Activity

can begin over individual drusen. Findings will help the identification of new therapeutic approaches and clinical study end points.

We present the first direct clinicopathologic correlation for FAF imaging of drusen-associated atrophy. Our data support 4 FAF stages of drusen-associated atrophy. Stage 2 is the earliest detected stage in which loss of screening by photoreceptor photopigment contributes to uniform hyperautofluorescence. Stages 3 and 4 comport with incomplete RPE and outer retinal atrophy as defined by the Classification of Atrophy Meetings group. Loss of RPE, ONL, and ELM in stage 4 indicates that atrophy can begin over individual drusen. Findings will help the identification of new therapeutic approaches and clinical study end points.

Tree nut allergies affect an estimated 1% of the US population and is lifelong in 90% of allergic individuals. Oral immunotherapy (OIT) for food allergies is an effective method to induce desensitization in a majority of participants in trials of peanut, egg, and milk OIT. Limited trials using tree nut OIT have been reported, possibly due to the lack of standardized drug products.

Food products used in OIT are considered drugs by the Food and Drug Administration (FDA) because they are intended to modulate the individuals’ immune responses to the food allergens. As such, OIT drug products must meet FDA standards for acceptable levels of microbes and undergo testing for allergenic proteins. We aimed to determine the suitability of walnut, cashew, hazelnut, and almond flours for use in OIT trials.

We employed gamma irradiation on commercially available walnut, cashew, hazelnut, and almond flours and tested their levels of microbial contamination, total protein, and allergen content, along with stability of these parameters over time.

Our results demonstrate that irradiation of tree nut flours greatly diminishes the levels of total aerobic bacteria, mold, yeast, Escherichia coli, and Salmonella, whereas there are no substantial changes in total protein or allergen content. Importantly, the microbial levels, protein, and allergen content remained stable over a 24-month period.

Irradiation of tree nut flours is a safe and effective method of processing to allow tree nut products to meet the FDA standards for OIT drug products.

Irradiation of tree nut flours is a safe and effective method of processing to allow tree nut products to meet the FDA standards for OIT drug products.

Gain-of-function mutations in STING1 underlie a type I interferonopathy termed SAVI (STING-associated vasculopathy with onset in infancy). This severe disease is variably characterized by early-onset systemic inflammation, skin vasculopathy, and interstitial lung disease (ILD).

To describe a cohort of patients with SAVI.

Assessment of clinical, radiological and immunological data from 21 patients (17 families) was carried out.

Patients carried heterozygous substitutions in STING1 previously described in SAVI, mainly the p.V155M. Most were symptomatic from infancy, but late onset in adulthood occurred in 1 patient. Systemic inflammation, skin vasculopathy, and ILD were observed in 19, 18, and 21 patients, respectively. Extensive tissue loss occurred in 4 patients. Severity of ILD was highly variable with insidious progression up to end-stage respiratory failure reached at teenage in 6 patients. Lung imaging revealed early fibrotic lesions. Failure to thrive was almost constant, with severe growth failuronopathies.

The largest worldwide cohort of SAVI patients yet described, illustrates the core features of the disease and extends the clinical and immunological phenotype to include overlap with other monogenic interferonopathies.

Recognizing anaphylaxis in infants and toddlers can be challenging for health care providers and caregivers, and current diagnostic criteria and anaphylaxis action plans do not specifically address this younger population.

To describe symptoms and signs observed by primary caregivers of infants and toddlers during severe food-induced allergic reactions.

We conducted a national online survey among primary caregivers of children who experienced a severe food-induced allergic reaction when less than 36 months of age. Respondents who were present during the child’s most severe reaction were asked to report symptoms and signs observed. The survey asked about infant- and toddler-specific symptoms and signs in lay language for caregivers. Data were compared with patient-reported data from past studies to identify distinct patterns among the younger population.

The survey was completed for 374 children (193 infants, 181 toddlers). The most common symptoms and signs reported were skin reactions (90%), facial ariteria, clinical guidelines, and anaphylaxis action plans may be enhanced to address this young, often nonverbal, population.

White matter hyperintensities (WMH) are estimated to occur in greater than 63% of older adults over the age of 60 years. WMH identified in the T2-weighted FLAIR images can be combined with T1-weighted images to enhance individualized current flow models of older adults by accounting for the presence of WMH and its effects on delivered tES current in the aging brain.

Individualized head models were derived from T1-weighted images of 130 healthy older adults (mean=71 years). Lesions segmented from FLAIR acquisition were added to individualized models. Current densities were computed in the brain and compared between models with and without lesions.

Integrating WMH into the models resulted in an overall decrease (up to 7%) in median current densities in the brain outside lesion regions. Changes in current density and total lesion volume was positively correlated (R

=0.31, p<0.0001).

Incorporating WMH into individualized models may increase the accuracy of predicted tES current flow in the aging brain.

Incorporating WMH into individualized models may increase the accuracy of predicted tES current flow in the aging brain.

Electrical stimulation applied to individual organs, peripheral nerves, or specific brain regions has been used to treat a range of medical conditions. In cardiovascular disease, autonomic dysfunction contributes to the disease progression and electrical stimulation of the vagus nerve has been pursued as a treatment for the purpose of restoring the autonomic balance. Menin-MLL Inhibitor Histone Methyltransferase inhibitor However, this approach lacks selectivity in activating function- and organ-specific vagal fibers and, despite promising results of many preclinical studies, has so far failed to translate into a clinical treatment of cardiovascular disease.

Here we report a successful application of optogenetics for selective stimulation of vagal efferent activity in a large animal model (sheep).

Twelve weeks after viral transduction of a subset of vagal motoneurons, strong axonal membrane expression of the excitatory light-sensitive ion channel ChIEF was achieved in the efferent projections innervating thoracic organs and reaching beyond the level of the diaphragm.