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Medulloblastoma is the most common malignant paediatric brain tumour, with ~30% mediated by Sonic hedgehog signalling. Vismodegib-mediated inhibition of the Sonic hedgehog effector Smoothened inhibits tumour growth but causes growth plate fusion at effective doses. Here, we report a nanotherapeutic approach targeting endothelial tumour vasculature to enhance blood–brain barrier crossing. We use fucoidan-based nanocarriers targeting endothelial P-selectin to induce caveolin-1-dependent transcytosis and thus nanocarrier transport into the brain tumour microenvironment in a selective and active manner, the efficiency of which is increased by radiation treatment. In a Sonic hedgehog medulloblastoma animal model, fucoidan-based nanoparticles encapsulating vismodegib exhibit a striking efficacy and marked reduced bone toxicity and drug exposure to healthy brain tissue. Overall, these findings demonstrate a potent strategy for targeted intracranial pharmacodelivery that overcomes the restrictive blood–brain barrier to achieve enhanced tumour-selective penetration and has therapeutic implications for diseases within the central nervous system.

International audience; The objective of this research is to examine how ultrasonication time affects agglomeration, stability, thermal conductivity, and viscosity of CuO nanofluid. Using different reaction conditions, distinct shaped CuO nanoparticles are synthesised and dispersed in an EG: DW (70:30) ratio with 0.3 vol%. Microscopic and TEM images are used to analyze colloidal solutions with varying sizes and shapes of nanoparticles. After 30 days of preparation, the zeta potential is measured to ensure that the suspension is stable. The Bridgman equation is used to compute thermal conductivity using sound velocity values. Viscosity of colloidal suspension is measured by viscometer. All of the studies are performed at 30° ± 2 °C room temperature for ultrasonication times ranging from 30–120 min. At an optimal sonication time of 80 min, there is less agglomeration and more stable particle dispersion. In comparison to other morphological suspensions, CuO spherical shape suspended nanofluid has the lowest viscosity and maximum thermal conductivity, as well as the most stable fluid. At the optimal sonication period, measured results demonstrate thermal increase and decreased viscosity, which could have implications for heat transfer applications.

To characterize the clinical features, risk factors, symptom time-course, and quality of life implications for parosmia among coronavirus disease (COVID)-related olfactory dysfunction patients.Individuals with olfactory dysfunction associated with laboratory-confirmed or clinically suspected COVID-19 infection were recruited from otolaryngology and primary care practices over a period from August 2020 to March 2021. Participants completed olfactory dysfunction and quality of life surveys.A total of 148 (64.1%) of 231 respondents reported parosmia at some point. Parosmia developed within 1 week of any COVID-19 symptom onset in 25.4% of respondents, but more than 1 month after symptom onset in 43.4% of respondents. Parosmia was associated with significantly better quantitative olfactory scores on Brief Smell Identification Test (8.7 vs. 7.5, P = .006), but demonstrated worse quality of life scores, including modified brief Questionnaire of Olfactory Dysfunction-Negative Statements and Sino-Nasal Outcome Test-22 scores (12.1 vs. 8.5, P .001; 26.2 vs. 23.2, P = .113). Participants who developed parosmia at any point were significantly younger and less likely to have history of chronic sinusitis than those who did not develop parosmia (40.2 vs. 44.9 years, P = .007; 7.2% vs. 0.7%, P = .006).COVID-19-associated olfactory dysfunction is frequently linked with development of parosmia, which often presents either at onset of smell loss or in a delayed fashion. Despite better quantitative olfactory scores, respondents with parosmia report decreased quality of life. A majority of respondents with persistent parosmia have sought treatment.3 Laryngoscope, 132:633-639, 2022.

Background: The COVID-19 pandemic forced otolaryngologists to seek new methods of providing patient care in a remote setting. The effect of this paradigm shift on patient satisfaction, however, remains unelucidated. This study compares patient satisfaction with telehealth visits during the COVID-19 pandemic to that with in-office visits during the same period in 2019. Methods: Press Ganey survey responses of patients seen by otolaryngologists within a large, academic, multicenter hospital system were gathered. Responses were included in analyses if they corresponded with a visit that occurred either in clinic March to December 2019 or via telehealth March to December 2020. Chi-Square Test of Independence and Fisher’s Exact Test were employed to detect differences between years. Binary logistic regressions were performed to detect the factors most predictive of positive telehealth experiences. Results: Patient overall satisfaction with in-office and telehealth visits did not differ significantly (76.4% in 2019 vs 78.0% in 2020 rated visit overall as “very good,” P = .09). Patients seen by a Head and Neck (odds ratio 4.13, 95% confidence interval 1.52-11.26, P = .005), Laryngology (OR 5.96, 95% CI 1.51-23.50, P = .01), or Rhinology (OR 4.02, 95% CI 1.55-10.43, P = .004) provider were significantly more likely to report a positive telehealth experience. Conclusions: Patients seen via telehealth during COVID-19 reported levels of satisfaction similar to those seen in-office the year prior. These telehealth satisfaction levels, however, are contextualized within the expected confines of a pandemic. Further research is required to determine whether satisfaction remains consistent as telemedicine becomes a ubiquitous component of medical practice.

Amyloid-beta (Aβ) deposition occurs in the early stages of Alzheimer’s disease (AD), but the early detection of Aβ is a persistent challenge. Herein, we engineered a near-infrared optical nanosensor capable of detecting Aβ intracellularly in live cells and intracranially in vivo. The sensor is composed of single-walled carbon nanotubes functionalized with Aβ wherein Aβ-Aβ interactions drive the response. We found that the Aβ nanosensors selectively responded to Aβ via solvatochromic modulation of the near-infrared emission of the nanotube. The sensor tracked Aβ accumulation in live cells and, upon intracranial administration in a genetic model of AD, signaled distinct responses in aged mice. This technology enables the interrogation of molecular mechanisms underlying Aβ neurotoxicity in the development of AD in living systems.

Objective: To compare patients with moderate-severe obstructive sleep apnea (OSA) undergoing traditional single and multilevel sleep surgery to those undergoing upper airway stimulation (UAS). Study Design: Case control study comparing retrospective cohort of patients undergoing traditional sleep surgery to patients undergoing UAS enrolled in the ADHERE registry. Setting: 8 multinational academic medical centers. Subjects and Methods: 233 patients undergoing prior single or multilevel traditional sleep surgery and meeting study inclusion criteria were compared to 465 patients from the ADHERE registry who underwent UAS. We compared preoperative and postoperative demographic, quality of life, and polysomnographic data. We also evaluated treatment response rates. Results: The pre and postoperative apnea hypopnea index (AHI) was 33.5 and 15 in the traditional sleep surgery group and 32 and 10 in the UAS group. The postoperative AHI in the UAS group was significantly lower. The pre and postoperative Epworth sleepiness scores (ESS) were 12 and 6 in both the traditional sleep surgery and UAS groups. Subgroup analysis evaluated those patients undergoing single level palate and multilevel palate and tongue base traditional sleep surgeries. The UAS group had a significantly lower postoperive AHI than both traditional sleep surgery subgroups. The UAS group had a higher percentage of patients reaching surgical success, defined as a postoperative AHI Conclusion: UAS offers significantly better control of AHI severity than traditional sleep surgery. Quality life improvements were similar between groups.

Introduction Endoscopic skull base surgery (ESBS) provides a safe, minimally invasive approach to treat benign and malignant skull base lesions. The significance of concomitant sinonasal pathology on imaging in patients undergoing ESBS and its effect on perioperative management is not well described. We sought to identify the prevalence and clinical significance of incidentally found radiographic sinus disease on preoperative imaging in patients undergoing ESBS and provide a protocol for management of these patients. Design A retrospective chart review was performed of consecutive patients who underwent ESBS from January 1, 2016 to June 30, 2018. Preoperative computed tomography (CT) scans were reviewed and scored using the Lund-Mackay (LM) staging system. Preoperative nasal endoscopy findings were analyzed. Any preoperative treatment based on these findings and changes in intraoperative management were examined. Results A total of 156 patients (81 women, 74 men) who underwent ESBS were reviewed. The average LM score was 2 ± 2.7 (range: 0–12). A total of 94 patients (60.3%) had evidence of radiographic sinus disease (LM score > 0) and 23 patients (14.7%) had presence of sphenoid sinus disease. Seven patients (4.5%) were treated preoperatively based on CT and/or nasal endoscopy findings. All patients who received preoperative treatment had evidence of sinus disease on imaging with an average score of 4.7 and were evaluated and treated within 1-2 weeks prior to ESBS. One patient had ESBS postponed until endoscopic sinus surgery was performed for extensive chronic rhinosinusitis (CRS) findings on imaging. Conclusion A review of preoperative imaging in patients undergoing ESBS can help identify concurrent sinonasal disease, which has the potential to alter preoperative as well as intraoperative management in these patients. We report a diligent but conservative approach for the treatment of concomitant CRS in the ESBS population with decision for preoperative treatment guided by various factors.

Medulloblastoma (MB) is the most common malignant pediatric brain tumor with ~30% mediated by Sonic hedgehog (SHH) signaling. While SHH effector Smoothened inhibition is promising, therapeutic index is reduced by high systemic doses required for sufficient intracranial drug concentrations. Treatment-related toxicities associated with radiation therapy result in lifelong morbidity, and SHH pathway inhibition in children notably results in permanent bone defects. Here, we found that nanoparticle-mediated P-selectin targeting on tumor vasculature induces caveolin-1-dependent transcellular passage across the blood-brain barrier. A vismodegib nanocarrier that targets P-selectin exhibited striking efficacy and markedly reduced both bone-related toxicities and drug exposure to healthy brain. These findings demonstrate a potent strategy and novel mechanism for targeted intracranial pharmacodelivery that overcomes the restrictive endothelial barrier to achieve enhanced tumor-selective penetration and has therapeutic implications for other diseases within the central nervous system.

OBJECTIVES/HYPOTHESIS Suboptimal ergonomics during endoscopic sinus surgery can lead to considerable physical discomfort and fatigue for the surgeon. The purpose of this pilot study is to objectively evaluate the ergonomic positions of trainee and attending surgeons while performing functional endoscopic sinus surgery (FESS). STUDY DESIGN Pilot prospective trial. METHODS Six surgeons (two attendings and four trainees) performed FESS while wearing 11 inertial measurement units (IMUs) affixed to either side of each major joint. Screen placement was standardized to be 1 m directly in front of the surgeon and on the patient's left, 0-15° declined from the surgeons' eyes. Bed height was standardized such that the workspace was 0 to 10 cm below the elbows. IMU data were analyzed to calculate joint angles. Ideal joint angles (i.e.

Objective To characterize the clinical features associated with sinonasal complaints after maxillectomy with free flap reconstruction as well as propose a screening and treatment algorithm. Methods Retrospective review of patients who underwent maxillectomy and free flap reconstruction at a tertiary care center. Results Fifty-eight patients were included, 25 (43.1%) of them had documented sinonasal complaints postoperatively. Eleven patients subsequently underwent revision surgery for sinonasal complaints. Among the 25 patients with sinonasal complaints, 22 patients (88.0%) had nasal crusting, 17 (68.0%) had nasal obstruction, 12 (48.0%) had rhinorrhea, 9 (36.0%) had facial pain or pressure, and 7 (28.0%) had foul odor. Twenty-two patients (88.0%) had multiple sinonasal complaints. There was a higher incidence of both sinonasal complaints and surgical intervention in patients who underwent adjuvant radiation, but this was not statistically significant (47.7% vs 28.6%, P = .235; 29.4% vs 7.1%, P = .265). Conclusions Sinonasal complaints are common following free flap reconstruction for a maxillectomy defect and should be screened for at postoperative visits, with early referral to a rhinologist for consideration of endoscopic sinus surgery. Nonsurgical treatment strategies include large-volume nasal saline irrigations, xylitol irrigations for persistent inflammatory symptoms, and culture-directed antibiotic irrigations for persistent infectious symptoms. Level of evidence 4 Laryngoscope, 2021.

BACKGROUND Predictive models to forecast the likelihood of specific outcomes after surgical intervention allow informed shared decision-making by surgeons and patients. Previous studies have suggested that existing general surgical risk calculators poorly forecast head and neck surgical outcomes. However, no large study has addressed this question while subdividing subjects by surgery performed. OBJECTIVES To determine the accuracy of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Surgical Risk Calculator in estimating length of hospital stay and risk of postoperative complications after free tissue transfer surgery. STUDY DESIGN A retrospective chart review of patients at one institution was performed using Current Procedural Terminology codes for anterolateral thigh (ALT) flap, fibula free flap (FFF), and radial forearm free flap (RFFF) reconstruction. Output data from the ACS NSQIP surgical risk calculator were compared with the observed rates in our patients. METHODS Incidences of cardiac complications, pneumonia, venous thromboembolism, return to the operating room, and discharge to skilled nursing facility (SNF) were compared to predicted incidences. Length of stay was also compared to the predicted length of stay. RESULTS Three hundred thirty-six free flap reconstructions with 197 ALT flaps, 85 RFFFs, and 54 FFFFs were included. Brier scores were calculated using ACS NSQIP forecast and actual incidences. No Brier score was

In recent work, CuO nanofluid is prepared with and without PVA (poly(vinyl alcohol)) coated surfactant nanoparticles suspension in distilled water: ethylene glycol (DW:EG) (60:40) ratio for 0.1 wt% and 0.5 wt% concentration of fluid by two-step technique. Our work describes a simple and cost effective chemical precipitation method to synthesis CuO nanoparticles with the addition of synthetic polymer (PVA) allows the modification of physical properties of copper oxide (CuO) nanoparticles. The scanning electron microscopy (SEM) shows the morphological difference in nanocrystallite size and shape between without surfactant coated nanoparticles and with PVA coated particles. XRD pattern of CuO particles reveal that high crystal quality with the monoclinic crystal structure where PVA coated particles have crystallite size 15 nm and without coating it is 31 nm. UV-Vis (ultraviolet absorption spectroscopy) spectra confirmed that the CuO absorption peak at 292 nm and 445 nm for CuO+ PVA. Fourier transform infrared spectra (FTIR) spectroscopy studies show the interaction between PVA and CuO nanoparticles. Experimental results concluded that for CuO + PVA nanofluid, particle size is smaller and showing more stable fluid from zeta potential values. Thermal conductivity results are carried from sound velocity of fluid by Bridgman's equation. As the particle concentration increases in fluid, thermal enhancement is noted. It was found that the viscosity of nanofluid is lower with a larger size particle at the same temperature and for the same concentration. Therefore, our result shows that CuO nanofluids have good potential for effective heat transfer application.

We present a study on the adsorption process of p-group atoms on the α-Al2O3 corundum phase (0 0 0 1) surface by the density functional theory. The band gap is tuneable from an insulator to wide bandgap semiconducting nature by adsorption of p-group atoms (B, C, N, O, F) owing physisorption and chemisorption process on the alumina (0 0 0 1) surface. Adsorption energies are also calculated for all complex systems for centre top, Al-top and O-top sites. The hybridization of adsorbed p-group atoms, tune the electronic properties along to the n-type and p-type nature, which light up the new way to develop possible nanodevice. We also carried out electronic band structure, projected density of state (PDOS), electron localised function (ELF) and optical properties to understand the behaviour of adsorbed adatoms on the substrate. The result concludes that extra adatoms with α-Al2O3 shows the excellent adsorption in an ultraviolet region and work as UV mirrors.

In the reported work, we have approached the interaction of the amino acids onto the antimonene (Sb) monolayer by using density functional theory (DFT). Here, we have considered glycine (Gly), glutamic (Glu), histidine (HIE/His) and phenylalanine (Phe) biomolecules for interaction. The structural, electronic and optical properties have been investigated to understand the behavior. The adsorption of the biomolecules on Sb monolayer show the physisorption process. The adsorption energy of the phenylalanine (Phe) biomolecules is the most favorable. The optical absorption peaks of systems come in the near visible region. The studies conclude that Sb monolayer is useful for the bio-integrated electronics based devices.

To forego misdiagnosis and biopsy-related complications, we explore a novel technique that embraces tissue elasticity to circumvent the current limitations in the accurate, non-invasive detection of prostate cancer. A MEDLINE® database search of literature pertinent to prostate elastography published in the last five years was guided using the following terms: tissue elasticity, ultrasound elastography, strain elastography, magnetic resonance elastography, and shear wave elastography. Ultrasound shear wave elastography (SWE) utilizes the propagation of induced shear waves to provide a quantitative measurement of elasticity of soft tissue. Studies attempting to prove SWE as a strong predictor of malignant prostatic tissue have validated its high specificity and sensitivity compared to the sub-50% range observed with magnetic resonance imaging or transrectal ultrasound. Because its median positive predictive value is also much higher than the sub-40% range attributed to more conventional techniques, SWE yields reduced false-negative biopsy rates. It furthermore exhibits higher intraobserver reproducibility compared to conventional ultrasound. Recent treatments have also utilized SWE for noninvasive prostate cancer tissue ablation. Future improvements include standardized cutoff ranges for quantifying elasticity of malignant tissue. The implementation of a scoring system to predict cancer aggressiveness and prognosis may eliminate the need for unwarranted repeat biopsies postdiagnosis.

In the present work, we investigate the effect of nanoparticle crystallite size and shape on the thermal, rheological and optical properties of low-cost copper oxide nanofluid. Nanofluids are prepared by suspending 0.3% volume of nanoparticles in the 70:30 ethylene glycol:distilled water mixture using ultrasonic vibration, and followed by the microwave irradiation. Our results indicate that the zeta potential values of the nanofluids decrease as nanoparticle anisotropy or aspect ratio increases, zeta potential values decreases. Moreover, the increase in the thermal conductivity of the nanofluids is maximum for the nanofluids prepared using nanorods having the highest aspect ratio of 5.84. The rheology data of the CuO nanofluids with different shapes of nanoparticles at a particle volume fraction of 0.3% indicates that the nanofluids predominantly show Newtonian behaviour, exemplified by the shear rate independent viscosity. Moreover, the rheological behaviour is observed to depend on crystallite size and the nanoparticles shape as marked by an increase in the viscosity which follows the order, spherical

Introduction Options for imaging for evaluation of pediatric patients with unilateral sensorineural hearing loss (USNHL) include computed tomography (CT) and magnetic resonance imaging (MRI). Although both CT and MR imaging provide valuable information in the evaluation of pediatric patients with USNHL, debate remains regarding which imaging modality is most ideal and should be the preferred study for these children. The objective of this study is to evaluate and compare the diagnostic yield of CT versus MRI in children with USNHL. Methods A multi-institutional retrospective chart review was conducted. Pediatric patients with hearing loss (diagnosis codes 389.00–389.22) seen between 2010 and 2012 at three tertiary care centers were identified. Only patients with USNHL and imaging studies were reviewed and results of CT and MRI for each patient were examined and compared. Cochleovestibular or central nervous system findings known to directly correlate to SNHL were noted as positive findings on imaging. McNemar's test was used to compare patients with positive CT and MRI results. Results A total of 219 patients between the ages of 0–18 years with USNHL who underwent CT and/or MRI were identified. Imaging abnormalities were found in 41/96 patients who underwent MRI with overall diagnostic yield of 42.7% and 69 of 188 patients who underwent CT with overall diagnostic yield of 36.7%. For patients who underwent both imaging modalities (n = 65), there was no statistically significant difference in positive findings detected by CT vs MRI (p > 0.05). Conclusions Both CT and MR imaging have similar overall diagnostic yield when used to evaluate children with USNHL. Parents and patients should be counseled regarding cost, test duration, radiation exposure, need for sedation, and diagnostic accuracy associated with each imaging modality and these factors should be considered to select the appropriate diagnostic study.

Background Late cancellations within 24 hours of surgery lead to decreased utilization of operating room time with loss of productivity, decreased access to care, and inconvenience to patients and staff. To date, no studies have analyzed 24-hour cancellations in a tertiary rhinology practice. Methods All procedures performed at a tertiary rhinology/skull base practice from January 2016 to December 2017 were reviewed. Twenty-four-hour cancellations were analyzed by procedure type and reason for cancellation. Avoidable cancellations were late cancellations that could have been prevented by review of medical records or communication by hospital staff with the patient before surgery. Univariate analysis was performed to determine predictive factors for cancellations. Results A total of 39 of 640 surgical cases were cancelled (6.1%) within 24 hours of surgery. Of these, 69.2% were inflammatory and 30.8% were skull base cases. The mean number of operating room minutes lost was 151 (60 of 210) for inflammatory and 263 (102 of 480) for skull base cases. Avoidable cancellations were seen in 25 of 35 (71.4%) cases. Patients undergoing inpatient or skull base surgery were more likely to have medical cancellations than patients undergoing outpatient or inflammatory surgery (91.7% vs 43.5%, p = 0.01; 83.3% vs 47.8%, p = 0.07). Conclusion This is the first study to analyze 24-hour cancellations in tertiary rhinology/skull base surgery. The results suggest that a majority of late cancellations are avoidable and that skull base and inpatient surgeries are more likely to be canceled for medical reasons. Further studies are required to better characterize surgical cancellations in rhinology and identify strategies to try to prevent them.

This article provides a review of modern techniques in the surgical management of the deviated septum with emphasis on the comparison of traditional versus endoscopic septoplasty approaches. Relevant anatomy and physiology of the nasal septum are discussed. A brief history of the evolution of the surgical approaches for the correction of a deviated septum is provided. Traditional and endoscopic septoplasty techniques are reviewed; the indications, advantages, and limitations of each approach are highlighted. Potential complications of septoplasty, with a focus on prevention and management, are also discussed.

Objective: Due to COVID-19, patients who had sinus or skull base surgery in February and early March 2020 were unable toreceive standard postoperative care. Currently, there is a lack of data on the short- and long-term impacts of this. Wesought to examine the effects of the interruption of care due to COVID-19 on sinus and skull base surgery patientoutcomes. Study Design: Retrospective chart review. Methods: A retrospective review was conducted examining outcomes and healthcare utilization of patients at our institutionwho underwent sinus or skull base surgery in February and March of 2020, and who experienced an interruption inpostoperative care due to the pandemic. We then compared these measures with those of patients from the same timeperiod in 2019, who did not experience an interruption in care. Patient characteristics including age, indication for surgery,extent of surgery, polyps, preoperative Lund-Mackay and sinonasal outcome (SNOT22) scores and history of prior sinus orskull base surgery were recorded. Study outcomes included 3 and 6 month postoperative SNOT22 and Modified Lund-Kennedy endoscopy scores, antibiotic usage, sinonasal debridements performed, and number of telephone calls andtelehealth visits in the postoperative period. Results: A total of 107 patients were included. Of the SNOT22 scores available, the average change between preoperativeand 3 month postoperative SNOT22 scores for 2020 ( n = 15) compared to 2019 patients ( n = 30) was not significantlydifferent (a decrease of 17.27 and 19.93, respectively;p = 0.68). The average change between preoperative and 6-monthpostoperative SNOT22 scores for 2020 ( n = 13) compared to 2019 patients ( n = 26) was also not significantly different (adecrease of 18.69 and 20.77, respectively;p = 0.75). The average number of oral postoperative antibiotics received did notsignificantly differ between 2020 ( n = 52) and 2019 ( n = 55) cohorts (0.18 vs. 0.09, respectively;p = 0.53). The averagenumber of postoperative telephone calls did not significantly differ between 2020 and 2019 patients (1.51 vs. 1.19;p = 0.95). Patients in 2019 received an average of 2.35 postoperative sinonasal debridements compared to 1.90 in 2020 ( p =0.03). The average number of postoperative telehealth visits for 2020 patients was 0.72. Of the 2020 patients, 50% werelost to follow-up at 3 months postoperatively compared to 18% in 2019 ( p = 0.0005) and 71% were lost to follow-up at 6months postoperatively in 2020 compared to 36% in 2019 ( p = 0.0003). Conclusion: Although there was an interruption in postoperative care due to COVID-19, patients in 2020 who returned forfollow-up 3 and 6 months after surgery did not report significantly different subjective sinonasal outcomes compared topatients in 2019. A significantly greater number of patients have been lost to follow-up in 2020 compared to 2019 and havenot received routine postoperative care. Further study is required to determine the impact of the interruption of care due toCOVID-19 on sinus and skull base surgery outcomes.

The facial artery and vein, frequently utilized in microvascular head and neck reconstruction, have traditionally been exposed via limited neck dissection or similar neck exploration techniques. However, when neck dissection is not required and/or increased superior pedicle reach is required, these vessels are amenable to isolation via a small aesthetically favorable incision just below the inferior mandible border at the facial notch. The technique described in the following chapter allows for facile vessel access and isolation with minimal morbidity and negligible risk to adjacent neural structures.

Background First described in the early 1990s, endoscopic orbital decompression has become increasingly popular and has been shown to be a safe and effective approach for surgical decompression of the medial and inferior orbit. Methods We present our preferred technique for performing an endoscopic orbital decompression, highlighting key pearls and pitfalls. Results An endoscopic wide maxillary antrostomy and sphenoethmoidectomy is performed in standard fashion. We prefer to resect the middle turbinate for optimal exposure and access. The medial orbital wall is skeletonized and the lamina papyracea is carefully elevated, preserving the underlying periorbita. The orbital floor medial to the infraorbital nerve is resected. Once the periorbita is fully exposed, parallel axial incisions along the medial orbit and orbital floor are made from posterior to anterior using a sickle knife, taking care not to bury the tip to avoid injuring underlying orbital contents. The remaining fibrous bands are incised and prolapse of orbital fat is observed. Post extubation bag mask ventilation is limited to avoid subcutaneous emphysema. Conclusion Compared to open techniques, endoscopic orbital decompression provides superior visualization of critical anatomical landmarks, assures healthy sinus functioning post procedure, offers a lower complication rate, and avoids external incisions.

Objective Nonphysician health care workers are involved in high-risk patient care during the COVID-19 pandemic, placing them at high risk of mental health burden. The mental health impact of COVID-19 in this crucial population has not been studied thus far. Thus, the objective of this study is to assess the psychosocial well-being of these providers. Study Design National cross-sectional online survey (no control group). Setting Academic otolaryngology programs in the United States. Subjects and Methods We distributed a survey to nonphysician health care workers in otolaryngology departments across the United States. The survey incorporated a variety of validated mental health assessment tools to measure participant burnout (Mini-Z assessment), anxiety (Generalized Anxiety Disorder–7), distress (Impact of Event Scale), and depression (Patient Health Questionnaire–2). Multivariable logistic regression analysis was performed to determine predictive factors associated with these mental health outcomes. Results We received 347 survey responses: 248 (71.5%) nurses, 63 (18.2%) administrative staff, and 36 (10.4%) advanced practice providers. A total of 104 (30.0%) respondents reported symptoms of burnout; 241 (69.5%), symptoms of anxiety; 292 (84.1%), symptoms of at least mild distress; and 79 (22.8%), symptoms of depression. Upon further analysis, development of these symptoms was associated with factors such as occupation, practice setting, and case load. Conclusion Frontline otolaryngology health care providers exhibit high rates of mental health complications, particularly anxiety and distress, in the wake of COVID-19. Adequate support systems must be put into place to address these issues.

Objectives Inadvertent intracranial injury from nasogastric tube (NGT) placement is a described and potentially fatal complication following endoscopic transsphenoidal hypophysectomy (TSH). This cadaver study assessed the role of middle turbinate (MT) preservation and medialization in preventing accidental skull base injury from NGT insertion after TSH. Methods: Standard approach for TSH was performed on 3 human cadavers. MTs were placed into neutral position (MTN), then medialized via suture pexy to the septum (MTP), and subsequently resected (MTR). After each stage, 3 blinded individuals passed a 10 F Dobhoff and a 16 F NGT on each side of each cadaver (5 passes per side). Using endoscopic visualization, each pass was scored by a blinded reviewer based on the first contact point of the tube (0 = nasopharynx, 1 = inferior sphenoid face, 2 = sphenoid sinus), with higher scores suggestive of increased risk of intracranial injury. Results: There were 270 Dobhoff and 270 NGT passes scored. Data was divided into 3 groups based on presence and position of the MT. Significant differences were demonstrated between all three groups [one-way ANOVA: Dobhoff F(2,267) = 6.981, p = 0.001], [NGT F(2,267) = 17.582, p

Cisplatin-induced acute kidney injury (CI-AKI) is a significant co-morbidity of chemotherapeutic regimens. While this condition is associated with substantially lower survival and increased economic burden, there is no pharmacological agent to effectively treat CI-AKI. The disease is hallmarked by acute tubular necrosis of the proximal tubular epithelial cells primarily due to increased oxidative stress. In our prior work, we developed a highly-selective kidney-targeted mesoscale nanoparticle (MNP) that accumulates primarily in the renal proximal tubular epithelial cells while exhibiting no toxicity. Here, we found that MNPs exhibit renal-selective targeting in multiple mouse models of tumor growth with virtually no tumor accumulation. We then evaluated the therapeutic efficacy of MNPs loaded with the reactive oxygen species scavenger edaravone in a mouse model of CI-AKI. We found a marked and significant therapeutic effect with this approach as compared to free drug or empty control MNPs, including improved renal function, histology, and diminution of oxidative stress. These results indicated that renal-selective MNP edaravone delivery holds substantial potential in the treatment of acute kidney injury among patients undergoing cisplatin-based chemotherapy.

OBJECTIVE The Sonic Hedgehog (SHH) medulloblastoma subgroup accounts for ~25% of all cases and has an intermediate prognosis. Current conventional therapies result in devastating morbidities including intellectual disability and secondary malignancies. Although molecularly targeted agents that inhibit the SHH pathway have demonstrated clinical efficacy, recent studies have shown on-target secondary toxicities on bone development suggesting new therapeutic approaches are needed. METHODS We investigated the efficacy of the SHH pathway inhibitor, Vismodegib packaged in a fucoidan-based nanoparticle (Fi-Vis) that targets P-selectin, a protein overexpressed on vascular endothelial cells and induced by low-dose ionizing radiation (XRT) in a time- and dose-dependent manner. This P-selectin targeting nanoparticle drug delivery system shows selectivity toward tumor vasculature and not normal brain vasculature in a genetic SHH medulloblastoma mouse model as assessed by ex vivo infrared imaging and two-photon intravital imaging. RESULTS Quantitative RT-PCR analysis of SHH medulloblastoma tissue following single dose XRT and Fi-Vis treatment (10mg/kg) showed a synergistic inhibition of Gli1 expression (>90% target inhibition). Furthermore, we demonstrate that very low dose XRT (0.25Gy) can induce P-selectin expression specifically within MB tumor vasculature and synergize with low dose Fi-Vis (10mg/kg) to significantly enhance mouse survival (p CONCLUSIONS These data suggest applicability of combined XRT and tumor vasculature-targeted nanotherapeutic dose de-escalation strategies for SHH medulloblastoma with implications for other pediatric and adult brain tumors.

BACKGROUND The endoscopic modified Lothrop procedure (EMLP) is commonly performed in recalcitrant frontal sinusitis, in part to achieve better penetration of medicated irrigations postoperatively. Although EMLP requires a septectomy for exposure, it is unknown whether septectomy size affects delivery of irrigations. In this study we evaluated the role of septectomy in delivery of irrigations to the EMLP cavity. METHODS EMLP was performed on fresh human cadavers with sequentially increasing septectomy (minimal septectomy: drilling across septum to combine frontal sinuses; standard septectomy: 1.5 cm anterior to middle turbinate and inferiorly to the midlevel of the turbinate; large septectomy: extension to nasal floor). Irrigation with fluorescein-labeled water was performed with a 240-mL irrigation bottle in the vertex position and recorded with a 30° endoscope fixed in a 4-mm trephine in the paramedian EMLP cavity. Two blinded reviewers scored irrigation distribution recordings (0 = nasal cavity only; 1 = frontal recess; 2 = medial distribution; 3 = lateral distribution; 4 = entire sinus lavage). Distribution scores were assessed with Wilcoxon rank sum analysis. RESULTS Six specimens (mean age, 75.2 ± 2.4; 50% female) were assessed. Interobserver scores were highly concordant (Kendall's W = 0.86, p < 0.01), internally validating the experiment. Distribution scores did not vary significantly when comparing minimal septectomy with standard or large septectomy (Z = 0.55, p = 0.58, Z = 0.37, p = 0.71). CONCLUSION Increasing septectomy does not improve irrigation delivery in patients undergoing EMLP. These results suggest that a limited septectomy for access to the bilateral frontal sinuses is all that is required for effective drug delivery postoperatively. This strategy may reduce morbidity associated with larger septectomies.

Direct targeting to the kidneys is a promising strategy to improve drug therapeutic index for the treatment of kidney diseases. We sought to investigate the renal selectivity and safety of kidney-targeted mesoscale nanoparticle technology. We found that direct intravenous administration of these particles resulted in 26-fold renal selectivity and localized negligibly in the liver or other organs. The nanoparticles targeted the renal proximal tubular epithelial cells, as evidenced by intravital microscopy and ex vivo imaging. Mice treated with the nanoparticles exhibited no negative systemic consequences, immune reaction, liver impairment, or renal impairment. The localization of material selectively to the renal tubules is uncommon, and this work portends the development of renal-targeted drugs for the treatment of kidney diseases.

Covalent bonding of organic functional groups to the sp2 carbon lattice of single-walled carbon nanotubes produces tunable sp3 quantum defects that fluoresce brightly in the second near-infrared region (NIR-II, 1000-1700 nm). Such synthetic defects, also known as organic color centers (OCCs), provide a molecular focal point that sensitively and selectively responds to the local dielectric environments. To take advantage of these unique electronic and optical properties of OCCs for biomedical applications, we discuss a new method that controls the biological interactions/biocompatibility of OCC-based nanosensors via their supramolecular interactions with polymers and other excipients. The resulting nanosensor sensitively detects local intracellular environments in live cells and in vivo. We assess the utility of the nanosensor for cancer research.

Unique properties of nanofluids as an absorber fluid, due to the smaller size of nanoparticles, which cover a larger surface area, make a bulkive evolution in heat transfer. Thermophysical properties of nanofluids are increased due to the potential of the nanoparticles surface area increased which is suspended in the conventional fluid. The initial parameter of thermophysical properties which is thermal conductivity (k) enhanced by some parameters like Brownian motion, interface resistance, morphology of suspended nanoparticles and aggregating in nanofluids are reviewed. In the present review paper, we have also mentioned the synthesis of nanofluids by various techniques; methods of stabilization, stability measurement techniques, and thermal conductivity and heat transfer properties, theoretical models of thermal conductivity and their applications are summarized.

In the recent work, we study on the structural and electronic properties of the graphene like Pd monolayer with the adsorption of oxygen adatoms by using first-principles calculations. The electronic band structure and projected density of states investigate that Pd-surface with oxygen molecule adsorption gives metallic behaviour. We found that the behaviour changed at M -point in the electronic band structure as adding oxygen atoms. The oxygen adsorption was dissociative until the Pd surface immersed with oxygen atoms. The electron charge density increases as the number of oxygen atoms on Pd-surface increases. The noticeable observation is that by adding 7th oxygen atom, they started to ripple from fixed Pd-surface without making a bond due to oxygen coverage increases. The results show that Pd monolayer has different applications as a oxygen catalyst and it can be utilized as the pellet, surface, and film materials to safeguard sustenance from oxidation.

Giant cell myocarditis (GCM), a rapidly progressive inflammation of the myocardium, is associated with fulminant heart failure, refractory ventricular arrhythmias, and conduction system abnormalities. Few case reports have noted orbital myositis as the initial clinical presentation. Our case demonstrates a unique presentation of GCM with only ocular symptoms, which unlike prior studies, rapidly progressed to heart failure, tachyarrhythmias, and conduction disease. Our case necessitated quick recognition and treatment with mechanical support making this the first known case of GCM with successful placement of biventricular assist devices and ultimately with heart transplantation.

Microalbuminuria is an important clinical marker of several cardiovascular, metabolic, and other diseases such as diabetes, hypertension, atherosclerosis, and cancer. The accurate detection of microalbuminuria relies on albumin quantification in the urine, usually via an immunoturbidity assay; however, like many antibody-based assessments, this method may not be robust enough to function in global health applications, point-of-care assays, or wearable devices. Here, we develop an antibody-free approach using synthetic molecular recognition by constructing a polymer to mimic fatty acid binding to the albumin, informed by the albumin crystal structure. A single-walled carbon nanotube, encapsulated by the polymer, as the transduction element produces a hypsochromic (blue) shift in photoluminescence upon the binding of albumin in clinical urine samples. This complex, incorporated into an acrylic material, results in a nanosensor paint that enables the detection of microalbuminuria in patient samples and comprises a rapid point-of-care sensor robust enough to be deployed in resource-limited settings., Microalbuminuria, a clinical marker associated with cancer and hypertension, defined by low albumin levels in the urine, is normally detected by immunoassay. Herein, a nanosensor paint was developed using a polymer to mimic fatty acid binding to albumin, transduced by carbon nanotube fluorescence.

To analyze the association of prior reported key quality metrics-neck dissection ≥18 nodes, radiation oncology referral for stage III/IV disease, unplanned surgery ≤14 days, and unplanned readmission ≤30 days-with disease-free survival (DFS) and overall survival (OS) in oral cavity cancer (OCC).A retrospective chart review.A tertiary care center from 1995 to 2016.Data from patients with OCC who underwent primary surgery were studied. The association of quality metrics and pathology with DFS/OS was determined by Cox proportional hazards regression analysis.A total of 514 patients were included, and 398 (77.4%) underwent elective neck dissection. Key metrics were not associated with DFS on analysis, but higher pathologic stage and extracapsular extension (ECE) were. When stratified by stage, unplanned readmission within 30 days was associated with decreased survival on multivariate analysis (HR = 0.40; 95% CI, 0.20-0.85;In this study, aggressive pathology, rather than adherence to key quality metrics, was associated with lower DFS and OS among patients with OCC. More studies are needed to elucidate the association of quality metrics with survival.

The abnormal accumulation of lipids within the endolysosomal lumen occurs in many conditions, including lysosomal storage disorders, atherosclerosis, non-alcoholic fatty liver disease (NAFLD), and drug induced phospholipidosis. Current methods cannot monitor endolysosomal lipid content in vivo, hindering preclinical drug development and research into the mechanisms linking endolysosomal lipid accumulation to disease progression. We developed a single-walled carbon nanotube-based optical reporter that non-invasively measures endolysosomal lipid accumulation via bandgap modulation of its intrinsic near-infrared emission. The reporter detected lipid accumulation in Niemann-Pick disease, atherosclerosis, and NAFLD models in vivo. By applying the reporter to the study of NAFLD, we found that elevated lipid quantities in hepatic macrophages caused by a high fat diet persist long after reverting to a normal diet. The reporter dynamically monitored endolysosomal lipid accumulation in vivo over time scales ranging from minutes to weeks, indicating its potential to accelerate preclinical research and drug development processes.

OBJECTIVE The Sonic Hedgehog (SHH) medulloblastoma subgroup accounts for ~25% of all cases and has an intermediate prognosis. Current therapies result in devastating morbidities including intellectual disability and secondary malignancies. Although molecularly targeted agents against the SHH pathway have demonstrated efficacy, on-target bone toxicities suggest new therapeutic approaches are needed. METHODS We investigated the SHH pathway inhibitor, vismodegib, packaged in a fucoidan-based nanoparticle (Fi-Vis) that targets P-selectin expressed on endothelial cells and induced by low-dose ionizing radiation (XRT) in a time- and dose-dependent manner. This P-selectin targeting nanoparticle shows selectivity toward tumor and not normal brain vasculature in a GEM SHH medulloblastoma model as assessed by ex vivo infrared imaging and molecular studies. RESULTS Quantitative RT-PCR analysis of SHH medulloblastoma following single dose XRT and Fi-Vis treatment (10mg/kg) showed synergistic reduction of Gli1 expression (>90% target inhibition). We demonstrate that low-dose XRT (0.25Gy) can induce P-selectin expression specifically on medulloblastoma tumor endothelium and synergize with low-dose Fi-Vis (10mg/kg) to significantly enhance mouse survival (p CONCLUSIONS These data suggest applicability of combined XRT and tumor vasculature-targeted nanotherapeutic dose de-escalation strategies for SHH medulloblastoma with implications for other pediatric brain tumors.

Covalent bonding of organic functional groups to the sp2 carbon lattice can produce tunable sp3 quantum defects that fluoresce brightly in the second near-infrared (NIR-II, 1000-1700 nm). Such synthetic defects, or ‘organic color centers’ (OCCs), provide a molecular focal point that sensitively and selectively responds to the local dielectric environments. To benefit from the unique electronic and optical properties of OCCs in biomedical applications, we present a new method that controls the biological interactions/biocompatibility of OCC-based nanosensors via their supramolecular interactions with polymers and other excipients. The resultig OCC-based nanosensor measures endolysosomal pH in live cells and in vivo. We discuss the utility of the nanosensor to real-time monitor the pharmacodynamics of anticancer drugs in solid tumors.