An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Physical Examination Variables Predict Response to Conservative Treatment of Nonchronic Plantar Fasciitis: Secondary Analysis of a Randomized, Placeboâ Controlled Footwear Study

BackgroundPlantar fasciitis is a common, disabling condition, and the prognosis of conservative treatment is difficult to predict.ObjectiveTo determine whether initial clinical findings could help predict patient response to conservative treatment that primarily consisted of supportive footwear and stretching.SettingPatients were recruited and seen at 2 outpatient podiatric clinics in the Chicago, Illinois, metropolitan area.PatientsSeventyâ seven patients with nonchronic plantar fasciitis were recruited. Patients were excluded if they had a heel injection in the previous 6 months or were currently using custom foot orthoses at the time of screening. Sixtyâ nine patients completed the final followâ up visit 3 months after receiving the footwear intervention.MethodsTreatment failure was considered a <50% reduction in heel pain at 3 month followâ up. Logistic regression models evaluated the possible association between more than 30 clinical and physical examination findings prospectively assessed at enrollment, and treatment response.ResultsInability to dorsiflex the ankle past â 5° (odds ratio [OR] 3.9, P = .024), nonsevere (â ¤7 on ordinal scale) firstâ step pain (OR 3.8, P = .021), and heel valgus in relaxed stance (OR 4.0, P = .014) each predicted treatment failure in multivariable analysis (receiver operating characteristic area under the curve = .769). Limited ankle dorsiflexion also correlated with greater heel pain severity at initial presentation (r = â 0.312, P = .006).ConclusionsPatients with severe ankle equinus were nearly 4 times more likely to experience a favorable response to treatment centered on home Achilles tendon stretching and supportive therapy. Thus, earlier use of more advanced therapies may be most appropriate in those presenting without severe ankle equinus or without severe first step pain. The findings from our study may not be clinically intuitive because patients with less severe equinus and less severe pain at presentation did worse with conservative care.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146867/1/pmrj436.pd

Biopsy depth after radiofrequency ablation of dysplastic Barrett's esophagus

After endoscopic radiofrequency ablation (RFA) of dysplastic Barrett's esophagus (BE), endoscopic biopsy samples are obtained to assess response to therapy. Whether these biopsies are of adequate depth to assess efficacy is unknown

Extended Sentinel Monitoring of Helicoverpa zea Resistance to Cry and Vip3Aa Toxins in Bt Sweet Corn: Assessing Changes in Phenotypic and Allele Frequencies of Resistance

Transgenic corn and cotton that produce Cry and Vip3Aa toxins derived from Bacillus thuringiensis (Bt) are widely planted in the United States to control lepidopteran pests. The sustainability of these Bt crops is threatened because the corn earworm/bollworm, Helicoverpa zea (Boddie), is evolving a resistance to these toxins. Using Bt sweet corn as a sentinel plant to monitor the evolution of resistance, collaborators established 146 trials in twenty-five states and five Canadian provinces during 2020–2022. The study evaluated overall changes in the phenotypic frequency of resistance (the ratio of larval densities in Bt ears relative to densities in non-Bt ears) in H. zea populations and the range of resistance allele frequencies for Cry1Ab and Vip3Aa. The results revealed a widespread resistance to Cry1Ab, Cry2Ab2, and Cry1A.105 Cry toxins, with higher numbers of larvae surviving in Bt ears than in non-Bt ears at many trial locations. Depending on assumptions about the inheritance of resistance, allele frequencies for Cry1Ab ranged from 0.465 (dominant resistance) to 0.995 (recessive resistance). Although Vip3Aa provided high control efficacy against H. zea, the results show a notable increase in ear damage and a number of surviving older larvae, particularly at southern locations. Assuming recessive resistance, the estimated resistance allele frequencies for Vip3Aa ranged from 0.115 in the Gulf states to 0.032 at more northern locations. These findings indicate that better resistance management practices are urgently needed to sustain efficacy the of corn and cotton that produce Vip3Aa

Updated Guidance Regarding The Risk ofAllergic Reactions to COVID-19 Vaccines and Recommended Evaluation and Management: A GRADE Assessment, and International Consensus Approach

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against \u3e 15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history

Durability of Radiofrequency Ablation in Barrett's Esophagus With Dysplasia

Radiofrequency ablation (RFA) can eradicate dysplasia and intestinal metaplasia in patients with dysplastic Barrett’s esophagus (BE), and reduce rates of esophageal adenocarcinoma. We assessed long-term rates of eradication, durability of neosquamous epithelium, disease progression, and safety of RFA in patients with dysplastic BE

Unexpected Rarity of the Pathogen <i>Batrachochytrium dendrobatidis</i> in Appalachian <i>Plethodon</i> Salamanders: 1957–2011

<div><p>Widespread population declines in terrestrial <i>Plethodon</i> salamanders occurred by the 1980s throughout the Appalachian Mountains, the center of global salamander diversity, with no evident recovery. We tested the hypothesis that the historic introduction and spread of the pathogenic fungus <i>Batrachochytrium dendrobatidis</i> (<i>Bd</i>) into the eastern US was followed by <i>Plethodon</i> population declines. We expected to detect elevated prevalence of <i>Bd</i> prior to population declines as observed for Central American plethodontids. We tested 1,498 <i>Plethodon</i> salamanders of 12 species (892 museum specimens, 606 wild individuals) for the presence of <i>Bd</i>, and tested 94 of those for <i>Batrachochytrium salamandrivorans (Bs)</i> and for ranavirus. Field samples were collected in 2011 from 48 field sites across a 767 km transect. Historic samples from museum specimens were collected at five sites with the greatest number and longest duration of collection (1957–987), four of which were sampled in the field in 2011. None of the museum specimens were positive for <i>Bd</i>, but four <i>P. cinereus</i> from field surveys were positive. The overall <i>Bd</i> prevalence from 1957–2011 for 12 <i>Plethodon</i> species sampled across a 757 km transect was 0.2% (95% CI 0.1–0.7%). All 94 samples were negative for <i>Bs</i> and ranavirus. We conclude that known amphibian pathogens are unlikely causes for declines in these <i>Plethodon</i> populations. Furthermore, these exceptionally low levels of <i>Bd</i>, in a region known to harbor <i>Bd</i>, may indicate that <i>Plethodon</i> specific traits limit <i>Bd</i> infection.</p></div