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Introduction: Mercury has long been prohibited for use in skin-lightening agents, but such products are still widely available in many parts of the world.Objective: To evaluate the characte...

The aim of this study was to determine the clinical safety and feasibility of a novel single-port flexible robot for Transoral Robotic Surgery (TORS).This was a prospective phase II / IDEAL stage 2 clinical trial of both benign and malignant lesions of the head and neck. The primary endpoint included conversion rates and perioperative complications within 30 days following surgery. The study was registered on www.ClinicalTrials.gov (NCT03010813). The Fisher's exact test and Mann-Whitney U test were used to compare categorical, and non-parametric data for the trial. A p value0.05 was considered to be statistically significant. Statistical analysis was performed with SPSS 20.0 (IBM Corp., Armonk, New York) RESULTS: Twenty-one patients safely underwent TORS with the da Vinci SP (Intuitive Surgical Inc., Sunnyvale, CA) demonstrating the feasibility of access to the nasopharynx, oropharynx, larynx and hypopharynx. There were no conversions of the robotic surgical system. There were no serious adverse events or adverse events related to the use of the robot at 30-day follow-up for all patients.In a prospective Phase II clinical trial, a novel single-port flexible robotic system appears safe and feasible to use for transoral endoscopic head and neck surgery to access the nasopharynx, oropharynx, larynx and hypopharynx.

Using a strong cooperative learning structure, an inquiry-based course Fire & Ice for non-science majors addresses the concepts of heat and temperature, as well as the historical development of these ideas. A coherent line of inquiry is developed based on the particulate nature of matter which guides students in constructing the concepts of kinetic molecular theory, absolute zero, thermal equilibrium, thermal conduction, energy conservation, and energy degradation. This is accomplished by interleaving hands-on explorations, question-based team discussions, data sharing, and whole class reviews. Student performance on an established thermal concept inventory shows significant improvement. Students also provided more mechanistic and detailed descriptions even as they struggle with precision of language. They perceived this course as different, challenging, accessible, social, and true to the label “inquiry.” A complete video and materials record of the course is available at the UNH Scholars Repository.

Objectives: The indication of transoral robotic surgery for hypopharyngeal cancer is limited because of poor accessibility. The aim of this study was to explore the efficacy of a curved laryngopharyngoscope used in combination with a next-generation flexible robotic surgical system for accessing and resecting the hypopharynx. Methods: A comparative evaluation of the curved laryngopharyngoscope versus standard straight-blade retractors using the flexible robotic surgical system was conducted on 2 cadavers. End points measured included visualization, accessibility, and ease of dissection for accessing and resecting the hypopharynx. Results: Visualization, accessibility, and dissection were superior with the curved laryngopharyngoscope in all subareas of the hypopharynx. The advantages of accessibility and visualization were much more evident in the cadaver with a high body mass index. Conclusions: These preclinical data suggest that using a curved laryngopharyngoscope in combination with a flexible robotic surgical system may lead to technical innovations concerning transoral surgery of the hypopharynx.

Biomarkers are crucial in oncology, from detection and monitoring to guiding management and predicting treatment outcomes. Histological assessment of tissue biopsies is currently the gold standard for oropharyngeal cancers, but is technically demanding, invasive, and expensive. This systematic review aims to review current markers that are detectable in biofluids, which offer promising non-invasive alternatives in oropharyngeal carcinomas (OPCs). A total of 174 clinical trials from the PubMed search engine in the last 5 years were identified and screened by 4 independent reviewers. From these, 38 eligible clinical trials were found and subsequently reviewed. The biomarkers involved, categorized by human papillomavirus (HPV)-status, were further divided according to molecular and cellular levels. Recent trials investigating biomarkers for both HPV-positive and HPV-negative OPCs have approaches from various levels and different biofluids including plasma, oropharyngeal swabs, and oral rinse. Promising candidates have been found to aid in detection, staging, and predicting prognosis, in addition to well-established factors including HPV-status, drinking and smoking status. These studies also emphasize the possibility of enhancing prediction results and increasing statistical significance by multivariate analyses. Liquid biopsies offer promising assistance in enhancing personalized medicine for cancer treatment, from lowering barriers towards early screening, to facilitating de-escalation of treatment. However, further research is needed, and the combination of liquid biopsies with pre-existing methods, including in vivo imaging and invasive techniques such as neck dissections, could also be explored in future trials.

PurposeThe inhibition of estrogen receptor alpha (ERα) or the activation of ERβ can inhibit papillary thyroid cancer (PTC), but the precise mechanism is not known. We aimed to explore the role of ERα and ERβ on the production of endogenous peroxisome proliferator-activated receptor gamma (PPARγ) ligands in PTC.Methods2 PTC cell lines, 32 pairs of PTC tissues and matched normal thyroid tissues were used in this study. The levels of endogenous PPARγ ligands 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), 13-S-hydroxyoctadecadienoic acid (13(S)-HODE), and15-deoxy-Δ12,14-prostaglandin J2 (PGJ2) were measured by ELISA.ResultsThe levels of PGJ2 and 15(S)-HETE were significantly reduced in PTC, but 13(S)-HODE was not changed. Activation of ERα or inhibition of ERβ significantly downregulated the production of PGJ2, 15(S)-HETE and 13(S)-HODE, whereas inhibition of ERα or activation of ERβ markedly upregulated the production of these three ligands. Application of endogenous PPARγ ligands inhibited growth, induced apoptosis of cancer cells, and promoted the efficacy of chemotherapy.ConclusionThe levels of endogenous PPARγ ligands PGJ2 and 15(S)-HETE are significantly decreased in PTC. The inhibition of ERα or activation of ERβ can inhibit PTC by stimulating the production of endogenous PPARγ ligands to induce apoptosis in cancer cells.

The editors would like to acknowledge and thank all of those who assisted us in 2020 by providing peer review of the submitted manuscripts. Reviewers serve without pay. The time, effort and experti...

BackgroundIn contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity.Methods and resultsCLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure.Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest.ConclusionIn patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes.ClinicalTrials identifierISRCTN43070564

Background Head and neck squamous cell carcinoma (HNSCC) currently lacks sensitive approaches to detect cancer‐related traits in body fluid. Methods Methylation of tumor suppressor genes (TSGs) (PAX5, EDNRB, and DCC) were measured in the oral rinses from 50 HNSCC and 58 control subjects using droplet digital PCR (ddPCR). Diagnostic accuracies in detecting HNSCC and the detection rate of recurrence in the post‐treatment monitoring were analyzed. Results ddPCR TSG methylation detection in oral rinses for diagnosis of HNSCC had an AUC of 0.892 for PAX5, 0.753 for EDNRB, and 0.729 for DCC. Significant drop of TSG methylation was observed after completion of surgery (p

Papillary thyroid cancer can dedifferentiate into a much more aggressive form of thyroid cancer, namely into anaplastic thyroid cancer. Nrf2 is commonly activated in papillary thyroid cancer, whereas its role in anaplastic thyroid cancer has not been fully explored. In this study, we used two cell lines and an animal model to examine the function of Nrf2 in anaplastic thyroid cancer. The role of Nrf2 in anaplastic thyroid cancer was investigated by a series of functional studies in two anaplastic thyroid cancer cell lines, FRO and KAT-18, and further confirmed with an in vivo study. The impact of Nrf2 on the sensitivity of anaplastic thyroid cancer cells to lenvatinib was also investigated to evaluate its potential clinical implication. We found that the expression of Nrf2 was significantly higher in anaplastic thyroid cancer cell line cells than in papillary thyroid cancer cells or normal control cells. Knockdown of Nrf2 in anaplastic thyroid cancer cells inhibited their viability and clonogenicity, reduced their migration and invasion ability in vitro, and suppressed their tumorigenicity in vivo. Mechanistically, knockdown of Nrf2 decreased the expression of Notch1. Lastly, knockdown of Nrf2 increased the sensitivity of anaplastic thyroid cancer cells to lenvatinib. As knockdown of Nrf2 reduced the metastatic and invasive ability of anaplastic thyroid cancer cells by inhibiting the Notch 1 signaling pathway and increased the cancer cell sensitivity to lenvatinib, Nrf2 could be a promising therapeutic target for patients with anaplastic thyroid cancer.

The WHO announced the coronavirus disease 2019 (COVID-19) outbreak as a pandemic in February 2020 with over 15 million confirmed cases of COVID-19 globally to date. Otolaryngologists are at a high risk of contracting COVID-19 during this pandemic if there is inadequate and improper personal protective equipment provision, as we are dealing with diseases of the upper-aerodigestive tract and routinely engaged in aerosol-generating procedures.This article discusses the background and transmission route for severe acute respiratory syndrome coronavirus 2, its viral load and temporal profile as well as precaution guidelines in outpatient and operative setting in otorhinolaryngology.As it is evident that COVID-19 can be transmitted at presymptomatic or asymptomatic period of infections, it is essential to practice ear, nose, and throat surgery with high vigilance in a safe and up-to-standard protection level during the pandemic. This article provides a summary for guidelines and recommendations in otorhinolaryngology.

Allogeneic hematopoietic stem cell transplantation is curative for transfusion-dependent thalassemia, but mixed chimerism (MC) may herald graft rejection. We report a child who failed bone marrow transplant (BMT) from matched unrelated donor (MUD) successfully salvaged with haploidentical peripheral blood stem cell transplant (PBSCT), but had MC in T-lymphocyte compartment despite near-complete donor chimerism in myeloid compartment. MC was successfully improved by repeated CD45RA-depleted donor lymphocyte infusion (DLI). A 2-year-old Chinese girl with beta-thalassemia major underwent 12/12-MUD BMT with HU/AZA/Cy/Flu/Bu/TT conditioning resulted in graft rejection. As donor refused second donation, rescue haploidentical PBSCT was performed with alemtuzumab/fludarabine/treosulfan conditioning. Harvest product was CD3/CD45RA depleted with extra products cryopreserved. Split cell chimerism performed 1-month after haplo-transplant showed 97% mother, 3% MUD, and 0% host for granulocytes but 38% mother, 62% MUD, and 0% host for CD3 + T cells. In view of low haploidentical donor chimerism in T-lymphocyte compartment, CD45RA-depleted DLI using cryopreserved product was performed on day + 38, after thymoglobulin 3 mg/kg given as T-cell depletion 3 days beforehand. T-cell chimerism improved to 51% mother and 49% MUD post-DLI. Second cryopreserved CD45RA-depleted DLI was given 17 days after the first DLI (day + 55), and 100% full chimerism of mother's T cells was gradually established without significant graft-versus-host disease (GVHD) or viral reactivation. To conclude, split lineage chimerism determination is beneficial to guide management strategy. For MC in T-cell compartment, CD45RA-depleted DLI is a potential alternative to unselected T cells as it carries lower risk of GVHD and infection.

Elevated wall temperatures and impinging shock interactions are prevalent features in hypersonic flight. Currently, there is a lack of literature regarding experimental studies examining both features in a flight-representative environment. This work details hot-wall, hypersonic, impinging shock/boundary-layer interaction experiments performed in the T4 Stalker Tube. The model configuration was a two-dimensional heated flat plate and a shock generator. The surface of the graphite flat plate was resistively heated to a mean temperature from and a lower unit Reynolds number. Moreover, the scaled separation of the present data showed a high discrepancy with existing separation correlations developed from a supersonic impinging shock and a hypersonic compression ramp, mainly due to the higher shock strength. Instead, the present data followed a scaling law that includes the pressure ratio across the impinging shock with a slight dependence on the wall temperature ratio.

Oral cancers occurring in different subsites can have distinct etiologies' and are a significant problem worldwide. In general, the incidence of oral cancers has declined over the last decade due to improvements in modifiable risk factors (tobacco and alcohol consumption). However, recent data suggest that the incidence of squamous cell carcinomas in the oral tongue and oropharynx are increasing. Human papilloma virus (HPV) is an important risk factor for oropharyngeal cancer and is associated with better treatment responses when compared with HPV-unrelated oropharyngeal cancer. Regardless of the subsite, there are no clinically available biomarkers for the early detection of these cancers and many are detected at an advanced stage and are associated with poor 5-year survival rates. Tumor tissue and serial needle biopsies are used to diagnose and prognosticate oral cancers but have important limitations. Besides being invasive and physically painful, these types of biopsies offer a limited view of a complex tumor due to inter- and intra-tumoral heterogeneity and a dynamic tumor microenvironment. Liquid biopsies offer a promising and alternative way to measure disease in real-time. Extracellular vesicles (EVs) are small particles that are secreted by all cells types and can be readily isolated from a wide range of biofluids. EVs are structurally stable and can horizontally transfer bioactive molecules to distant sites throughout the body in concentrated forms that exceed what can be delivered in a soluble format. As EVs represent their cell of origin, biofluid derived EVs are heterogeneous and are comprised of a complex repertoire of host- and cancer-derived particles. This review article has focused on studies that have used transcriptomics and proteomics to explore the function and clinical significance of EVs in oral cavity and oropharyngeal cancers.

Head and neck cancer (HNC) is a fatal and debilitating disease that is characterized by steady, poor survival rates despite advances in treatment. There is an urgent and unmet need to improve our understanding of what drives this insidious cancer and causes poor outcomes. Extracellular vesicles (EVs) are small vesicles that originate from tumor cells, immune cells, and other cell types and are secreted into plasma, saliva, and other bio-fluids. EVs represent dynamic, real-time changes of cells and offer an exciting opportunity to improve our understanding of HNC biology that may translate to improved clinical practice. Considering the amplified interest in EVs, we have sought to provide a contemporary review of the most recent and salient literature that is shaping the field. Herein, we discuss the functionality of EVs in HNCs and their clinical potential with regards to biomarker and therapeutic capabilities.

To monitor road safety, billions of records can be generated by Controller Area Network bus each day on public transportation. Automation to determine whether certain driving behaviour of drivers on public transportation can be considered safe on the road using artificial intelligence or machine learning techniques for big data analytics has become a possibility recently. Due to the high false classification rates of the current methods, our goal is to build a practical and accurate method for road safety predictions that automatically determine if the driving behaviour is safe on public transportation. In this paper, our main contributions include (1) a novel feature extraction method because of the lack of informative features in raw CAN bus data, (2) a novel boosting method for driving behaviour classification (safe or unsafe) to combine advantages of deep learning and shallow learning methods with much improved performance, and (3) an evaluation of our method using a real-world data to provide accurate labels from domain experts in the public transportation industry for the first time. The experiments show that the proposed boosting method with our proposed features outperforms seven other popular methods on the real-world dataset by 5.9% and 5.5%.

Cisplatin is a chemotherapy drug that has been used to treat a number of cancers for decades, and is still one of the most commonly used anti-cancer agents. However, some patients do not respond to cisplatin while other patients who were originally sensitive to cisplatin eventually develop chemoresistance, leading to treatment failure or/and tumor recurrence.Different mechanisms contribute to cisplatin resistance or sensitivity, involving multiple pathways or/and processes such as DNA repair, DNA damage response, drug transport, and apoptosis. Among the various mechanisms, it appears that microRNAs play an important role in determining the resistance or sensitivity. In this article, we analyzed and summarized recent findings in this area, with the aim that these data can aid further research and understanding, leading to the eventual reduction of cisplatin resistance.microRNAs can positively or negatively regulate cisplatin resistance by acting on molecules or/and pathways related to apoptosis, autophagy, hypoxia, cancer stem cells, NF-κB, and Notch1. It appears that the modulation of relevant microRNAs can effectively re-sensitize cancer cells to cisplatin regimen in certain types of cancers including breast, colorectal, gastric, liver, lung, ovarian, prostate, testicular, and thyroid cancers.

MAPK mutations favor HNSCC survival, revealing the broad clinical utility of MAPK pathway mutations in prognosis and potentially in precision immunotherapy., MAPK pathway mutations affect one-fifth of head and neck squamous cell carcinoma (HNSCC). Unexpectedly, MAPK pathway aberrations are associated with remarkably long patient survival, even among patients with TP53 mutations (median ∼14 yr). We explored underlying outcome-favoring mechanisms with omics followed by preclinical models. Strikingly, multiple hotspot and non-hotspot MAPK mutations (A/BRAF, HRAS, MAPK1, and MAP2K1/2) all abrogated ErbB3 activation, a well-established HNSCC progression signal. Inhibitor studies functionally defined ERK activity negatively regulating phospho-ErbB3 in MAPK-mutants. Furthermore, pan-pathway immunoprofiling investigations identified MAPK-mutant tumors as the only “CD8+ T-cell–inflamed” tumors inherently bearing high-immunoreactive, constitutive cytolytic tumor microenvironments. Immunocompetent MAPK-mutant HNSCC models displayed active cell death and massive CD8+ T-cell recruitment in situ. Consistent with CD8+ T-inflamed phenotypes, MAPK-mutant HNSCC patients, independent of tumor-mutational burden, survived 3.3–4 times longer than WT patients with anti-PD1/PD-L1 immunotherapies. Similar prognosticity was noted in pan-cancers. We uncovered clinical, signaling, and immunological uniqueness of MAPK-mutant HNSCC with potential biomarker utilities predicting favorable patient survival.

Background Otolaryngologists represent a subset of health care workers uniquely vulnerable to COVID‐19 transmission. Given the segmentation of extant guidelines concerning precautions and protective equipment for SARS‐CoV2, we aimed to provide consolidated recommendations regarding appropriate personal protective equipment (PPE) in head neck surgery during the COVID‐19 era. Methods Guidelines published by international and US governing bodies were reviewed in conjunction with published literature concerning COVID‐19 transmission risk, testing, and PPE, to compile situation‐specific recommendations for head and neck providers managing COVID‐19 patients. Results High‐quality data regarding the aerosolization potential of head and neck instrumentation and appropriate PPE during head and neck surgeries are lacking. However, extrapolation of recommendations by governing bodies suggests strongly that head and neck mucosal instrumentation warrants strict adherence to airborne‐level precautions. Conclusion We present a series of situation‐specific recommendations for PPE use and other procedural precautions for otolaryngology providers to consider in the COVID‐19 era.

In India, oral cancer is the most common head and neck cancer (HNC) in men, mainly caused by the consumption of smoked and smokeless tobacco. During the current pandemic, delaying surgery for even 1 or 2 months may lead to more extensive surgery or inoperability, where only supportive care can be provided. Being semi‐emergent in nature, treatment for these patients is currently on hold or delayed in most centers across the country. This study was conducted to assess the impact of COVID‐19 pandemic and inability of the health system to treat HNC in a timely fashion and how surgeons are coping to this emergent situation. This article highlights the situation in India, a country burdened with one of the highest incidence rates of HNC.

This research builds upon Hunt and Vitell's ethical decision-making model to examine consumers' engagement in green behaviors. Using survey data collected from Hong Kong and the United States and with structural equation modelling and bootstrap analyses, it shows that consumers' prevention focus and promotion focus positively affect their ethical idealism (βHK,US = 0.29, 0.19) and relativism (βHK,US = 0.15, 0.21), respectively. Furthermore, idealism positively influences consumers' corresponding ethical judgments (βHK,US = 0.18, 0.31) and decisions, and this influence is higher when the focal green behavior is high in moral intensity (βHK,US = 0.13, 0.12). Contrarily, ethical relativism has a negative impact on the same judgments (βHK,US = −0.11, −0.10) and decisions, and this impact is stronger when consumers' attention to social comparison information is low (βHK,US = 0.10, 0.11). This research contributes to the literature on green behaviors, regulatory focus and consumer ethics, and offers practical insights into promoting green behaviors among consumers.

Head and neck cancer patients with tracheostomies and laryngectomies, as well as their healthcare providers, face unique challenges in the context of the current COVID‐19 pandemic. This document consolidates best available evidence to date and presents recommendations to minimize the risks of aerosolization and SARS‐CoV‐2 exposures in both the inpatient and outpatient settings. The cornerstones of these recommendations include the use of closed‐circuit ventilation whenever possible, cuffed tracheostomy tubes, judicious use of heat moisture exchange units, appropriate personal protective equipment for providers and patients, meticulous hand hygiene, and minimal manipulation of tracheostomy tubes.

Magnesium (Mg) has been known to play vital roles in regulating growth and various metabolic processes. In recent years, the association between Mg and tumorigenesis has raised more and more attention. However, the effects of Mg on the progression of head and neck carcinoma (HNC), as well as the mechanism behind it, remain undefined. In this study, the roles of Mg in tumorigenic activities were tested in CAL27 and FaDu cells as well as in a xenograft tumor model in nude mice. We demonstrated that a moderate increase in extracellular Mg contributed to the proliferation, migration, and invasion of 2 HNC cell lines, while the addition of Mg in drinking water promoted the growth of xenograft tumors in mice without altering their serum Mg levels. Moreover, TRPM7, a major Mg transporter, was shown to be essential for the tumorigenic activities of HNC and the Mg-induced promotive effects on HNC cells and was further shown to be associated with the activation of AKT/mTOR (mammalian target of rapamycin) signaling. In a preliminary clinical study, we determined the Mg ion concentrations in the stimulated saliva from 72 patients with nasopharynx carcinoma and 12 healthy individuals. Our data revealed that the salivary Mg levels of subjects with nasopharynx carcinoma were significantly higher than those of the healthy controls. This is correlated with our finding showing TRPM7 to be overexpressed in tumor tissues harvested from 9 patients with HNC. Therefore, we can conclude that salivary Mg level, within a certain range, could act as a risk factor for the progression of HNC, which involves the activation of AKT/mTOR signaling pathways through the TRPM7 channel. The control of salivary Mg level and the intervention of TRPM7 should not be ignored during the study of HNC.

Results are presented on the freejet testing of a 75%-scale replica of the HIFiRE 7 scramjet. The HIFiRE 7 scramjet flowpath includes a two-dimensional forebody, a rectangular-to-elliptical shape t...

This study examines the performance implications of guanxi-related perk expenditures among listed Chinese firms. Specifically, it investigates how these expenditures influence long-term market-based corporate performance (Tobin's Q and market share) as compared with marketing expenditures. It also examines if political connections moderate this influence. Overall, the findings suggest that guanxi-related perks play an essential marketing role in enhancing long-term corporate success. Furthermore, although marketing expenditures exert much stronger influence on Tobin's Q than guanxi-related perks do, they exert no significant influence on market share. In summary, despite firms' much heavier investments in traditional marketing activities than guanxi-related perk activities, the findings highlight the significant performance contribution that guanxi-related perks can still make to a firm. Moreover, this study reveals that political connections weaken the positive impact of guanxi-related perks on both performance measures, thus reminding executives of the dampening effect of these connections on the effective use of perk spending.

Evasion of autophagy is key for intracellular survival of bacteria in host cells, but its involvement in persistent infection by Helicobacter pylori, a bacterium identified to invade gastric epithelial cells, remains obscure. The aim of this study was to functionally characterize the role of autophagy in H. pylori infection. Autophagy was assayed in H. pylori-infected human gastric epithelium and the functional role of autophagy was determined via genetic or pharmacological ablation of autophagy in mouse and cell line models of H. pylori infection. Here, we showed that H. pylori inhibited lysosomal function and thereby promoted the accumulation of autophagosomes in gastric epithelial cells. Importantly, inhibiting autophagosome formation by pharmacological inhibitors or genetic ablation of BECN1 or ATG5 reduced H. pylori intracellular survival, whereas inhibition of lysosomal functions exerted an opposite effect. Further experiments demonstrated that H. pylori inhibited lysosomal acidification and the retrograde trafficking of mannose-6-phosphate receptors, both of which are known to positively regulate lysosomal function. We conclude that H. pylori subverts autophagy into a pro-survival mechanism through inhibition of lysosomal clearance of autophagosomes. Disruption of autophagosome formation offers a novel strategy to reduce H. pylori colonization in human stomachs. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Summary Topical treatments in ophthalmologic therapy are significant for the development of allergic contact dermatitis (ACD) in the periorbital region. Preservatives, antibiotics, glucocorticoids, and beta-blocker eye drops are defined as drugs with the highest sensitizing potential. The unavailability of patch test batteries containing substances of ophthalmological use makes it difficult for this diagnosis. In the present report, we describe six patients who developed ACD induced by different agents presenting in eye drops, confirmed with the cutaneous patch tests. The ACD diagnosis due to ophthalmic medications can be challenging, since many different agents can cause it, and the sensitivity of these cutaneous tests is low. Thus, early diagnosis is essential to avoid the complications of ACD on the skin and ocular disorders related to chronic periorbital eczema.

Large-scale free-piston driven expansion tubes have uniquely high total pressure capabilities which make them an important resource for development of access-to-space scramjet engine technology. However, many aspects of their operation are complex, and their test flows are fundamentally unsteady and difficult to measure. While computational fluid dynamics methods provide an important tool for quantifying these flows, these calculations become very expensive with increasing facility size and therefore have to be carefully constructed to ensure sufficient accuracy is achieved within feasible computational times. This study examines modelling strategies for a Mach 10 scramjet test condition developed for The University of Queensland’s X3 facility. The present paper outlines the challenges associated with test flow reconstruction, describes the experimental set-up for the X3 experiments, and then details the development of an experimentally tuned quasi-one-dimensional CFD model of the full facility. The 1-D model, which accurately captures longitudinal wave processes, is used to calculate the transient flow history in the shock tube. This becomes the inflow to a higher-fidelity 2-D axisymmetric simulation of the downstream facility, detailed in the Part 2 companion paper, leading to a validated, fully defined nozzle exit test flow.

This paper presents the second part of a study aiming to accurately characterise a Mach 10 scramjet test flow generated using a large free-piston-driven expansion tube. Part 1 described the experimental set-up, the quasi-one-dimensional simulation of the full facility, and the hybrid analysis technique used to compute the nozzle exit test flow properties. The second stage of the hybrid analysis applies the computed 1-D shock tube flow history as an inflow to a high-fidelity two-dimensional-axisymmetric analysis of the acceleration tube. The acceleration tube exit flow history is then applied as an inflow to a further refined axisymmetric nozzle model, providing the final nozzle exit test flow properties and thereby completing the analysis. This paper presents the results of the axisymmetric analyses. These simulations are shown to closely reproduce experimentally measured shock speeds and acceleration tube static pressure histories, as well as nozzle centreline static and impact pressure histories. The hybrid scheme less successfully predicts the diameter of the core test flow; however, this property is readily measured through experimental pitot surveys. In combination, the full test flow history can be accurately determined.

Objectives To describe the first experience with a free vastus lateralis muscle-only flap to be used to cover and protect the exposed skull base and carotid artery from radiotherapy-induced skull base osteoradionecrosis (ORN). Design Retrospective review of a case series. Setting Tertiary academic medical center. Participants Post treatment nasopharyngeal carcinoma patients with skull base ORN. Main Outcome Measures Coverage of the internal carotid artery (ICA). Results Four patients underwent the procedure. Following the procedure, all patients were documented to have adequate viable soft tissue covering their ICA. Topical nasal steroids were prescribed to all patients as florid granulation tissue was noted to occur overlying the muscle flap in the early postoperative period. There were no flap failures. All patients noted an improvement in speech, cacosmia, and nasal crusting. No significant epistaxis occurred following surgery. Choanal stenosis was noted in three patients. Conclusion For skull base ORN resulting from the treatment of nasopharyngeal carcinoma (NPC) with radiotherapy that fails conservative management, an open approach to the nasopharynx, that allows debridement then placement of a vastus lateralis muscle-only free flap for coverage, offers a unique and viable approach to the management of this challenging condition.

Diabetes is a significant chronic disease that in limited studies has been linked with olfactory dysfunction. We investigated the cross-sectional association between diabetes and olfactory dysfunction in 3151 adults aged ≥40 years who participated in US National Health and Nutrition Examination Survey 2013-2014 with information on olfactory dysfunction and diabetes. Diabetes was defined from fasting serum glucose ≥126 mg/dL, oral glucose tolerance test ≥200 mg/dL, HbA1c levels ≥6.5%, physician-diagnosed diabetes, or current use of oral hypoglycemic agents and/or insulin. Self-reported olfactory dysfunction was defined as a positive answer to any of the following questions: 1) "Have you had problem with smell in the past 12 months?"; 2) "Have you had a change in the ability to smell since age 25?", or 3) "Do you have phantom smells?". Participants were considered to have severe hyposmia or anosmia if they had