Search

Background: Complications during endoscopic sinus surgery often result from unfavorable anatomy. The prevalence rates of such anatomic findings vary tremendously in the literature, in part due to the small, homogenous populations previously studied., Objective: To characterize the prevalence of sinonasal anatomic variants among ethnic groups and genders seen at an academic medical center., Methods: This is a retrospective cross-sectional study of adult subjects who underwent CT imaging of the sinuses from January 2019 to November 2020 at a tertiary academic setting. CT scans were analyzed systematically by 3 trained study personnel for the presence of critical sinus anatomic variants that endoscopic sinus surgeons typically evaluate for preoperatively. Chi-squared tests and analyses of variance were conducted to detect differences in the prevalence of structural findings between genders and races/ethnicities., Results: A total of 489 subjects (57% female) were included: 44 Asian, 14 Black/African American, 101 Hispanic/Latino, 203 White, 127 Other. The prevalence of the following anatomical variants differed by race/ethnicity: Haller cells, Type 3 optic nerve, Onodi cells, maxillary septations, sphenoid lateral recess, anterior clinoid process pneumatization, and carotid artery dehiscence. Asian subjects had higher rates of Haller cells (48% vs 16%, P  < .001) and Type 3 optic nerve (18% vs 4%, P  = .022) compared to Hispanic subjects, as well as a higher prevalence of Onodi cells (39% vs 17%, P  = .003) compared to White subjects. Males had a higher prevalence of mesenteric anterior ethmoid arteries (62% vs 45%, P  < .001) and dehiscent carotid arteries (30% vs 21%, P  = .024)., Conclusion: Certain sinonasal anatomic variants, which have direct implications for complications during endoscopic sinus surgery, were found to be significantly more prevalent in some demographic groups. Surgeons should be aware of these differences in their review of preoperative imaging for safe surgical planning.

High-performance chiroptical synaptic phototransistors are successfully demonstrated using heterojunctions composed of a self-assembled nanohelix of a π-conjugated molecule and a metal oxide semiconductor. To impart strong chiroptical activity to the device, a diketopyrrolopyrrole-based π-conjugated molecule decorated with chiral glutamic acid is newly synthesized; this molecule is capable of supramolecular self-assembly through noncovalent intermolecular interactions. In particular, nanohelix formed by intertwinded fibers with strong and stable chiroptical activity in a solid-film state are obtained through hydrogen-bonding-driven, gelation-assisted self-assembly. Phototransistors based on interfacial charge transfer at the heterojunction from the chiroptical nanohelix to the metal oxide semiconductor show excellent chiroptical detection with a high photocurrent dissymmetry factor of 1.97 and a high photoresponsivity of 218 A W -1 . The chiroptical phototransistor demonstrates photonic synapse-like, time-dependent photocurrent generation, along with persistent photoconductivity, which is attributed to the interfacial charge trapping. Through the advantage of synaptic functionality, a trained convolutional neural network successfully recognizes noise-reduced circularly polarized images of handwritten alphabetic characters with better than 89.7% accuracy., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

We previously showed that folic acid prescriptions for any indication were associated with lower rates of suicidal behaviour. Given that future randomised clinical trials are likely to focus on psychiatric disorders carrying elevated risk for suicide, we now report on the moderating effects of prior suicidal behaviour, psychiatric diagnoses and psychotropic medications on potential antisuicidal effects of folic acid. Data were obtained from the MarketScan Commercial Claims and Encounters databases that cover 164 million insured persons from 2005-2017, from which a cohort of 866 586 patients was derived. Analysis revealed no significant moderation effects on the antisuicidal effect of folic acid. These findings indicate that the potential benefit of folic acid for preventing suicidal behaviour is comparable in psychiatric populations at higher risk of suicide and that it may be additive to any benefit from psychotropic medications.

The photoelectrochemical behavior of Rh cluster-deposited hematite (α-Fe 2 O 3 ) photoanodes (α-Fe 2 O 3 @Rh) was investigated. The interactions between Rh clusters and α-Fe 2 O 3 nanorods were elucidated both experimentally and computationally. A facile UV-assisted solution casting deposition method allowed the deposition of 2 nm Rh clusters on α-Fe 2 O 3 . The deposited Rh clusters effectively enhanced the photoelectrochemical performance of the α-Fe 2 O 3 photoanode, and electrochemical impedance spectroscopy (EIS) and Mott-Schottky analysis were applied to understand the working mechanism for the α-Fe 2 O 3 @Rh photoanodes. The results revealed a distinctive carrier transport mechanism for α-Fe 2 O 3 @Rh and increased carrier density, while the absorbance spectra remained unchanged. Furthermore, density functional theory (DFT) calculations of the oxygen evolution reaction (OER) mechanism corresponded well with the experimental results, indicating a reduced overpotential of the rate-determining step. In addition, DFT calculation models based on the X-ray diffraction (XRD) measurements and X-ray photoelectron spectroscopy (XPS) results provided precise water-splitting mechanisms for the fabricated α-Fe 2 O 3 and α-Fe 2 O 3 @Rh nanorods. Owing to enhanced carrier generation and hole transfer, the optimum α-Fe 2 O 3 @Rh3 sample showed 78% increased photocurrent density, reaching 1.12 mA/cm -2 at 1.23 V RHE compared to that of the pristine α-Fe 2 O 3 nanorods electrode.

Background: Juvenile nasopharyngeal angiofibromas (JNAs) are characterized by expansive and destructive growth, often invading the midline/paranasal sinuses, pterygopalatine fossa, and infratemporal fossa and can extend into the orbit, cavernous sinus, or intracranially., Objective: To evaluete the major benefits of the extended endoscopic endonasal approach (EEA) for JNA resection as compared with more traditional and invasive transpalatal and transfacial approaches. When JNAs extend into lateral anatomic compartments, the optimal operative trajectory often requires additional approach strategies or surgical staging., Methods: We retrospectively reviewed 8 cases of large JNAs arising in symptomatic adolescent boys (University of Pittsburgh Medical Center Stages II, III, and V) and discuss anatomic and tumor considerations guiding the decision of a pure EEA vs combined EEA and sublabial transmaxillary approach (Caldwell-Luc)., Results: A pure extended EEA was used in 6 JNA cases (UPMC Stages II-III); a multiportal EEA + Caldwell-Luc maxillotomy was used in 2 cases. One of the 2 patients (UPMC Stage V) previously treated with multiportal EEA + Caldwell-Luc maxillotomy underwent staged left temporal/transzygomatic craniotomy, obtaining gross total resection. Seven patients ultimately underwent complete removal without recurrence. One patient with a small residual JNA (UPMC II) underwent stereotactic radiosurgery without progression to date., Conclusion: JNAs with lateral extension into the infratemporal fossa often benefited from additional lateral exposure using a Caldwell-Luc maxillotomy. Cases with significant skull base and/or dural involvement may undergo staged surgical treatment; temporalis + transzygomatic craniotomy is often useful for second-stage approaches for residual tumor in these lateral infratemporal or intracranial regions. SRS should be considered for residual tumor if additional surgery is not warranted., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Fluorescent dissolved organic matter (FDOM) in surface water has broad implications on water quality research and operations. Solid phase extraction (SPE) is the most widely used technique to extract FDOM. However, fluorescent elution preferences by common solvents and content of quantifiable chromophores in waste fraction remain largely unknown, both quantitatively and qualitatively. In this work, the preferential selection of various types of FDOM captured by and lost from SPE as characterized by the fluorescence excitation-emission matrix (EEM) were investigated. Three elution solvents (methanol, acetone, and dichloromethane) were adopted to elute the DOM that was enriched on a typical SPE sorbent. Results revealed that high polarity (methanol) and medium polarity (acetone) solvents eluted the highest variety and quantity of humic acid-like substances (Region V), while the low polarity (dichloromethane) elution solvent was more suitable for eluting tyrosine (Region I) and tryptophan (Region II). Compared to eluting only with methanol, sequential elution and recombination using the three aforementioned solvents demonstrated a significant increase in not only DOC recovery (by 7%), but fluorescence integral values and fluorescence characteristics covering collectively much larger fluorescence regions that more closely resembled raw water. For the first time, the fluorescence EEM of waste after loading the sample revealed a previously overlooked FDOM loss of 20%, caused by ineffective adsorption onto the solid phase resin. Substantial carbonaceous and nitrogenous FDOM were present in this fraction (the fluorescence intensity of aromatic protein in waste exceeds 20% of that in raw water), indicating possible underestimations of FDOM-related research in areas such as disinfection byproduct and toxicity work. The results of this study provide both a qualitative and quantitative characterization of the elution and lost products of SPE in capturing FDOM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: To identify changes in otolaryngologists' opioid prescribing trends for Medicare beneficiaries associated with the enactment of state laws that limit the duration of prescriptions to 3-7 days in the years 2016 and 2017 in the United States., Methods: Through the Centers for Medicare and Medicaid Services (CMS) database, we retrieved data on Medicare enrollment and on the total days prescribed and total number of beneficiaries for the drugs codeine/acetaminophen, hydrocodone/acetaminophen, oxycodone HCl, oxycodone/acetaminophen, and tramadol HCl, by each otolaryngologist prescriber in 13 states from January 2013 to December 2019. We modeled trends using linear spline regression models that controlled for Medicare beneficiaries' state-level socio-demographic characteristics' fixed effects., Results: Across the 13 states, the number of days of all five opioids prescribed per beneficiary declined by 8.35 (SD = 12.61). The most commonly prescribed opioid type by otolaryngologists during the 5-year study period was tramadol HCl (28.72 days/beneficiary) followed by oxycodone HCl (19.99 days/beneficiary). All opioids had declines in prescription days over this time window and higher rates of decline in the years following law passage. Four states experienced statistically significant declines in the prescriptions of all opioids after the year of legislation passage ( p  < .05). Some states that had the greatest inclines in opioid prescriptions in the years prior to law enactment also experienced the greatest reductions in the time after legislation enactment., Conclusions: Opioid prescribing practices of otolaryngologists may have been affected by opioid prescription duration limiting laws passed in 13 states in 2016 and 2017., Level of Evidence: Level 4., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objective: To understand the effect of age on health-related quality of life (HRQoL) in patients with hearing loss and determine how primary language mediates this relationship., Study Design: Cross-sectional study., Setting: General otolaryngology clinic in Los Angeles., Methods: Demographics, medical records, and HRQoL data of adult patients presenting with otology symptoms were reviewed. HRQoL was measured using the Short-Form 6-Dimension utility index. All patients underwent audiological testing. A path analysis was performed to generate a moderated path analysis with HRQoL as the primary outcome., Results: This study included 255 patients (mean age = 54 years; 55% female; 27.8% did not speak English as a primary language). Age had a positive direct association with HRQoL ( p  < .001). However, the direction of this association was reversed by hearing loss. Older patients exhibited significantly worse hearing ( p  < .001), which was negatively associated with HRQoL ( p  < .05). Primary language moderated the relationship between age and hearing loss. Specifically, patients who did not speak English as a primary language had significantly worse hearing ( p  < .001) and therefore worse HRQoL ( p  < .01) than patients who spoke English as a primary language with hearing loss. Increasing age was associated with bilateral hearing loss compared to unilateral hearing loss ( p  < .001) and subsequently lower HRQoL ( p  < .001). Polypharmacy ( p  < .01) and female gender ( p  < .01) were significantly associated with lower HRQoL., Conclusion: Among otolaryngology patients with otology symptoms, older age and not speaking English as a primary language were associated with worse hearing and subsequently lower HRQoL., Competing Interests: None., (© 2023 The Authors. OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Although the benefits outweigh the risks, COVID-19 vaccines have been associated with an increased risk of myocarditis and pericarditis. This report is based on a national US veteran population with confirmed myocarditis/pericarditis following mRNA COVID-19 vaccines according to the near real-time active surveillance program of Veterans Affairs., Methods: This study is based on a cohort evaluation of all adults administered ≥1 mRNA COVID-19 vaccine, including boosters, in the Veterans Health Administration between 14 December 2020 and 9 October 2022. ICD-10-CM diagnosis codes were used to identify potential safety signals in near real time through a database analysis. All potential cases of myocarditis/pericarditis identified in the database analysis underwent in-depth chart review and case validation by a team of pharmacists and expert clinicians. Our main outcome was the incidence rate of confirmed myocarditis/pericarditis among vaccine recipients (overall and those aged 18-39 years) within 21 days of a first, second, or booster dose of a mRNA COVID-19 vaccine. We calculated the ratio of observed events among COVID-19 vaccine recipients over expected events from historical vaccine recipient controls (2015-2020) in the Veterans Health Administration. We used confirmed cases to calculate incidence rates and 95% CIs., Results: Through 9 October 2022, 3 877 453 doses of BNT162b2 (Pfizer-BioNTech) and 4 221 397 doses of mRNA-1273 (Moderna) were administered as first or second dose across Veterans Affairs, and 1 012 561 BNT162b2 and 1 156 160 mRNA-1273 booster doses were administered. Among all doses, the rapid cycle analysis identified 178 potential cases of myocarditis/pericarditis among vaccinees of any age and 22 potential cases among those aged 18-39 years. Of these, 33 cases, including 6 among those 18-39 years old, were confirmed after in-depth chart review and validation, corresponding with an overall incidence rate per million ranging from 0.46 (95% CI, .01-2.55) for Moderna dose 1 to 6.91 (95% CI, 2.78-14.24) for Pfizer booster. Among those aged 18-39, incidence rates ranged from 7.1 (95% CI, .18-39.56) for Moderna dose 2 to 19.76 (95% CI, 5.38-50.58) for Pfizer dose 2. Patients with confirmed cases were hospitalized for a mean 4.1 days (range, 1-15). The final disposition for 32 (97%) of 33 cases was discharge to home., Conclusions: This report is a real-world demonstration of the Veterans Affairs' active surveillance system for vaccines. Although the rapid cycle analysis initially identified 178 potential cases of myocarditis/pericarditis, only 1 of 5 cases was confirmed to be related to a COVID-19 vaccine after chart review. These findings highlight the paramount importance of active surveillance and chart validation for rare but serious adverse events related to COVID-19 vaccines., Competing Interests: Potential conflicts of interest. K. H., C. S., N. H., M. B., F. C., B. T., and L. P. are employees of VA Center for Medication Safety. All other authors report no potential conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Epigenetic alterations, especially histone methylation, are key factors in cell migration and invasion in cancer metastasis. However, in lung cancer metastasis, the mechanism by which histone methylation regulates metastasis has not been fully elucidated. Here, we found that the histone methyltransferase SMYD2 is overexpressed in lung cancer and that knockdown of SMYD2 could reduce the rates of cell migration and invasion in lung cancer cell lines via direct downregulation of SMAD3 via SMYD2-mediated epigenetic regulation. Furthermore, using an in vitro epithelial-mesenchymal transition (EMT) system with a Transwell system, we generated highly invasive H1299 (In-H1299) cell lines and observed the suppression of metastatic features by SMYD2 knockdown. Finally, two types of in vivo studies revealed that the formation of metastatic tumors by shSMYD2 was significantly suppressed. Thus, we suggest that SMYD2 is a potential metastasis regulator and that the development of SMYD2-specific inhibitors may help to increase the efficacy of lung cancer treatment., (© 2023. The Author(s).)

Aims/hypothesis: Non-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes may more easily progress towards severe forms of non-alcoholic steatohepatitis (NASH) and cirrhosis. Although the Wnt effector transcription factor 7-like 2 (TCF7L2) is closely associated with type 2 diabetes risk, the role of TCF7L2 in NAFLD development remains unclear. Here, we investigated how changes in TCF7L2 expression in the liver affects hepatic lipid metabolism based on the major risk factors of NAFLD development., Methods: Tcf7l2 was selectively ablated in the liver of C57BL/6N mice by inducing the albumin (Alb) promoter to recombine Tcf7l2 alleles floxed at exon 5 (liver-specific Tcf7l2-knockout [KO] mice: Alb-Cre;Tcf7l2 f/f ). Alb-Cre;Tcf7l2 f/f and their wild-type (Tcf7l2 f/f ) littermates were fed a high-fat diet (HFD) or a high-carbohydrate diet (HCD) for 22 weeks to reproduce NAFLD/NASH. Mice were refed a standard chow diet or an HCD to stimulate de novo lipogenesis (DNL) or fed an HFD to provide exogenous fatty acids. We analysed glucose and insulin sensitivity, metabolic respiration, mRNA expression profiles, hepatic triglyceride (TG), hepatic DNL, selected hepatic metabolites, selected plasma metabolites and liver histology., Results: Alb-Cre;Tcf7l2 f/f essentially exhibited increased lipogenic genes, but there were no changes in hepatic lipid content in mice fed a normal chow diet. However, following 22 weeks of diet-induced NAFLD/NASH conditions, liver steatosis was exacerbated owing to preferential metabolism of carbohydrate over fat. Indeed, hepatic Tcf7l2 deficiency enhanced liver lipid content in a manner that was dependent on the duration and amount of exposure to carbohydrates, owing to cell-autonomous increases in hepatic DNL. Mechanistically, TCF7L2 regulated the transcriptional activity of Mlxipl (also known as ChREBP) by modulating O-GlcNAcylation and protein content of carbohydrate response element binding protein (ChREBP), and targeted Srebf1 (also called SREBP1) via miRNA (miR)-33-5p in hepatocytes. Eventually, restoring TCF7L2 expression at the physiological level in the liver of Alb-Cre;Tcf7l2 f/f mice alleviated liver steatosis without altering body composition under both acute and chronic HCD conditions., Conclusions/interpretation: In mice, loss of hepatic Tcf7l2 contributes to liver steatosis by inducing preferential metabolism of carbohydrates via DNL activation. Therefore, TCF7L2 could be a promising regulator of the NAFLD associated with high-carbohydrate diets and diabetes since TCF7L2 deficiency may lead to development of NAFLD by promoting utilisation of excess glucose pools through activating DNL., Data Availability: RNA-sequencing data have been deposited into the NCBI GEO under the accession number GSE162449 ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE162449 )., (© 2023. The Author(s).)

Keloids are skin tumours caused by aberrant growth of dermal fibroblasts. Cellular senescence contributes to aging and various pathological conditions, including cancer, atherosclerosis, and fibrotic diseases. However, the effects of cellular senescence and senolytic drugs on keloids remain largely unknown. This study investigated senescent fibroblasts in keloids and assessed the effects of dasatinib on these cells. Tissues acquired from keloid removal surgery were analysed for senescence-associated β-galactosidase-positive cells, p16 expression, and the effects of dasatinib treatment on keloids. Keloid tissue was xenotransplanted into mice, and the effect of intralesional dasatinib injection on keloid growth was observed. The results showed that the numbers of β-galactosidase-positive and p16-expressing cells were higher in the keloids compared with in the controls. Dasatinib induced selective clearance of senescent cells and decreased procollagen expression in cultured keloid fibroblasts. In this xenotransplant keloid mouse model, intralesional injection of dasatinib reduced gross keloid tissue weight and the expression of both procollagen and p16. In addition, dasatinib-treated keloid fibroblasts conditioned medium reduced procollagen and p16 expression in cultured keloid fibroblasts. In conclusion, these results suggest that an increased number of senescent fibroblasts may play an important role in the pathogenesis of keloids. Therefore, dasatinib could be an alternative treatment for patients with keloids.

Objectives: The combined effects of age and gender on health-related quality of life (HRQoL) in otolaryngology patients are unclear. This study tested the hypothesis that the effect of age on HRQoL differs by gender in otolaryngology patients., Methods: Patients seen in a general otolaryngology clinic were included in this retrospective chart review. HRQoL was measured by the SF-6D score. Patient characteristics, including demographics and category of chief otolaryngology complaint, were extracted from medical records. A multivariable linear regression analysis was used to analyze the combined effect of age and gender on HRQoL. The model was adjusted for race, ethnicity, number of complaint categories, and number of medications., Results: The study included 728 patients (age mean = 52, SD = 18; 48% male). Multivariable linear regression models found a significant interaction effect between age and gender (β = 0.213, p < 0.05). For younger patients, female gender was protective; however, at age greater than 35 years, female gender was a risk factor for decreased HRQoL. Compared to Black patients, Asian and other race patients reported significantly greater HRQoL (β = 0.207, p < 0.05 for Asian; β = 0.126, p < 0.05 for other races). Additionally, an antagonistic interaction effect was found between age and number of category of otolaryngology complaints in moderating HRQoL (β = 0.468, p < 0.001)., Conclusion: Age affects HRQoL differently in men than in women. Among otolaryngology patients, women experience a greater decrease in HRQoL as they age., Level of Evidence: 4 Laryngoscope, 133:801-806, 2023., (© 2022 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: The utilization of image-guided navigation during endoscopic sinus surgery (ESS) has increased significantly since its introduction. However, the most common associated complications are still unknown. This study describes and analyzes adverse events related to image-guided ESS., Study Design: Cross-sectional analysis., Setting: The Food and Drug Administration's 2018-2022 MAUDE database (Manufacturer and User Facility Device Experience)., Methods: The MAUDE database was searched for all reports on adverse events involving sinus navigation systems used in ESS from 2018 to 2022. Reported events were reviewed and categorized., Results: During the study period, there were 1857 adverse events from 1565 reports, which were divided into device-related (n = 1834, 98.8%) and patient-related (n = 23, 1.2%) complications. The most common device-related complications were nonfunctionality of the system (n = 512, 27.9%), device imprecision (n = 427, 23.3%), and device sensing problems (n = 277, 15.1%). The most common patient-related complications were cerebrospinal fluid (CSF) leak (n = 14, 60.9%), intracranial injury (n = 4, 17.4%), and bleeding/hemorrhage (n = 3, 13.1%). Imprecision was associated with increased risk of navigation abortion by the surgeon (odds ratio, 1.50 [95% CI, 1.38-1.65]; P < .001) and increased risk of CSF leak (odds ratio, 16.5 [95% CI, 3.66-74.0]; P < .001) as compared with other device-related complications., Conclusions: The most commonly reported device- and patient-related adverse events associated with image-guided sinus navigation systems were device nonfunction, imprecision, device sensing difficulties, and CSF leak. When imprecise navigation occurred, there was an increased likelihood of CSF leak and navigation abortion by the surgeon. Health care providers should be mindful of these possible complications when electing to use image-guided sinus navigation during ESS., (© 2022 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Objective: To assess sociodemographic differences in the prevalence of self-reported dysphagia and treatment and to identify barriers in access to care., Study Design: Cross-sectional analysis., Setting: National healthcare survey database., Methods: The 2012 National Health Interview Survey was used to analyze adults who reported a swallowing problem in the prior 12 months. Associations of sociodemographic variables with dysphagia prevalence and treatment as well as access to care were determined by multivariate logistic regression., Results: Among 235 million adults in the United States, 9.4 ± 0.3 million (4.0 % ± 0.1 %) adults (mean age 52.1 ± 0.6 years; 60.2 % female) reported swallowing problems, only 19.2 % ± 2.0 % of whom reported receiving treatment or therapy for their swallowing problem. In a multivariate model controlling for sociodemographic factors, female gender, older age, lower income level, public insurance status and unemployment were independently associated with increased odds of reporting dysphagia, while also associated with decreased odds of receiving treatment. Conversely, Black, Hispanic and other racial/ethnic minorities were less likely to report swallowing problems, but among those who did report dysphagia, non-white adults were more likely to receive treatment. Barriers leading to delayed care for women, low-income adults and adults with public or no health insurance included cost, not being able to get an appointment soon enough, limited office hours, inability to get through to an office by phone, lack of transportation, and long office wait times., Conclusion: Sociodemographic groups at higher risk for dysphagia are less likely to receive treatment. Targeted interventions are needed to address barriers to care., Level of Evidence: IV., Competing Interests: Conflict of interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Intranasal corticosteroids (INCS) are a commonly prescribed medication to treat various rhinological conditions. However, no prior studies have looked at factors and patterns that influence the rates of INCS prescriptions among Medicare beneficiaries in the United States., Objective: This study aims to describe the patterns of INCS prescriptions by otolaryngologists for Medicare beneficiaries in the United States between 2013 and 2017., Methods: Data on the most common INCS prescriptions by otolaryngologists for Medicare beneficiaries were obtained from the 2013 to 2017 Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File (PUF) and the Part D Public Use Files from the Centers for Medicare and Medicaid Services (CMS). INCS prescriptions were analyzed by cost, state, provider, and regional temperature. State temperature data was collected through the National Centers for Environmental Information., Results: From 2013 to 2017, the total claims per beneficiary for fluticasone, mometasone, and triamcinolone combined increased from 2.31 to 2.39. Combined cost/beneficiary was similar for mometasone and triamcinolone at 102.47 and 103.60 respectively, while it was much lower for fluticasone at 39.12. There was a strong correlation between otolaryngology providers per beneficiary in each state and total claims per state with a correlation coefficient of .79. Additionally, comparing the average state temperature to the claims/beneficiary yielded a moderately strong correlation coefficient of .44, suggesting that temperature was a possible factor for INCS prescription patterns., Conclusions: INCS prescriptions by otolaryngologists and the number of INCS beneficiaries have increased between 2013 and 2017. Over the same time period, the costs of fluticasone and triamcinolone have decreased while the cost of mometasone increased. Total providers by state correlated with claims per state. Additionally, average annual temperature was positively correlated with INCS claims per beneficiary in each state.

Background: This large-scale pharmacoepidemiologic study was conducted to confirm a previous signal for decreased risk of suicide attempt following prescription fills for benztropine., Methods: We used a within-person exposure-only cohort design to study the dynamic association between benztropine prescription fills over a 12-month period and suicidal events (suicide attempts and intentional self-harm) in 62,493 patients with private health insurance (MarketScan - MS) who filled a new benztropine prescription between 2011 and 2019. A discrete-time survival analysis was used to analyze the data, adjusting for age, sex, diagnoses related to suicidal behavior, Parkinson's disease, medical comorbidities, history of suicide attempts, concomitant CNS medications, and time-varying antipsychotic use., Results: Overall, there were 486 suicidal events (0.8%) following the index end-date of the one-year baseline period. Benztropine use was associated with fewer suicidal events (HR=0.63, 95% CI = 0.50, 0.80). Patients treated with antipsychotics and benztropine had a similar reduction in suicidal events as patients treated with benztropine alone in both within-subject and between-subject analyses. Similar associations were found for patients with bipolar disorder or schizophrenia, and those treated with newer versus older generation antipsychotics. Dose-response and duration response relationships were found, with an overall 6% reduction in suicidal events per 1 mg equivalent dosage per month, that was similar in those treated and those not treated with antipsychotics., Interpretations: Benztropine was found to lower suicidal event rates, comparably in those receiving or not receiving antipsychotic medications, regardless of the presence of major psychiatric disorders. This observation warrants testing in a randomized clinical trial., Funding: No funding sources were utilized for this manuscript., Competing Interests: Declaration of Competing Interest Dr. Gibbons has served as an expert witness in cases related to suicide for the US Department of Justice, and Pfizer, Wyeth, and GSK pharmaceutical companies and founded the company Adaptive Testing Technologies that distributes computerized adaptive mental health tests. These activities have been reviewed and approved by the University of Chicago in accordance with its conflict-of-interest policies. This study was reviewed and deemed exempt from review by the University of Chicago institutional review board. Dr. Mann receives royalties from the Research Foundation for Mental Hygiene for commercial use of the C-SSRS. Dr Lavigne reported serving as a consultant for CVS Health outside of the submitted work. Dr. Hur reports no financial relationships with commercial interests., (Copyright © 2023. Published by Elsevier B.V.)

Controlling the dimensional aspect of conductive coordination polymers is currently a key scientific interest. Herein, solution-based dimension control strategies are proposed for copper chloride thiourea (CuCl-TU) coordination polymers that enable centimeter-scale, 2D nanosheet formation for use as transparent electrodes. Despite the wide bandgap of CuCl-TU polymers (4.33 eV), through polaron-mediated electron transfer, the electrical conductivity of the 2D sheet at room temperature is able to reach 4.45 S cm -1 without intentional doping. This leads to a highly anisotropic electronic conductivity of up to the order of ≈10 3 differences, depending on the material orientation. Furthermore, by substituting alternative thiourea candidates, it is demonstrated that it is possible to predesign CuCl-TU structures with the desired functionality, stability, and porosity through dimensional control. These findings provide a blueprint to design next-generation transparent conducting materials that can operate at room temperature, thereby expanding their applicability to different fields., (© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Competing Interests: The authors have nothing to disclose.

Reprogramming M2-type, pro-tumoral tumor-associated macrophages (TAMs) into M1-type, anti-tumoral macrophages is a key strategy in cancer therapy. In this study, we exploited epigenetic therapy using the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) and the histone deacetylation inhibitor trichostatin A (TSA), to reprogram M2-type macrophages into an M1-like phenotype. Treatment of M2-type macrophages with the combination of 5-aza-dC and TSA decreased the levels of M2 macrophage cytokines while increasing those of M1 macrophage cytokines, as compared to the use of either therapy alone. Conditioned medium of M2 macrophages treated with the combination of 5-aza-dC and TSA sensitized the tumor cells to paclitaxel. Moreover, treatment with the combination inhibited tumor growth and improved anti-tumor immunity in the tumor microenvironment. Depletion of macrophages reduced the anti-tumor growth activity of the combination therapy. Profiling of miRNAs revealed that the expression of miR-7083-5p was remarkably upregulated in M2 macrophages, following treatment with 5-aza-dC and TSA. Transfection of miR-7083-5p reprogrammed the M2-type macrophages towards an M1-like phenotype, and adoptive transfer of M2 macrophages pre-treated with miR-7083-5p into mice inhibited tumor growth. miR-7083-5p inhibited the expression of colony-stimulating factor 2 receptor alpha and CD43 as candidate targets. These results show that epigenetic therapy upon treatment with the combination of 5-aza-dC and TSA skews M2-type TAMs towards the M1-like phenotype by upregulating miR-7083-5p, which contributes to the inhibition of tumor growth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vadevoo, Gunassekaran, Yoo, Kwon, Hur, Chae and Lee.)

Objectives: To quantify national and state-level prescribing and cost trends for the 3 most prescribed nasal sprays by otolaryngologists in the Medicare population., Methods: Through the Centers for Medicare and Medicaid Services (CMS) database and the Kaiser Family Foundation, we retrieved data on Medicare enrollment and on claims and costs of fluticasone propionate, azelastine HCl, and ipratropium bromide prescribed by otolaryngologists from January 1, 2013 to December 31, 2017., Results: From 2013 to 2017, CMS reimbursed $128.8 million for 5.2 million claims of fluticasone propionate, azelastine HCl, and ipratropium bromide prescribed by otolaryngologists. The national claim rate for fluticasone propionate increased 6.5% per year from 2013 to 2015 and then decreased 4.3% per year from 2015 to 2017 while azelastine HCl and ipratropium bromide consistently increased annually (19.0% and 12.2% respectively) from 2013 to 2017. The cost for fluticasone propionate decreased 33.0% a year from 2013 to 2015 and then increased 5.4% annually to $13.60 per claim in 2017. Azelastine HCl decreased 14.8% annually from $91.30 to $50.23 per claim and ipratropium bromide increased 5.2% annually to $34.78 in 2017. Variations in the claim rate and cost for all 3 nasal sprays were observed in some states., Conclusions: Otolaryngologists are prescribing azelastine HCl and ipratropium at an increasingly higher rate in the Medicare population, while the rate for fluticasone propionate has been decreasing nationally. Utilization and costs of nasal sprays also vary geographically across the United States.

Importance: Suicide is a leading cause of death in the United States, having increased more than 30% from 2000 to 2018. An inexpensive, safe, widely available treatment for preventing suicidal behavior could reverse this trend., Objective: To confirm a previous signal for decreased risk of suicide attempt following prescription fills for folic acid in a national pharmacoepidemiologic study of patients treated with folic acid., Design, Setting, and Participants: A within-person exposure-only cohort design was used to study the dynamic association between folic acid (vitamin B9) prescription fills over a 24-month period and suicide attempts and intentional self-harm. Data were collected from a pharmacoepidemiologic database of US medical claims (MarketScan) for patients with private health insurance who filled a folic acid prescription between 2012 and 2017. The same analysis was repeated with a control supplement (cyanocobalamin, vitamin B12). Data were analyzed from August 2021 to June 2022., Exposure: Folic acid prescription fills., Main Outcome and Measure: Suicide attempt or intentional self-harm resulting in an outpatient visit or inpatient admission as identified by codes from the International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification., Results: Data on 866 586 patients were collected; 704 514 (81.30%) were female, and 90 296 (10.42%) were 60 years and older. Overall, there were 261 suicidal events during months covered by a folic acid prescription (5 521 597 person-months) for a rate of 4.73 per 100 000 person-months, compared with 895 suicidal events during months without folic acid (8 432 340) for a rate of 10.61 per 100 000 person-months. Adjusting for age and sex, diagnoses related to suicidal behavior, diagnoses related to folic acid deficiency, folate-reducing medications, history of folate-reducing medications, and history of suicidal events, the hazard ratio (HR) for folic acid for suicide events was 0.56 (95% CI, 0.48-0.65), with similar results for the modal dosage of 1 mg of folic acid per day (HR, 0.57; 95% CI, 0.48-0.69) and women of childbearing age (HR, 0.60; 95% CI, 0.50-0.73). A duration-response analysis (1-mg dosage) revealed a 5% decrease in suicidal events per month of additional treatment (HR, 0.95; 95% CI, 0.93-0.97). The same analysis for the negative control, cyanocobalamin, found no association with suicide attempt (HR, 1.01; 95% CI, 0.80-1.27)., Conclusions and Relevance: This large-scale pharmacoepidemiologic study of folic acid found a beneficial association in terms of lower rates of suicide attempts. The results warrant the conduct of a randomized clinical trial with suicidal ideation and behavior as outcomes of interest. If confirmed, folic acid may be a safe, inexpensive, and widely available treatment for suicidal ideation and behavior.

Ubiquitin-specific protease 1 (USP1) is a deubiquitinase involved in DNA damage repair by modulating the ubiquitination of major regulators, such as PCNA and FANCD2. Because USP1 is highly expressed in many cancers, dysregulation of USP1 contributes to cancer therapy. However, the role of USP1 and the mechanisms underlying chemotherapy remain unclear. In this study, we found high USP1 expression in tumor tissues and that it correlated with poor prognosis in RCC. Mechanistically, USP1 enhanced survivin stabilization by removing ubiquitin. Pharmacological inhibitors (ML23 and pimozide) and siRNA targeting USP1 induced downregulation of survivin expression. In addition, ML323 upregulated DR5 expression by decreasing miR-216a-5p expression at the post-transcriptional level, and miR-216a-5p mimics suppressed the upregulation of DR5 by ML323. Inhibition of USP1 sensitized cancer cells. Overexpression of survivin or knockdown of DR5 markedly prevented the co-treatment with ML323 and TRAIL-induced apoptosis. These results of in vitro were proved in a mouse xenograft model, in which combined treatment significantly reduced tumor size and induced survivin downregulation and DR5 upregulation. Furthermore, USP1 and survivin protein expression showed a positive correlation, whereas miR-216a-5p and DR5 were inversely correlated in RCC tumor tissues. Taken together, our results suggest two target substrates of USP1 and demonstrate the involvement of survivin and DR5 in USP1-targeted chemotherapy., (© 2022. The Author(s).)

Objectives: To explore the degree to which patients undergoing unilateral endoscopic sinus surgery (ESS) experience post-operative contralateral sinonasal symptoms and determine risk factors for contralateral symptomatology following unilateral ESS., Methods: Patients who underwent unilateral surgery for chronic rhinosinusitis (CRS) were contacted and asked if they felt symptomatic on the contralateral side at that point in time. Nasal Obstruction Symptom Evaluation (NOSE) scores were obtained based on contralateral symptomatology they recalled at the following time points: pre-ESS, 1 month post-ESS, and 3 months post-ESS. Demographics, contralateral symptomatology, and NOSE scores were compared between those with 2 or fewer sinusotomies versus 3 or more sinusotomies., Results: Of the 97 patients included in this study, 24% of patients reported contralateral congestion, a median of 24 months post-ESS, and more than 10% of patients reported other contralateral symptoms including swelling, rhinorrhea, difficulty breathing, and hyposmia post-ESS. Those with 2 or fewer sinusotomies were more likely to feel that they had developed worsened sensation of contralateral sinus swelling ( P = .008). The median amount of time from the participants' index surgery until the time they were interviewed was 24 months. There were no differences in long-term contralateral symptomatology between those who did and did not have septoplasty (27%)., Conclusion: Patients who have unilateral ESS for CRS may experience long-term contralateral symptoms. Having a septoplasty did not affect contralateral symptoms., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Cannabis is the most commonly used illicit substance in the US and worldwide. Understanding the association between cannabis use and sinonasal symptoms may help clinicians and patients better understand the symptomatology associated with cannabis use., Objective: To assess the association between frequency of cannabis use and presence of sinonasal symptoms in a nationally representative sample of US adults., Design, Setting, and Participants: This population-based, retrospective cross-sectional study included adults aged 20 to 69 years who had completed data on sinonasal symptoms and substance use for the 2013 to 2014 National Health and Nutrition Examination Survey. The data were analyzed in February 2022., Exposures: Cannabis use frequency., Main Outcomes and Measures: Presence of sinonasal symptoms, demographic information, and medical history were obtained from National Health and Nutrition Examination Survey questionnaires. Presence of any sinonasal symptoms was defined as responding yes to any of a series of questions assessing rhinologic symptoms. Regular cannabis users were defined as using cannabis 15 or more times within the last 30 days. Nonregular users were defined as using cannabis fewer than 15 times within the last 30 days. Multivariable models were used to examine the association between frequency of cannabis use and presence of sinonasal symptoms while adjusting for demographic characteristics and medical comorbidities., Results: The study included 2269 adults with a mean (SD) age of 36.5 (12.4) years (1207 women [53.2%]; 330 Asian [14.5%], 739 Black [32.6%], 461 Hispanic [20.3%], and 656 White [28.9%] individuals). The prevalence of sinonasal symptoms among regular cannabis users (45.0%; 95% Cl, 38.9%-51.1%) was lower than the prevalence among never users (64.5%; 95% Cl, 58.3%-68.8%). Compared with adults who had never used cannabis, regular cannabis users were less likely to have sinonasal symptoms (odds ratio, 0.22, 95% CI, 0.10-0.50). Current tobacco smokers were more likely to have sinonasal symptoms (odds ratio, 1.96; 95% CI, 1.17-3.28). The most common sinonasal symptoms reported were nasal congestion (62.8%; 95% Cl, 60.2%-65.4%) and change in smell (17.8%; 95% Cl, 15.2%-20.9%)., Conclusions and Relevance: This cross-sectional study found that the prevalence of sinonasal symptoms was lower among regular cannabis users. Further research is needed to elucidate the mechanisms underlying the association between cannabis use and sinonasal symptoms.

Circular RNAs (circRNAs) are potential biomarkers owing to their stability, tissue specificity, and abundance. This study aimed to evaluate the clinical significance of hsa&#95;circ&#95;0003570 expression and to investigate its potential as a biomarker in hepatocellular carcinoma (HCC). We evaluated hsa&#95;circ&#95;0003570 expression in 121 HCC tissue samples, its association with clinicopathological characteristics, and overall and progression-free survival. Hsa&#95;circ&#95;0003570 expression was downregulated in HCC tissues. Low hsa&#95;circ&#95;0003570 expression was more common in tumors larger than 5 cm (odds ratio (OR), 6.369; 95% confidence interval (CI), 2.725−14.706; p < 0.001), vessel invasion (OR, 5.128; 95% CI, 2.288−11.494; p < 0.001); advanced tumor-node metastasis stage (III/IV; OR, 4.082; 95% CI, 1.866−8.929; p < 0.001); higher Barcelona Clinic Liver Cancer stage (B/C; OR, 3.215; 95% CI, 1.475−6.993; p = 0.003); and higher AFP (>200 ng/mL; OR, 2.475; 95% CI, 1.159−5.291; p = 0.018). High hsa&#95;circ&#95;0003570 expression was an independent prognostic factor for overall survival (hazard ratio (HR), 0.541; 95% confidence interval (CI), 0.327−0.894; p = 0.017) and progression-free survival (HR, 0.633; 95% CI, 0.402−0.997; p = 0.048). Hsa&#95;circ&#95;0003570 is a potential prognostic biomarker in patients with HCC, and further validation of hsa&#95;circ&#95;0003570 is needed.

Competing Interests: None disclosed.

Competing Interests: Conflicts of interest None disclosed.

Swimming pools adopt chlorination to ensure microbial safety. Giardia has attracted attention in swimming pool water because of its occurrence, pathogenicity, and chlorine resistance. To control Giardia concentrations in pool water and reduce the microbial risk, higher chlorine doses are required during disinfection. Unfortunately, this process produces carcinogenic disinfection byproducts that increase the risk of chemical exposure. Therefore, quantitatively evaluating the comparative microbial vs. chemical exposure risks that stem from chlorination inactivation of Giardia in swimming pool water is an issue that demands attention. We simulated an indoor swimming pool disinfection scenario that followed common real-world disinfection practices. A quantitative microbial risk assessment coupled with a chemical exposure risk assessment was employed to compare the Giardia microbial exposure risk (MER) and the trihalomethane chemical exposure risk (CER) to humans. The results demonstrated a 22% decrease in MER- and CER-induced health exposure risk, from 8.45E-5 at 8:00 to 6.60E-5 at 19:00. Both the MER and CER decreased gradually, dropping to 3.26E-5 and 3.35E-5 at 19:00, respectively. However, the CER exceeded the MER after 18:30 and became the dominant factor affecting the total exposure risk. Past the 18 hr mark, the contribution of trihalomethane CER far exceeded the risk aversion from microbial inactivation, leading to a net increase in total exposure risk despite the declining MER. Swimmers may consider swimming after 19:00, when the total exposure risk is the lowest. Lowering water temperature and/or pH were identified as the most sensitive factors to minimize the overall health exposure risk., (Copyright © 2022. Published by Elsevier B.V.)

Nitrification and biofilm growth within distribution systems remain major issues for drinking water treatment plants utilizing chloramine disinfection. Many chloraminated plants periodically switch to chlorine disinfection for several weeks to mitigate these issues, known as "chlorine burns". The evaluation of disinfection byproduct (DBP) formation during chlorine burns beyond regulated DBPs is scarce. Here, we quantified an extensive suite of 80 regulated and emerging, unregulated DBPs from 10 DBP classes in drinking water from two U.S. drinking water plants during chlorine burn and chloramination treatments. Total organic halogen (TOX), including total organic chlorine, total organic bromine, and total organic iodine, was also quantified, and mammalian cell cytotoxicity of whole water mixtures was assessed in chlorine burn waters for the first time. TOX and most DBPs increased in concentration during chlorine burns, and one emerging DBP, trichloroacetaldehyde, reached 99 μg/L. THMs and HAAs reached concentrations of 249 and 271 μg/L, respectively. Two highly cytotoxic nitrogenous DBP classes, haloacetamides and haloacetonitriles, increased during chlorine burns, reaching up to 14.2 and 19.3 μg/L, respectively. Cytotoxicity did not always increase from chloramine treatment to chlorine burn, but a 100% increase in cytotoxicity was observed for one plant. These data highlight that consumer DBP exposure during chlorine burns can be substantial.

High-intensity aerobic exercise (90% of the maximal heart rate) can effectively suppress cancer cell proliferation in vivo . However, the molecular effects of exercise and its relevance to cancer prevention remain uninvestigated. In this study, mice with colorectal cancer were subjected to high-intensity aerobic exercise, and mRNA-seq analysis was performed on the heart, lungs, and skeletal muscle tissues to analyze the genome-wide molecular effects of exercise. The skeletal muscle-derived genes with exercise-dependent differential expression were further evaluated for their effects on colorectal cancer cell viability. Compared to the results obtained for the control groups (healthy and cancer with no exercise), the regular and high-intensity aerobic physical activity in the mice produced positive results in comprehensive parameters (i.e., food intake, weight gain, and survival rate). A heatmap of differentially expressed genes revealed markedly different gene expression patterns among the groups. RNA-seq analysis of 23,282 genes expressed in the skeletal muscle yielded several anticancer effector genes (e.g., Trim63 , Fos , Col1a1 , and Six2 ). Knockdown and overexpression of selected anticancer genes repressed CT26 murine colorectal carcinoma cell proliferation by 20% ( p < 0.05). Our findings, based on the aerobic exercise cancer mouse model, suggest that high-intensity aerobic exercise results in a comprehensive change in the expression patterns of genes, particularly those that can affect cancer cell viability. Such an approach may identify key exercise-regulated genes that can help the body combat cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jee, Park, Hur, Kang and Kim.)

The clinical aspects of hypertrophic scarring vary according to personal constitution and body part. However, the mechanism of hypertrophic scar (HS) formation remains unclear. MicroRNAs (miRNAs) are known to contribute to HS formation, however, their detailed role remains unknown. In this study, candidate miRNAs were identified and analyzed as biomarkers of hypertrophic scarring for future clinical applications. HSfibroblasts and normal skin fibroblasts from patients were used for profiling and validation of miRNAs. An HS mouse model with xenografted human skin on nude mice was established. The miRNA expression between normal human, normal mouse, and mouse HS skin tissues was compared. Circulating miRNA expression levels in the serum of normal mice and mice with HSs were also analyzed. Ten upregulated and twenty-one downregulated miRNAs were detected. Among these, miR-365a/b-3p and miR-16-5p were identified as candidate miRNAs with statistically significant differences; miR-365a/b-3p was significantly upregulated ( p = 0.0244). In mouse studies, miR-365a/b-3p expression levels in skin tissue and serum were higher in mice with HSs than in the control group. These results indicate that miRNAs contribute to hypertrophic scarring and that miR-365a/b-3p may be considered a potential biomarker for HS formation.

The human microbiome plays an essential role in the human immune system, food digestion, and protection from harmful bacteria by colonizing the human intestine. Recently, although the human microbiome affects colorectal cancer (CRC) treatment, the mode of action between the microbiome and CRC remains unclear. This study showed that propionate suppressed CRC growth by promoting the proteasomal degradation of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) through HECT domain E3 ubiquitin protein ligase 2 (HECTD2) upregulation. In addition, EHMT2 downregulation reduced the H3K9me2 level on the promoter region of tumor necrosis factor α-induced protein 1 (TNFAIP1) as a novel direct target of EHMT2. Subsequently, TNFAIP1 upregulation induced the apoptosis of CRC cells. Furthermore, using Bacteroides thetaiotaomicron culture medium, we confirmed EHMT2 downregulation via upregulation of HECTD2 and TNFAIP1 upregulation. Finally, we observed the synergistic effect of propionate and an EHMT2 inhibitor (BIX01294) in 3D spheroid culture models. Thus, we suggest the anticancer effects of propionate and EHMT2 as therapeutic targets for colon cancer treatment and may provide the possibility for the synergistic effects of an EHMT2 inhibitor and microbiome in CRC treatment., (© 2021. The Author(s).)

In this study, we aimed to investigate healthcare access and utilization among patients with limited English proficiency (LEP). We analyzed aggregated data from the 2018 California Health Interview Survey, a large population-based survey. Survey weighted univariate and multivariable logistic regression analyses were conducted. A total of 21,177 participants were included with 8.2% having LEP. Compared to participants with proficient English, LEP participants were less likely to have a usual place to go to when sick other than the ER or have a preventive care visit in the past year after adjusting for sociodemographic characteristics. However, LEP participants were also less likely to need to see a medical specialist and less likely to delay necessary medical care compared to English proficient participants. While patients with LEP were less likely to have access to preventative care, they were also less likely to delay necessary care., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study reveals key disinfection byproduct (DBP) toxicity drivers in drinking water across the United States. DBPs, which are ubiquitous in drinking water, form by the reaction of disinfectants, organic matter, bromide, and iodide and are generally present at 100-1000× higher concentrations than other contaminants. DBPs are linked to bladder cancer, miscarriage, and birth defects in human epidemiologic studies, but it is not known as to which DBPs are responsible. We report the most comprehensive investigation of drinking water toxicity to date, with measurements of extracted whole-water mammalian cell chronic cytotoxicity, over 70 regulated and priority unregulated DBPs, and total organic chlorine, bromine, and iodine, revealing a more complete picture of toxicity drivers. A variety of impacted waters were investigated, including those impacted by wastewater, agriculture, and seawater. The results revealed that unregulated haloacetonitriles, particularly dihaloacetonitriles, are important toxicity drivers. In seawater-impacted water treated with chloramine, toxicity was driven by iodinated DBPs, particularly iodoacetic acids. In chlorinated waters, the combined total organic chlorine and bromine was highly and significantly correlated with toxicity ( r = 0.94, P < 0.01); in chloraminated waters, total organic iodine was highly and significantly correlated with toxicity ( r = 0.80, P < 0.001). These results indicate that haloacetonitriles and iodoacetic acids should be prioritized in future research for potential regulation consideration.

Objective: Severe acute respiratory syndrome coronavirus-2 spreads through respiratory fluids. We aim to quantify aerosolized particles during laryngology procedures to understand their potential for transmission of infectious aerosol-based diseases., Study Design: Prospective quantification of aerosol generation., Methods: Airborne particles (0.3-25 μm in diameter) were measured during live-patient laryngology surgeries using an optical particle counter positioned 60 cm from the oral cavity to the surgeon's left. Measurements taken during the procedures were compared to baseline concentrations recorded immediately before each procedure. Procedures included direct laryngoscopy with general endotracheal anesthesia (GETA), direct laryngoscopy with jet ventilation, and carbon dioxide (CO 2 ) laser use with or without jet ventilation, all utilizing intermittent suction., Results: Greater than 99% of measured particles were 0.3 to 1.0 μm in diameter. Compared to baseline, direct laryngoscopy was associated with a significant 6.71% increase in cumulative particles, primarily 0.3 to 1.0 μm particles (P < .0001). 1.0 to 25 μm particles significantly decreased (P < .001). Jet ventilation was not associated with a significant change in cumulative particles; when analyzing differential particle sizes, only 10 to 25 μm particles exhibited a significant increase compared to baseline (+42.40%, P = .002). Significant increases in cumulative particles were recorded during CO 2 laser use (+14.70%, P < .0001), specifically in 0.3 to 2.5 μm particles. Overall, there was no difference when comparing CO 2 laser use during jet ventilation versus GETA., Conclusions: CO 2 laser use during laryngology surgery is associated with significant increases in airborne particles. Although direct laryngoscopy with GETA is associated with slight increases in particles, jet ventilation overall does not increase particle aerosolization., Level of Evidence: 3 Laryngoscope, 131:2759-2765, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Overdose due to concomitant use of opioids and benzodiazepines has been raised as a major public health concern, although little research has examined whether this risk extends to intentional overdose or other self-harm. This study examined whether prescription opioids and benzodiazepines interact to increase the rate of suicide attempt and intentional self-harm., Methods: The study analyzed 4,762,438 users of opioids, benzodiazepines, both drugs concomitantly, or neither drug from the MarketScan Commercial Claims and Encounters databases (2014-2016). The four groups were matched using inverse probability of treatment weighting and a difference in difference design was used to examine associations with risk of suicide attempt, intentional self-harm and drug overdose, including suicide death resulting in a medical claim., Results: There was a small association for opioids (HR=1.23; 95% CI 1.06-1.43) but a larger association for benzodiazepines (HR=2.55; 95% CI 2.12-3.05) with suicide attempt, intentional self-harm, and drug overdose. The medication interaction was opposite to the expected direction (HR=0.70; 95% CI 0.55-0.89), indicating that risk associated with concomitant use was lower than would be expected on an additive basis. Sensitivity analyses found no evidence of increased risk due to interaction between the two drug classes., Conclusions: Increased risk of suicide attempt, intentional self-harm and drug overdose for concomitant use of opioids and benzodiazepines is in large part attributable to benzodiazepine use alone. In typically prescribed quantities, opioids and benzodiazepines may not represent a drug interaction in terms of yielding increased risk of suicide attempt and intentional self-harm resulting in medical care., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Reuse of water requires the removal of contaminants to ensure human health. We report the relative estrogenic activity (REA) of reuse treatment design scenarios for water, wastewaters, and processed wastewaters before and after pilot-scale treatment systems tested at select military facilities. The comparative relationships between REA, several composite toxicological endpoints, and spectroscopic indicators were evaluated for different reuse treatment trains. Four treatment processes including conventional and advanced treatments reduced the estrogenicity by at least 33%. Biologically based methods reduced estrogenicity to below detection levels. Conventional treatment scenarios led to significantly less reduction of adverse biological endpoints compared to the advanced treatment scenarios. Incorporating the anaerobic membrane bioreactor reduced more endpoints with higher reduction percentages compared to the sequencing batch reactor design. Membrane technology and advanced oxidation generated reductions across all biological endpoints, from 65% (genotoxicity) to 100% (estrogenicity). The design scenarios featuring a low-cutoff mechanical screen filter, intermittent activated carbon biofilter, and membrane filtration achieved the highest percent reduction and produced water with the lowest negative biological endpoints. Spectroscopic indicators demonstrated case-specific relationships with estrogenicity and toxicity. Estrogenicity consistently correlated with cytotoxicity and thiol reactivity, indicating the potential for preliminary estrogenicity screening using thiol reactivity.

Objectives: Chronic rhinosinusitis (CRS) affects approximately 12% of the population and leads to increased health care utilization and indirect costs exceeding $20 billion annually in the United States. The Lund-Mackay score (LMS) measures radiographic disease severity for CRS but poorly correlates with symptom scores. The association between LMS and health care utilization in CRS patients has not yet been investigated. The study aimed to assess the association between health care utilization and CRS radiographic severity using LMS., Methods: CRS patients enrolled in a clinical registry were evaluated. Nasal endoscopy findings and LMS were recorded for patients with sinus CT imaging. Patient symptom scores, demographic characteristics, and health care utilization measures were collected. The relationship between these factors and LMS was examined., Results: A total of 556 patients met inclusion criteria. Mean age was 45.3 years, 53.4% were male, and 41.7% had nasal polyps. There was no difference in sex, smoking history, 22-item Sino-nasal Outcome Test scores, or past medical history factors between patients with high (≥8, n = 410) and low (<8, n = 146) LMS. Among high LMS patients, 73.7% underwent endoscopic sinus surgery (ESS) compared to 55.5% with low LMS ( P  < .01), and a greater percentage of patients had nasal polyps (49.3% vs 20.5%, P  < .01). On multivariable logistic regression, high LMS patients used fewer antibiotic courses (OR: 0.68 [0.51-0.91]), but were more likely to be managed with ESS (OR: 2.28 [1.41-3.73]), and have nasal polyps (OR: 2.11 [1.16-3.93]) compared to low LMS patients. There was no significant difference in the number of steroid courses, over the counter pill use, provider visits, work/school days missed, or symptom duration between the two LMS groups., Conclusion: CRS patients with severe radiographic disease are more likely to have nasal polyps, undergo ESS, and take fewer antibiotic courses. However, there is no association between radiographic disease severity and other measures of health care utilization., Level of Evidence: 2b, individual retrospective cohort study., Competing Interests: The authors declare that there is no conflict of interest., (© 2021 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Nail dermoscopy (onychoscopy) is a valuable diagnostic tool for evaluating diseases in the nail apparatus. It is non-invasive, allowing clinicians to prioritize particular nails for biopsy. Thus, it can improve diagnostic accuracy and expedite treatment. Evaluating inflammatory nail disorders using onychoscopy is a relatively new approach to clinical assessment and has the potential to augment clinical care. This review highlights key dermoscopic features of major inflammatory nail disorders, including trachyonychia, nail psoriasis, nail lichen planus, onychotillomania, nail lichen striatus and allergic contact dermatitis due to artificial nails. It also illustrates their management and differential diagnoses, including onychomycosis, onycholysis, nail dystrophy due to systemic amyloidosis and malignant nail tumours. Limitations of this review included the low amount of literature on this topic and non-standardized terminology used among research-ers. As onychoscopy is a relatively new technique, further studies and standardization of terminology are warranted to consolidate the role of dermoscopy in evaluating inflammatory nail disorders.

Circular RNAs (circRNAs) represent potential biomarkers because of their highly stable structure and robust expression pattern in clinical samples. The aim of this study was to evaluate the expression of a recently identified circRNA, hsa&#95;circ&#95;0005986; determine its clinical significance; and evaluate its potential as a biomarker of hepatocellular carcinoma (HCC). We evaluated hsa&#95;circ&#95;0005986 expression in 123 HCC tissue samples, its clinical significance, and its association with patients' clinicopathological characteristics and survival. Hsa&#95;circ&#95;0005986 expression was downregulated in HCC tissues. Low hsa&#95;circ&#95;0005986 expression was more common in tumors larger than 5 cm [odds ratio (OR), 3.19; 95% confidence interval (CI), 1.51-6.76; p = 0.002], advanced TNM stage (III/IV; OR, 2.39; 95% CI, 1.16-4.95; p = 0.018), and higher BCLC stage (B/C; OR, 2.71; 95% CI, 1.30-5.65; p = 0.007). High hsa&#95;circ&#95;0005986 expression was associated with improved survival and was an independent prognostic factor for overall [hazard ratio (HR), 0.572; 95% CI, 0.339-0.966; p = 0.037] and progression-free (HR, 0.573; 95% CI, 0.362-0.906; p = 0.017) survival. Moreover, the circRNA-miRNA-mRNA network was constructed using RNA-seq/miRNA-seq data and clinical information from TCGA-LIHC dataset. Our findings indicate a promising role for hsa&#95;circ&#95;0005986 as a prognostic biomarker in patients with HCC., (© 2021. The Author(s).)

Adipose tissue and skeletal muscle is associated with non-alcoholic fatty liver disease (NAFLD). This study evaluates the association between body composition and histologic severity in patients with NAFLD. Using the cross-sectional CT images at the level of L3 vertebra and the histologic findings of 178 patients with biopsy-proven NAFLD, we analyzed the correlation of the histologic findings to the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI), which is defined as the body composition area (cm 2 ) by height squared (m 2 ). The clinical and laboratory features with body composition were analyzed to determine the risk factors for advanced fibrosis. The VATI significantly increased in severe non-alcoholic steatohepatitis (NASH) or advanced fibrosis. In addition, the VATI was correlated with the NAFLD activity score (NAS) and the fibrosis stage. In multivariate analyses, age (odds ratio (OR), 1.09; 95% confidence interval (CI), 1.02-1.19; p = 0.025), severe NASH (OR, 8.66; 95% CI, 2.13-46.40; p = 0.005), and visceral adiposity (OR, 6.77; 95% CI, 1.81-29.90; p = 0.007) were independently associated with advanced fibrosis in patients with NAFLD. Visceral adiposity is correlated with the histologic severity of NAFLD, which is independently associated with advanced fibrosis.

We studied the electrochemical synthesis of NH 3 on Fe-CuS/C catalysts in an alkaline aqueous solution under ambient conditions. The metal chalcogenide catalyst is active in the nitrogen reduction reaction (NRR) for approximately 45 min with an NH 3 production yield of 16 μg h -1 cm -2 at -0.4 V RHE , while it decomposes to CuO. The rapid degradation of the catalyst hinders the precise investigation of the NH 3 production activity in longer time measurements. Herein, the electrochemical NH 3 production rate is enhanced with increased overpotentials when the degradation effect is mitigated in the measurement, which was difficult to observe in the NRR reports. In the Tafel analysis, the exchange current density, heterogeneous rate constant, and transfer coefficient of the Fe-CuS/C catalyst on the NRR were estimated. When the electrode degradation is mitigated, one of the best NH 3 production activities among the reported metal sulfide electrochemical NRR catalysts is obtained, which is 42 μg h -1 cm -2 at -0.6 V RHE .

The therapeutic effects of mesenchymal stem cells (MSCs) in musculoskeletal diseases (MSDs) have been verified in many human and animal studies. Although some tissues contain MSCs, the number of cells harvested from those tissues and rate of proliferation in vitro are not enough for continuous transplantation. In order to produce and maintain stable MSCs, many attempts are made to induce differentiation from pluripotent stem cells (iPSCs) into MSCs. In particular, it is also known that the paracrine action of stem cell-secreted factors could promote the regeneration and differentiation of target cells in damaged tissue. MicroRNAs (miRNAs), one of the secreted factors, are small non-coding RNAs that regulate the translation of a gene. It is known that miRNAs help communication between stem cells and their surrounding niches through exosomes to regulate the proliferation and differentiation of stem cells. While studies have so far been underway targeting therapeutic miRNAs of MSDs, studies on specific miRNAs secreted from MSCs are still minimal. Hence, our ultimate goal is to obtain sufficient amounts of exosomes from iPSC-MSCs and develop them into therapeutic agents, furthermore to select specific miRNAs and provide safe cell-free clinical setting as a cell-free status with purpose of delivering them to target cells. This review article focuses on stem cell therapy on MSDs, specific microRNAs regulating MSDs and updates on novel approaches.

Background: Mac-2 binding protein glycosylation isomer (M2BPGi) has been established as a non-invasive biomarker for liver fibrosis. We evaluated the diagnostic efficacy of M2BPGi compared with those of other liver fibrosis markers in liver fibrosis in non-alcoholic fatty liver disease (NAFLD)., Methods: We analyzed serum M2BPGi levels in 113 NAFLD patients. A pathologist graded liver fibrosis histopathologically. The diagnostic efficacies of serum M2BPGi and other liver fibrosis markers (aspartate aminotransferase to platelet ratio index, fibrosis index based on four factors, and NAFLD fibrosis score [NFS]) were evaluated using correlation, area under the ROC curve (AUC), logistic regression, and C-statistics., Results: Serum M2BPGi level and other liver fibrosis markers showed a moderate correlation with fibrosis grade. The AUC values of M2BPGi were 0.761, 0.819, 0.866, and 0.900 for diagnosing fibrosis (F)>0, F>1, F>2, and F>3, respectively. Logistic regression analysis showed M2BPGi as the only independent factor associated with F>2 and F>3. Although C-statistics showed that NFS was the best diagnostic factor for F>2 and F>3, M2BPGi with NFS had an increased C-statistics value, indicating that it is a better diagnostic model., Conclusions: The serum M2BPGi level increased with liver fibrosis severity and could be a good biomarker for diagnosing advanced fibrosis and cirrhosis in NAFLD patients. A well-controlled, prospective study with a larger sample size is needed to validate the diagnostic power of M2BPGi and other fibrosis markers in NAFLD.

Abstract: The level of long interspersed nuclear element-1 (LINE-1) methylation, representing the global deoxyribonucleic acid methylation level, could contribute to the prognosis of cancer via the activation of oncogenes. This study was performed to evaluate the prognostic implications of LINE-1 hypomethylation in patients with hepatocellular carcinoma (HCC) and the possible mechanisms related to oncogene activation.Seventy-seven HCC patients between October 2014 and September 2015 were enrolled in this prospective study. Quantitative pyrosequencing was performed to assess the LINE-1 methylation level of HCC and matched non-HCC tissue samples. The expression of suppression of tumorigenicity 18 was measured by immunohistochemistry and its correlation with LINE-1 methylation levels was examined.LINE-1 was significantly hypomethylated in the HCC tissue compared with the matched nontumor tissue (64.0 ± 11.6% vs 75.6 ± 4.0%, P < .001). LINE-1 hypomethylation was an independent risk factor for overall survival (hazard ratio = 27.291, P = .032) and disease progression (hazard ratio = 5.298, P = .005). The expression of suppression of tumorigenicity 18 was higher in the hypomethylated LINE-1 HCC tissue than the hypermethylated LINE-1 tumor tissue (P = .030).LINE-1 hypomethylation may serve as a potential prognostic marker for patients with HCC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)