Neonatal hypoxia impairs serotonin release and cognitive functions in adult mice.

Children who experienced moderate perinatal asphyxia (MPA) are at risk of developing long lasting subtle cognitive and behavioral deficits, including learning disabilities and emotional problems. The prefrontal cortex (PFC) regulates cognitive flexibility and emotional behavior. Neurons that release serotonin (5-HT) project to the PFC, and compounds modulating 5-HT activity influence emotion and cognition. Whether 5-HT dysregulations contribute to MPA-induced cognitive problems is unknown. We established a MPA mouse model, which displays recognition and spatial memory impairments and dysfunctional cognitive flexibility. We found that 5-HT expression levels, quantified by immunohistochemistry, and 5-HT release, quantified by in vivo microdialysis in awake mice, are reduced in PFC of adult MPA mice. MPA mice also show impaired body temperature regulation following injection of the 5-HT1A receptor agonist 8-OH-DPAT, suggesting the presence of deficits in 5-HT auto-receptor function on raphe neurons. Finally, chronic treatment of adult MPA mice with fluoxetine, an inhibitor of 5-HT reuptake transporter, or the 5-HT1A receptor agonist tandospirone rescues cognitive flexibility and memory impairments. All together, these data demonstrate that the development of 5-HT system function is vulnerable to moderate perinatal asphyxia. 5-HT hypofunction might in turn contribute to long-term cognitive impairment in adulthood, indicating a potential target for pharmacological therapies.

Associations between perinatal risk and physical health in pre-adolescence in the Adolescent Brain Cognitive Development (ABCD) Study®: the unexpected relationship with sleep disruption.

BACKGROUND: To investigate relationships among different physical health problems in a large, sociodemographically diverse sample of 9-to-10-year-old children and determine the extent to which perinatal health factors are associated with childhood physical health problems. METHODS: A cross-sectional study was conducted utilizing the Adolescent Brain Cognitive Development℠ (ABCD) Study (n = 7613, ages 9-to-10-years-old) to determine the associations among multiple physical health factors (e.g., prenatal complications, current physical health problems). Logistic regression models controlling for age, sex, pubertal development, household income, caregiver education, race, and ethnicity evaluated relationships between perinatal factors and childhood physical health problems. RESULTS: There were significant associations between perinatal and current physical health measures. Specifically, those who had experienced perinatal complications were more likely to have medical problems by 9-to-10 years old. Importantly, sleep disturbance co-occurred with several physical health problems across domains and developmental periods. CONCLUSION: Several perinatal health factors were associated with childhood health outcomes, highlighting the importance of understanding and potentially improving physical health in youth. Understanding the clustering of physical health problems in youth is essential to better identify which physical health problems may share underlying mechanisms. IMPACT: Using a multivariable approach, we investigated the associations between various perinatal and current health problems amongst youth. Our study highlights current health problems, such as sleep problems at 9-to-10 years old, that are associated with a cluster of factors occurring across development (e.g., low birth weight, prenatal substance exposure, pregnancy complications, current weight status, lifetime head injury). Perinatal health problems are at large, non-modifiable (in this retrospective context), however, by identifying which are associated with current health problems, we can identify potential targets for intervention and prevention efforts.

How long does it take to scale-up obesity prevention interventions?

OBJECTIVE: The scale-up of evidence-based interventions is necessary to reverse high rates of obesity. However, scale-up doesn't occur frequently nor in a timely manner. While it has been estimated that takes 14-17 years for research translation to occur, the time taken to scale-up prevention interventions is largely unknown. This study examined the time taken to scale-up obesity prevention interventions across four scale-up pathways. METHODS: A sample of obesity prevention interventions that had been scaled-up or implemented at scale were found using a structured search strategy. Included interventions were mapped against four scale-up pathways and timeframes associated with each stage of the scale-up pathway were identified to determine the time taken to scale-up. RESULTS: Of the 90 interventions found that were scaled-up to at least a city-wide level, less than half reported a comprehensive research pathway to scale-up and a third did not report any evidence of efficacy or effectiveness prior to scale-up. The time taken to scale-up ranged from 0 to 5 years depending on the pathway taken. Those following a comprehensive pathway took approximately 5 years to scale-up, while interventions that had only one evidence generating step took between 1 and 1.5 years to scale-up. For the remaining interventions, scale-up occurred immediately post-development without evidence generation. CONCLUSIONS: Our findings indicate that the scale-up of obesity prevention interventions can occur more quickly than previous estimates of 14-17 years. Our findings support previous research that scale-up of interventions occurs through a variety of pathways and often scale-up occurs in absence of prior evidence of effectiveness.

Spectrum of Cognitive Biases in Diagnostic Radiology.

Cognitive biases are systematic thought processes involving the use of a filter of personal experiences and preferences arising from the tendency of the human brain to simplify information processing, especially when taking in vast amounts of data such as from imaging studies. These biases encompass a wide spectrum of thought processes and frequently overlap in their concepts, with multiple biases usually in operation when interpretive and perceptual errors occur in radiology. The authors review the gamut of cognitive biases that occur in radiology. These biases are organized according to their expected stage of occurrence while the radiologist reads and interprets an imaging study. In addition, the authors propose several additional cognitive biases that have not yet, to their knowledge, been defined in the radiologic literature but are applicable to diagnostic radiology. Case examples are used to illustrate potential biases and their impact, with emergency radiology serving as the clinical paradigm, given the associated high imaging volumes, wide diversity of imaging examinations, and rapid pace, which can further increase a radiologist's reliance on biases and heuristics. Potential strategies to recognize and overcome one's personal biases at each stage of image interpretation are also discussed. Awareness of such biases and their unintended effects on imaging interpretations and patient outcomes may help make radiologists cognizant of their own biases that can result in diagnostic errors. Identification of cognitive bias in departmental and systematic quality improvement practices may represent another tool to prevent diagnostic errors in radiology. ©RSNA, 2024 See the invited commentary by Larson in this issue.

Sustaining health obesity prevention programs: Lessons from real-world population settings.

Current understanding of what sustains public health programs is derived primarily from evaluations of programs delivered for only a few years. To improve program planning and knowledge on program sustainment, we examined real-world population programs that have been delivered for >2 years. Our focus was physical activity and nutrition programs for obesity prevention. We identified programs through published literature and searched through publicly available information on the theoretical factors determining sustainment. We reviewed 90 programs and explored intervention characteristics, provider, delivery and process level factors, and the outer environment influences. Programs were sustained on average 15 years and more frequently characterised as behavioural change skills programs targeting children, funded by non-government organisations and delivered by community organisations. Most programs had undergone some modification (n = 55). Differences between programs were observed across key factors: Programs sustained 15+ years were mainly behaviour skills programs (n = 21); and characterised by interactive designs (i.e., face-to-face or digital) over static innovations (i.e., print material) compared with those sustained <15 years (p = 0.024). While government funding supported many of the programs (n = 45;), those sustained 15+ years were more likely to have been commercially funded (p = 0.044); and were less likely to have current community involvement (p = 0.013). Differences in ownership and funding were also observed across countries. While multiple factors may influence program sustainment, longer delivered programs where distinguished by their program characteristics and outer contextual factors, suggesting such factors may have an important role in sustaining programs in the longer-term.

Systolic hypertension as side effect of topical low dose atropine drops.

Purpose: To present a case of increased systemic hypertension and pupil dilation related to low dose atropine eyedrops. Observations: A thirteen-year-old male with progressive myopia received atropine 0.05% ophthalmic drops to slow down myopia progression. He exhibited systemic systolic hypertension, photophobia, and bilateral nonreactive mydriasis. The atropine drops were discontinued, and his blood pressure and pupillary function normalized. Conclusions and importance: This case demonstrates sensitivity to low dose atropine with increased systemic blood pressure and pupillary dilation.

Female Leadership in Pediatric Ophthalmology: A Descriptive Analysis.

PURPOSE: To examine female representation among current chiefs of pediatric ophthalmology services of academic medical centers and children's hospitals, as well as program directors of ophthalmology residency and pediatric ophthalmology fellowship programs in the United States. METHODS: Data collection for this cross-sectional study occurred between December 2023 and February 2024, using publicly available sources to compile a list of academic medical centers and children's hospitals, as well as ophthalmology residency programs and pediatric ophthalmology fellowship programs that participated in the 2023-2024 San Francisco Match. Chi-squared analyses were performed using Excel 2021 software, where a P value less than .05 was considered statistically significant. RESULTS: Of the dedicated pediatric ophthalmology services across academic medical centers and children's hospitals in the United States, 38.3% (64/167) are led by a female chief. Female representation was greater at children's hospitals (40.0%, 36/90) than at academic medical centers (36.4%, 28/77), although no significant difference was observed (P = .69). Gender distribution was near equivalent at both academic training program levels, with slightly more female directors of fellowship programs (45.7%, 21/46) than ophthalmology residency programs (42.3%, 52/123) (P = .33). CONCLUSIONS: The authors report near equivalent female representation in the leadership of academic training programs at the residency and fellowship level. However, the proportion of female pediatric ophthalmology division chiefs lags behind the actual gender composition of the workforce. Given the increasing prevalence of female pediatric ophthalmologists, promotion of concordant representation in leadership is necessary to reflect the changing sociocultural landscape and to close the gender gap. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].

Review of the Disparities in Access to Pediatric Eye Care Among Low Socioeconomic Status and Underrepresented Racial Minority Groups Exacerbated by the Economic Downturn in Pediatric Ophthalmology.

PURPOSE: To explore the association between race and socioeconomic status on health disparities in pediatric eye care, characterize the status of diversity within the pediatric ophthalmology workforce, and propose potential solutions to improve access to vision care, particularly for children from vulnerable populations. METHODS: The major studies examining the socioeconomic and racial disparities in visual outcomes and the impact of diversity in the ophthalmology workforce were reviewed. RESULTS: Currently, the pediatric ophthalmology workforce has limited racial diversity, and increasing the number of underrepresented in medicine providers has potential to improve access to pediatric eye care, particularly for underserved populations. Mobile eye clinics, school-based vision programs, and health literacy initiatives may engage communities to bring eye care directly to children and enhance follow-up. CONCLUSIONS: Families with lower socioeconomic status may represent a vulnerable population facing significant access to pediatric eye care barriers, particularly for asymptomatic pediatric eye conditions. Emphasis on strategies that directly engage communities and bring free vision care to families should be given to improve disparities in visual health outcomes. Ophthalmologists and pediatric ophthalmologists should be aware of the current racial underrepresentation within the pediatric ophthalmology workforce, and the importance of workforce diversity in accelerating physician-patient concordance and access to eye care. [J Pediatr Ophthalmol Strabismus. 2024;61(3):172-178.].

Pseudoxanthoma elasticum-associated angioid streaks near a scleral buckle.

Purpose: We report a patient with pseudoxanthoma elasticum (PXE) with angioid streaks near a scleral buckle site. Observations: A 46-year-old male with PXE presented for evaluation of blurry vision and was found to have classic PXE findings in both eyes and angioid streaks adjacent to the site of a scleral buckle in his left eye. He underwent multimodal imaging, genetic testing, and intravitreal aflibercept in the right eye. Conclusions and importance: Bruch's membrane is known to be fragile in PXE, and patients are often counseled about the heightened risk of playing contact sports. This report raises the question of whether tension from a scleral buckle in the setting of a calcified and brittle BM may increase the likelihood of angioid streaks near the buckle site. In the setting of retinal detachment, it may be worthwhile to carefully weigh the pros and cons of vitrectomy versus buckle for PXE patients.

Amblyopia and physical activity in adolescents.

Introduction: Physical activity in adolescence plays an important role in reducing the lifetime risk of chronic disease. Recent studies have shown that individuals with amblyopia may have difficulties with coordinating balance and may be at greater risk of developing fine motor impairments. The purpose of this study was to determine if there is an association between the presence of amblyopia and physical activity (PA) in adolescents. Methods: Adolescent patients aged 12-18 years with a history of childhood amblyopia were age- and gender-matched to control patients with no other ocular pathology aside from refractive error. Each participant's best corrected visual acuity and refractive error were recorded in addition to their height and weight to calculate body mass index (BMI). A 32-question electronic survey was used to calculate self-reported physical activity level (PAL) score and type of PA over the previous seven days. The Ainsworth Compendium of Physical Activities was taken as a reference to calculate Metabolic Equivalent of Task (MET) minutes for the most frequently performed activity. Results: A total of 26 adolescents with amblyopia (10 strabismic, 16 anisometropic) and 26 healthy controls were recruited. The MET-minute values were 2404.3 ± 2313.9 in the control group and 905.6 ± 1196.0 in the amblyopia group (p = .008). The PAL scores were similar between amblyopia and control groups (1.15 ± 0.70 versus 1.24 ± 0.60, p = .63); however, BMI was significantly higher in amblyopia participants (25.2 ± 6.3 versus 21.1 ± 5.4, p = .003). When compared with controls, amblyopes perceived physical activity to be of significantly lower importance in their lives compared to controls (p = .009). Discussion: Amblyopic adolescents may represent a population with increased vulnerability to significantly lower energy expenditure and higher BMI. Future studies with a larger number of participants and further investigation into the impact of refractive error on physical activity are warranted.

Are they the same? Disentangling the concepts of implementation science research and population scale-up.

A new discipline, implementation science, has emerged in recent years. This has resulted in confusion between what 'implementation science' is and how it differs from real-world scale-up of health interventions. While there is considerable overlap, in this perspective, we seek to highlight some of the differences between these two concepts in relation to their origin, drivers, research methods and implications for population impact and practice. We recognise that implementation science generates new information on optimal methods and strategies to facilitate the uptake of evidence-based practices. This new knowledge can be used as part of any scaling-up endeavour. However, real-world scale-up is influenced to a much greater extent by political and strategic needs and key actors and generally requires the support of governments or large agencies that can fund population-level scale-up. Furthermore, scale-up often occurs in the absence of any evidence of effectiveness. Therefore, while implementation science and scale-up both ultimately aim to facilitate the uptake of interventions to improve population health, their immediate intentions differ, and these distinctions are worth highlighting for policymakers and researchers.

A Coalition to Advance Treatments for Parkinson's Disease, Dementia with Lewy Bodies, and Related Disorders.

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share underlying neuropathology. Despite overlapping biology, therapeutic development has been approached separately for these clinical syndromes and there remains no treatment to slow, stop or prevent progression of clinical symptoms and development disability for people living with PD or DLB. Recent advances in biomarker tools, however, have paved new paths for biologic definition and staging of PD and DLB under a shared research framework. Patient-centered research funding organizations see the opportunity for a novel biological staging system for PD and DLB to accelerate and increase success of therapeutic development for the patient communities they serve. Amid growing momentum in the field to develop biological definitions for these neurodegenerative diseases, 7 international nonprofit organizations focused on PD and DLB came together to drive multistakeholder discussion and input on a biological staging system for research. The impact of these convenings to date can be seen in changes incorporated into a proposed biological staging system and growing alignment within the field to rapidly apply new scientific knowledge and biomarker tools to inform clinical trial design. In working together, likeminded nonprofit partners who were initially catalyzed by the significant potential for a biological staging system also realized the power of a shared voice in calling the field to action and have since worked together to establish a coalition to advance precompetitive progress and reduce hurdles to developing better treatments for PD, DLB and biologically related disorders. Plain Language Summary. Disease-focused nonprofit organizations serve to speed new treatments for patients through research funding and advocacy. In the Parkinson's disease (PD) and dementia with Lewy bodies (DLB) fields, several international nonprofit organizations came together to facilitate multistakeholder input on a new biological staging system for research. Stakeholders gathered included researchers, clinicians, drug developers, regulatory agencies, additional nonprofits, and people affected by PD and DLB. This example, fueled by a shared perspective that new drug development tools will improve clinical trials and get better treatments to patients sooner, serves as a model for continued collaborations across the PD and DLB fields. A new, international coalition of nonprofit organizations has emerged to support advancement of treatments to slow, stop, and one day prevent PD, DLB and related disorders, in part, by facilitating future multistakeholder collaborations.

A multi-center analysis of visual outcomes following open globe injury.

The purpose of this study was to examine how demographics, etiology, and clinical examination findings are related to visual outcomes in subjects with open globe injury (OGI) across a large and generalizable sample. A retrospective cohort analysis was performed using data collected from the electronic medical records of four tertiary university centers for subjects with OGI presenting from 2018 to 2021. Demographic information, injury mechanisms, clinical exam findings, visual acuity (VA) at presentation and most recent follow-up were recorded. In subjects with bilateral OGIs, only right eyes were included. A modified ocular trauma score (OTS) using presenting VA, the presence of perforating injury, OGI, and afferent pupillary defect was calculated. The risk of subjects' demographic characteristics, ocular trauma etiology, clinical findings and modified OTS on the presence of monocular blindness at follow-up were assessed using univariable and multivariable regression models. 1426 eyes were identified. The mean age was 48.3 years (SD: ± 22.4 years) and the majority of subjects were men (N = 1069, 75.0%). Univariable analysis demonstrated that subjects of Black race were 66% (OR: 1.66 [1.25-2.20]; P < 0.001) more likely to have monocular blindness relative to White race at follow-up. OTS Class 1 was the strongest predictor of blindness (OR: 38.35 [21.33-68.93]; P < 0.001). Based on multivariable analysis, lower OTS category (OTS Class 1 OR: 23.88 [16.44-45.85]; P < 0.001) moderately predicted visual outcomes (R2 = 0.275, P < 0.001). OGI has many risks of poor visual outcome across patient groups that vary by demographic category, mechanism of injury, and clinical presentation. Our findings validate that a modified OTS remains a strong predictor of visual prognosis following OGI in a large and generalizable sample.

MRI Features of Free Liquid Silicone in the Transgender Female Breast.

OBJECTIVE: To define MRI features of free liquid silicone injection (FLSI) of the breast in transgender women considering surgical management. METHODS: This study was IRB-approved. MRI images from transgender women with FLSI imaged between 2009 and 2019 were reviewed. Presence and location of fibrotic masses (FMs) in the breast(s) and pectoralis muscle and patterns of granulomas were correlated with clinicopathologic findings. Background enhancement was quantified. Comparisons were performed using two-tailed Fisher exact and Student's t test. RESULTS: Of 21 transgender women with FLSI (mean age 46.8 years), 13/21 (61.9%) had a dominant FM measuring over 4 cm; these were limited to breast and pectoralis in 6/21 (28.6%), breast in 9/21 (42.9%), and pectoralis only in 2/21 (9.5%). Four of 21 patients (19.0%) had no FMs, and 4/21 (19.0%) had masses under 4 cm. Mean size of the dominant FM was 7.4 cm (range 4-12 cm). FMs were enhancing in 5/13 (38.5%) and contained T2 high signal granulomas in 8/13 (61.5%). While 18/21 (85.8%) of cases showed mild to moderate overall background enhancement, the majority 7/13 (61.5%) of dominant FM were non-enhancing. About half of cases (11/21, 52.4%) had diffuse foci, and half (10/21, 47.6%) had diffuse foci and masses throughout the breast and pectoralis muscle. These foci and masses displayed T2 high signal in 13/21 (61.9%). There were no occult carcinomas observed. CONCLUSION: MRI performed on symptomatic FLSI patients considering surgical treatment is helpful in assessing the extent of silicone infiltration and fibrotic reaction of the breast and pectoralis muscle.

Occurrence of mesothelial/monocytic incidental cardiac excrescences in material from open-heart procedures: case reports and literature review

Mesothelial/monocytic incidental cardiac excrescences (MICE) are unusual findings during the histological analysis of material from the pericardium, mediastinum, or other tissues collected in open-heart surgery. Despite their somewhat worrisome histological appearance, they show a benign clinical course, and further treatment is virtually never necessary. Hence, the importance of recognizing the entity relays in its differential diagnosis, as an unaware medical pathologist may misinterpret it for a malignant neoplasm. Other mesothelial and histiocytic proliferative lesions, sharing very close histological morphology and immunohistochemistry features with MICE, have been described in sites other than the heart or the mediastinum. This similarity has led to the proposal of the common denomination "histiocytosis with raisinoid nuclei." We report three cases from the pathology archives of the Heart Institute of São Paulo University (Incor/HC-FMUSP), diagnosed as "mesothelial/monocytic incidental cardiac excrescence," with immunohistochemical documentation, and provide a literature review of this entity.