School Connectedness and Risk for Sexual Intercourse and Nonconsensual Sex in Adolescence.

The CDC reports that 30% of high school students have engaged in sexual intercourse. Evidence suggests biological, personal, peer, societal, and family variables affect when a child will initiate sex. The school environment plays an important role in a child's development. Evidence suggests that greater attachment to the school community can modify sexual risk-taking activity in adolescents. Future of Families and Child Wellbeing Study (FFCWS) comprises a cohort of approximately 4,700 families of children born in the U.S. between 1998-2000, over-sampled for non-marital births in large U.S. cities. Adolescents (N = 3,444 of 4,663 eligible) completed the wave six teen survey at approximately age 15. School connectedness was self-reported with four items measuring inclusiveness, closeness, happiness, and safety felt by the adolescent in their school environment. Sexual intercourse and nonconsensual sex were self-reported by the adolescent. Hierarchical regression analyses were conducted examining sexual intercourse, nonconsensual sex, risk factors, and school connectedness. In this sample of adolescents (48% female, 49% Black, 25% Hispanic, ages 14-19), school connectedness appears to reduce boys' risk of nonconsensual sex (OR = 0.29, p < 0.01), and reduce girls' risk of engaging in sexual intercourse (OR = 0.55, p < 0.01). Findings suggest gender differences in the association between school connectedness and sexual practices in adolescents. School connectedness may confer protection for boys' risk of nonconsensual sex, and for girls' risk of engaging in sexual intercourse. Further exploration of the relationship between school connectedness may allow for recommendations into preventative measures for teenage sexual behaviors.

Varying Syntax to Enhance Verb-Focused Intervention for 30-Month-Olds With Language Delay: A Concurrent Multiple Baseline Design.

PURPOSE: The purpose of this study is to determine if 2.5-year-olds with language delay would learn verbs (spill) when presented with varying syntactic structure ("The woman is spilling the milk"/"The milk is spilling"; milk = patient or theme) in a therapeutic context. Children with language delay have proportionally small inventories of verbs, which limits expressive language development. Children who have typical language development learn verbs more robustly when presented with alternating arguments than with a single argument structure. METHOD: Three toddlers with expressive language delay (29-30 months of age) participated in a verb-focused treatment study using a concurrent multiple baseline design. Participants were shown action videos accompanied by sentences with varied argument structure for each target verb. To assess learning pre- and posttreatment, participants were asked to demonstrate actions corresponding to each verb. RESULTS: Visual inspection and tau analyses reveal significant posttreatment gains of target verbs taught with varying argument structures. CONCLUSIONS: Our results indicate that learning verbs with high variability of argument roles may facilitate a strong link between lexical representations of verbs and their syntactic structures. Using argument structure variability to teach verbs as an intervention strategy has great potential and should be tested further in larger group studies.

Comparison of Tumor Bed Delineation Using a Novel Radiopaque Filament Marker Versus Surgical Clips for Targeting Breast Cancer Radiotherapy.

BACKGROUND: Accuracy of tumor bed (TB) delineation is essential for targeting boost doses or partial breast irradiation. Multiple studies have shown high interobserver variability with standardly used surgical clip markers (CMs). We hypothesize that a radiopaque filament marker (FM) woven along the TB will improve TB delineation consistency. METHODS: An FDA-approved FM was intraoperatively used to outline the TB of patients undergoing lumpectomy. Between January 2020 and January 2022, consecutive patients with FM placed after either (1) lumpectomy or (2) lumpectomy with oncoplastic reconstruction were identified and compared with those with CM. Six "experts" (radiation oncologists specializing in breast cancer) across 2 institutions independently defined all TBs. Three metrics (volume variance, dice coefficient, and center of mass [COM] deviation). Two-tailed paired samples t tests were performed to compare FM and CM cohorts. RESULTS: Twenty-eight total patients were evaluated (14 FM and 14 CM). In aggregate, differences in volume between expert contours were 29.7% (SD ± 58.8%) with FM and 55.4% (SD ± 105.9%) with CM ( P < 0.001). The average dice coefficient in patients with FM was 0.54 (SD ± 0.15), and with CM was 0.44 (SD ± 0.22) ( P < 0.001). The average COM deviation was 0.63 cm (SD ± 0.53 cm) for FM and 1.05 cm (SD ± 0.93 cm) for CM; ( P < 0.001). In the subset of patients who underwent lumpectomy with oncoplastic reconstruction, the difference in average volume was 21.8% (SD ± 20.4%) with FM and 52.2% (SD ± 64.5%) with CM ( P <0.001). The average dice coefficient was 0.53 (SD ± 0.12) for FM versus 0.39 (SD ± 0.24) for CM ( P < 0.001). The average COM difference was 0.53 cm (SD ± 0.29 cm) with FM versus 1.25 cm (SD ± 1.08 cm) with CM ( P < 0.001). CONCLUSION: FM consistently outperformed CM in the setting of both standard lumpectomy and complex oncoplastic reconstruction. These data suggest the superiority of FM in TB delineation.

Delta-8-THC association with psychosis: A case report with literature review.

Background: Cannabis (Δ9-THC) is the most commonly consumed illicit drug. The Agricultural Improvement Act of 2018 removed hemp, a strain of Cannabis sativa, as a controlled substance. This law allowed the plant to be processed into its components, which contain <0.3% Δ9-THC. As a result, delta-8-tetrahydrocannabinol (Δ8-THC), a federally unregulated substance, grew in popularity in 2020. Δ8-THC is readily available in most gas stations or head shops and may be considered harmless by patients. However, an increasing number of patients admitted for psychiatric hospitalization report use, with limited literature on the effects. Case presentations: This case report describes three individual cases of patients who required admission to a university psychiatric hospital after the regular use solely of Δ8-THC. All three patients developed psychotic and paranoid symptoms concurrently with the use of Δ8-THC, with a severity exceeding their previous historical presentations. The presenting psychotic symptoms were also atypical for all three patients. New-onset violence and visual hallucinations were noted in two of the patients, one patient with no previous psychiatric history and one patient while on a therapeutic dose of his antipsychotic. In the third case, a new onset of bizarre, fixed delusions of puppies dissolving in the bathtub developed. Conclusion: This report adds to the limited body of evidence on Δ8-THC documenting a temporal association between Δ8-THC use and the development of psychotic symptoms. A strong body of research already correlates the continued use of Δ9-THC with psychosis, and Δ8-THC acts at the same CB1 and CB2 receptors as Δ9-THC. Therefore, it is hypothesized that Δ8-THC may have similar adverse psychiatric effects as Δ9-THC. These conclusions are not without speculation, due to the need for self or collateral-reporting of Δ8-THC use as urine drug screening cannot distinguish Δ8-THC from Δ9-THC, and the patients' symptoms could be explained by medication non-adherence and primary psychotic disorders. However, physicians should be encouraged to gather a specific history of Δ8-THC use and treat patients with Δ8-THC-related intoxication and symptoms.

Fetuin-A adsorption to tunable polydimethylsiloxane and subsequent macrophage response.

Surface modifications can be applied to biomaterials to alter the various surface properties that influence protein-material interactions and the cellular response. The plasma protein fetuin-A has been found to adsorb to many biomaterials but details of its interactions with polydimethylsiloxane (PDMS) and roles in regulating the immune response are not clear. Here, PDMS modifications are achieved by altering the ratio of PDMS formulations to control elastic modulus, and by coating PDMS with polydopamine (PDA) to attach fetuin-A. Surface characterization confirmed that altering the PDMS formulation changed the elastic modulus without affecting surface wetting properties. Surface roughness was measured using atomic force microscopy and surface chemistry was determined using X-ray photoelectron spectroscopy, with only minor changes detected on the softest samples. PDA deposition on PDMS was confirmed and contact angle measurements demonstrated an increase in hydrophilicity. Fetuin-A adsorption was influenced by the PDMS formulations, adsorption changed in a competitive plasma environment, and PDA was able to immobilize the greatest amount of fetuin-A. The inflammatory effects of fetuin-A were investigated, and data suggests that the elastic modulus influences cytokine secretion from macrophages at certain timepoints, a result likely due to varied protein amounts and orientations/conformations in response to material stiffness. The addition of a PDA layer demonstrated the potentially cytokine mitigating effect upon fetuin-A immobilization when compared to unmodified PDMS samples. The results provide new insight into the interactions of fetuin-A with PDMS and PDA, and the potential immune regulatory properties of fetuin-A modified materials.

Unsealed Source: Scope of Practice for Radiopharmaceuticals Among United States Radiation Oncologists.

Purpose: Our purpose was to determine the utilization of and barriers to implementation of radiopharmaceutical therapy (RPT) among U.S. radiation oncologists. Methods and Materials: An anonymous, voluntary 21-item survey directed toward attending radiation oncologists was distributed via social media platforms (Twitter, LinkedIn, Facebook, Student Doctor Network). Questions assessed practice characteristics, specific RPT prescribing patterns, RPT prescribing interest, and perceived barriers to RPT implementation. Nonparametric χ2 test was used for correlation statistics. Results: Of the 142 respondents, 131 (92.3%) practiced in the United States and were included for this analysis. Respondents were well balanced in terms of practicing region, population size served, practice setting, and years in practice. Forty-eight percent (n = 63) reported prescribing at least 1 RPT. An additional 7% (n = 8) participate in RPT administration without billing themselves. Among those that actively prescribed RPT, the mean cumulative cases per month was 4.2 (range, 1-5). The most commonly prescribed radionuclides were radium-223 (40%; mean 2.8 cases/mo), iodine-131 (18%; mean 2.3 cases/mo), yttrium-90 (13%; mean 3.4 cases/mo), "other" (8%), samarium-153 (6%; mean 1.0 cases/mo), and strontrium-89 and phosphorous-32 (2% each; mean 1.8 and 0.4 cases/mo, respectively). Of those who answered "other," lutetium-177 dotatate was most commonly prescribed (8%). No significant (P < .05) association was noted between practice type, practice location, years of practice, or practice volume with utilization of any RPTs. Most radiation oncologists (56%, n = 74) responded they would like to actively prescribe more RPT, although 27% (n = 35) were indifferent, and 17% (n = 22) said they would not like to prescribe more RPT. Perceived barriers to implementation were varied but broadly categorized into treatment infrastructure (44%, n = 57), interspecialty relations (41%, n = 53), lack of training (23%, n = 30), and financial considerations (16%, n = 21). Conclusions: Among surveyed U.S. radiation oncologists, a significant number reported prescribing at least 1 RPT. The majority expressed interest in prescribing additional RPT. Wide-ranging barriers to implementation exist, most commonly interspecialty relations, treatment infrastructure, lack of training, and financial considerations.

Sex Differentially Alters Secretion of Brain Extracellular Vesicles During Aging: A Potential Mechanism for Maintaining Brain Homeostasis.

Extracellular vesicles (EVs) in the brain play a role in neuronal homeostasis by removing intracellular material and regulating cell-to-cell communication. Given that sex and aging differentially modulate brain networks, we investigated sex-dependent differences in EV levels and content in the brain during aging. EVs were isolated from the brains of 3, 6, 12, 18, and 24 month-old female and male C57BL/6 J mice, and the levels of different EV species determined. While the number of plasma membrane-derived microvesicles and a subset of late endosomes-derived exosomes increased with age in the brain of female mice, no significant changes were seen in males. Mitochondria-derived mitovesicles in the brain increased during aging in both sexes, a change that may reflect aging-dependent alterations in mitochondrial function. These findings reveal enhanced turnover during aging in female brains, suggesting a mechanism for advantageous successful female brain aging and sex-depending different susceptibility to age-related neurodegenerative diseases.

Adverse childhood experiences and adolescent mental health: Understanding the roles of gender and teenage risk and protective factors.

Adverse Childhood Experiences (ACEs) have been linked to a host of negative outcomes in adolescence. However, research on the impact of ACEs on adolescent mental health has produced mixed results, leaving it unclear how ACEs may relate to depression and anxiety during adolescence. Moreover, this body of work has neglected how gender, risk and protective factors may influence these relationships, despite research demonstrating gender differences in both responses to adversity and in the impact of risk and protective factors on maladaptive outcomes in adolescence. Drawing on a sample of at-risk youth from the Fragile Families and Child Wellbeing Study (N = 2455; age 14-18; 48 % female, 50 % Black, 23 % Hispanic), the current study examines the association between ACEs during early childhood (i.e., ages 1 to 5) and anxious and depressive tendencies reported during adolescence. Models are stratified by gender and incorporate six types of teenage risk and protective factors (peer bullying, delinquent peers, low self-control, parental attachment, collective efficacy, and school connectedness). Results showed support for gender differences in the associations between ACEs and boys' and girls' mental health symptoms. Initially, ACEs were associated with an increased risk of both depressive and anxious tendencies in boys, but the total ACEs score was only significantly associated with an increased risk for depressive symptoms in girls. After accounting for teenage protective factors, ACEs were related to a decreased risk of depressive and anxious symptoms among girls only. Findings have important implications for refining intervention and prevention strategies focusing on mitigating the harms of ACEs.

Immune Reconstitution Inflammatory Syndrome Complicating Cryptococcal Meningitis in a Pediatric Heart Transplant Patient.

Immune reconstitution inflammatory syndrome can be a complication of cryptococcal meningitis after immune reconstitution from antiretroviral therapy in HIV or reduced immune suppression in transplant recipients. In this case report, the authors discuss the diagnosis and management of cryptococcal-associated immune reconstitution inflammatory syndrome in a 10-year-old pediatric heart transplant recipient.

Orthotopic heart transplant in a pediatric patient with mixed connective tissue disease.

BACKGROUND: Patients with autoimmune inflammatory syndromes such as mixed connective tissue disease (MCTD) and systemic lupus erythematosus have previously been considered marginal candidates for orthotopic heart transplant (OHT). METHODS: A retrospective chart review was completed for this case report. RESULTS: We present the case of an 11-year-old girl with known MCTD who developed congestive heart failure refractory to medical therapy and underwent OHT. CONCLUSIONS: Despite her autoimmune condition, this patient has not experienced antibody-mediated rejection post-transplant and her inflammatory symptoms have greatly improved.

Size-dependent flight capacity and propensity in a range-expanding invasive insect.

For capital-breeding insects, all resources available for adult metabolic needs are accumulated during larval feeding. Therefore, body size at adult eclosion represents the total energetic capacity of the individual. For female capital breeders, body size is strongly correlated with lifetime fecundity, while in males, body size, which correlates with fitness, is less understood. In capital-breeding species with wingless, flightless, or dispersal-limited females, flight potential for male Lepidoptera has important implications for mate-finding and may be correlated with body size. At low population densities, failure to mate has been identified as an important Allee effect and can drive the success or failure of invasive species at range edges and in species of conservation concern. Th capital-breeding European subspecies of Lymantria dispar (L.), was introduced to North America in 1869 and now ranges across much of eastern North America. In L. dispar, females are flightless and mate-finding is entirely performed by males. We quantified male L. dispar flight capacity and propensity relative to morphological and physiological characteristics using fixed-arm flight mills. A range of male body sizes was produced by varying the protein content of standard artificial diets while holding other dietary components constant. Wing length, a proxy for body size, relative thorax mass, and forewing aspect were all important predictors of total flight distance and maximum speed. These results have important implications for mate-finding and invasion dynamics in L. dispar and may apply broadly to other capital-breeding insects.

Validating Modern NRG Oncology Pelvic Nodal and Groupe Francophone de Radiothérapie Urologique Prostate Bed Contouring Guidelines for Post-Prostatectomy Salvage Radiation: A Secondary Analysis of the LOCATE Trial.

PURPOSE: We used the patterns of recurrence on 18F-fluciclovine positron emission tomography (PET)-computed tomography (CT) in patients enrolled in the LOCATE trial after prostatectomy to evaluate how well the most recent NRG Oncology and Groupe Francophone de Radiothérapie Urologique (GFRU) contouring recommendations encompassed all sites of recurrence in the prostate fossa and pelvic nodes in comparison to former Radiation Therapy Oncology Group (RTOG) recommendations. METHODS AND MATERIALS: Patients with biochemically recurrent prostate cancer after radical prostatectomy with a positive finding within the prostate fossa or pelvic nodes on 18F-fluciclovine PET/CTs were identified from the LOCATE patient population. Areas of gross disease were delineated. Prostate fossa contours were delineated using both the 2010 RTOG consensus guidelines and the recently published 2020 GFRU consensus guidelines. Pelvic nodes were contoured with both the 2009 RTOG consensus guidelines and the 2020 NRG consensus guidelines. The performance of the contouring guidelines was assessed by determining what proportion of gross recurrent lesions were encompassed completely or marginally. RESULTS: Of the 213 patients within the LOCATE trial, 45 patients were eligible for analysis with positive 18F-fluciclovine PET findings. Of the 30 total prostate fossa recurrences, the 2010 RTOG contour covered 20 (67%) and missed or marginally covered 10 (33%). The 2020 GFRU contour covered 27 recurrences (90%), and missed or marginally covered 3 (10%). Of the 43 total nodal recurrences, the 2009 RTOG pelvic nodal contour covered 29 nodes (67%), and missed or marginally covered 14 (32%). The 2020 NRG pelvic nodal contour covered 43 nodes (100%), with no misses or marginal coverage. CONCLUSIONS: This secondary analysis of the LOCATE trial exemplifies the improved coverage of the latest prostate fossa contouring recommendations from the GFRU. Similarly, it also validates the updated 2020 NRG pelvic nodal contouring guidelines by demonstrating improved coverage of recurrent disease in this patient population.

Electron Microscopy Imaging Applications of Room Temperature Ionic Liquids in the Biological Field: A Review.

For biological imaging using electron microscopy (EM), the use of room-temperature ionic liquids (RTILs) has been proposed as an alternative to traditional lengthy preparation methods. With their low vapor pressures and conductivity, RTILs can be applied onto hard-to-image soft and/or wet samples without dehydration - allowing for a more representative, hydrated state of material and opening the possibility for visualization of in situ physiological processes using conventional EM systems. However, RTILs have yet to be utilized to their full potential by microscopists and microbiologists alike. To this end, this review aims to provide a comprehensive summary of biological applications of RTILs for EM to bridge the RTIL, in situ microscopy, and biological communities. We outline future research avenues for the use of RTILs for the EM observation of biological samples, notably i) RTIL selection and optimization, ii) applications for live cell processes and iii) electron beam and ionic liquid interaction studies.

Mitovesicles are a novel population of extracellular vesicles of mitochondrial origin altered in Down syndrome.

Mitochondrial dysfunction is an established hallmark of aging and neurodegenerative disorders such as Down syndrome (DS) and Alzheimer's disease (AD). Using a high-resolution density gradient separation of extracellular vesicles (EVs) isolated from murine and human DS and diploid control brains, we identify and characterize a previously unknown population of double-membraned EVs containing multiple mitochondrial proteins distinct from previously described EV subtypes, including microvesicles and exosomes. We term these newly identified mitochondria-derived EVs "mitovesicles." We demonstrate that brain-derived mitovesicles contain a specific subset of mitochondrial constituents and that their levels and cargo are altered during pathophysiological processes where mitochondrial dysfunction occurs, including in DS. The development of a method for the selective isolation of mitovesicles paves the way for the characterization in vivo of biological processes connecting EV biology and mitochondria dynamics and for innovative therapeutic and diagnostic strategies.

Aerobic exercise increases sprouting angiogenesis in the male rat motor cortex.

Exercise is beneficial to brain health, and historically, the advantageous effects of exercise on the brain have been attributed to neuronal plasticity. However, it has also become clear that the brain vascular system also exhibits plasticity in response to exercise. This plasticity occurs in areas involved in movement, such as the motor cortex. This experiment aimed to further characterize the effects of exercise on structural vascular plasticity in the male rat motor cortex, by specifically identifying whether features of angiogenesis, the growth of new capillaries, or changes in vessel diameter were present. Male rats in the exercise group engaged in a 5-week bout of voluntary wheel running, while a second group of rats remained sedentary. After the exercise regimen, vascular corrosion casts, resin replicas of the brain vasculature, were made for all animals and imaged using a scanning electron microscope. Results indicate sprouting angiogenesis was the primary form of structural vascular plasticity detected in the motor cortex under these aerobic exercise parameters. Additionally, exercised rats displayed a slight increase in capillary diameter and expanded endothelial cell nuclei diameters in this region.

Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-ß oligomerizes.

Pleiotropic roles are proposed for brain extracellular vesicles (EVs) in the development of Alzheimer's disease (AD). Our previous studies have suggested a beneficial role for EVs in AD, where the endosomal system in vulnerable neurons is compromised, contributing to the removal of accumulated material from neurons. However, the involvement of EVs in propagating AD amyloidosis throughout the brain has been considered because the amyloid-ß precursor protein (APP), APP metabolites, and key APP cleaving enzymes were identified in association with EVs. Here, we undertook to determine whether the secretase machinery is actively processing APP in EVs isolated from the brains of wild-type and APP overexpressing Tg2576 mice. We found that full-length APP is cleaved in EVs incubated in the absence of cells. The resulting metabolites, both α- and ß-APP carboxyl-terminal fragments and APP intracellular domain accumulate in EVs over time and amyloid-ß dimerizes. Thus, EVs contribute to the removal from neurons and transport of APP-derived neurotoxic peptides. While this is potentially a venue for propagation of the pathology throughout the brain, it may contribute to efficient removal of neurotoxic peptides from the brain.

Effects of seed morphology and elaiosome chemical composition on attractiveness of five Trillium species to seed-dispersing ants.

Morphological and chemical attributes of diaspores in myrmecochorous plants have been shown to affect seed dispersal by ants, but the relative importance of these attributes in determining seed attractiveness and dispersal success is poorly understood. We explored whether differences in diaspore morphology, elaiosome fatty acids, or elaiosome phytochemical profiles explain the differential attractiveness of five species in the genus Trillium to eastern North American forest ants. Species were ranked from least to most attractive based on empirically-derived seed dispersal probabilities in our study system, and we compared diaspore traits to test our hypotheses that more attractive species will have larger diaspores, greater concentrations of elaiosome fatty acids, and distinct elaiosome phytochemistry compared to the less attractive species. Diaspore length, width, mass, and elaiosome length were significantly greater in the more attractive species. Using gas chromatography-mass spectrometry, we found significantly higher concentrations of oleic, linoleic, hexadecenoic, stearic, palmitoleic, and total fatty acids in elaiosomes of the more attractive species. Multivariate assessments revealed that elaiosome phytochemical profiles, identified through liquid chromatography-mass spectrometry, were more homogeneous for the more attractive species. Random forest classification models (RFCM) identified several elaiosome phytochemicals that differed significantly among species. Random forest regression models revealed that some of the compounds identified by RFCM, including methylhistidine (α-amino acid) and d-glucarate (carbohydrate), were positively related to seed dispersal probabilities, while others, including salicylate (salicylic acid) and citrulline (L-α-amino acid), were negatively related. These results supported our hypotheses that the more attractive species of Trillium-which are geographically widespread compared to their less attractive, endemic congeners-are characterized by larger diaspores, greater concentrations of fatty acids, and distinct elaiosome phytochemistry. Further advances in our understanding of seed dispersal effectiveness in myrmecochorous systems will benefit from a portrayal of dispersal unit chemical and physical traits, and their combined responses to selection pressures.

Successful Full-term Pregnancies After High-dose Pelvic Radiotherapy for Ewing Sarcoma: A Case Report.

Survivors of childhood cancer are at risk of long-term sequelae that arise as a consequence of cancer treatment. Radiation and chemotherapy treatment in pediatric female patients can have detrimental impacts on fertility, particularly in those with pelvic tumor involvement. We report 2 successful natural full-term pregnancies with vaginal delivery in a woman 12 years after biopsy, irradiation (55.5 Gy), and multi-agent chemotherapy for treatment of pelvic Ewing sarcoma. Both children were born healthy, with no complications in pregnancy or delivery. Fertility preservation and risk assessment following chemotherapy/radiation therapy is evolving, providing new data to effectively counsel and treat young women.

3-(4-Iodo-phen-yl)-2,3-di-hydro-1H-benzo[f]chromen-1-one.

In the title compound, C19H13IO2, the dihedral angle between the naphthyl ring system and the pendant iodo-phenyl ring is 72.48 (11)°. In the crystal, C-H⋯π inter-actions and I⋯O [3.293 (2) Å] halogen bonds are observed, which combine to generate a herringbone packing motif.

A pleiotropic role for exosomes loaded with the amyloid ß precursor protein carboxyl-terminal fragments in the brain of Down syndrome patients.

Down syndrome (DS) is characterized by cognitive deficits throughout the life span and with the development of aging-dependent Alzheimer's type neuropathology, which is related to the triplication of the amyloid ß precursor protein (APP) gene. A dysfunctional endosomal system in neurons is an early characteristic of DS and APP metabolites accumulate in endosomes in DS neurons. We have previously shown enhanced release of exosomes in the brain of DS patients and the mouse model of DS Ts[Rb(12.1716)]2Cje (Ts2), and by DS fibroblasts, as compared with diploid controls. Here, we demonstrate that exosome-enriched extracellular vesicles (hereafter called EVs) isolated from DS and Ts2 brains, and from the culture media of human DS fibroblasts are enriched in APP carboxyl-terminal fragments (APP-CTFs) as compared with diploid controls. Moreover, APP-CTFs levels increase in an age-dependent manner in EVs isolated from the brain of Ts2 mice. The release of APP-CTFs-enriched exosomes may have a pathogenic role by transporting APP-CTFs into naïve neurons and propagating these neurotoxic metabolites, which are also a source of amyloid ß, throughout the brain, but also provides a benefit to DS neurons by shedding APP-CTFs accumulated intracellularly.