Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation.

Respiratory syncytial virus (RSV) is a leading cause of infant mortality, and there are currently no licensed vaccines to protect this vulnerable population. A comprehensive understanding of infant antibody responses to natural RSV infection would facilitate vaccine development. Here, we isolated more than 450 RSV fusion glycoprotein (F)-specific antibodies from 7 RSV-infected infants and found that half of the antibodies recognized only two antigenic sites. Antibodies targeting both sites showed convergent sequence features, and structural studies revealed the molecular basis for their recognition of RSV F. A subset of antibodies targeting one of these sites displayed potent neutralizing activity despite lacking somatic mutations, and similar antibodies were detected in RSV-naive B cell repertoires, suggesting that expansion of these B cells in infants may be possible with suitably designed vaccine antigens. Collectively, our results provide fundamental insights into infant antibody responses and a framework for the rational design of age-specific RSV vaccines.

Incidence and sex differences of diabetes among youth: a 50-year population-based cohort study.

AIMS: Although the literature on childhood diabetes has traditionally focused on Type 1 diabetes (T1D), youth-onset Type 2 diabetes (T2D) and its associated morbidities have become increasingly prevalent. This study reports on the incidence and demographics of a population-based cohort of children diagnosed with diabetes over a 50-year period. METHODS: Medical records of patients < 22 years diagnosed with diabetes from January 1, 1970, through December 31, 2019, were retrospectively reviewed using the Rochester Epidemiology Project, a database of clinics and hospitals in Olmsted County, Minnesota. RESULTS: Of 606 children diagnosed with diabetes, 519 (85.6%) were diagnosed with T1D at a mean age of 10.9 ± 5.3 years. 87 (14.4%) were diagnosed with T2D at a mean age of 17.4 ± 3.4 years. The incidence of T2D increased 23-fold (p < 0.001) over the five-decade period (5 per 100,000 children/year) while T1D remained stable (26 per 100,000 children/year; p = 0.08). The mean body mass index at T2D diagnosis (35.5 kg/m2 ± 10.4) was significantly higher than in T1D (18.9 kg/m2 ± 4.6 [95% CI for difference 14.2-19.0]; p < 0.0001). Sixty-nine percent of children diagnosed with T2D were female, and the hazard ratio of developing diabetic retinopathy in females with T2D compared to males was 6.83 (95% CI 1.53-30.44; p = 0.012). CONCLUSIONS: The incidence of youth-onset T2D increased significantly over the 50-year period while the incidence of T1D remained stable. A higher proportion of females were diagnosed with youth-onset T2D. Females with T2D were more than six times likelier to develop diabetic retinopathy than males.

Planning an artificial intelligence diabetic retinopathy screening program: a human-centered design approach.

Diabetic retinopathy (DR) is a leading cause of vision loss in the United States and throughout the world. With early detection and treatment, sight-threatening sequelae from DR can be prevented. Although artificial intelligence (AI) based DR screening programs have been proven to be effective in identifying patients at high risk of vision loss, adoption of AI in clinical practice has been slow. We adapted the United Kingdom Design Council's Double-Diamond model to design a strategy for care delivery which integrates an AI-based screening program for DR into a primary care setting. Methods from human-centered design were used to develop a strategy for implementation informed by context-specific barriers and facilitators. The purpose of this community case study is to present findings from this work in progress, including a system of protocols, educational documents and workflows created using key stakeholder input.

Ocular Sequelae in a Population-Based Cohort of Youth Diagnosed With Diabetes During a 50-Year Period.

IMPORTANCE: Despite the increasing prevalence of type 2 diabetes (T2D) diagnosed in childhood, little is known about the natural history of ocular sequelae in youth-onset T2D compared with type 1 diabetes (T1D). OBJECTIVE: To assess the risk of developing diabetes-associated ocular complications among youth diagnosed with diabetes. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based medical record review included all residents of Olmsted County, Minnesota (95.7% White in 1990), diagnosed with diabetes at younger than 22 years (hereinafter referred to as children) from January 1, 1970, through December 31, 2019. MAIN OUTCOMES AND MEASURES: Risk of developing ocular complications over time. RESULTS: Among 1362 individuals with a diagnostic code of diabetes, medical record reviews confirmed a diagnosis of T1D or T2D in 606 children, of whom 525 (86.6%) underwent at least 1 eye examination (mean [SD] age at diabetes diagnosis, 12.1 [5.4] years; 264 [50.3%] male). Diabetes-associated ocular complications occurred in 147 of the 461 children (31.2%) with T1D and in 17 of the 64 children (26.6%) with T2D. The hazard ratio illustrating the risk between T2D and T1D rates was 1.88 (95% CI, 1.13-3.12; P = .02) for developing any diabetic retinopathy (nonproliferative or greater), 2.33 (95% CI, 0.99-5.50; P = .048) for proliferative diabetic retinopathy, 1.49 (95% CI, 0.46-4.89; P = .50) for diabetic macular edema, 2.43 (95% CI, 0.54-11.07; P = .24) for a visually significant cataract, and 4.06 (95% CI, 1.34-12.33; P = .007) for requiring pars plana vitrectomy by 15 years after the diagnosis of diabetes. CONCLUSIONS AND RELEVANCE: Diabetic retinopathy, proliferative diabetic retinopathy, and the need for pars plana vitrectomy occurred within a shorter diabetes duration for children with T2D compared with T1D in this population-based cohort. Children with T2D had almost twice the risk of developing retinopathy compared with those with T1D. These findings suggest that to prevent serious ocular complications, children with T2D may require ophthalmoscopic evaluations at least as frequently as or more frequently than children with T1D.