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Background SARS-CoV-2 epidemiology implicates airborne transmission; aerosol infectiousness and impacts of masks and variants on aerosol shedding are not well understood. Methods We recruited COVID-19 cases to give blood, saliva, mid-turbinate and fomite (phone) swabs, and 30-minute breath samples while vocalizing into a Gesundheit-II, with and without masks at up to two visits two days apart. We quantified and sequenced viral RNA, cultured virus, and assayed sera for anti-spike and anti-receptor binding domain antibodies. Results We enrolled 49 seronegative cases (mean days post onset 3.8 ±2.1), May 2020 through April 2021. We detected SARS-CoV-2 RNA in 45% of fine (≤5 µm), 31% of coarse (>5 µm) aerosols, and 65% of fomite samples overall and in all samples from four alpha-variant cases. Masks reduced viral RNA by 48% (95% confidence interval [CI], 3 to 72%) in fine and by 77% (95% CI, 51 to 89%) in coarse aerosols; cloth and surgical masks were not significantly different. The alpha variant was associated with a 43-fold (95% CI, 6.6 to 280-fold) increase in fine aerosol viral RNA, compared with earlier viruses, that remained a significant 18-fold (95% CI, 3.4 to 92-fold) increase adjusting for viral RNA in saliva, swabs, and other potential confounders. Two fine aerosol samples, collected while participants wore masks, were culture-positive. Conclusion SARS-CoV-2 is evolving toward more efficient aerosol generation and loose-fitting masks provide significant but only modest source control. Therefore, until vaccination rates are very high, continued layered controls and tight-fitting masks and respirators will be necessary.

Background: SARS-CoV-2 epidemiology implicates airborne transmission; mask source-control efficacy for, variant impact on, and infectiousness of aerosols are not well understood. Methods: We recruited COVID-19 cases to give blood, saliva, mid-turbinate and fomite (phone) swabs, and 30-minute breath samples while vocalizing into a Gesundheit-II, with and without masks at up to two visits two days apart. We quantified and sequenced viral RNA, cultured virus, and assayed sera for anti-spike and anti-receptor binding domain antibodies. Results: We enrolled 61 participants with active infection, May 2020 through April 2021. Among 49 seronegative cases (mean days post onset 3.8 ±2.1), we detected SARS-CoV-2 RNA in 45% of fine (≥5 μm), 31% of coarse (>5 μm) aerosols, and 65% of fomite samples overall and in all samples from four alpha variant cases. Masks reduced viral RNA by 48% (95% confidence interval [CI], 3 to 72%) in fine and by 77% (95% CI, 51 to 89%) in coarse aerosols. The alpha variant was associated with a 43-fold (95% CI, 6.6 to 280-fold) increase in fine aerosol viral RNA that remained a significant 18-fold (95% CI, 3.4 to 92-fold) increase adjusting for viral RNA in saliva, in mid-turbinate swabs, and other potential confounders. Two fine aerosol samples, collected days 2-3 post illness onset, while participants wore masks, were culture-positive. Conclusion: SARS-CoV-2 is evolving toward more efficient airborne transmission and loose-fitting masks provide significant but only modest source control. Therefore, until vaccination rates are very high, continued layered controls and tight-fitting masks and respirators will be necessary.

The findings of this manuscript are increasingly important with new variants that appear to have shorter incubation periods emerging, which may be more prone to detection in saliva before detection in nasal swabs. Therefore, there is an urgent need to provide the science to support the use of a detection method that is highly sensitive and widely acceptable to the public to improve screening rates and early detection.

BackgroundSaliva is an attractive sample for detecting SARS-CoV-2 because it is easy to collect and minimally invasive. However, contradictory reports exist concerning the sensitivity of saliva versus nasal swabs.MethodsWe recruited and followed close contacts of COVID-19 cases for up to 14 days from their last exposure and collected self-reported symptoms, mid-turbinate swabs (MTS) and saliva every two or three days. Ct values and frequency of viral detection by MTS and saliva were compared. Logistic regression was used to estimate the probability of detection by days since symptom onset for the two sample types.ResultsWe enrolled 58 contacts who provided a total of 200 saliva and MTS sample pairs; 14 contacts (13 with symptoms) had one or more positive samples. Overall, saliva and MTS had similar rates of viral detection (p=0.78). Although Ct values for saliva were significantly greater than for MTS (p=0.014), Cohen’s Kappa demonstrated substantial agreement (κ=0.83). However, sensitivity varied significantly with time relative to symptom onset. Early in the course of infection (days -3 to 2), saliva had 12 times (95%CI: 1.2, 130) greater likelihood of detecting viral RNA compared to MTS. After day 2, there was a non-significant trend to greater sensitivity using MTS samples.ConclusionSaliva and MTS specimens demonstrated high agreement, making saliva a suitable alternative to MTS nasal swabs for COVID-19 detection. Furthermore, saliva was more sensitive than MTS early in the course of infection, suggesting that it may be a superior and cost-effective screening tool for COVID-19.Key PointsSaliva is more sensitive in detecting symptomatic cases of COVID-19 than MTS early in the course of infection.Saliva performs best in the pre-symptomatic period.Saliva and MTS demonstrated high agreement making saliva a suitable and cost-effective COVID-19 screening tool.

Magnetic stimulation (MS) is a novel approach for treating urinary incontinence (UI), but its applicability remains unclear. This systematic review and meta-analysis were conducted to evaluate the effects of MS treatment on UI. A literature search was performed in EMBASE, PubMed and Cochrane Library (from May 2018 to August 2018), and all randomized control trials (RCTs) published in English were screened to determine whether they met the inclusion criteria. A manual search of the reference lists of the retrieved studies was also performed. Eleven studies involving 612 patients were included in this review. According to the results of the meta-analysis, MS therapy relieved UI symptoms evaluated using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score (mean difference [MD] −3.03, 95% CI −3.27 to −2.79). In addition, the frequency of UI in the MS treatment group was also alleviated compared with sham group (MD −1.42, 95% CI −2.15 to −0.69). Finally, MS treatment improved the quality of life of patients with UI (standardized mean difference [SMD] −1.00, 95% CI −1.24 to −0.76). Our meta-analysis preliminarily indicates that MS treatment is an effective therapeutic modality for patients with UI. Nevertheless, additional large, high quality RCTs with a longer follow-up period that use consistent stimulation methods and analyse comparable outcomes are required to validate the efficacy.

Background Partial bladder outlet obstruction (PBOO) promotes bladder detrusor hyperplasia, increases bladder pressure, and decreases bladder compliance. To extensively explore its underlying mechanism, our study aimed to investigate the effect of pathological hydrostatic pressure on human bladder smooth muscle cell (hBSMC) proliferation and contraction through β‐adrenoceptor (ADRB) signaling in vitro. Methods hBSMCs were subjected to pathological hydrostatic pressure (100 cm H2O) to investigate the effect of ADRBs on the proliferation and contraction of hBSMCs treated with its agonists and/or antagonists. Results Firstly, exposure to 100 cm H2O hydrostatic pressure significantly upregulated the expression of α‐smooth muscle actin (α‐SMA) in hBSMCs at 6 hours, and promoted cell proliferation at 24 hours. When subjected to hydrostatic pressure alone, hBSMCs treated with ADRB2 and ADRB3 agonists for 6 hours inhibited α‐SMA expression compared with untreated cells. By contrast, hBSMCs treated with ADRB2 agonists for 24 hours suppressed cell proliferation compared with untreated cells. The two classical pathways of ADRB, protein kinase A (PKA), and exchange factor directly activated by cAMP (EPAC) inhibited the contraction of hBSMCs under hydrostatic pressure via regulating mothers against decapentaplegic homolog 2 (SMAD2) activity. The proliferation of hBSMCs was mainly regulated by the EPAC pathway through extracellular signal‐regulated kinase 1/2 (ERK1/2) activity. Conclusion The contraction of hBSMCs under hydrostatic pressure was regulated by ADRB2 and ADRB3 via the PKA/EPAC‐SMAD2 pathway, and the proliferation of hBSMCs was regulated by ADRB2 via the EPAC‐ERK1/2 pathway. Compared with ADRB3, ADRB2 played a predominant role under pathological hydrostatic pressure. These findings markedly uncovered the underlying mechanism of ADRBs in PBOO and provided new insights into the efficient treatment of patients with PBOO.

A series of 4-aryl-N-arylcarbonyl-2-aminothiazoles of scaffold 4 was designed and synthesized as Hec1/Nek2 inhibitors. Structural optimization of 4 led to compound 32 bearing C-4' 4-methoxyphenoxy and 4-(o-fluoropyridyl)carbonyl groups that showed low nanomolar in vitro antiproliferative activity (IC50: 16.3-42.7 nM), high intravenous AUC (64.9 μM·h, 2.0 mg/kg) in SD rats, and significant in vivo antitumor activity (T/C = 32%, 20 mg/kg, IV) in mice bearing human MDA-MB-231 xenografts. Cell responses resulting from Hec1/Nek2 inhibition were observed in cells treated with 32, including a reduced level of Hec1 coimmunoprecipitated with Nek2, degradation of Nek2, mitotic abnormalities, and apoptosis. Compound 32 showed selectivity toward cancer cells over normal phenotype cells and was inactive in a [(3)H]astemizole competitive binding assay for hERG liability screening. Therefore, 32 is as a good lead toward the discovery of a preclinical candidate targeting Hec1/Nek2 interaction.