Automated Analysis of Nuclear Parameters in Oral Exfoliative Cytology Using Machine Learning.

BACKGROUND: As oral cancer remains a major worldwide health concern, sophisticated diagnostic tools are needed to aid in early diagnosis. Non-invasive methods like exfoliative cytology, albeit with the help of artificial intelligence (AI), have drawn additional interest. AIM: The study aimed to harness the power of machine learning algorithms for the automated analysis of nuclear parameters in oral exfoliative cytology. Further, the analysis of two different AI systems, namely convoluted neural networks (CNN) and support vector machine (SVM), were compared for accuracy. METHODS: A comparative diagnostic study was performed in two groups of patients (n=60). The control group without evidence of lesions (n=30) and the other group with clinically suspicious oral malignancy (n=30) were evaluated. All patients underwent cytological smears using an exfoliative cytology brush, followed by routine Hematoxylin and Eosin staining. Image preprocessing, data splitting, machine learning, model development, feature extraction, and model evaluation were done. An independent t-test was run on each nuclear characteristic, and Pearson's correlation coefficient test was performed with Statistical Package for the Social Sciences (SPSS) software (IBM SPSS Statistics for Windows, Version 28.0. IBM Corp, Armonk, NY, USA). RESULTS:  The study found substantial variations between the study and control groups in nuclear size (p<0.05), nuclear shape (p<0.01), and chromatin distribution (p<0.001). The Pearson correlation coefficient of SVM was 0.6472, and CNN was 0.7790, showing that SVM had more accuracy. CONCLUSION: The availability of multidimensional datasets, combined with breakthroughs in high-performance computers and new deep-learning architectures, has resulted in an explosion of AI use in numerous areas of oncology research. The discerned diagnostic accuracy exhibited by the SVM and CNN models suggests prospective improvements in early detection rates, potentially improving patient outcomes and enhancing healthcare practices.

Association Between Sarcopenia and Chronic Renal Failure (Overt and Concealed) in Chronic Obstructive Pulmonary Disease (COPD) Patients: A Cross-Sectional Study.

Background Sarcopenia, a syndrome characterized by a progressive decline in skeletal muscle mass, strength, and function, is frequently associated with chronic diseases such as chronic obstructive pulmonary disease (COPD). Chronic kidney disease (CKD) is a prevalent condition among patients with sarcopenia. Reports suggest that between 15% and 55% of stable COPD patients have sarcopenia. Therefore, the present study aims to determine the association between sarcopenia and chronic renal failure (overt and concealed) in COPD patients. Methodology This institutional-based cross-sectional study was conducted on patients diagnosed with COPD. Hospitalized adult COPD patients who gave consent were included. Sociodemographic information such as age, gender, residence, and prolonged length of stay in the hospital (categorized by a median of 10 days, considering its data distribution in our sample) was obtained using electronic medical records. Skeletal muscle %, visceral fat %, and body fat % were calculated using a bio-electrical impedance analysis device (Omron Body Composition Monitor, Model HBF-702T). Additionally, the strength of the hand grip was measured using a hand dynamometer. Sarcopenia was assessed following the criteria set by the Asian Working Group on Sarcopenia (AWGS). Chronic renal failure (CRF) was assessed by calculating the glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) Study Group equation. Quantitative data were compared using an independent sample t-test. The association was determined using chi-square and multivariate logistic regression analyses. A p-value of <0.05 was considered significant. Results The study found that the proportion of sarcopenia in COPD patients was 52%, with overt and concealed CRF prevalence rates of 31.5% and 27%, respectively. Sarcopenic individuals had significantly lower FEV1 and FEV1/FVC compared to non-sarcopenic patients. The incidence of sarcopenia significantly increased with rising BODE index (body mass index (BMI, B), airflow obstruction (O) as measured by the post-bronchodilator FEV1 (percentage of predicted value), dyspnea (D) assessed by the modified Medical Research Council (MMRC) score, and exercise tolerance (E) measured by 6-minute walking distance) and mMRC (modified Medical Research Council dyspnea scale) dyspnea scale scores. Both concealed CRF and overt CRF patients had four times higher odds of having sarcopenia (AOR=4). Conclusion The study reveals a high prevalence of sarcopenia and provides evidence for the association between sarcopenia and chronic renal failure in COPD patients. These findings underscore the importance of early detection and management of sarcopenia and CRF in COPD patients to optimize their clinical outcomes.

Pediatric cochlear implants and myringotomy tubes: a systematic review.

OBJECTIVE: To evaluate the intraoperative findings and post-operative complications associated with patients who have current or history of myringotomy tubes undergoing a cochlear implantation. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were followed. Studies from Pubmed, Cochrane, Embase, Web of Science, and Scopus were included. Studies were independently screened and analyzed by 2 reviewers. Publications assessing pediatric patients with current or history of myringotomy tubes at time of cochlear implantation were reviewed. Discrepancies were resolved by a team of 4 reviewers. RESULTS: 172 studies were screened, 15 met inclusion criteria, and 12 were incorporated into the study. All 12 of the studies were retrospective cohort studies. Meta-analysis showed no significant relationship between intraoperative findings at time of cochlear implantation (presence of effusion, granulation tissue, edematous middle ear tissue) and myringotomy tube insertion (p = 0.63). Additionally, there was no significant relationship between current or history of myringotomy tube and acute otitis media episode after CI (p = 0.25). CONCLUSION: There was no association noted between perioperative outcomes of pediatric cochlear implantation and myringotomy tube. This information will be helpful for surgeons planning to perform cochlear implantation in the pediatric population.

Spotlight on the Mucormycosis Outbreak: A Deadly Fungal Infection That Followed the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic along with its treatment has brought myriad potential complications including the heightened risk of secondary fungal infections like mucormycosis. Mucormycosis is a rare angioinvasive fungal infection that has traditionally been highly fatal despite surgical intervention and antifungal medications. AIM: To re-evaluate the risk factors, epidemiology, and possible COVID-19-associated conditions on a larger sample size than the existing data. METHODOLOGY: We studied the possible risk factors, clinical presentations, treatment, and outcome of 203 patients with mucormycosis in a single-center retrospective-prospective observational study for three months at a tertiary care hospital after obtaining due permission from the institutional ethics committee. RESULTS: The mean age of patients was 52 ± 11.5 years, and 92.61% had a history of COVID-19 infection. Around 86.7% of patients were suffering from diabetes mellitus with 50% being already known cases whereas the other 50% developed post-COVID-19 infection; 65.02% of patients were administered corticosteroids during their COVID-19 treatment. About 51.72% of patients required hospital admission and among them, 16.25% of patients required ICU support. The mean oxygen saturation (SpO2) levels on admission were 84.61 ± 12.96%, and 38.92% of patients required mechanical respiratory support. The mean duration between COVID-19 infection and the onset of mucormycosis was 18.80 ± 16.61 days. The most common clinical presentations were facial pain and swelling (26.6%) and ophthalmic symptoms including eye swelling, pain, and ptosis (25.12%). Antifungal treatment was given to all the patients and 89.36% of the patients underwent surgical debridement of fungal mass. At the end of three months, 60.59% of the 188 patients survived with improvement, 13.30% had no improvement and/or deterioration of health, and 18.72% succumbed to mucormycosis. Intracranial involvement and leukocytosis were positively associated with mortality whereas surgical intervention was significant for positive outcomes at the end of three months in patients with mucormycosis (p<0.05). CONCLUSION: The sudden rise of mucormycosis during the second wave of COVID-19 can be attributed to uncontrolled blood sugar levels along with high corticosteroid usage as well as various nosocomial factors during the COVID-19 treatment. Early and aggressive treatment with surgical intervention and antifungal drugs can improve disease outcomes.

Customizable, reconfigurable, and anatomically coordinated large-area, high-density electromyography from drawn-on-skin electrode arrays.

Accurate anatomical matching for patient-specific electromyographic (EMG) mapping is crucial yet technically challenging in various medical disciplines. The fixed electrode construction of multielectrode arrays (MEAs) makes it nearly impossible to match an individual's unique muscle anatomy. This mismatch between the MEAs and target muscles leads to missing relevant muscle activity, highly redundant data, complicated electrode placement optimization, and inaccuracies in classification algorithms. Here, we present customizable and reconfigurable drawn-on-skin (DoS) MEAs as the first demonstration of high-density EMG mapping from in situ-fabricated electrodes with tunable configurations adapted to subject-specific muscle anatomy. The DoS MEAs show uniform electrical properties and can map EMG activity with high fidelity under skin deformation-induced motion, which stems from the unique and robust skin-electrode interface. They can be used to localize innervation zones (IZs), detect motor unit propagation, and capture EMG signals with consistent quality during large muscle movements. Reconfiguring the electrode arrangement of DoS MEAs to match and extend the coverage of the forearm flexors enables localization of the muscle activity and prevents missed information such as IZs. In addition, DoS MEAs customized to the specific anatomy of subjects produce highly informative data, leading to accurate finger gesture detection and prosthetic control compared with conventional technology.

Circular economy approach for sustainable solid waste management: A developing economy perspective.

The notion of circular economy (CE) strengthens the approach to sustainable development (SD). It is perceived that the adoption of CE can unlock half a trillion dollars of economic value in India by the year 2030. However, embracing the CE concept can be considered a panacea to the existing issues associated with solid waste management (SWM). The proposed study explores current waste management practices and assesses the inadequacy to infer the CE as a solution for successful waste management practices. The work provides an overview of SWM in India and emphasizes the inclusion of CE in the Indian SWM sector. The comprehensive review depicts existing, and emerging waste management approaches to form a CE by processing the waste efficiently and fuelling an SD movement. The cradle-to-cradle approach in CE, national solid waste compliances/legislation, key initiatives taken by the Governments, and the influence of industry and legal framework on CE were also discussed. The work will facilitate policy and decision-makers to include CE in the Indian SWM sector.

Wearable bioelectronics fabricated in situ on skins.

In recent years, wearable bioelectronics has rapidly expanded for diagnosing, monitoring, and treating various pathological conditions from the skin surface. Although the devices are typically prefabricated as soft patches for general usage, there is a growing need for devices that are customized in situ to provide accurate data and precise treatment. In this perspective, the state-of-the-art in situ fabricated wearable bioelectronics are summarized, focusing primarily on Drawn-on-Skin (DoS) bioelectronics and other in situ fabrication methods. The advantages and limitations of these technologies are evaluated and potential future directions are suggested for the widespread adoption of these technologies in everyday life.

A unique presentation of Crouzon-like syndrome: Complex craniosynostosis in the absence of genetic mutations or familial predisposition - A case report.

Background: Crouzon syndrome is a rare genetic disorder characterized by premature fusion of skull sutures during skull development, resulting in various craniofacial abnormalities and complex craniosynostosis is a condition in which more than one such sutures of the skull fuse prematurely. Case Description: Herein, we present a case of a 5-year-old male diagnosed with Crouzon-like syndrome and complex craniosynostosis involving multiple cranial sutures, including metopic, sagittal, coronal (right and left), and lambdoid sutures, and without any identifiable mutations on karyotyping. The patient underwent successful surgical intervention with a satisfactory outcome, highlighting the importance of early diagnosis and intervention to prevent or minimize associated neurological manifestations and craniofacial abnormalities. Conclusion: Our case report underscores the involvement of multiple cranial sutures in complex craniosynostosis and the absence of identifiable mutations or family history of similar craniofacial abnormalities, providing important insights into the diagnosis and management of this condition.

Emergence of Cerebral Mucormycosis in the Post-COVID Period: A Detailed Analysis of Risk Factors, Clinical Progression, and Management of This Opportunistic Fungal Infection.

BACKGROUND: An epidemic of Mucorales was reported following the second wave of COVID-19 in India, and intracranial extension of the same was one of the most dreadful complications. METHODS: A total of 62 patients with cerebral mucormycosis were recruited and followed up till 12 weeks to evaluate the risk factors, incidence, clinical manifestations, management, and prognosis of cerebral mucormycosis. FINDINGS: A median age of 51.5 years with male predominance (74%) was noted. The majority of subjects reported a history of COVID infection (93.5%) and diabetes mellitus (83.87%). The first symptom of mucormycosis appeared after a mean period of 17.63 ± 8.9 days following COVID. Facial swelling and ptosis were the most common symptoms. Only 55% of patients had neurological presentations, and hemiparesis was the most common neurological sign (30.6%). Radiologically, the involvement of maxillary sinus (90.32%) and ethmoid sinus (87.10%) was commonly noted. Cerebral findings included temporal lobe (50%) and parietal lobe (30.06%) involvement, cavernous sinus thrombosis (30.06%), and internal carotid artery thrombosis (22.58%). Acute cerebral infarction was notable in 37% of subjects (p-value=0.0015, significant association with the outcome). Conventional and liposomal amphotericin B were used in 91.94% and 53.23% of patients, respectively. Retrobulbar amphotericin injections used in 11.3% of subjects significantly affected the outcome (p-value=0.03, significant). Posaconazole step-down therapy was used in 72.5% of subjects (p-value=0.0005, significant). Surgical interventions were performed in 53 (85.48%) subjects (p-value=0.004, significant). Functional endoscopic sinus surgery was the most common (in 64.52% of subjects), followed by maxillectomy (20.97% of subjects) and craniotomy (17.7% of subjects). At the end of 12 weeks, 33.87% of patients died and 59.68% were alive; the rest (6.45%) were lost to follow-up. INTERPRETATION: The absence or late presentation of neurological symptoms led to a delayed diagnosis of cerebral mucormycosis. The presence of acute cerebral infarction indicated a worse prognosis. However, there was a significant influence of step-down posaconazole therapy, retrobulbar amphotericin injections, and surgical intervention on the prognosis of cerebral mucormycosis.

Drawn-on-Skin Sensors from Fully Biocompatible Inks toward High-Quality Electrophysiology.

The need to develop wearable devices for personal health monitoring, diagnostics, and therapy has inspired the production of innovative on-demand, customizable technologies. Several of these technologies enable printing of raw electronic materials directly onto biological organs and tissues. However, few of them have been thoroughly investigated for biocompatibility of the raw materials on the cellular, tissue, and organ levels or with different cell types. In addition, highly accurate multiday in vivo monitoring using such on-demand, in situ fabricated devices has yet to be done. Presented herein is the first fully biocompatible, on-skin fabricated electronics for multiple cell types and tissues that can capture electrophysiological signals with high fidelity. While also demonstrating improved mechanical and electrical properties, the drawn-on-skin ink retains its properties under various writing conditions, which minimizes the variation in electrical performance. Furthermore, the drawn-on-skin ink shows excellent biocompatibility with cardiomyocytes, neurons, mice skin tissue, and human skin. The high signal-to-noise ratios of the electrophysiological signals recorded with the DoS sensor over multiple days demonstrate its potential for personalized, long-term, and accurate electrophysiological health monitoring.

Artificial neuromorphic cognitive skins based on distributed biaxially stretchable elastomeric synaptic transistors.

Cephalopod (e.g., squid, octopus, etc.) skin is a soft cognitive organ capable of elastic deformation, visualizing, stealth, and camouflaging through complex biological processes of sensing, recognition, neurologic processing, and actuation in a noncentralized, distributed manner. However, none of the existing artificial skin devices have shown distributed neuromorphic processing and cognition capabilities similar to those of a cephalopod skin. Thus, the creation of an elastic, biaxially stretchy device with embedded, distributed neurologic and cognitive functions mimicking a cephalopod skin can play a pivotal role in emerging robotics, wearables, skin prosthetics, bioelectronics, etc. This paper introduces artificial neuromorphic cognitive skins based on arrayed, biaxially stretchable synaptic transistors constructed entirely out of elastomeric materials. Systematic investigation of the synaptic characteristics such as the excitatory postsynaptic current, paired-pulse facilitation index of the biaxially stretchable synaptic transistor under various levels of biaxial mechanical strain sets the operational foundation for stretchy distributed synapse arrays and neuromorphic cognitive skin devices. The biaxially stretchy arrays here achieved neuromorphic cognitive functions, including image memorization, long-term memorization, fault tolerance, programming, and erasing functions under 30% biaxial mechanical strain. The stretchy neuromorphic imaging sensory skin devices showed stable neuromorphic pattern reinforcement performance under both biaxial and nonuniform local deformation.

Adenoid cystic carcinoma: A case report and review of literature.

Adenoid cystic carcinoma (ADCC) is an uncommon tumor of head and neck, whose clinical patterns are characterized by slow growth, perineural invasion and distant metastasis. Cribriform, tubular and solid are the three recognized histopathological patterns which are seen in ADCC. We report a case of ADCC involving palate with an update on the current understanding of its clinical behavior, molecular biology, pathogenesis, histopathological aspect, treatment and prognosis.

Enamel renal syndrome: A case report with review of literature.

Amelogenesis imperfecta (AI) is a developmental, inherited disorder affecting dental enamel. Preterm and low birth weight children are prone to many serious medical problems during the neonatal period, which may affect the development of oral tissues. We report a case of AI presenting with renal disease and thereby highlighting the importance of early diagnosis of this possible association to prevent renal failure and death of the patient.

Eco-innovations and sustainability in solid waste management: An indian upfront in technological, organizational, start-ups and financial framework.

Technological interventions and eco-innovative solutions are necessary to cope with the adverse environmental impacts of waste accumulation. The notion to consider "waste as a resource and recycling of the same for getting the value of the waste" has truly transformed the approach towards solid waste management (SWM). Technological eco-innovations rely on the automation of waste segregation, collection, route optimization, digital apps for creating communication (enhanced efficiency by 40-85%) and treatment technologies. The regulatory framework with amendments in rules, new policies, schemes, smart city missions are responsible for the implementation of "Tech-innovations" at the ground level and has shown societal benefits. India has significantly shown progress in sustainable development goals (SDGs) score from 50.93 to 60.23 (year 2000-2019). The innovative and sustainable waste management practices in India have increased contribution to renewable energy (approx. 2554 MW/annum), 15-billion-USD business opportunity by the circular economy, 25-30% resale profit from processed E-waste, increased co-operative collaborations, trailblazing start-ups, improved SDG 3,7,8,9,11,12,13, improved market for green products and services, brilliant institutional and regional innovations addressing the issue of climate change. The present article critically reviews the exemplary eco-innovations (technological and non-technological) including resource recovery and viable technologies for SWM in India. The review also illustrates the lacunae (in awareness, bioproducts adoption and advanced technologies), recommendations based on findings and future research areas. The paper can also assist researchers, entrepreneurs and the policy makers for improving the status of SWM in India as well as other developing countries with the same societal and economic status.

Wearable electronics for skin wound monitoring and healing.

Wound healing is one of the most complex processes in the human body, supported by many cellular events that are tightly coordinated to repair the wound efficiently. Chronic wounds have potentially life-threatening consequences. Traditional wound dressings come in direct contact with wounds to help them heal and avoid further complications. However, traditional wound dressings have some limitations. These dressings do not provide real-time information on wound conditions, leading clinicians to miss the best time for adjusting treatment. Moreover, the current diagnosis of wounds is relatively subjective. Wearable electronics have become a unique platform to potentially monitor wound conditions in a continuous manner accurately and even to serve as accelerated healing vehicles. In this review, we briefly discuss the wound status with some objective parameters/biomarkers influencing wound healing, followed by the presentation of various novel wearable devices used for monitoring wounds and accelerating wound healing. We further summarize the associated device working principles. This review concludes by highlighting some major challenges in wearable devices toward wound healing that need to be addressed by the research community.

Bullying and Children who are Deaf or Hard-of-hearing: A Scoping Review.

OBJECTIVE/HYPOTHESIS: The goal of this scoping review is to evaluate and synthesize the published research regarding bullying and children who are deaf or hard-of-hearing (DHH). STUDY DESIGN: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping review (PRISMA-ScR) statement was used as the guideline for conducting this review. METHODS: This review included studies assessing pediatric (0-21 years) DHH children. Seventy records underwent the initial title-abstract screening, 33 underwent full-text review, and 23 studies met inclusion criteria. During the data extraction process, an additional six were excluded, resulting in a total of 17 evaluated studies. RESULTS: Of the 17 studies assessed, nine compared peer victimization of DHH children and their hearing peers. Of those, seven studies reported that hearing loss (HL) is significantly associated with increased victimization. Two studies found that HL is significantly associated with decreased bullying perpetration. Notably, bullying in DHH children was not associated with a visible sign of disability, such as a hearing assistive device. Rather, variables such as educational setting, parental, and peer support are more likely to mediate bullying in this population. CONCLUSIONS: DHH children have a higher risk of peer victimization and may bully others less often than their hearing peers. Studies described the health consequences of bullying in children who are DHH, including sleep issues and anxiety. These consequences may have implications for the patients' overall HL management. Additional research regarding bullying interventions and prevention in this population should be conducted. LEVEL OF EVIDENCE: NA Laryngoscope, 131:1884-1892, 2021.

Social Isolation and Loneliness in the Hearing-Impaired Pediatric Population: A Scoping Review.

OBJECTIVE: To review existing publications in order to evaluate the effect of hearing loss on social isolation and loneliness in the pediatric population. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Review (PRISMA-ScR) guidelines were followed. Eight databases were searched. Studies were independently screened and analyzed by two reviewers. Publications were included if pediatric hearing-impaired individuals and social isolation or loneliness were studied. Discrepancies were resolved by a team of five reviewers. RESULTS: Thirty-three studies were included in this review. Sixty percent of studies (12/20) found that hearing loss was related to loneliness and 64.7% found that children with hearing loss experienced more social isolation (11/17). The Asher Loneliness and Dissatisfaction Questionnaire was commonly used to assess loneliness. No commonly used tool for assessing social isolation was found. Six articles found that school type was not associated with loneliness. Difficulty communicating was the most mentioned factor leading to loneliness and social isolation. Frequent recommendations to improve social integration included facilitating interactions with the hearing-impaired and educating the nonhearing-impaired to normalize the disability. CONCLUSION: The majority of studies found that hearing impairment results in a higher prevalence of social isolation and loneliness. However, an association cannot be definitively claimed due to the lack of uniform assessment tools. This review emphasizes the need for standardized methods to assess loneliness and social isolation and highlights methods to improve social integration for the hearing impaired. Laryngoscope, 131:1869-1875, 2021.

Risk Factors for Rhinosinusitis After Endoscopic Transsphenoidal Adenomectomy.

OBJECTIVE: Patients undergoing endoscopic transsphenoidal adenomectomy (eTSA) for pituitary tumors are at risk for postoperative complications, including rhinosinusitis. We aimed to determine if preoperative sinonasal disease is a risk factor for postoperative rhinosinusitis (PRS). STUDY DESIGN: Retrospective review. SETTING: Tertiary academic center in U.S. SUBJECTS AND METHODS: Patients with a diagnosis of pituitary adenoma who underwent eTSA between 2007-2016. PRS patients were matched to non-PRS patients or sex, age, tumor size, skull base reconstruction with intranasal tissue grafting, and concurrent septoplasty. Groups were statistically analyzed for potential preoperative risk factors of sinonasal disease (patient-reported, radiographic, endoscopic). RESULTS: 49 of 987 patients who underwent eTSA developed PRS (44.9% male, 71.4% Caucasian, mean age 49.3y). On analysis of individual risk factors, there was a significantly higher proportion of patients with a history of prior sinonasal surgery in the PRS group than the non-PRS group (25.5% vs. 6.5%, p = 0.01); however, this group difference became insignificant on multivariate analysis. There were no significant group differences with regard to history of sinus infections, nasal symptoms, seasonal allergies, radiographic abnormalities, or sinonasal disease on endoscopy. CONCLUSION: This is the first study to investigate preoperative sinonasal disease as a risk factor for PRS after eTSA. The risk factors considered did not demonstrate definitive risk for PRS, although a history of prior sinonasal surgery should be investigated further.

Non-Hodgkins lymphoma - A case report and review of literature.

Lymphomas are solid tumors of the immune system and include 14% of all head and neck malignancies. Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of lymphoproliferative disorders originating in B-, T-, or natural killer T-cells. They have a wide range of histological appearances and clinical features at presentation, which can make diagnosis difficult. A 58-year-old male patient presented with a 1-month history of swelling in the upper right back tooth region, which developed after extraction. On intraoral examination, there was small nodular lesion proliferation from the extracted socket. Biopsy specimen on histological examination revealed sheets of small round cells with hyperchromatic nucleus resembling lymphoblast. Immunohistochemistry (IHC) confirms the NHL of T-cell origin. This article is an attempt to correlate the clinical presentation and histological importance of small round cell tumors of the jaw and to discuss the differential diagnosis of small round cell tumors. Typically, a multimodal approach is employed, and the principal ancillary technique that have been found to be useful in classification is IHC.

Understanding the mechanism of bias signaling of the insulin-like growth factor 1 receptor: Effects of LL37 and HASF.

The development of biased agonist drugs is widely recognized to be important for the treatment of many diseases, including cardiovascular disease. While GPCR biased agonism has been heavily characterized there is a distinct lack of information with respect to RTK biased agonism both in the identification of biased agonists as well as their attendant mechanisms. One such RTK, the Insulin-like Growth Factor 1 Receptor (IGF1R) plays an important role in a range of biological and disease processes. The micropeptide LL37 has been described as a biased agonist of the IGF1R. We were interested to further understand the mechanism by which LL37 promotes biased signaling through the IGF1R. We found that LL37 biased agonism is dependent on ß-arrestin 2. Moreover, BRET assays indicated that LL37 biased agonism is explained by the inability of LL37 to promote the recruitment of IRS1 to the IGF1R compared to IGF1. LL37 promotes an altered association of IGF1R with GRK6, which could also serve as an explanation for bias. We also demonstrated a functional consequence of this bias by showing that while LL37 can promote cell proliferation, it does not induce protein synthesis, unlike IGF1, which does both. We have recently identified HASF, a natural protein released by mesenchymal stem cells, as a novel ligand of the IGF1R. HASF is a paracrine factor with potent cardioprotective and cardio-regenerative properties which also acts via IGF1R biased signaling, preferentially activated ERK over Akt.