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1.
Oper Res Let ; 542024 May.
Article in English | MEDLINE | ID: mdl-38560724

ABSTRACT

We consider the problem of optimally designing a system for repeated use under uncertainty. We develop a modeling framework that integrates the design and operational phases, which are represented by a mixed-integer program and discounted-cost infinite-horizon Markov decision processes, respectively. We seek to simultaneously minimize the design costs and the subsequent expected operational costs. This problem setting arises naturally in several application areas, as we illustrate through examples. We derive a bilevel mixed-integer linear programming formulation for the problem and perform a computational study to demonstrate that realistic instances can be solved numerically.

2.
J Neurosurg Case Lessons ; 6(23)2023 Dec 04.
Article in English | MEDLINE | ID: mdl-38048560

ABSTRACT

BACKGROUND: Esthesioneuroblastoma (ENB) is a rare neoplasm of the sinonasal tract. Currently, the optimal treatment includes maximal resection combined with radiotherapy and/or chemotherapy. Although ENBs often recur and have an aggressive clinical course, spinal metastases are extremely rare and the underlying molecular mechanisms are poorly understood. OBSERVATIONS: Here, the authors describe a 50-year-old male with an aggressive ENB, initially treated with resection and chemotherapy/radiation, who developed multiple thoracic and lumbar spinal metastases. The authors performed targeted exome sequencing on both the resected primary tumor and biopsied spinal metastases, which revealed 12 total variants of unknown clinical significance in genes associated with the PI3K/AKT/mTOR pathway, chromatin remodeling, DNA repair, and cell proliferation. Six of these variants were restricted to the metastatic lesion and included missense mutations with predicted functional effects in GRM3, DNMT3B, PLCG2, and SPEN. LESSONS: This report discusses the potential impact of these variants on tumor progression and metastasis, as well as the implications for identifying potential new biomarkers and therapies.

3.
Structure ; 31(12): 1589-1603.e6, 2023 12 07.
Article in English | MEDLINE | ID: mdl-37776857

ABSTRACT

Human thirty-eight-negative kinase-1 (TNK1) is implicated in cancer progression. The TNK1 ubiquitin-associated (UBA) domain binds polyubiquitin and plays a regulatory role in TNK1 activity and stability. No experimentally determined molecular structure of this unusual UBA domain is available. We fused the UBA domain to the 1TEL variant of the translocation ETS leukemia protein sterile alpha motif (TELSAM) crystallization chaperone and obtained crystals diffracting as far as 1.53 Å. GG and GSGG linkers allowed the UBA to reproducibly find a productive binding mode against its host 1TEL polymer and crystallize at protein concentrations as low as 0.2 mg/mL. Our studies support a mechanism of 1TEL fusion crystallization and show that 1TEL fusion crystals require fewer crystal contacts than traditional protein crystals. Modeling and experimental validation suggest the UBA domain may be selective for both the length and linkages of polyubiquitin chains.


Subject(s)
Molecular Chaperones , Polyubiquitin , Humans , Polyubiquitin/chemistry , Protein Binding , Crystallization , Protein Structure, Tertiary , Protein Domains , Molecular Chaperones/metabolism , Fetal Proteins/metabolism , Protein-Tyrosine Kinases/metabolism
4.
Dalton Trans ; 52(37): 13290-13303, 2023 Sep 26.
Article in English | MEDLINE | ID: mdl-37668189

ABSTRACT

Optically active C2-symmetric bis(aminophenols) based on (R)-2,2'-diaminobinaphthyl (BiniqH4) and (R,R)-2,3-butanediyldianthranilate (BdanH4) have been prepared by condensation of the diamines with 3,5-di-tert-butylcatechol. Group 10 bis(iminosemiquinone) complexes (R)-(Biniq)M (M = Pd, Pt) and (C,R,R)-(Bdan)Pd have been prepared by oxidatively metalating the corresponding ligands. In (R)-(Biniq)M, the C2 axis passes through the approximate square plane of the bis(iminosemiquinone)metal core, while in (C,R,R)-(Bdan)Pd the C2 axis is perpendicular to this plane. In the latter compound, the (R,R)-butanediyl strap binds selectively over one enantioface of the metal complex in a conformation where the methyl groups are anti to one another. Osmium oxo complexes with the intrinsically chiral OsO(amidophenoxide)2 chromophore are obtained by metalation of OsO(OCH2CH2O)2 with (R,R)-BdanH4. Both the (A,R,R) and (C,R,R) diastereomers can be observed, with metalation in refluxing toluene selectively giving the latter isomer. The electronic structures of the complexes are illuminated by the circular dichroism spectra, in conjuction with the optical spectra and TDDFT calculations.

5.
bioRxiv ; 2023 Jun 14.
Article in English | MEDLINE | ID: mdl-37398013

ABSTRACT

Human thirty-eight-negative kinase-1 (TNK1) is implicated in cancer progression. The TNK1-UBA domain binds polyubiquitin and plays a regulatory role in TNK1 activity and stability. Sequence analysis suggests an unusual architecture for the TNK1 UBA domain, but an experimentally-validated molecular structure is undetermined. To gain insight into TNK1 regulation, we fused the UBA domain to the 1TEL crystallization chaperone and obtained crystals diffracting as far as 1.53 Å. A 1TEL search model enabled solution of the X-ray phases. GG and GSGG linkers allowed the UBA to reproducibly find a productive binding mode against its host 1TEL polymer and to crystallize at protein concentrations as low as 0.1 mg/mL. Our studies support a mechanism of TELSAM fusion crystallization and show that TELSAM fusion crystals require fewer crystal contacts than traditional protein crystals. Modeling and experimental validation suggest the UBA domain may be selective for both the length and linkages of polyubiquitin chains.

6.
Inorg Chem ; 62(29): 11718-11730, 2023 Jul 24.
Article in English | MEDLINE | ID: mdl-37437186

ABSTRACT

The bis(iminoxolene)iridium complex (Diso)2IrCl (Diso = N-(2,6-diisopropylphenyl)-4,6-di-tert-butyl-2-imino-o-benzoquinone) reacts with pyridine to give trans-(Diso)2Ir(py)Cl as the kinetic product, with cis-(Diso)2Ir(py)Cl formed as the exclusive thermodynamic product upon heating. Electronic spectra and density functional theory calculations point to very similar electronic structures for the cis and trans isomers, with a nonbonding iminoxolene-centered HOMO and a metal-iminoxolene π* LUMO. The triplet states of cis-(Diso)2Ir(py)Cl and cis-[(Diso)2Ir(py)2]+ (but not trans-(Diso)2Ir(py)Cl) are unusually low in energy (1000-1500 cm-1 above the singlets), as shown by variable-temperature NMR spectroscopy. The low-energy triplets are attributed to a change in dihedral angle in the iminoxolenes, which allows a partial π interaction that cannot be achieved in the trans octahedral compounds. Mechanistic studies of the trans-cis isomerization in toluene indicate that the reaction proceeds via isomerization of the five-coordinate species to a form with cis iminoxolene ligands and an apical oxygen. This form is high in energy due to the loss of a secondary iminoxolene-to-iridium π-donor interaction that is possible in the trans form but not in the cis form for the square pyramidal structures. This stereoelectronic effect, combined with the poorer binding of pyridine in trans-(Diso)2Ir(py)Cl due to the interactions of the N-aryl substituents with the pyridine, makes the pyridine dissociate faster from the trans isomer by a factor of 108 at room temperature.

7.
Chem Commun (Camb) ; 59(63): 9618-9621, 2023 Aug 03.
Article in English | MEDLINE | ID: mdl-37462618

ABSTRACT

Both pseudo-octahedral and pseudo-square pyramidal bis-iminoxolene complexes trans-(Diso)2RuCl2 and trans-(Diso)2Ru(PPh3) are structurally distorted, with the ruthenium atom slipping off the twofold axis of the idealized coordination polyhedra. These distortions take place because they allow or enhance π interactions between ruthenium and the iminoxolene π orbitals.

8.
Am J Rhinol Allergy ; 37(5): 558-562, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37194285

ABSTRACT

BACKGROUND: There is limited evidence supporting the usage of prophylactic antibiotics in the setting of nasal packing for epistaxis. It is unclear what current antiobiotic usage patterns are by otolaryngologists. OBJECTIVES: Characterize the antibiotic prescribing practices employed by otolaryngologists in the management of epistaxis patients treated with packing as well as the underlying rationale. Explore the impact of experience, geography, and academic affiliation on treatment decisions. METHODS: An anonymous survey of antibiotic prescribing patterns for patients with epistaxis requiring nasal packing was distributed to all physician members of the American Rhinologic Society. Responses to each question were descriptively summarized including 95% confidence intervals and were linked to demographics using Fisher's exact tests. RESULTS: One thousand one hundred and thirteen surveys were distributed with 307 responses (27.6%). Antibiotic prescription rates varied based on packing type, with 20.0% prescribing antibiotics for dissolvable packing compared to 84.2% to 84.6% for nondissolvable packing. The absorbance of nondissolvable packing does not impact the decision to prescribe antibiotics (P > .999). Precisely 69.7% (95% CI: 64.0%-74.8%) stop antibiotics immediately following packing removal. Precisely 85.6% (95% CI: 81.6%-89.9%) cite the risk of toxic shock syndrome (TSS) when prescribing antibiotics. Notable regional differences include greater utilization of amoxicillin-clavulanate in the Midwest (67.6%) and Northeast (61.4%) as compared with the South (42.1%) and West (45.1%) (P = .013). Further, years in practice were positively associated with several patterns including prescribing antibiotics for patients with dissolvable packing (P = .008), citing prevention of sinusitis as a rationale for antibiotic use (P < .001), and a higher likelihood of having treated a patient with TSS (P = .002). CONCLUSIONS: Antibiotic use in patients with epistaxis controlled with nondissolvable packing is common. Treatment patterns are influenced by geography, years in practice, and practice type. LEVEL OF EVIDENCE: 4.


Subject(s)
Anti-Bacterial Agents , Sinusitis , Humans , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Epistaxis/drug therapy , Epistaxis/prevention & control , Amoxicillin-Potassium Clavulanate Combination/therapeutic use , Sinusitis/drug therapy
9.
Med J (Ft Sam Houst Tex) ; (Per 23-4/5/6): 5-7, 2023.
Article in English | MEDLINE | ID: mdl-37042499

ABSTRACT

Several published case reports describe the intentional ingestion of cyclotrimethylenetrinitramine, more commonly referred to as Composite-4 (C4), by military personnel. This putty-like explosive material, used for breaching operations, can produce euphoric effects through polyisobutylene; however, the additional ingredient of Research Department Explosive (RDX), or "Cyclonite," can cause significant central nervous system disruption resulting in seizures. We report a unique case cluster of active-duty personnel with intentional C4 ingestion and wide-ranging symptoms, including seizures. Unit personnel discovered this cluster after progressive patient presentations. This report illustrates the spectrum of C4 ingestion effects, as well as the need for investigation to ensure prompt medical evaluation and management of those suspected of consumption.


Subject(s)
Military Personnel , Seizures , Humans , Evidence-Based Medicine , Eating
10.
Cureus ; 14(8): e27726, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36106233

ABSTRACT

Introduction The use of all-terrain vehicles (ATVs) has become increasingly popular as an outdoor recreational activity among people living in the United States, particularly in areas such as the southeast. There are significant risks involved with riding ATVs, especially in the pediatric population, due to lack of training and experience. The purpose of this study was to evaluate the outcomes of pediatric patients involved in ATV-associated accidents. Methods This study is a retrospective review of 98 pediatric patients ages 15 years and younger involved in ATV accidents who were admitted to a pediatric hospital between January 2015 and December 2020. Outcomes, including types of injuries sustained, length of hospital stay, length of ICU stay, and injury severity score (ISS) were analyzed between age groups (0-5, 6-10, and 11-15). Results The mean hospital stay across all age groups was 1.7 ± 1.9 days, mean ICU stay was 3.8 ± 4.0 days, and mean injury severity score (ISS) was 5.9 ±4.8. The 11-15-year-old age group had a significantly longer hospital stay and higher ISS scores compared to both of the younger age groups (0-5 and 6-10 years old). There was no difference in ICU days between the age groups. Orthopedic injuries were the most common type of injury, occurring in 55% of all patients, followed by head injuries in 29% of patients, and spinal fractures in 2% of patients. The most common orthopedic fracture in the 11-15-year-old group was tibia/fibula, while humerus fractures were the most common type of fracture in the 0-5 and 6-10 year age groups. Orthopedic procedures were required in 35% of all included patients. There was no statistically significant difference in types of injuries and types of fractures sustained between each group. Chest injuries, including pneumothorax, lung contusions, and rib fractures, occurred most often in the older age group 11-15 years (n=65). Those who experienced chest injuries had a higher ISS, although it was not statistically significant (p=0.06) compared to those who did not have chest injuries. There was no difference in hospital or ICU length of stay in patients with chest injuries. Conclusions The results of this study demonstrate the outcomes of pediatric patients admitted for ATV accidents at a rural Appalachian pediatric hospital and provide an overview of the most common injuries involved in this trauma mechanism. Pediatric patients aged 11-15 years of age involved in ATV accidents are at risk for longer hospital length of stay and higher ISS compared to younger age groups. Additionally, patients ages 11-15 were more susceptible to chest injuries following ATV accidents. The results of this study will be used to develop a standardized trauma protocol for the management of this specific trauma mechanism in the pediatric population based on common injury patterns among each age group.

11.
Otolaryngol Clin North Am ; 55(5): 965-982, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36088149

ABSTRACT

Complementary and integrative medicine therapies in the treatment of allergy and allergic rhinitis (AR) are divided broadly into the categories of nutritional supplements, herbal supplements, Ayurvedic, and Chinese traditional medicine. Some therapies are likely completely safe, such as Manuka honey, with no known side effects. Others have significant risks, such as ephedra, which was ultimately banned for use by the Food and Drug Administration. The efficacy of these therapies is varied and under-researched. The therapies with the strongest evidence in the treatment of allergy and AR are Manuka honey, butterbur, and Sinupret.


Subject(s)
Integrative Medicine , Rhinitis, Allergic , Humans , Rhinitis, Allergic/therapy
12.
Open Biol ; 12(3): 210271, 2022 03.
Article in English | MEDLINE | ID: mdl-35232248

ABSTRACT

While conducting pilot studies into the usefulness of fusion to TELSAM polymers as a potential protein crystallization strategy, we observed novel properties in crystals of two TELSAM-target protein fusions, as follows. (i) A TELSAM-target protein fusion can crystallize more rapidly and with greater propensity than the same target protein alone. (ii) TELSAM-target protein fusions can be crystallized at low protein concentrations. This unprecedented observation suggests a route to crystallize proteins that can only be produced in microgram amounts. (iii) The TELSAM polymers themselves need not directly contact one another in the crystal lattice in order to form well-diffracting crystals. This novel observation is important because it suggests that TELSAM may be able to crystallize target proteins too large to allow direct inter-polymer contacts. (iv) Flexible TELSAM-target protein linkers can allow target proteins to find productive binding modes against the TELSAM polymer. (v) TELSAM polymers can adjust their helical rise to allow fused target proteins to make productive crystal contacts. (vi). Fusion to TELSAM polymers can stabilize weak inter-target protein crystal contacts. We report features of these TELSAM-target protein crystal structures and outline future work needed to validate TELSAM as a crystallization chaperone and determine best practices for its use.


Subject(s)
Molecular Chaperones , Polymers , Crystallization , Crystallography, X-Ray , Molecular Chaperones/chemistry , Polymers/chemistry
13.
Inorg Chem ; 61(14): 5547-5562, 2022 Apr 11.
Article in English | MEDLINE | ID: mdl-35357169

ABSTRACT

N-(2,6-Diisopropylphenyl)-4,6-di-tert-butyl-o-iminobenzoquinone (Diso) reacts with the (cyclooctadiene)iridium chloride dimer to form a monoiminoxolene complex, (Diso)Ir(cod)Cl. Reaction of 2 equiv of the iminoquinone with chlorobis(cyclooctene)iridium dimer affords the bis-iminoxolene (Diso)2IrCl. This five-coordinate complex adopts a distorted square pyramidal structure with an apical chloride ligand and undergoes halide exchange to form an air-stable iodide complex. (Diso)2IrCl can be reduced by one electron to form neutral, square planar (Diso)2Ir, while oxidation with PhICl2 gives octahedral trans-(Diso)2IrCl2. The cis isomer can be prepared by air oxidation of (Diso)2IrCl; cis/trans isomerization is not observed even on prolonged heating. Structural and spectroscopic features of the complexes are consistent with the presence of strong, covalent π bonding between the metal and the iminoxolene ligands, with structural data suggesting between 45 and 60% iridium character in the π bonding orbitals, depending on the ancillary ligands. The spectroscopic similarity of (Diso)2Ir and (Diso)2IrCl to their cobalt congeners suggests that the first-row metal complexes likewise have appreciably covalent metal-iminoxolene π bonds.

15.
Pediatr Emerg Care ; 38(2): e635-e638, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-33298822

ABSTRACT

OBJECTIVE: Because training in pediatric disaster medicine (PDM) is neither required nor standardized for pediatric residents, we designed and integrated a PDM course into the curriculum of a pediatric residency program and assessed if participation increased participants' knowledge of managing disaster victims. METHODS: We adapted and incorporated a previously studied PDM course into a small-sized pediatric residency program. The curriculum consisted of didactic lectures and experiential learning via simulation with structured debriefing. With IRB approval, the authors conducted a longitudinal series of pretests and posttests to assess knowledge and perceptions. RESULTS: Sixteen eligible residents completed the intervention. Before the course, none of the residents reported experience treating disaster victims. Pairwise comparison of scores revealed a 35% improvement in scores immediately after completing the course (95% confidence interval, 22.73%-47.26%; P < 0.001) and a 23.73% improvement 2 months later (95% confidence interval, 7.12%-40.34%; P < 0.01). CONCLUSIONS: Residents who completed this course increased their knowledge of PDM with moderate retention of knowledge gained. There was a significant increase in perceived ability to manage patients in a disaster situation after this educational intervention and the residents' confidence was preserved 2 months later. This PDM course may be used in future formulation of a standardized curriculum.


Subject(s)
Disaster Medicine , Disasters , Internship and Residency , Child , Clinical Competence , Curriculum , Disaster Medicine/education , Humans , Pilot Projects
16.
Water Environ Res ; 93(11): 2648-2669, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34346118

ABSTRACT

This paper presents the Green Stormwater Infrastructure Social Spatial Adoption (G-SSA) model, a cellular automata agent-based model that simulates the behavior of private property owners responding to incentives to adopt on-site green stormwater infrastructure (GSI). Concepts such as small-world social networks, opinion dissemination, and diffusion of innovation are used to capture dynamic social, spatial, and temporal aspects of green stormwater infrastructure adoption. Demographic information, site constraints, GSI practice type and costs, and financial incentive information are integrated into modeling rules that influence adoption dynamics. A methodology is presented that describes how these concepts have been translated into an agent-based modeling platform that provides the opportunity to explore modeling dynamics and output. Model output confirms the viability of the methodology and produces results that inform future efforts to explore the G-SSA model. PRACTITIONER POINTS: Agent-based modeling (ABM) can evaluate the expected impact of market-based approaches for green stormwater infrastructure (GSI) adoption and O&M services. ABM can simulate years of implementation of GSI program incentives, which vary from stormwater fee reduction to subsidy payments to tradable credits revenues generated. Publicly available demographic data combined with behavioral economic relationships can build models to evaluate how municipalities can meet regulatory goals for urban retrofits using market-based approaches to encourage GSI adoption.


Subject(s)
Rain , Systems Analysis , Cities
17.
Inorg Chem ; 60(6): 4004-4014, 2021 Mar 15.
Article in English | MEDLINE | ID: mdl-33657323

ABSTRACT

Oxobis(iminoxolene)osmium(VI) compounds (Rap)2OsO (Rap = 2-(4-RC6H4N)-4,6-tBu2C6H2O) are readily deoxygenated by phosphines and phosphites to give five-coordinate (Rap)2Os(PR'3) or six-coordinate (Rap)2Os(PR'3)2. Structural data indicate that this net two-electron reduction is accompanied by apparent oxidation of the iminoxolene ligands due to their greater ability to engage in π donation to the reduced deoxy form of the osmium complex. In (Rap)2Os(PR'3)2, the HOMO is a ligand-based combination of the iminoxolene redox-active orbitals, while the LUMO is a highly covalent metal-iminoxolene π* orbital. In the trans isomer, the HOMO is required to be ligand-localized by symmetry, while in the cis isomer, the ligands adopt a conformation that minimizes metal-ligand π* interactions in the HOMO. Kinetic studies indicate that the deoxygenations involve the rate-determining attack of the phosphorus(III) reagent on the five-coordinate oxo complexes. Varying the substituents of the aryl groups on the iminoxolene ligands or on the triarylphosphines has little effect on the rate of oxygen atom transfer, with the best correlation shown between oxygen atom transfer rates and the HOMO-LUMO gap of the oxo complexes. This suggests that the osmium oxo group shows a balance between electrophilic and nucleophilic character in its oxygen atom transfer reactions with phosphorus(III) reagents.

18.
Am J Otolaryngol ; 42(3): 102928, 2021.
Article in English | MEDLINE | ID: mdl-33545447

ABSTRACT

OBJECTIVE: The purpose of this paper is to review the literature and compile key clinically relevant applications of telemedicine for use in otolaryngology relevant to the post-COVID-19 era. STUDY DESIGN: Systematic Literature Review. DATA SOURCES: Pubmed and Google Scholar. REVIEW METHODS: Pubmed and Google Scholar were queried using combined key words such as "telemedicine," "covid" and "otolaryngology." The searches were completed in March-August 2020. Additional queries were made with particular subspecialty phrases such as "rhinology" or "otology" to maximize yield of relevant titles. Relevant articles were selected for abstract review. Applicable abstracts were then selected for review of the full text. RESULTS: Initial search identified 279 results. These were screened for relevance and 100 abstracts were selected for review. Abstracts were excluded if they were not in English, not related to otolaryngology, or if the full text was unavailable for access. Of these, 37 articles were selected for complete review of the full text. CONCLUSION: The sudden healthcare closures during the COVID-19 pandemic resulted in a sharp increase in the use of telemedicine, particularly in subspecialty fields. Otolaryngologists are at a unique risk of infection resulting from the examination of the head and neck and aerosol-generating procedures due to the predilection of viral particles for the nasal cavities and pharynx. The COVID-19 pandemic may have served as a catalyst to implement telemedicine into clinical practice, however identifying ways to integrate telemedicine long term is key for a sustainable and viable practice in the post-COVID-19 era. Although many states are now finding themselves on the down-sloping side of their infection rate curve, many others remain at the apex. Additionally, the risk of future waves of this pandemic, or the onset of another pandemic, should not be overlooked. Practice modification guidelines that mitigate infection risk by utilizing telemedicine would be useful in these instances. Telemedicine can help to reduce infection spread by limiting unnecessary in-person interactions and help conserve personal protective equipment (PPE) by facilitating remote care with the added benefits of expanding care to broad geographic areas, limiting cost, time, and travel burden on patients and families, and enabling consistent follow up.


Subject(s)
COVID-19/epidemiology , Otolaryngology , Practice Patterns, Physicians'/statistics & numerical data , Telemedicine/methods , Humans , Pandemics , SARS-CoV-2
19.
Ear Nose Throat J ; 100(2_suppl): 192S-196S, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32951446

ABSTRACT

INTRODUCTION: Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the global pandemic of coronavirus disease 2019 (COVID-19). From the first reported cases in December 2019, the virus has spread to over 4 million people worldwide. Human-to-human transmission occurs mainly through the aerosolization of respiratory droplets. Transmission also occurs through contact with contaminated surfaces and other fomites. Improved antisepsis of human and nonhuman surfaces has been identified as a key feature of transmission reduction. There are no previous studies of povidone iodine (PVP-I) against SARS-CoV-2. This study evaluated nasal and oral antiseptic formulations of PVP-I for virucidal activity against SARS-CoV-2. This is the first report on the efficacy of PVP-I against the virus that causes COVID-19. METHODS: Povidone iodine nasal antiseptic formulations and PVP-I oral rinse antiseptic formulations from 1% to 5% concentrations as well as controls were studied for virucidal efficacy against the SARS-CoV-2. Test compounds were evaluated for ability to inactivate SARS-CoV-2 as measured in a virucidal assay. SARS-CoV-2 was exposed directly to the test compound for 60 seconds, compounds were then neutralized, and surviving virus was quantified. RESULTS: All concentrations of nasal antiseptics and oral rinse antiseptics evaluated completely inactivated the SARS-CoV-2. CONCLUSIONS: Nasal and oral PVP-I antiseptic solutions are effective at inactivating the SARS-CoV-2 at a variety of concentrations after 60-second exposure times. The formulations tested may help to reduce the transmission of SARS-CoV-2 if used for nasal decontamination, oral decontamination, or surface decontamination in known or suspected cases of COVID-19.


Subject(s)
Anti-Infective Agents, Local/pharmacology , COVID-19/prevention & control , Microbial Viability/drug effects , Povidone-Iodine/pharmacology , SARS-CoV-2/drug effects , Administration, Topical , COVID-19/transmission , Humans , In Vitro Techniques , Mouth Mucosa , Mouthwashes , Nasal Lavage , Nasal Mucosa
20.
JAMA Otolaryngol Head Neck Surg ; 146(11): 1054-1058, 2020 11 01.
Article in English | MEDLINE | ID: mdl-32940656

ABSTRACT

Importance: Research is needed to demonstrate the efficacy of nasal povidone-iodine (PVP-I) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objective: To evaluate the in vitro efficacy of PVP-I nasal antiseptic for the inactivation of SARS-CoV-2 at clinically significant contact times of 15 and 30 seconds. Interventions: The SARS-CoV-2, USA-WA1/2020 strain, virus stock was tested against nasal antiseptic solutions consisting of aqueous PVP-I as the sole active ingredient. Povidone-iodine was tested at diluted concentrations of 0.5%, 1.25%, and 2.5% and compared with controls. The test solutions and virus were incubated at mean (SD) room temperature of 22 (2) °C for time periods of 15 and 30 seconds. Design and Setting: This controlled in vitro laboratory research study used 3 different concentrations of study solution and ethanol, 70%, as a positive control on test media infected with SARS-CoV-2. Test media without virus were added to 2 tubes of the compounds to serve as toxicity and neutralization controls. Ethanol, 70%, was tested in parallel as a positive control and water only as a negative control. Main Outcomes and Measures: The primary study outcome measurement was the log reduction value after 15 seconds and 30 seconds of given treatment. Surviving virus from each sample was quantified by standard end point dilution assay, and the log reduction value of each compound was compared with the negative (water) control. Results: Povidone-iodine nasal antiseptics at concentrations (0.5%, 1.25%, and 2.5%) completely inactivated SARS-CoV-2 within 15 seconds of contact as measured by log reduction value of greater than 3 log10 of the 50% cell culture infectious dose of the virus. The ethanol, 70%, positive control did not completely inactivate SARS-CoV-2 after 15 seconds of contact. The nasal antiseptics tested performed better than the standard positive control routinely used for in vitro assessment of anti-SARS-CoV-2 agents at a contact time of 15 seconds. No cytotoxic effects on cells were observed after contact with each of the nasal antiseptics tested. Conclusions and Relevance: Povidone-iodine nasal antiseptic solutions at concentrations as low as 0.5% rapidly inactivate SARS-CoV-2 at contact times as short as 15 seconds. Intranasal use of PVP-I has demonstrated safety at concentrations of 1.25% and below and may play an adjunctive role in mitigating viral transmission beyond personal protective equipment.


Subject(s)
Anti-Infective Agents, Local/administration & dosage , Infection Control/methods , Nose/virology , Povidone-Iodine/administration & dosage , SARS-CoV-2/drug effects , Administration, Intranasal , COVID-19/transmission , COVID-19/virology , Dose-Response Relationship, Drug , Humans
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