate that gold-coated polyurethane electrospun nanofibers (AuNF) have strong and reproducible SERS spectra of surface-adsorbed analytes. By functionalizing AuNF with pH-responsive reporter 4-mercaptobenzoic acid (MBA), we have developed an accurate pH SERS sensor for the extracellular microenvironment. We cultured HepG2/C3A on the surface of MBA-AuNF and measured an acidic shift in pHe at the cell-fiber interface. Following exposure to staurosporine, an apoptosis-inducing drug, we observed changes in the HepG2/C3A cellular morphology indicative of controlled cell death, and detected an increase in the pHe of HepG2/C3A. These results demonstrate how subtle changes in pHe, induced by the metabolic activity of cells, can be measured with our novel SERS sensor MBA-AuNF. The excellent pH measurement performance of MBA-AuNF provides a unique platform to study extracellular pH on the microscale and will help to deepen our understanding of pHe in disease pathology.

COVID-19 Imaging: What We Know Now and What Remains Unknown.

Infection with SARS-CoV-2 ranges from an asymptomatic condition to a severe and sometimes fatal disease, with mortality most frequently being the result of acute lung injury. The role of imaging has evolved during the pandemic, with CT initially being an alternative and possibly superior testing method compared with reverse transcriptase-polymerase chain reaction (RT-PCR) testing and evolving to having a more limited role based on specific indications. Several classification and reporting schemes were developed for chest imaging early during the pandemic for patients suspected of having COVID-19 to aid in triage when the availability of RT-PCR testing was limited and its level of performance was unclear. Interobserver agreement for categories with findings typical of COVID-19 and those suggesting an alternative diagnosis is high across multiple studies. Furthermore, some studies looking at the extent of lung involvement on chest radiographs and CT images showed correlations with critical illness and a need for mechanical ventilation. In addition to pulmonary manifestations, cardiovascular complications such as thromboembolism and myocarditis have been ascribed to COVID-19, sometimes contributing to neurologic and abdominal manifestations. Finally, artificial intelligence has shown promise for use in determining both the diagnosis and prognosis of COVID-19 pneumonia with respect to both radiography and CT.

A Review of Clinical and Imaging Features of Diffuse Pulmonary Hemorrhage.

OBJECTIVE. The purpose of this article is to review the clinical and imaging features of diffuse pulmonary hemorrhage. CONCLUSION. Diffuse pulmonary hemorrhage is a life-threatening syndrome associated with a wide variety of underlying pathologic categories. Nonspecific clinical and imaging features pose challenges to promptly diagnosing this condition. Chest radiography commonly shows alveolar opacification, and CT reveals the extent of disease. Integration of clinical, radiologic, laboratory, and pathologic findings facilitates timely diagnosis and etiologic identification.

CardiOvaScular Mechanisms In Covid-19: methodology of a prospective observational multimodality imaging study (COSMIC-19 study).

BACKGROUND: 8-28% of patients infected with COVID-19 have evidence of cardiac injury, and this is associated with an adverse prognosis. The cardiovascular mechanisms of injury are poorly understood and speculative. We aim to use multimodality cardiac imaging including cardiac magnetic resonance (CMR) imaging, computed tomography coronary angiography (CTCA) and positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG-PET/CT) to identify the cardiac pathophysiological mechanisms related to COVID-19 infections. METHODS: This is a single-centre exploratory observational study aiming to recruit 50 patients with COVID-19 infection who will undergo cardiac biomarker sampling. Of these, 30 patients will undergo combined CTCA and 18F-FDG-PET/CT, followed by CMR. Prevalence of obstructive and non-obstructive atherosclerotic coronary disease will be assessed using CTCA. CMR will be used to identify and characterise myocardial disease including presence of cardiac dysfunction, myocardial fibrosis, myocardial oedema and myocardial infarction. 18F-FDG-PET/CT will identify vascular and cardiac inflammation. Primary endpoint will be the presence of cardiovascular pathology and the association with troponin levels. DISCUSSION: The results of the study will identify the presence and modality of cardiac injury associated COVID-19 infection, and the utility of multi-modality imaging in diagnosing such injury. This will further inform clinical decision making during the pandemic. TRIAL REGISTRATION: This study has been retrospectively registered at the ISRCTN registry (ID ISRCTN12154994) on 14th August 2020. Accessible at https://www.isrctn.com/ISRCTN12154994.

Fellow selection protocols in sleep surgery: a national survey of sleep surgery program directors.

PURPOSE: To determine the factors that sleep medicine/surgery fellowship program directors look for in applicants. METHODS: Program directors from 9 sleep medicine/surgery fellowship programs in the USA were sent an anonymous online survey. They were asked to select the five most important academic factors (of a list of 17) when evaluating potential fellowship candidates, then rank those five in order of importance. They were then asked to do the same for the most important subjective criteria (of a list of 12). RESULTS: Eight of 10 survey responses met inclusion criteria. Of the academic factors, strength of letters of recommendation, reputation of letter writer, and letters from sleep surgeons ranked highest. As for the subjective criteria, faculty assessment of the applicant on interview was ranked highest, followed by initiative and personality "fit" with the program. The reputation of an applicant's residency was ranked as more important than the reputation of their medical school. An applicant's performance in residency was assessed as more predictive of their performance in fellowship than performance during the interview process or position on the rank order list for the match. Only one program has a United States Medical Licensing Examination (USMLE) Step, and a different program has an Otolaryngology Training Examination (OTE) score cutoff. CONCLUSION: Letters of recommendation and interview are the most important factors in the selection process for hybrid sleep medicine and surgery fellowship programs, followed by research and residency program reputation. Sleep surgery-specific experience is helpful.

E-Cigarette Burns and Explosions: What are the Patterns of Oromaxillofacial Injury?

PURPOSE: With the recent increase in popularity of electronic cigarette use in the United States, its harmful effects are not only limited to smoke inhalation, but also to the possibility of e-cigarette device malfunction. The purpose of this review is to characterize oromaxillofacial trauma secondary to electronic cigarette device explosion. METHODS: For this systematic review, PubMed and Embase were searched in October 2019 using the following search terms: e-cigarette burns, e-cigarette injury, and e-cigarette explosions, which yielded 400 studies. Basic science research, animal studies, non-English studies, and reports of non-oromaxillofacial injuries were excluded. Study subject demographics, mechanism of trauma, injury type, treatment, and sequelae were recorded and analyzed. RESULTS: Of all studies, 20 studies met inclusion criteria, including 14 case reports and 6 case series, with a total of 21 study subjects. For cases that reported sex, 100% were male (20) with a mean age of 29.5 years. Most common lacerations and/or burns involved the lips (10/21), tongue (8/21), soft palate and/or hard palate (4/21), and nose (5/21). Thirteen subjects underwent surgeries including oral-maxillofacial surgery or dental implants (7/13), bone graft repair (3/13), open reduction and internal fixation for preservation of sinus outflow tracts (2/13), foreign body removal from the cervical spine (1/13), and iridectomy (1/13). Reported complications included bone loss secondary to traumatic fracture, tinnitus and hearing loss, lip paralysis secondary to persistent edema, major depressive disorder/ post-traumatic stress disorder, persistent sinusitis, photophobia, and bilateral axillary and hand contractures. CONCLUSIONS: Electronic cigarette device malfunction and explosion carries great risk for acute oromaxillofacial trauma that may be disfiguring. With the increasing popularity of electronic cigarette use, clinicians and patients should be advised regarding dangers of electronic cigarette use.

Nasal Analysis of Classic Animated Movie Villains versus Hero Counterparts.

Opposing facial features between animated villains and heroes have historically been used to demonstrate contrasting morality between characters, and this could have an impact on how humans view someone as good or evil in everyday life. Studies have been done investigating classic dermatologic features of villainous characters. This principle can be applied to nasal features as well. A search for "top animated characters" was performed. Characters were chosen from American Film Institute's "The Top Tens," Rolling Stone's "25 Best Pixar Movie Characters," and Screenrant's "The 30 Best Animated Movie Characters of All Time." Twenty villains and twenty hero counterparts from respective films were chosen. Classic nasal features were analyzed. Twenty villains (14 male, 6 female) and 20 heroes (12 male, 8 female) were analyzed. Sixteen villains (80%) had greater than normal nasal frontal angle versus 18 heroes (90%). Thirteen villains (65%) had an acute nasolabial angle versus two heroes (10%). Two villains (10%) had excess columellar show versus seven heroes (35%). Seven villains (35%) and one hero (5%) had a dorsal hump. Twelve villains (60%) had an overprojected chin versus three heroes (15%). Villains in pre-2000s films more frequently had a dorsal hump, overprojected chin, ptotic tip, pollybeak deformity, and bulbous tip. Heroes in pre-2000s films more frequently had an overrotated tip. Villains and heroes commonly have a greater than normal nasofrontal angle. Villains more commonly have an acute nasolabial angle, underrotated tip, overprojected chin, dorsal hump, and pollybeak deformity. Heroes more commonly have a large nasolabial angle and overrotated tip. Further research in conjunction with psychologists is required to obtain concrete data on how this affects whether an individual in real life is seen as good or evil, and the impact this has on interactions in society, including in the medical field.

Telemedicine in International Cleft Care: A Systematic Review.

BACKGROUND: Cleft lip and cleft palate (CLP) are among the world's most common congenital malformation and has a higher prevalence in developing nations due to environmental and genetic factors. Global efforts have been developed in order to prevent and treat the malformation. Telemedicine has been implemented in various humanitarian global missions with success and is currently the primary means of care due to COVID-19. OBJECTIVE: To assess the benefits and barriers of telehealth in the care of patients with CLP through a global approach. METHODS: Systematic review of the PubMed and Cochrane Review databases with relevant terms related to telemedicine in cleft lip and palate surgery. RESULTS: Eight articles fit the inclusion criteria and suggested benefits with the use of telemedicine in regard to education, preoperative, and postoperative care as well as increased access to underserved populations. Barriers included connectivity and accessibility concerns. CONCLUSION: Telehealth is a beneficial way to evaluate patients with CLP in developing countries with proper care and follow-up to reduce complications and to improve health outcomes.