Diagnosis and Treatment of Vernal Keratoconjunctivitis: A Qualitative Study of Caregiver, Patient, and Clinician Experience in the United States.

PURPOSE: To better understand the patient journey and challenges in the diagnosis and treatment of patients with vernal keratoconjunctivitis (VKC). METHODS: This qualitative study assessed the experience of caregivers of children with VKC (n = 7) and of clinicians who treat VKC (n = 16) in the United States. The structured interviews were conducted to identify key "pain points", obstacles, and trends on the path to diagnosis. RESULTS: Like an earlier study conducted in the United Kingdom, this study found low awareness of the nature and severity of VKC among U.S. caregivers and non-specialist providers, and a tendency among young patients and their caregivers to downplay initial symptoms. Medical intervention was delayed as caregivers treated symptoms with over-the-counter medications; 88% (14 of 16) of specialists reported frequent misdiagnosis and mistreatment by pediatricians and primary care providers who were initial points of care. Time to appropriate referral ranged from 1 to 2 weeks to 3 months, in part due to convoluted referral pathways that were universal points of frustration for caregivers and specialists. CONCLUSIONS: Limited awareness of VKC remains a barrier to timely identification and management of this rare but disruptive ocular surface disease. Caregivers underestimate symptom severity, pediatricians and primary care providers often misdiagnose VKC as allergy or infection, and referrals to appropriate specialists are delayed until symptoms are severe. Early identification is essential to improving the diagnostic journey and treatment of VKC. [J Pediatr Ophthalmol Strabismus. 2024;61(4):252-256.].

The Interaction Effect of Pronunciation and Lexicogrammar on Comprehensibility: A Case of Mandarin-Accented English.

Scholars have argued that comprehensibility (i.e., ease of understanding), not nativelike performance, should be prioritized in second language learning, which inspired numerous studies to explore factors affecting comprehensibility. However, most of these studies did not consider potential interaction effects of these factors, resulting in a limited understanding of comprehensibility and less precise implications. This study investigates how pronunciation and lexicogrammar influences the comprehensibility of Mandarin-accented English. A total of 687 listeners were randomly allocated into six groups and rated (a) one baseline and (b) one of six experimental recordings for comprehensibility on a 9-point scale. The baseline recording, a 60 s spontaneous speech by an L1 English speaker with an American accent, was the same across groups. The six 75-s experimental recordings were the same in content but differed in (a) speakers' degree of foreign accent (American, moderate Mandarin, and heavy Mandarin) and (b) lexicogrammar (with errors vs. without errors). The study found that pronunciation and lexicogrammar interacted to influence comprehensibility. That is, whether pronunciation affected comprehensibility depended on speakers' lexicogrammar, and vice versa. The results have implications for theory-building to refine comprehensibility, as well as for pedagogy and testing priorities.

Arginine Modulates Carbapenem Deactivation by OXA-24/40 in Acinetobacter baumannii.

The resistance of Gram-negative bacteria to ß-lactam antibiotics stems mainly from ß-lactamase proteins that hydrolytically deactivate the ß-lactams. Of particular concern are the ß-lactamases that can deactivate a class of ß-lactams known as carbapenems. Carbapenems are among the few anti-infectives that can treat multi-drug resistant bacterial infections. Revealing the mechanisms of their deactivation by ß-lactamases is a necessary step for preserving their therapeutic value. Here, we present NMR investigations of OXA-24/40, a carbapenem-hydrolyzing Class D ß-lactamase (CHDL) expressed in the gram-negative pathogen, Acinetobacter baumannii. Using rapid data acquisition methods, we were able to study the "real-time" deactivation of the carbapenem known as doripenem by OXA-24/40. Our results indicate that OXA-24/40 has two deactivation mechanisms: canonical hydrolytic cleavage, and a distinct mechanism that produces a ß-lactone product that has weak affinity for the OXA-24/40 active site. The mechanisms issue from distinct active site environments poised either for hydrolysis or ß-lactone formation. Mutagenesis reveals that R261, a conserved active site arginine, stabilizes the active site environment enabling ß-lactone formation. Our results have implications not only for OXA-24/40, but the larger family of CHDLs now challenging clinical settings on a global scale.