Automated retinal image quality assessment on the UK Biobank dataset for epidemiological studies.

Morphological changes in the retinal vascular network are associated with future risk of many systemic and vascular diseases. However, uncertainty over the presence and nature of some of these associations exists. Analysis of data from large population based studies will help to resolve these uncertainties. The QUARTZ (QUantitative Analysis of Retinal vessel Topology and siZe) retinal image analysis system allows automated processing of large numbers of retinal images. However, an image quality assessment module is needed to achieve full automation. In this paper, we propose such an algorithm, which uses the segmented vessel map to determine the suitability of retinal images for use in the creation of vessel morphometric data suitable for epidemiological studies. This includes an effective 3-dimensional feature set and support vector machine classification. A random subset of 800 retinal images from UK Biobank (a large prospective study of 500,000 middle aged adults; where 68,151 underwent retinal imaging) was used to examine the performance of the image quality algorithm. The algorithm achieved a sensitivity of 95.33% and a specificity of 91.13% for the detection of inadequate images. The strong performance of this image quality algorithm will make rapid automated analysis of vascular morphometry feasible on the entire UK Biobank dataset (and other large retinal datasets), with minimal operator involvement, and at low cost

Characterization of the Pediatric Acute-Onset Neuropsychiatric Syndrome Phenotype

Objective: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a subtype of obsessive compulsive disorder (OCD) marked by an abrupt onset or exacerbation of neuropsychiatric symptoms. We aim to characterize the phenotypic presentation of youth with PANS. Methods: Forty-three youth (ages 4–14 years) meeting criteria for PANS were assessed using self-report and clinician-administered measures, medical record reviews, comprehensive clinical evaluation, and laboratory measures. Results: Youth with PANS presented with an early age of OCD onset (mean=7.84 years) and exhibited moderate to severe obsessive compulsive symptoms upon evaluation. All had comorbid anxiety and emotional lability, and scored well below normative means on all quality of life subscales. Youth with elevated streptococcal antibody titers trended toward having higher OCD severity, and presented more frequently with dilated pupils relative to youth without elevated titers. A cluster analysis of core PANS symptoms revealed three distinct symptom clusters that included core characteristic PANS symptoms, streptococcal-related symptoms, and cytokine-driven/physiological symptoms. Youth with PANS who had comorbid tics were more likely to exhibit a decline in school performance, visuomotor impairment, food restriction symptoms, and handwriting deterioration, and they reported lower quality of life relative to youth without tics. Conclusions: The sudden, acute onset of neuropsychiatric symptoms, high frequency of comorbidities (i.e., anxiety, behavioral regression, depression, and suicidality), and poor quality of life capture the PANS subgroup as suddenly and severely impaired youth. Identifying clinical characteristics of youth with PANS will allow clinicians to diagnose and treat this subtype of OCD with a more strategized and effective approach

A Pilot Trial of Cognitive-Behavioral Therapy Augmentation of Antibiotic Treatment in Youth with Pediatric Acute-Onset Neuropsychiatric Syndrome-Related Obsessive-Compulsive Disorder

Background: This study reports an open trial of family-based cognitive-behavioral therapy (CBT) in children and adolescents with obsessive-compulsive disorder (OCD) exhibiting an onset pattern consistent with pediatric acute-onset neuropsychiatric syndrome (PANS). Methods: Eleven primarily Caucasian youth with PANS-related OCD (range=4–14 years; 6 boys) who were incomplete responders to antibiotic treatment, received family-based CBT delivered either face-to-face or via web camera. Results: All participants completing treatment (8 of 8) were considered improved at posttreatment, and average obsessive-compulsive symptom severity was reduced by 49%. Significant reductions in obsessive-compulsive symptom severity and in clinician- and parent-rated OCD-related impairment were noted. Reductions in parent- and child-rated anxiety, child-rated OCD-related impairment, and comorbid neuropsychiatric symptoms were not statistically significant. Conclusions: Gains were maintained at follow-up, with 100% (6 of 6) of those assessed remaining improved. Implications for treatment and further research are discussed

A Pilot Trial of Cognitive-Behavioral Therapy Augmentation of Antibiotic Treatment in Youth with Pediatric Acute-Onset Neuropsychiatric Syndrome-Related Obsessive-Compulsive Disorder

Background: This study reports an open trial of family-based cognitive-behavioral therapy (CBT) in children and adolescents with obsessive-compulsive disorder (OCD) exhibiting an onset pattern consistent with pediatric acute-onset neuropsychiatric syndrome (PANS). Methods: Eleven primarily Caucasian youth with PANS-related OCD (range=4–14 years; 6 boys) who were incomplete responders to antibiotic treatment, received family-based CBT delivered either face-to-face or via web camera. Results: All participants completing treatment (8 of 8) were considered improved at posttreatment, and average obsessive-compulsive symptom severity was reduced by 49%. Significant reductions in obsessive-compulsive symptom severity and in clinician- and parent-rated OCD-related impairment were noted. Reductions in parent- and child-rated anxiety, child-rated OCD-related impairment, and comorbid neuropsychiatric symptoms were not statistically significant. Conclusions: Gains were maintained at follow-up, with 100% (6 of 6) of those assessed remaining improved. Implications for treatment and further research are discussed

Characterization of the Pediatric Acute-Onset Neuropsychiatric Syndrome Phenotype

Objective: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a subtype of obsessive compulsive disorder (OCD) marked by an abrupt onset or exacerbation of neuropsychiatric symptoms. We aim to characterize the phenotypic presentation of youth with PANS. Methods: Forty-three youth (ages 4–14 years) meeting criteria for PANS were assessed using self-report and clinician-administered measures, medical record reviews, comprehensive clinical evaluation, and laboratory measures. Results: Youth with PANS presented with an early age of OCD onset (mean=7.84 years) and exhibited moderate to severe obsessive compulsive symptoms upon evaluation. All had comorbid anxiety and emotional lability, and scored well below normative means on all quality of life subscales. Youth with elevated streptococcal antibody titers trended toward having higher OCD severity, and presented more frequently with dilated pupils relative to youth without elevated titers. A cluster analysis of core PANS symptoms revealed three distinct symptom clusters that included core characteristic PANS symptoms, streptococcal-related symptoms, and cytokine-driven/physiological symptoms. Youth with PANS who had comorbid tics were more likely to exhibit a decline in school performance, visuomotor impairment, food restriction symptoms, and handwriting deterioration, and they reported lower quality of life relative to youth without tics. Conclusions: The sudden, acute onset of neuropsychiatric symptoms, high frequency of comorbidities (i.e., anxiety, behavioral regression, depression, and suicidality), and poor quality of life capture the PANS subgroup as suddenly and severely impaired youth. Identifying clinical characteristics of youth with PANS will allow clinicians to diagnose and treat this subtype of OCD with a more strategized and effective approach

A Pilot Trial of Cognitive-Behavioral Therapy Augmentation of Antibiotic Treatment in Youth with Pediatric Acute-Onset Neuropsychiatric Syndrome-Related Obsessive-Compulsive Disorder

Background: This study reports an open trial of family-based cognitive-behavioral therapy (CBT) in children and adolescents with obsessive-compulsive disorder (OCD) exhibiting an onset pattern consistent with pediatric acute-onset neuropsychiatric syndrome (PANS). Methods: Eleven primarily Caucasian youth with PANS-related OCD (range=4–14 years; 6 boys) who were incomplete responders to antibiotic treatment, received family-based CBT delivered either face-to-face or via web camera. Results: All participants completing treatment (8 of 8) were considered improved at posttreatment, and average obsessive-compulsive symptom severity was reduced by 49%. Significant reductions in obsessive-compulsive symptom severity and in clinician- and parent-rated OCD-related impairment were noted. Reductions in parent- and child-rated anxiety, child-rated OCD-related impairment, and comorbid neuropsychiatric symptoms were not statistically significant. Conclusions: Gains were maintained at follow-up, with 100% (6 of 6) of those assessed remaining improved. Implications for treatment and further research are discussed

Characterization of the Pediatric Acute-Onset Neuropsychiatric Syndrome Phenotype

Objective: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a subtype of obsessive compulsive disorder (OCD) marked by an abrupt onset or exacerbation of neuropsychiatric symptoms. We aim to characterize the phenotypic presentation of youth with PANS. Methods: Forty-three youth (ages 4–14 years) meeting criteria for PANS were assessed using self-report and clinician-administered measures, medical record reviews, comprehensive clinical evaluation, and laboratory measures. Results: Youth with PANS presented with an early age of OCD onset (mean=7.84 years) and exhibited moderate to severe obsessive compulsive symptoms upon evaluation. All had comorbid anxiety and emotional lability, and scored well below normative means on all quality of life subscales. Youth with elevated streptococcal antibody titers trended toward having higher OCD severity, and presented more frequently with dilated pupils relative to youth without elevated titers. A cluster analysis of core PANS symptoms revealed three distinct symptom clusters that included core characteristic PANS symptoms, streptococcal-related symptoms, and cytokine-driven/physiological symptoms. Youth with PANS who had comorbid tics were more likely to exhibit a decline in school performance, visuomotor impairment, food restriction symptoms, and handwriting deterioration, and they reported lower quality of life relative to youth without tics. Conclusions: The sudden, acute onset of neuropsychiatric symptoms, high frequency of comorbidities (i.e., anxiety, behavioral regression, depression, and suicidality), and poor quality of life capture the PANS subgroup as suddenly and severely impaired youth. Identifying clinical characteristics of youth with PANS will allow clinicians to diagnose and treat this subtype of OCD with a more strategized and effective approach

Supramolecular arrangement of protein in nanoparticle structures predicts nanoparticle tropism for neutrophils in acute lung inflammation

Myerson JW, Patel PN, Rubey KM, et al. Supramolecular arrangement of protein in nanoparticle structures predicts nanoparticle tropism for neutrophils in acute lung inflammation. Nature Nanotechnology. 2022;17(1):86-97.This study shows that the supramolecular arrangement of proteins in nanoparticle structures predicts nanoparticle accumulation in neutrophils in acute lung inflammation (ALI). We observed homing to inflamed lungs for a variety of nanoparticles with agglutinated protein (NAPs), defined by arrangement of protein in or on the nanoparticles via hydrophobic interactions, crosslinking and electrostatic interactions. Nanoparticles with symmetric protein arrangement (for example, viral capsids) had no selectivity for inflamed lungs. Flow cytometry and immunohistochemistry showed NAPs have tropism for pulmonary neutrophils. Protein-conjugated liposomes were engineered to recapitulate NAP tropism for pulmonary neutrophils. NAP uptake in neutrophils was shown to depend on complement opsonization. We demonstrate diagnostic imaging of ALI with NAPs; show NAP tropism for inflamed human donor lungs; and show that NAPs can remediate pulmonary oedema in ALI. This work demonstrates that structure-dependent tropism for neutrophils drives NAPs to inflamed lungs and shows NAPs can detect and treat ALI