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Objectives To determine the effect of povidone-iodine (PVP-I) nasal sprays on nasopharyngeal (NP) viral load as assessed by cycle threshold on quantitative polymerase chain reaction (qPCR) of SARS-CoV-2 in outpatients. Study design Three arm, triple blinded, randomized, placebo-controlled clinical trial. Methods Participants were randomized within 5 days of testing positive for COVID-19 to receive nasal sprays containing either placebo (0.9% saline), 0.5% PVP-I, or 2.0% PVP-I. NP swabs for qPCR analysis were taken at baseline, 1-hour post-PVP-I spray (2 sprays/nostril), and 3 days post-PVP-I spray (20 sprays/nostril). Symptom and adverse event questionnaires were completed at baseline, day 3, and day 5. University of Pennsylvania Smell Identification Tests (UPSIT) were completed at baseline and day 30. Results Mean cycle threshold (Ct) values increased over time in all groups, indicating declining viral loads, with no statistically significant difference noted in the rate of change between placebo and PVP-I groups. 2.0% PVP-I group showed statistically significant improvement in all symptom categories, however also reported a high rate of nasal burning. Olfaction via UPSIT showed improvement by at least one category in all groups. There were no hospitalizations or mortalities within 30 days of study enrollment. Conclusion Saline and low concentration PVP-I nasal sprays are well tolerated. Similar reductions in SARS-CoV-2 nasopharyngeal viral load were seen over time in all groups. All treatment groups showed improvement in olfaction over 30 days. These data suggest that dilute versions of PVP-I nasal spray are safe for topical use in the nasal cavity, but that PVP-I does not demonstrate virucidal activity in COVID-19 positive outpatients. This article is protected by copyright. All rights reserved.

Evidence shows that chronic rhinosinusitis (CRS) is associated with prior presence of autoimmune diseases; however, large-scale population-based studies in the literature are limited. We conducted a population-based case–control study investigating the association between CRS and premorbid autoimmune diseases by using the National Health Insurance Research Database in Taiwan. The CRS group included adult patients newly diagnosed with CRS between 2001 and 2013. The date of diagnosis was defined as the index date. The comparison group included individuals without CRS, with 1:4 frequency matching for gender, age, and index year. Premorbid diseases were forward traced to 1996. Univariate and multivariate logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals. The CRS group consisted of 30,611 patients, and the comparison group consisted of 122,444 individuals. Patients with CRS had a higher significant association with premorbid autoimmune diseases (adjusted OR 1.39 [1.28–1.50]). Specifically, patients with CRS had a higher significant association with ankylosing spondylitis, polymyositis, psoriasis, rheumatoid arthritis, sicca syndrome, and systemic lupus erythematosus (adjusted OR 1.49 [1.34–1.67], 3.47 [1.12–10.8], 1.22 [1.04–1.43], 1.60 [1.31–1.96], 2.10 [1.63–2.72], and 1.69 [1.26–2.25]). In subgroup analysis, CRS with and without nasal polyps demonstrated a significant association with premorbid autoimmune diseases (adjusted OR 1.34 [1.14–1.58] and 1.50 [1.38–1.62]). In addition, CRS with fungal and non-fungal infections also demonstrated a significant association with premorbid autoimmune diseases (adjusted OR 2.02 [1.72–2.49] and 1.39 [1.28–1.51]). In conclusion, a significant association between CRS and premorbid autoimmune diseases has been identified. These underlying mechanisms need further investigation.

Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-β1 levels between smokers and non-smokers., Graphical Abstract, Nakayama et al. discover key variabilities in expression of SARS-CoV-2 entry factors among human head and neck mucosal tissues. They demonstrate that SARS-CoV-2 preferentially infects the nasal cavity and trachea. They uncover an association between smoking and higher SARS-CoV-2 in the human proximal airway, in part because of differences in IFN-β1 expression.

Emerging evidence suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with disparate inflammatory characteristics between different racial groups and geographies. Currently, little is known about possible underlying distinguishing factors between these inflammatory differences.Our aim was to interrogate differences in CRSwNP disease between White/non-Asian patients and Japanese patients by using whole transcriptome and single-cell RNA gene expression profiling of nasal polyps (NPs).We performed whole transcriptome RNA sequencing with endotype stratification of NPs from 8 White patients (residing in the United States) and 9 Japanese patients (residing in Japan). Reproducibility was confirmed by quantitative PCR in an independent validation set of 46 White and 31 Japanese patients. Single-cell RNA sequencing (scRNAseq) was used to stratify key cell types for contributory transcriptional signatures.Unsupervised clustering analysis identified 2 major endotypes that were present within both cohorts of patients with NPs and had previously been reported at the cytokine level: (1) type 2 endotype and (2) non-type 2 endotype. Importantly, there was a statistically significant difference in the proportion of these endotypes between these geographically distinct subgroups with NPs (P = .03). Droplet-based single-cell RNA sequencing further identified prominent type 2 inflammatory transcript expression: C-C motif chemokine ligand 13 (CCL13) and CCL18 in M2 macrophages, as well as cystatin SN (CST1) and CCL26 in basal, suprabasal, and secretory epithelial cells.NPs from both racial groups harbor the same 2 major endotypes, which we have determined to be present in differing ratios between each cohort with CRSwNP disease. Distinct inflammatory and epithelial cells contribute to the type 2 inflammatory profiles observed.

Emerging evidence points toward an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While preexisting diabetes is associated with severe COVID-19, it is unclear whether COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic β cells can be infected by SARS-CoV-2 and cause β cell depletion. We found that the SARS-CoV-2 receptor, ACE2, and related entry factors (TMPRSS2, NRP1, and TRFC) are expressed in β cells, with selectively high expression of NRP1. We discovered that SARS-CoV-2 infects human pancreatic β cells in patients who succumbed to COVID-19 and selectively infects human islet β cells in vitro. We demonstrated that SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion and induces β cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic β cell signaling, similar to that observed in type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce β cell killing., Graphical abstract, Diabetic patients are at risk for severe COVID-19, but the virus may further damage insulin-secreting β cells. Wu et al. found that patient β cells are virally infected and the highly expressed neuropilin-1 receptor is critical for viral entry, causing cell death and reduced insulin secretion, exacerbating diabetes in patients.

The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen., Understanding how SARS-CoV-2 gains initial entry into the human body is a key step towards the development of prophylaxes and therapeutics for COVID-19. Here, the authors show that ACE2, the receptor for SARS-CoV-2, is abundantly expressed in the motile cilia of the human nasal and respiratory tract and is not affected by the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.

Background/aim Functional endoscopic sinus surgery (FESS) is frequently conducted for restoring sinus ventilation and function. Postoperative care is critical for success. However, loss to follow-up is disturbing. The specific aim of this study was to identify critical factors contributing to loss of patients to follow-up and how to improve it. Patients and methods A total of 221 patients with chronic rhinosinusitis undergoing FESS were enrolled. Patients were divided into three groups according to their follow-up after surgery: Less than 1 month (short-term), 1-3 months (medium-term) and more than 3 months (long-term). The gender, age, smoking status, comorbidities, laterality, Lund-Mackay score, 22-question Sinonasal Outcome Test, nasal obstruction Visual Analogue Scale and mucociliary clearance were evaluated for their contribution to better compliance in follow-up. Results The results revealed that older patients had better compliance in follow-up compared with younger ones (p=0.0093). Other factors were not contributory (p>0.05). Conclusion In contrast to the US, older patients in Taiwan have better compliance in postoperative follow-up, while younger ones require more education on the importance of follow-up.

We investigated the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of healthy human donors. We detected ACE2 protein expression within the cilia organelle of ciliated airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during respiratory transmission. We further determined whether ACE2 expression in the cilia of upper respiratory cells was influenced by patient demographics, clinical characteristics, co-morbidities, or medication use, and found no evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) increases ACE2 protein expression.

Food allergy is a significant medical problem that affects up to 8% of children in developed countries. At present, there are no curative therapies available in routine practice and management of food allergy involves strict allergen avoidance, education, and prompt treatment upon accidental exposure. Oral immunotherapy (OIT) is an efficacious experimental approach to food allergy and has been shown to provide a substantial benefit in terms of allergen desensitization. However, OIT is associated with high rates of allergic reactions, and the period of protection offered by OIT appears to be limited and highly variable. Recurrence of allergen sensitivity after a period of treatment discontinuation is commonly observed. With the aim of overcoming these limitations of OIT, several trials have studied omalizumab (anti-IgE monoclonal antibody) as an adjuvant treatment for patients undergoing OIT. Results from these trials have shown that the addition of omalizumab to OIT leads to a significant decrease in the frequency and severity of reactions, which allows for an increase in the threshold of tolerance to food allergens. This review provides a summary of the current literature and addresses some of the key questions that remain regarding the use of omalizumab in conjunction with OIT.

The ability of the sigma(1) receptor to interact with a huge range of drug structural classes coupled with its wide distribution in the body has contributed to it being implicated as a possible therapeutic target for a broad array of disorders ranging from substance abuse to depression to Alzheimer's disease. Surprisingly, the reported affinity values for some sigma(1) receptor ligands vary more than 50-fold. The potential of the sigma(1) receptor as a pharmacotherapeutic target prompted us to develop an unambiguous assay system for measuring the affinity of ligands to the cloned human sigma(1) receptor. In the course of characterizing this system and determining the true affinity values for almost three dozen compounds, it was discovered that some dopamine D(4) receptor selective compounds bind sigma(1) receptors with high affinity. A systematic analysis of haloperidol-like compounds revealed a clear structure-affinity relationship amongst clinically relevant butyrophenones. The antidepressant fluvoxamine, the drug of abuse methamphetamine, and the neurosteroid progesterone were amongst the many ligands whose interactions with the sigma(1) receptor were confirmed with our screening assay.

Previous studies indicate that the Sigma-1 ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) protects the brain from ischemia. Less clear is whether protection is mediated by agonism or antagonism of the Sigma-1 receptor, and whether drugs already in use for other indications and that interact with the Sigma-1 receptor might also prevent oxidative damage due to conditions such as cerebral ischemic stroke. The antipsychotic drug haloperidol is an antagonist of Sigma-1 receptors and in this study it potently protects against oxidative stress-related cell death in vitro at low concentrations. The protective potency of haloperidol and a number of other butyrophenone compounds positively correlate with their affinity for a cloned Sigma-1 receptor, and the protection is mimicked by a Sigma-1 receptor-selective antagonist (BD1063), but not an agonist (PRE-084). In vivo, an acute low dose (0.05 mg/kg s.c.) of haloperidol reduces by half the ischemic lesion volume induced by a transient middle cerebral artery occlusion. These in vitro and in vivo pre-clinical results suggest that a low dose of acutely administered haloperidol might have a novel application as a protective agent against ischemic cerebral stroke and other types of brain injury with an ischemic component.

SUMMARYThe triploid Rhoeo spatacea (X=6) exhibited random distribution of the chromosomes at anaphase I, and the number of chromosomes in the gametes will range from monoploid to diploid, i.e. from 6 to 12. Among 89 pollen mother cells (PMC) without laggards, 4 (4,49%) had 6–12 distribution, 11 (12,36%) had 7–11, 44 (49.44%) ah 8–10 distribution which was most frequently observed, and 30 (33.71%) had 9–9 distribution.Lagging chromosomes were found in 32.06% of the 131 PMC examined. The number of laggards in PMC ranged from one to four, with one laggard being most frequently found. The observed frequencies of various types of chromosome distribution in PMC with one or two laggards also fit the calculated frequencies based on random chromosome distribution.Despite of the irregularities in the meiotic division, triploid Rhoeo demonstrated a rather high pollen viability, 45.09%, probably due to a greater tolerance of the hypermonoploid or hypodiploid pollen for changes in chromosome number and balance.