Oxymetazoline as a predictor of turbinate reduction surgery outcomes: Objective support from a prospective, single-blinded, computational fluid dynamics study.

BACKGROUND: A patient's subjective response to topical nasal decongestant is often used to screen for turbinate reduction surgery suitability. However, this anecdotal strategy has not been objectively and quantitatively evaluated. METHODS: Prospective, longitudinal, and single-blinded cohort study employing computational fluid dynamic modeling based on computed tomography scans at baseline, 30 min postoxymetazoline, and 2 months postsurgery on 11 patients with chronic turbinate hypertrophy. RESULTS: Nasal obstruction symptom evaluation (NOSE) and visual analogue scale (VAS) obstruction scores significantly improved from baseline to postoxymetazoline and again to postsurgery (NOSE: 71.82 ± 14.19 to 42.27 ± 25.26 to 22.27 ± 21.04; VAS: 6.09 ± 2.41 to 4.14 ± 2.20 to 2.08 ± 1.56; each interaction p < 0.05), with significant correlation between the latter two states (r∼0.37-0.69, p < 0.05). Oxymetazoline had a broader anatomical impact throughout inferior and middle turbinates than surgery (many p < 0.05); however, the improvement in regional airflow is similar (most p > 0.05) and predominantly surrounding the inferior turbinate. Strong postoxymetazoline to postsurgery correlations were observed in decreased nasal resistance (r = 0.79, p < 0.05), increased regional airflow rates (r = -0.47 to -0.55, p < 0.05) and regional air/mucosa shear force and heat flux (r = 0.43 to 0.58, p < 0.05); however, only increasing peak heat flux significantly correlated to symptom score improvement (NOSE: r = 0.48, p < 0.05). CONCLUSION: We present the first objective evidence that the "topical decongestant test" can help predict turbinate reduction surgery outcomes. The predictive effect is driven by similar improvementin regional airflow that leading to improved air/mucosa stimulations (peak heat flux) rather than through reduced nasal resistance.

The role of revision sinus surgery in the initiation of dupilumab therapy: A real-world study of molecular and cellular features.

KEY POINTS: A persistent type 2 endotype signature exists in recalcitrant chronic rhinosinusitis with nasal polyps mucosa on dupilumab. Revision sinus surgery immediately prior to dupilumab reduces long-term interleukin (IL)-4/IL-13 tissue mRNA. Pre-dupilumab revision surgery is associated with reduced tissue eosinophils and GATA-3+ cells.

Competency-Based Medication Administration and Error Reporting.

BACKGROUND: Accuracy is needed with medication administration, a skill that involves rule-based habits and clinical reasoning. This pilot study investigated the use of an evidence-based checklist for accuracy with oral medication administration and error reporting among prelicensure nursing students. Checklist items were anchored in the mnemonic C-MATCH-REASON© (Client, Medication, ADRs, Time, Client History, Route, Expiration date, Amount, Site, Outcomes, Notation). METHOD: Nineteen participants randomly assigned to crossover sequence AB or BA (A: checklist; B: no checklist) practiced simulation scenarios with embedded errors. Nursing faculty used an observation form to track error data. RESULTS: Using the C-MATCH-REASON© checklist compared with not using the checklist supported rule adherence (p = .005), knowledge-based error reduction (p = .011), and total error reduction (p = .010). The null hypothesis was not rejected for errors found (p = .061) nor reported (p = .144), possibly due to sample size. CONCLUSION: C-MATCH-REASON© was effective for error reduction. Study replication with a larger sample is warranted. [J Nurs Educ. 2024;63(5):320-327.].

Advantages and caveats of endoscopic to the infratemporal fossa as isolated and combined techniques.

Objective: Identify the benefits and caveats of combining minimal access approaches to the infratemporal fossa (ITF), such as the endoscopic transnasal, endoscopic transorbital, endoscopic transoral, and endoscopic sublabial transmaxillary approaches to address extensive lesions not amenable to a single approach. The study provides anatomical metrics including area of exposure and degree of surgical freedom. Methods: Five human cadaveric specimens (10 sides) were dissected to expose and methodically analyze the anatomical intricacies of the ITF using the following minimal access approaches: endoscopic transnasal transpterygoid (EETA), endoscopic sublabial transmaxillary, endoscopic transorbital via infraorbital foramen, and endoscopic transoral techniques. Area of exposure at the pterygopalatine fossa and surgical freedom at the ITF were obtained for each approach. Results: The endoscopic sublabial transmaxillary sinus and the combined approach afford a significantly greater exposure than an isolated EETA. The difference in exposure (mean) between the endoscopic sublabial transmaxillary and EETA was 1.62 ± 0.85 cm2 (p < 0.001), and the difference between the combined approach and EETA was 4.25 ± 0.85 cm2 (p < 0.001). Conclusions: Combining minimal access endoscopic approaches to the ITF can provide significantly greater exposure than an isolated EETA; thus, providing enhanced access to address lesions with extensive involvement of the ITF, especially those with superolateral and inferolateral extensions. In addition, some approaches may have an adjunctive role to the resection, such as the endoscopic transoral approach offering the potential for early control of the internal maxillary artery and its branches, some of which may be supplying the tumor in the ITF; or the endoscopic transorbital approach yielding a direct line of sight to the superior ITF and middle cranial fossa. Level of Evidence: NA.

Reproducible preclinical models of androgen receptor driven human prostate cancer bone metastasis.

BACKGROUND: Preclinical models recapitulating the metastatic phenotypes are essential for developing the next-generation therapies for metastatic prostate cancer (mPC). We aimed to establish a cohort of clinically relevant mPC models, particularly androgen receptor positive (AR+) bone metastasis models, from LuCaP patient-derived xenografts (PDX) that reflect the heterogeneity and complexity of mPC. METHODS: PDX tumors were dissociated into single cells, modified to express luciferase, and were inoculated into NSG mice via intracardiac injection. The progression of metastases was monitored by bioluminescent imaging. Histological phenotypes of metastases were characterized by immunohistochemistry and immunofluorescence staining. Castration responses were further investigated in two AR-positive models. RESULTS: Our PDX-derived metastasis (PDM) model collection comprises three AR+ adenocarcinomas (ARPC) and one AR- neuroendocrine carcinoma (NEPC). All ARPC models developed bone metastases with either an osteoblastic, osteolytic, or mixed phenotype, while the NEPC model mainly developed brain metastasis. Different mechanisms of castration resistance were observed in two AR+ PDM models with distinct genotypes, such as combined loss of TP53 and RB1 in one model and expression of AR splice variant 7 (AR-V7) expression in another model. Intriguingly, the castration-resistant tumors displayed inter- and intra-tumor as well as organ-specific heterogeneity in lineage specification. CONCLUSION: Genetically diverse PDM models provide a clinically relevant system for biomarker identification and personalized medicine in metastatic castration-resistant prostate cancer.

Stem cell dynamics and cellular heterogeneity across lineage subtypes of castrate-resistant prostate cancer.

To resist lineage-dependent therapies such as androgen receptor inhibition, prostate luminal epithelial adenocarcinoma cells often adopt a stem-like state resulting in lineage plasticity and phenotypic heterogeneity. Castrate-resistant prostate adenocarcinoma can transition to neuroendocrine (NE) and occasionally to amphicrine, co-expressed luminal and NE, phenotypes. We developed castrate-resistant prostate cancer (CRPC) patient-derived organoid models that preserve heterogeneity of the originating tumor, including an amphicrine model displaying a range of luminal and NE phenotypes. To gain biological insight and to identify potential treatment targets within heterogeneous tumor cell populations, we assessed the lineage hierarchy and molecular characteristics of various CRPC tumor subpopulations. Transcriptionally similar stem/progenitor (St/Pr) cells were identified for all lineage populations. Lineage tracing in amphicrine CRPC showed that heterogeneity originated from distinct subclones of infrequent St/Pr cells that produced mainly quiescent differentiated amphicrine progeny. By contrast, adenocarcinoma CRPC progeny originated from St/Pr cells and self-renewing differentiated luminal cells. Neuroendocrine prostate cancer (NEPC) was composed almost exclusively of self-renewing St/Pr cells. Amphicrine subpopulations were enriched for secretory luminal, mesenchymal, and enzalutamide treatment persistent signatures that characterize clinical progression. Finally, the amphicrine St/Pr subpopulation was specifically depleted with an AURKA inhibitor, which blocked tumor growth. These data illuminate distinct stem cell (SC) characteristics for subtype-specific CRPC in addition to demonstrating a context for targeting differentiation-competent prostate SCs.

How Does Oxymetazoline Change Nasal Aerodynamics and Symptomatology in Patients with Turbinate Hypertrophy?

OBJECTIVES: Oxymetazoline relieves nasal obstructive symptoms via vasoconstriction, however, the changes in nasal structures and aerodynamics that impact symptoms the most remain unclear. METHODS: This prospective, longitudinal, and single blinded cohort study applied Computational Fluid Dynamic (CFD) modeling based on CT scans at baseline and post-oxymetazoline on 13 consecutive patients with chronic nasal obstruction secondary to inferior turbinate hypertrophy from a tertiary medical center. To account for placebo effect, a sham saline spray was administered with subject blindfolded prior to oxymetazoline, with 30 min rest in between. Nasal Obstruction Symptom Evaluation (NOSE) and unilateral Visual Analogue Scale (VAS) scores of nasal obstructions were collected at baseline, after sham, and 30 min after oxymetazoline. RESULTS: Both VAS and NOSE scores significantly improved from baseline to post-oxymetazoline (NOSE: 62.3 ± 12.4 to 31.5 ± 22.5, p < 0.01; VAS: 5.27 ± 2.63 to 3.85 ± 2.59, p < 0.05), but not significantly from baseline to post-sham. The anatomical effects of oxymetazoline were observed broadly throughout the entire length of the inferior and middle turbinates (p < 0.05). Among many variables that changed significantly post-oxymetazoline, only decreased nasal resistance (spearman r = 0.4, p < 0.05), increased regional flow rates (r = -0.3 to -0.5, p < 0.05) and mucosal cooling heat flux (r = -0.42, p < 0.01) in the inferior but not middle turbinate regions, and nasal valve Wall Shear Stress (WSS r = -0.43, p < 0.05) strongly correlated with symptom improvement. CONCLUSION: Oxymetazoline broadly affects the inferior and middle turbinates, however, symptomatic improvement appears to be driven more by global nasal resistance and regional increases in airflow rate, mucosal cooling, and WSS, especially near the head of the inferior turbinate. LEVEL OF EVIDENCE: 3: Well-designed, prospective, single blinded cohort trial. Laryngoscope, 134:1100-1106, 2024.

Investigating the association between characteristics of local crisis care systems and service use in an English national survey.

BACKGROUND: In England, a range of mental health crisis care models and approaches to organising crisis care systems have been implemented, but characteristics associated with their effectiveness are poorly understood. AIMS: To (a) develop a typology of catchment area mental health crisis care systems and (b) investigate how crisis care service models and system characteristics relate to psychiatric hospital admissions and detentions. METHOD: Crisis systems data were obtained from a 2019 English national survey. Latent class analyses were conducted to identify discernible typologies, and mixed-effects negative binomial regression models were fitted to explore associations between crisis care models and admissions and detention rates, obtained from nationally reported data. RESULTS: No clear typology of catchment area crisis care systems emerged. Regression models suggested that provision of a crisis telephone service within the local crisis system was associated with a 11.6% lower admissions rate and 15.3% lower detention rate. Provision of a crisis cafe was associated with a 7.8% lower admission rates. The provision of a crisis assessment team separate from the crisis resolution and home treatment service was associated with a 12.8% higher admission rate. CONCLUSIONS: The configuration of crisis care systems varies considerably in England, but we could not derive a typology that convincingly categorised crisis care systems. Our results suggest that a crisis phone line and a crisis cafe may be associated with lower admission rates. However, our findings suggest crisis assessment teams, separate from home treatment teams, may not be associated with reductions in admission and detentions.

Tumor-derived biomarkers predict efficacy of B7H3 antibody-drug conjugate treatment in metastatic prostate cancer models.

Antibody-drug conjugates (ADCs) are a promising targeted cancer therapy; however, patient selection based solely on target antigen expression without consideration for cytotoxic payload vulnerabilities has plateaued clinical benefits. Biomarkers to capture patients who might benefit from specific ADCs have not been systematically determined for any cancer. We present a comprehensive therapeutic and biomarker analysis of a B7H3-ADC with pyrrolobenzodiazepine(PBD) payload in 26 treatment-resistant, metastatic prostate cancer (mPC) models. B7H3 is a tumor-specific surface protein widely expressed in mPC, and PBD is a DNA cross-linking agent. B7H3 expression was necessary but not sufficient for B7H3-PBD-ADC responsiveness. RB1 deficiency and/or replication stress, characteristics of poor prognosis, and conferred sensitivity were associated with complete tumor regression in both neuroendocrine (NEPC) and androgen receptor positive (ARPC) prostate cancer models, even with low B7H3 levels. Non-ARPC models, which are currently lacking efficacious treatment, demonstrated the highest replication stress and were most sensitive to treatment. In RB1 WT ARPC tumors, SLFN11 expression or select DNA repair mutations in SLFN11 nonexpressors governed response. Importantly, WT TP53 predicted nonresponsiveness (7 of 8 models). Overall, biomarker-focused selection of models led to high efficacy of in vivo treatment. These data enable a paradigm shift to biomarker-driven trial designs for maximizing clinical benefit of ADC therapies.

Using patient-derived tumor organoids from common epithelial cancers to analyze personalized T-cell responses to neoantigens.

Adoptive cell transfer of tumor-infiltrating lymphocytes (TIL) can mediate durable complete responses in some patients with common epithelial cancers but does so infrequently. A better understanding of T-cell responses to neoantigens and tumor-related immune evasion mechanisms requires having the autologous tumor as a reagent. We investigated the ability of patient-derived tumor organoids (PDTO) to fulfill this need and evaluated their utility as a tool for selecting T-cells for adoptive cell therapy. PDTO established from metastases from patients with colorectal, breast, pancreatic, bile duct, esophageal, lung, and kidney cancers underwent whole exomic sequencing (WES), to define mutations. Organoids were then evaluated for recognition by autologous TIL or T-cells transduced with cloned T-cell receptors recognizing defined neoantigens. PDTO were also used to identify and clone TCRs from TIL targeting private neoantigens and define those tumor-specific targets. PDTO were successfully established in 38/47 attempts. 75% were available within 2 months, a timeframe compatible with screening TIL for clinical administration. These lines exhibited good genetic fidelity with their parental tumors, especially for mutations with higher clonality. Immunologic recognition assays demonstrated instances of HLA allelic loss not found by pan-HLA immunohistochemistry and in some cases WES of fresh tumor. PDTO could also be used to show differences between TCRs recognizing the same antigen and to find and clone TCRs recognizing private neoantigens. PDTO can detect tumor-specific defects blocking T-cell recognition and may have a role as a selection tool for TCRs and TIL used in adoptive cell therapy.

Platelets from blood diversion pouches (DPs) are a suitable alternative for functional, bioenergetic, and metabolomic analyses.

BACKGROUND: The collection of the first blood flow into a diversion pouch (DP) has become widely adopted in blood donation systems to reduce whole-blood unit contamination from skin bacteria. The strict control of pre-analytical variables, such as blood collection and proper anticoagulant selection, is critical to diminish experimental variability when studying different aspects of platelet biology. We hypothesize that the functional, mitochondrial, and metabolomic profiles of platelets isolated from the DP are not different from the ones isolated from standard venipuncture (VP), thus representing a suitable collection method of platelets for experimental purposes. MATERIALS AND METHODS: Whole blood from the blood DP or VP was collected. Platelets were subsequently isolated and washed following standard protocols. Platelet function was assessed by flow cytometry, light transmission aggregometry, clot retraction, and under flow conditions using the total thrombus formation analyzer (T-TAS). Mitochondrial function and the platelet metabolome profiles were determined by the Seahorse extracellular flux analyzer (Agilent, Santa Clara, CA, USA) and ultra-high-pressure liquid chromatography-mass spectrometry metabolomics, respectively. RESULTS: Platelets isolated from VP and the DP have similar functional, mitochondrial, and metabolic profiles with no significant differences between both groups at baseline and upon activation by any of the assays mentioned above. DISCUSSION: The findings of our study support the use of platelets from the DP for performing functional and metabolic studies on platelets from a wide range of blood donors. The DP may serve as an alternative blood collection method to standard VP, allowing the study of diverse aspects of platelet biology, such as age, sex, race, and ethnicity, in many eligible individuals for blood donation.

Pediatric Laryngeal Coccidioidomycosis: A Case Series in an Endemic Region.

BACKGROUND: Laryngeal coccidioidomycosis is a rare but life-threatening manifestation of coccidioidomycosis. Data in children are sparse and limited to case reports. We conducted this study to review the characteristics of laryngeal coccidioidomycosis in children. METHODS: We performed a retrospective review of patients ≤21 years of age with laryngeal coccidioidomycosis who were treated from January 2010 to December 2017. We collected demographic data, clinical and laboratory studies and patient outcomes. RESULTS: Five cases of pediatric laryngeal coccidioidomycosis were reviewed. All children were Hispanic and 3 were female. The median age was 1.8 years and the median duration of symptoms before diagnosis was 24 days. The most common symptoms included fever (100%), stridor (60%), cough (100%) and vocal changes (40%). Airway obstruction requiring tracheostomy and/or intubation for airway management was present in 80%. The most frequent location of lesions was the subglottic area. Coccidioidomycosis complement fixation titers were frequently low and culture/histopathology of laryngeal tissue was necessary to make a definitive diagnosis. All patients required surgical debridement and were treated with antifungal agents. None of the patients had recurrence during the follow-up period. CONCLUSIONS: This study suggests that laryngeal coccidioidomycosis in children presents with refractory stridor or dysphonia and severe airway obstruction. Favorable outcomes can be achieved with a comprehensive diagnostic work-up and aggressive surgical and medical management. With the rise in cases of coccidioidomycosis, physicians should have a heightened awareness regarding the possibility of laryngeal coccidioidomycosis when encountering children who have visited or reside in endemic areas with stridor or dysphonia.

Prostate organoids: emerging experimental tools for translational research.

Organoid technology has provided new translational research opportunities in oncology, in part by enabling the development of patient-representative living biobanks. Prostate cancer research historically has been constrained to a small number of in vitro models, limiting the ability to translate experimental conclusions for contemporary, heterogeneous patient populations. The facility of organoid culture methods to maintain luminal prostate epithelia, the common lineage of prostate cancers, has greatly expanded the phenotypic and genotypic diversity of available tractable models, including luminal stem/progenitor cells and progressive patient-derived cancers. Biobanks of patient prostate cancer organoids enable increased accuracy in predicting therapeutic efficacy and informative clinical trial designs. Here, we discuss how prostate organoid technology is currently being used, the promising areas of future therapeutic applications, and the current obstacles to be overcome.

Complete Genome Sequence of a Bovine Coronavirus Isolated from a Goat in Pennsylvania, USA.

We report a complete genome sequence of bovine coronavirus (BCoV) isolated from a goat in the state of Pennsylvania in 2022. BCoV often causes calf scours and winter dysentery in cattle.

Endoscopic Endonasal Transcavernous Posterior Clinoidectomy With Inferior Hypophyseal Artery Preservation for a Cavernous Sinus Hemangioma: Technical Case Report.

BACKGROUND AND IMPORTANCE: Unilateral inferior hypophyseal artery (IHA) sacrifice is routinely performed during endoscopic endonasal transcavernous interdural posterior clinoidectomy. However, unilateral IHA sacrifice presents the risk of temporary postoperative diabetes insipidus. We present a case demonstrating the feasibility of endoscopic endonasal transcavernous posterior clinoidectomy without IHA sacrifice. CLINICAL PRESENTATION: A 62-year-old man presented with progressive weakness of his left oculomotor and abducens nerves. MRI of the brain revealed a small lesion suspicious for hemangioma in the posterior compartment of the left cavernous sinus. Following an endoscopic endonasal transcavernous approach using the interdural peeling technique, an IHA-sparing posterior clinoidectomy was performed to provide access to the tumor in the posterior cavernous sinus. After complete resection, the patient's symptoms improved and a diagnosis of cavernous sinus hemangioma was confirmed by histopathology. CONCLUSION: Unilateral IHA preservation may be performed safely when performing a transcavernous interdural posterior clinoidectomy. IHA preservation can be readily achieved if the artery is redundant, the lesion is small and located in the posterior cavernous sinus, and there is a short posterior clinoid, ultimately avoiding the risk of transient postoperative diabetes insipidus.

Community empowerment: A concept analysis.

AIM: To report an analysis of the concept of community empowerment. DESIGN: Concept analysis. DATA SOURCES: Literature published in the CINAHL, PubMed, Scopus and Medline electronic databases from 2016 to 2022 were systematically searched from 30 July to 1 October 2022. METHOD: The amended guideline from Walker and Avant's approach (2011) to concept analysis was performed in nine stages: choosing a concept, determining the purpose of analysis, identifying definitions of the concept, defining attributes, identifying a model case, identifying antecedents, identifying consequences, defining empirical referents and applying the concept to nursing practice. RESULTS: Community empowerment is a fundamental idea in health promotion that may assist communities in defining priorities, making choices, developing strategies and executing them to improve health and minimize inequalities in health. Community empowerment is an effective tool that advanced practice nurses (APNs) may employ to eliminate health inequities and promote community health. CONCLUSION: This concept analysis is one step towards broadening nurses' understanding of one of the ideas of health promotion. Additionally, the concept of community empowerment represents an opportunity for additional research in nursing that is applicable to communities. IMPACT: Community empowerment has served as a guiding paradigm for both theory and practice in health promotion. Also, it is recognized that social, economic and environmental elements have a direct effect on health status. However, community empowerment research in advanced nursing practices is limited. This paper will guide future nursing research on community empowerment that goes beyond involvement and engagement, for this is an effective strategy APNs can use to address health disparities and improve community health.

Endoscopic Multiport Approach for Exenteration of the Infratemporal Fossa.

OBJECTIVE: To demonstrate anatomic relationships pertinent to the endoscopic multiport approach to the infratemporal fossa (ITF). Discuss advantages and limitations of each individual approach. STUDY DESIGN: Cadaveric study. METHODS: Endoscopic and endoscopic-assisted endonasal transpterygoid, sublabial transmaxillary, endoscopic transorbital, and endoscopic transoral approaches to accessing the ITF were completed in five silicone-injected fresh cadaveric specimens (10 sides) with the assistance of 0, 30, and 450 rods-lens endoscopes. Image guidance was used to confirm and document the anatomical relationships encountered in each approach. RESULTS: The endonasal endoscopic transpterygoid approach provides better visualization and more direct exposure to median structures. Endoscopic-assisted sublabial transmaxillary approach enhances the field of exposure, angle of attack, and ease of instrumentation to the lateral part of the ITF. Endoscopic-assisted transorbital approach via the inferior orbital fissure provided cephalic and anterior access. Endoscopic-assisted transoral approach complements the access to lesions extending inferior to the hard palate or far lateral to the mandibular condyle. CONCLUSIONS: A combination of minimal access infratemporal approaches can provide adequate exposure of the entire ITF while avoiding some of the morbidity associated with open approaches. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1367-1374, 2023.

High-Throughput Neutralization and Serology Assays Reveal Correlated but Highly Variable Humoral Immune Responses in a Large Population of Individuals Infected with SARS-CoV-2 in the US between March and August 2020.

The ability to measure neutralizing antibodies on large scale can be important for understanding features of the natural history and epidemiology of infection, as well as an aid in determining the efficacy of interventions, particularly in outbreaks such as the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Because of the assay's rapid scalability and high efficiency, serology measurements that quantify the presence rather than function of serum antibodies often serve as proxies of immune protection. Here, we report the development of a high-throughput, automated fluorescence-based neutralization assay using SARS-CoV-2 virus to quantify neutralizing antibody activity in patient specimens. We performed large-scale testing of over 19,000 COVID-19 convalescent plasma (CCP) samples from patients who had been infected with SARS-CoV-2 between March and August 2020 across the United States. The neutralization capacity of the samples was moderately correlated with serological measurements of anti-receptor-binding domain (RBD) IgG levels. The neutralizing antibody levels within these convalescent-phase serum samples were highly variable against the original USA-WA1/2020 strain with almost 10% of individuals who had had PCR-confirmed SARS-CoV-2 infection having no detectable antibodies either by serology or neutralization, and ~1/3 having no or low neutralizing activity. Discordance between neutralization and serology measurements was mainly due to the presence of non-IgG RBD isotypes. Meanwhile, natural infection with the earliest SARS-CoV-2 strain USA-WA1/2020 resulted in weaker neutralization of subsequent B.1.1.7 (alpha) and the B.1.351 (beta) variants, with 88% of samples having no activity against the BA.1 (omicron) variant. IMPORTANCE The ability to directly measure neutralizing antibodies on live SARS-CoV-2 virus in individuals can play an important role in understanding the efficacy of therapeutic interventions or vaccines. In contrast to functional neutralization assays, serological assays only quantify the presence of antibodies as a proxy of immune protection. Here, we have developed a high-throughput, automated neutralization assay for SARS-CoV-2 and measured the neutralizing activity of ~19,000 COVID-19 convalescent plasma (CCP) samples collected across the United States between March and August of 2020. These data were used to support the FDA's interpretation of CCP efficacy in patients with SARS-CoV-2 infection and their issuance of emergency use authorization of CCP in 2020.

Topical permethrin may increase blacklegged tick (Ixodes scapularis) repellency but is associated with cutaneous irritation in horses.

OBJECTIVE: To evaluate the safety of repeated applications of permethrin concentrations (0% control, 1.5%, 5%, and 10%) to the necks and faces of horses and assess the efficacy and longevity of permethrin as an equine tick repellent. ANIMALS: 5 healthy adult Quarter Horses. PROCEDURES: Each treatment was applied to the neck of each horse (0.01 m2) 4 times a day, for up to 10 days. An 8-mm biopsy was taken to evaluate postexposure dermal responses. Any treatments that were not withdrawn were applied to a quadrant of the horse's face 4 times a day, for up to 5 days. For tick bioassays, a treatment was applied to 1 leg of a horse and 5 female blacklegged ticks (Ixodes scapularis) were evaluated as "repelled" or "not repelled" by the treatment. The bioassays were repeated up to 5 days, but treatment application took place only on the first day of the experiment. RESULTS: Histological results of neck biopsies indicated that more repeated exposures or higher concentrations resulted in more dermal damage. Tick bioassays showed that 5% and 10% permethrin had the greatest efficacy and longevity as a tick repellent, but the differences in tick repellency were not significant overall. CLINICAL RELEVANCE: While there was a nonsignificant trend of higher permethrin concentrations repelling more ticks with longer-lasting residual repellent effects, higher concentrations also produced greater skin damage after repeated exposures. These opposing findings emphasize the need for better tick prevention and control methods that balance safety and efficacy for the equine community.