RNA viruses encoding high- or low-fidelity RNA-dependent RNA polymerases (RdRp) are attenuated. The ability to predict residues of the RdRp required for faithful incorporation of nucleotides represents an essential step in any pipeline intended to exploit perturbed fidelity as the basis for rational design of vaccine candidates. We used x-ray crystallography, molecular dynamics simulations, NMR spectroscopy, and pre-steady-state kinetics to compare a mutator (H273R) RdRp from poliovirus to the wild-type (WT) enzyme. We show that the nucleotide-binding site toggles between the nucleotide binding-occluded and nucleotide binding-competent states. The conformational dynamics between these states were enhanced by binding to primed template RNA. For the WT, the occluded conformation was favored; for H273R, the competent conformation was favored. The resonance for Met-187 in our NMR spectra reported on the ability of the enzyme to check the correctness of the bound nucleotide. Kinetic experiments were consistent with the conformational dynamics contributing to the established pre-incorporation conformational change and fidelity checkpoint. For H273R, residues comprising the active site spent more time in the catalytically competent conformation and were more positively correlated than the WT. We propose that by linking the equilibrium between the binding-occluded and binding-competent conformations of the nucleotide-binding pocket and other active-site dynamics to the correctness of the bound nucleotide, faithful nucleotide incorporation is achieved. These studies underscore the need to apply multiple biophysical and biochemical approaches to the elucidation of the physical basis for polymerase fidelity.

During the first two decades of the 21st century, there have been three coronavirus infection outbreaks raising global health concerns by severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the SARS-CoV-2. Although the reported imaging findings of coronavirus infection are variable and nonspecific, the most common initial chest radiograph (CXR) and computed tomography (CT) findings are ground-glass opacities and consolidation with peripheral predominance and eventually spread to involve both lungs as the disease progresses. These findings can be explained by the immune pathogenesis of coronavirus infection causing diffuse alveolar damage. Although it is insensitive in mild or early coronavirus infection, the CXR remains as the first-line and the most commonly used imaging modality. That is because it is rapid and easily accessible and helpful for monitoring patient progress during treatment. CT is more sensitive to detect early parenchymal lung abnormalities and disease progression, and can provide an alternative diagnosis. In this pictorial review, various coronavirus infection cases are presented to provide imaging spectrums of coronavirus infection and present differences in imaging among them or from other viral infections, and to discuss the role of imaging in viral infection outbreaks.

BACKGROUND: Limited data exists on the impact of COVID-19 on national changes in cardiac procedure activity, including patient characteristics and clinical outcomes before and during the COVID-19 pandemic. METHODS AND RESULTS: All major cardiac procedures (n = 374,899) performed between 1st January and 31st May for the years 2018, 2019 and 2020 were analysed, stratified by procedure type and time-period (pre-COVID: January-May 2018 and 2019 and January-February 2020 and COVID: March-May 2020). Multivariable logistic regression was performed to examine the odds ratio (OR) of 30-day mortality for procedures performed in the COVID period.Overall, there was a deficit of 45,501 procedures during the COVID period compared to the monthly averages (March-May) in 2018-2019. Cardiac catheterisation and device implantations were the most affected in terms of numbers (n = 19,637 and n = 10,453) whereas surgical procedures such as MVR, other valve replacement/repair, ASD/VSD repair and CABG were the most affected as a relative percentage difference (&#916;) to previous years' averages. TAVR was the least affected (&#916;-10.6%). No difference in 30-day mortality was observed between pre-COVID and COVID time-periods for all cardiac procedures except cardiac catheterisation (OR 1.25 95% confidence interval (CI) 1.07-1.47, p = 0.006) and cardiac device implantation (OR 1.35 95% CI 1.15-1.58, p < 0.001). CONCLUSION: Cardiac procedural activity has significantly declined across England during the COVID-19 pandemic, with a deficit in excess of 45000 procedures, without an increase in risk of mortality for most cardiac procedures performed during the pandemic. Major restructuring of cardiac services is necessary to deal with this deficit, which would inevitably impact long-term morbidity and mortality.

BACKGROUND: COVID-19 has had adverse psychological impact on the general population. Most surveys published till date are online questionnaires targeting general population/health care providers. There is lack of data on the psychological impact of disease on newly diagnosed COVID-19 patients. METHODS: The study was conducted at a tertiary care hospital, actively involved in the management of COVID patients. Newly diagnosed COVID-19 patients who had presented to the outpatient COVID care clinic were interviewed face to face by an interviewer using Impact of Event Scale-Revised (IES-R), a validated and universally accepted research questionnaire. RESULTS: Most of the respondents were males (83.2%), mean age: 40.8 years. 31.7% were graduates and 58.5% were actively employed. Fever (57.4%), cough (37.6%), and progressive breathlessness (08.9%) were the three most common clinical symptoms. The mean score on IES-R was 31.8. 30.7% respondents had suffered severe psychological impact, 30.7% had minimal impact. 19.8% and 1.8% had mild and moderate psychological impact respectively. On linear regression analysis, increasing age had statistically significant corelation with increasing scores on IES-R scale (p = 0.004). Educational qualifications of the patient had negative corelation (Pearson correlation=? 0.117) while none of the clinical parameters had any statistically significant correlation with the patients' psychological impact scores. CONCLUSION: COVID-19 patients are at an increased risk of suffering from disease-related adverse psychological impact. Certain risk groups especially like the elderly need close follow-up for early diagnosis and management. Future studies may be required to assess and manage post-traumatic stress disorder that may arise in the aftermath of pandemic.

BACKGROUND: Cognitive impairment is one most common problem experienced by patients receiving chemotherapy and evidence suggests that cytokines might play an important role. Various studies were conducted to evaluate the role of cytokines in chemotherapy-related cognitive impairment (CRCI). However, the association between CRCI due to cytokines is not well established. Thus, this systematic review aims to assess the role of cytokines in chemotherapy associated with cognitive impairment in breast cancer patients. METHODS: This systematic review was conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) guidelines. Intense literature search was carried out for inclusion criteria in major databases including PubMed and Clinicaltrials.gov on August 2021. Studies assessing cognitive parameters through objective and subjective assessment in breast cancer patients receiving chemotherapy were included. RESULTS: A total of 4052 studies were identified and 15 studies were included in this systematic review. We found that IL-6, IL-1?, and TNF- were associated with varying degrees of cognitive impairment in breast cancer patients receiving chemotherapy. CONCLUSION: This systematic review showed a correlation between various cytokines and chemotherapy-associated cognitive decline in breast cancer patients.

The severe acute respiratory syndrome coronavirus (SARS-CoV) first emerged in 2003, causing the SARS epidemic which resulted in a 10% fatality rate. The advancements in metagenomic techniques have allowed the identification of SARS-like coronaviruses (SL-CoVs) sequences that share high homology to the human SARS-CoV epidemic strains from wildlife bats, presenting concrete evidence that bats are the origin and natural reservoir of SARS-CoV. The application of reverse genetics further enabled that characterization of these bat CoVs and the prediction of their potential to cause disease in humans. The knowledge gained from such studies is valuable in the surveillance and preparation of a possible future outbreak caused by a spill-over of these bat SL-CoVs.

When animals and cells are infected with a virus, interferon is produced. Viral-nucleic acid is considered to be one of actual components for interferon induction. In addition, viral glycoproteins trigger interferon induction in lymphoid cells by membrane-membrane interaction via a lectin-like activity. A biological significance of lectin-like activity of viral glycoproteins is discussed.

Greenhouse gas (GHG) emissions must decrease rapidly in order to keep temperatures from exceeding 1 5 C above pre-industrial levels It is unclear if the oil and gas majors will contribute towards this goal by decarbonising at the speed and scale required Therefore, this study focuses on BP, Chevron, ExxonMobil, and Royal Dutch Shell, the top four investor-owned companies by size of direct and indirect historical GHG emissions Scientists at these companies knew that their products contributed to global warming by the late 1970s or earlier For decades these companies have used a variety of tactics to slow down and shape the low-carbon transition alongside continued exploration and extraction Discussion about the potential for these companies to meet self-imposed GHG emissions reduction targets and shift towards low-carbon technologies have been a distraction from the central question of whether they will phase out exploration for, and extraction of, oil and gas Despite the growing disruption of the oil and gas sector, accelerated by the Covid-19 pandemic, we conclude it is unlikely that the executives and directors at these four companies will decide to proactively decarbonise in line with climate science This raises the need for further external pressure, in particular by governments, as policy makers have played a key role in previous energy transitions

Rousettus bat coronavirus HKU9 (Ro-BatCoV HKU9), a recently identified coronavirus of novel Betacoronavirus subgroup D, from Leschenault's rousette, was previously found to display marked sequence polymorphism among genomes of four strains. Among 10 bats with complete RNA-dependent RNA polymerase (RdRp), spike (S), and nucleocapsid (N) genes sequenced, three and two sequence clades for all three genes were codetected in two and five bats, respectively, suggesting the coexistence of two or three distinct genotypes of Ro-BatCoV HKU9 in the same bat. Complete genome sequencing of the distinct genotypes from two bats, using degenerate/genome-specific primers with overlapping sequences confirmed by specific PCR, supported the coexistence of at least two distinct genomes in each bat. Recombination analysis using eight Ro-BatCoV HKU9 genomes showed possible recombination events between strains from different bat individuals, which may have allowed for the generation of different genotypes. Western blot assays using recombinant N proteins of Ro-BatCoV HKU9, Betacoronavirus subgroup A (HCoV-HKU1), subgroup B (SARSr-Rh-BatCoV), and subgroup C (Ty-BatCoV HKU4 and Pi-BatCoV HKU5) coronaviruses were subgroup specific, supporting their classification as separate subgroups under Betacoronavirus. Antibodies were detected in 75 (43%) of 175 and 224 (64%) of 350 tested serum samples from Leschenault's rousette bats by Ro-BatCoV HKU9 N-protein-based Western blot and enzyme immunoassays, respectively. This is the first report describing coinfection of different coronavirus genotypes in bats and coronavirus genotypes of diverse nucleotide variation in the same host. Such unique phenomena, and the unusual instability of ORF7a, are likely due to recombination which may have been facilitated by the dense roosting behavior and long foraging range of Leschenault's rousette.

BACKGROUND: Morbidity and mortality from COVID\19 caused by novel coronavirus SARS\CoV\2 is accelerating worldwide and novel clinical presentations of COVID\19 are often reported. The range of human cells and tissues targeted by SARS\CoV\2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS\CoV\2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID\19. METHODS: We performed RNA sequencing and explored available RNA\Seq databases to study gene expression and co\expression of ACE2, CD147 (BSG), CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4(+) and CD8(+) T cells, B cells and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID\19 risk factor status. RESULTS: ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA and PPIB), CD26 (DPP4) and related molecules were expressed in both, epithelium and in immune cells. We also observed a distinct age\related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2\ and CD147\related genes in the bronchial biopsy, BAL or blood. Additionally, CD147\related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of ACE2\ and CD147\related genes in the lesional skin of patients with atopic dermatitis. CONCLUSIONS: Our data suggest different receptor repertoire potentially involved in the SARS\CoV\2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related with age, gender, obesity and smoking, as well as with the disease status might contribute to COVID\19 morbidity and severity patterns.

Coronaviruses are enveloped, positive-stranded RNA viruses considered to be promising vectors for vaccine development, as (i) genes can be deleted, resulting in attenuated viruses; (ii) their tropism can be modified by manipulation of their spike protein; and (iii) heterologous genes can be expressed by simply inserting them with appropriate coronaviral transcription signals into the genome. For any live vector, genetic stability is an essential requirement. However, little is known about the genetic stability of recombinant coronaviruses expressing foreign genes. In this study, the Renilla and the firefly luciferase genes were systematically analyzed for their stability after insertion at various genomic positions in the group 1 coronavirus feline infectious peritonitis virus and in the group 2 coronavirus mouse hepatitis virus. It appeared that the two genes exhibit intrinsic differences, the Renilla gene consistently being maintained more stably than the firefly gene. This difference was not caused by genome size restrictions, by different effects of the encoded proteins, or by different consequences of the synthesis of the additional subgenomic mRNAs. The loss of expression of the firefly luciferase was found to result from various, often large deletions of the gene, probably due to RNA recombination. The extent of this process appeared to depend strongly on the coronaviral genomic background, the luciferase gene being much more stable in the feline than in the mouse coronavirus genome. It also depended significantly on the particular genomic location at which the gene was inserted. The data indicate that foreign sequences are more stably maintained when replacing nonessential coronaviral genes.

The intense global efforts are directed towards development of vaccines to halt the COVID-19 virus pandemic. There are 160 candidate vaccines under clinical trials across the world using different molecular targets and techniques. This race for the vaccine has several challenges and ethical issues like compressed timelines, generation and proper management of resources and finances, risks to the participating volunteers due to curtailed research trial processes, geopolitical contentions, misinformation through social media and parallel race with drugs. We feel that the fundamental principles of ethics: autonomy, beneficence, non-maleficence and justice should not be violated in this hastened vaccine development process. We recommend constitute a Consortium on a global platform to formulate, provide and monitor a comprehensive ethical umbrella to the process of vaccine development.

The global effort to develop a vaccine for coronavirus disease 2019 (COVID-19) has already produced 2 candidates, each requiring 2 doses, with reported efficacies exceeding 90% The US Food and Drug Administration (FDA) has granted Emergency Use Authorization for both vaccines (Pfizer-BioNTech and Moderna) Their reported efficacies greatly exceed the 50% threshold the FDA cited in a June 2020 guidance document Additional vaccine candidates at earlier stages of development hold the promise of single dosing, simpler storage requirements, and more rapid immunity after vaccination Here, a study that aims to quantify the speed-versus-efficacy tradeoff using a previously published model of a COVID-19 vaccination program is offered

We consider a game for a continuum of non-identical players evolving on a finite state space. Their heterogeneous interactions are represented by a graphon, which can be viewed as the limit of a dense random graph. The player's transition rates between the states depend on their own control and the interaction strengths with the other players. We develop a rigorous mathematical framework for this game and analyze Nash equilibria. We provide a sufficient condition for a Nash equilibrium and prove existence of solutions to a continuum of fully coupled forward-backward ordinary differential equations characterizing equilibria. Moreover, we propose a numerical approach based on machine learning tools and show experimental results on different applications to compartmental models in epidemiology.

OBJECTIVES: Iran is facing a big challenge controlling the COVID-19 outbreak and it is unclear to how individuals are engaging in preventive behaviors. This study aimed to investigate changes in preventive behaviors during the first three months of the COVID-19 outbreak in Iran. METHOD: This cross-sectional survey was conducted on 1477 adults aged 18years and older in 31 provinces of Iran. Data was collected by an anonymous online questionnaire. RESULT: Overall, engagement in preventive behaviors was relatively acceptable and more than 45% of subjects always carried out all preventive behaviors. Engaging in the all preventive behaviors had a peak in the second month and obviously declined during third month. Engagement in some preventive behaviors such as "wearing a face mask" and "keeping a safe distance from others" observed less than other behaviors. There was statistically significant difference in the engagement in preventive behaviors by gender and occupation (P<0.001). CONCLUSION: Although engagement in preventive behaviors was relatively acceptable at first two months of the outbreak, it has declined gradually. This is a warning for public health decision makers. COVID-19 is still a crucial issue in Iran and it is necessary that government decision be based on the fact that Iranian people must live with a coronavirus for months, with full caution and compliance toward all preventive care protocols.

BACKGROUND: For cancer survivors, there is a paucity of fear of recurrence (FOR) interventions that integrate empirically supported mind-body and psychological skills for managing FOR and are delivered in scalable formats. OBJECTIVE: To adapt an evidence-based resiliency intervention to address FOR among cancer survivors. METHODS: A multidisciplinary team of researchers, clinicians, and patient stakeholders followed an iterative intervention adaptation process (ORBIT). In Step 1, we sought to define key FOR management skills through a literature review and feedback from stakeholders. In Step 2, we integrated findings into a treatment manual and refined procedures for in-person delivery to groups of cancer survivors, defined as adults who had completed primary cancer treatment for non-metastatic cancer. In Step 3, we conducted a single arm trial to assess initial acceptability and change in FOR severity with 23 cancer survivors (N=4 intervention groups). In Step 4, we conducted additional qualitative interviews with 28 cancer survivors (N=6 focus groups stratified by FOR severity, N=15 individual interviews) to define adaptive and maladaptive strategies for coping with FOR and to identify preferences for delivery. In Step 5, we refined the treatment manual and procedures for testing in a future pilot randomized feasibility trial. RESULTS: We identified critical feedback using a combination of qualitative and quantitative methods. The single arm trial suggested preliminary feasibility and sustained reductions in FOR severity, yet need for refinement (i.e., eligibility, delivery modality), prompting additional qualitative interviews for further targeting. The resulting intervention (IN FOCUS) is comprised of virtual, synchronous, group-delivered sessions that offer an integrated approach to FOR management by teaching cognitive-behavioral techniques, meditation, relaxation training, adaptive health behaviors, and positive psychology skills. Sessions are targeted by applying skills to FOR and associated healthcare engagement. CONCLUSIONS: IN FOCUS is a targeted intervention for teaching mind-body resiliency skills to groups of cancer survivors with elevated FOR. Next steps are testing feasibility in a pilot randomized trial.

OBJECTIVES: The aim of this study was to report the prevalence of a honeycomb appearance of the spleen in a population of referral cats presented for ultrasound examination, and to determine the diagnostic value of this finding vs the definitive diagnosis, the splenic cytological and haematological results. METHODS: Data were obtained from the medical records (2016C2018) of cats that had an ultrasonographic honeycomb appearance of the spleen, a splenic cytological diagnosis and a complete blood count. RESULTS: Twenty-five cats were included. Prevalence of the honeycomb pattern was 6.8%. None of the spleen was considered normal on cytology and four types of lesions were found: lymphoid hyperplasia (64%), neoplasia (16%), extramedullary haematopoiesis (12%) and splenitis (8%). A honeycomb pattern was successfully identified with a linear high-frequency probe in all cats, but only in 36% of cases with the micro-convex probe. Follow-up information was available for four cats, in which the honeycomb appearance persisted up to 105 days after the first examination; there was persistence of the honeycomb pattern in all cases. Cats with a splenic cytological diagnosis of extramedullary haematopoiesis had the lowest haemoglobin plasma concentration (P = 0.011). CONCLUSIONS AND RELEVANCE: Honeycomb appearance of the spleen is uncommon in cats and, in our study, was systematically associated with cytological alterations; most of the time it was benign (84%). The use of a high-frequency linear probe improves its detection rate. No epidemiological, ultrasonographic or clinical criteria allow differentiation between the different types of infiltration and fine-needle aspiration is therefore recommended.

OBJECTIVE: Psychiatric disorders have been associated with unfavourable outcome following respiratory infections. Whether this also applies to coronavirus disease 2019 (COVID-19) has been scarcely investigated. METHODS: Using the Danish administrative databases, we identified all patients with a positive real-time reverse transcription-polymerase chain reaction test for COVID-19 in Denmark up to and including 2 January 2021. Multivariable cox regression was used to calculate 30-day absolute risk and average risk ratio (ARR) for the composite end point of death from any cause and severe COVID-19 associated with psychiatric disorders, defined using both hospital diagnoses and redemption of psychotropic drugs. RESULTS: We included 144,321 patients with COVID-19. Compared with patients without psychiatric disorders, the standardized ARR of the composite outcome was significantly increased for patients with severe mental illness including schizophrenia spectrum disorders 2.43 (95% confidence interval [CI], 1.79-3.07), bipolar disorder 2.11 (95% CI, 1.25-2.97), unipolar depression 1.70 (95% CI, 1.38-2.02), and for patients who redeemed psychotropic drugs 1.70 (95% CI, 1.48-1.92). No association was found for patients with other psychiatric disorders 1.13 (95% CI, 0.86-1.38). Similar results were seen with the outcomes of death or severe COVID-19. Among the different psychiatric subgroups, patients with schizophrenia spectrum disorders had the highest 30-day absolute risk for the composite outcome 3.1% (95% CI, 2.3-3.9%), death 1.2% (95% CI, 0.4-2.0%) and severe COVID-19 2.7% (95% CI, 1.9-3.6%). CONCLUSION: Schizophrenia spectrum disorders, bipolar disorder, unipolar depression and psychotropic drug redemption are associated with unfavourable outcomes in patients with COVID-19.

RATIONALE: The identification of minimally invasive and easily-accessible biomarkers to support the management of coronavirus disease 2019 (COVID-19) in hospitalized patients constitutes a hot topic in clinical research. MicroRNAs (miRNAs) have been proposed as clinical indicators to assist in medical decision-making. Here, we aimed to examine the circulating miRNA profile of hospitalized COVID-19 patients and to evaluate its potential as a source of biomarkers for the management of the disease. METHODS: Observational, prospective and multicenter study which included 84 patients with a positive nasopharyngeal swab PCR test for SARS-CoV-2, recruited during the first pandemic wave in Spain (March-May 2020). Patients were stratified according to disease severity: hospitalized patients admitted to the clinical wards without requiring critical care (n = 47) and hospitalized patients admitted to the ICU (n = 37). An additional study considering ICU non-survivors (n=17) and survivors (n = 20) was performed. Expression profiling of 41 miRNAs was performed in plasma samples using RT-qPCR. The panel included miRNAs associated with: i) immune/inflammatory response;ii) lung damage;iii) respiratory viral infections;iv) myocardial damage;v) coagulation. Quality control was performed using spike-ins and hemolysis tests. Predictive models were constructed using a variable selection process based on LASSO regression. RESULTS: Ten circulating miRNAs were deregulated in ICU compared to ward patients. LASSO analysis identified a signature of three miRNAs that displayed an optimal discrimination ability to distinguish between ICU and ward patients (AUC = 0.88) (Figure 1A). Among ICU patients, six miRNAs were downregulated when comparing nonsurvivors to survivors. A signature based on two miRNAs was found to be a relevant predictor of mortality during ICU stay (AUC = 0.84) (Figure 1B). The discrimination potential of the miRNA signature was higher than the observed for clinical laboratory parameters such as leukocyte counts (including neutrophil count, lymphocyte count and the neutrophil-tolymphocyte ratio), CRP or D-dimer (maximum AUC for these variables = 0.76). CONCLUSIONS: The severity of COVID-19 impacts on the circulating miRNA profile. The results suggest the potential usefulness of the circulating miRNA signature for the management of the disease over contemporaneous tests, at least in ICU patients.

BACKGROUND: Often thought of as a minor health concern, sore throat or pharyngitis is an important public health issue. It is one of the most common symptoms of upper respiratory diseases including COVID-19 and is a leading cause of physician visits and antibiotic prescriptions. However, few over-the-counter medications are proven to heal sore throat inflammation. METHODS: Adenocarcinomic human alveolar basal epithelial cells (A549 cells) and three dimensional organotypic human respiratory tissues were used to study inflammation and various treatment effects on respiratory epithelia. The cells and tissues were studied both in the presence and absence of bradykinin, one of the first inflammatory mediators of pharyngitis. Inflammation was measured by analyzing the levels of prostaglandin E2 (PGE2), interleukin 8 (IL-8), and leukotriene B4 (LTB4), transepithelial electrical resistance (TEER), and lactate dehydrogenase (LDH) release. Tissue morphology was analyzed by immunohistochemistry. RESULTS: In studying pharyngitis using organotypic human respiratory tissue stimulated with bradykinin, we saw an increase in PGE2 and interleukin-8 (IL-8) in response to bradykinin. Acetyl salicylic acid (ASA), a nonspecific COX inhibitor, was able to mitigate a bradykinin-induced increase in PGE2 in our studies. However, ASA was inflammatory above its therapeutic window, increasing the levels of PGE2 and IL-8 above those seen with bradykinin stimulation alone. We describe a novel, scientifically validated treatment for sore throat, that contains a low dose of ASA and other anti-inflammatory ingredients. CONCLUSION: This study elucidates the complex mechanisms involved in healing pharyngitis, an inflammatory condition of the upper respiratory epithelia. An ASA-based formula (Biovanta) mitigated bradykinin-induced inflammation more strongly than ASA alone in organotypic human respiratory tissues. Surprisingly, we found that many of the most common over the counter sore throat therapies exacerbate inflammation and IL-8 in organotypic human respiratory tissues, suggesting these common treatments may increase the likelihood of further respiratory complications.