An examination of obsessive-compulsive symptom domains, depression, and quality of life within an online survey sample.

Obsessive-compulsive disorder (OCD) is a heterogeneous and highly impairing disorder that is frequently comorbid with other conditions. Participants in this study were 212 individuals recruited through Mechanical Turk who filled out validated measures of obsessive-compulsive symptoms, quality of life (QoL), generalized anxiety, and depressive symptoms. Analyses examined the influences of each symptom variable on QoL and the mediating role of depression as an indirect link between unacceptable thoughts (UT) and QoL. Depressive symptoms had a significant negative relationship with multiple domains of functioning. Generalized anxiety was not significant. Higher endorsement of UT symptoms was related to lower physical, emotional, and social QoL. Depression partially mediated the relationship between UT symptoms and physical, emotional, and social health. Depressive symptoms are important to consider in clinical work surrounding OCD. The significant associations between UT symptoms and QoL in a nonclinical population illustrate a relevant area for future intervention, public awareness, and education.

The Role of Executive Functioning and Academic Achievement in the Academic Self-Concept of Children and Adolescents Referred for Neuropsychological Assessment.

The current study evaluated a model of youth academic self-concept which incorporates practical executive functioning behaviors and academic achievement. Though greater academic achievement has been linked to both positive self-concept and better executive functioning, these constructs have not been examined simultaneously. It was hypothesized that academic achievement would mediate the association between problems with executive functioning and academic self-concept such that youth with more problems with executive functioning would have lower academic achievement and, in turn, lower academic self-concept. Clinical data was analyzed from a diagnostically heterogeneous sample of youth (n = 122) who underwent neuropsychological evaluation. Problems with executive functioning were assessed using the Behavior Rating Inventory of Executive Function. Academic achievement was assessed using the Woodcock⁻Johnson Tests of Achievement or Wechsler Individual Achievement Test. Academic self-concept was assessed using the youth-report version of the Behavioral Assessment System for Children. Surprisingly, findings indicate that academic achievement is not significantly associated with problems with executive functioning or academic self-concept. However, greater problems with executive functioning are associated with decreased academic self-concept. The overall model included several covariates and accounted for 10% of the variance in academic self-concept. Findings suggest that executive skills may be essential for aligning academic achievement with classroom performance. Though various child characteristic covariates were included, the model accounted for a small amount of variance suggesting that future studies should examine contributing contextual factors.

Self-encapsulating Poly(lactic-co-glycolic acid) (PLGA) Microspheres for Intranasal Vaccine Delivery.

Herein we describe a formulation of self-encapsulating poly(lactic-co-glycolic acid) (PLGA) microspheres for vaccine delivery. Self-healing encapsulation is a novel encapsulation method developed by our group that enables the aqueous loading of large molecules into premade PLGA microspheres. Calcium phosphate (CaHPO4) adjuvant gel was incorporated into the microspheres as a protein-trapping agent for improved encapsulation of antigen. Microspheres were found to have a median size of 7.05 ± 0.31 µm, with a w/w loading of 0.60 ± 0.05% of ovalbumin (OVA) model antigen. The formulation demonstrated continuous release of OVA over a 49-day period. Released OVA maintained its antigenicity over the measured period of >21 days of release. C57BL/6 mice were immunized via the intranasal route with prime and booster doses of OVA (10 µg) loaded into microspheres or coadministered with cholera toxin B (CTB), the gold standard of mucosal adjuvants. Microspheres generated a Th2-type response in both serum and local mucosa, with IgG antibody responses approaching those generated by CTB. The results suggest that this formulation of self-encapsulating microspheres shows promise for further study as a vaccine delivery system.

Toward a Single-Dose Vaccination Strategy with Self-Encapsulating PLGA Microspheres.

Poly(lactic-co-glycolic acid) (PLGA) microspheres have been widely examined for vaccine applications due to their attractive features of biocompatibility, biodegradability, ability to be internalized by antigen-presenting cells, and long-term antigen release. However, one of the major challenges for PLGA particle vaccines is the potential for antigen instability and loss of antigenicity and immunogenicity. To address this challenge, we have developed a new method of "self-healing" encapsulation in PLGA microspheres, where pre-made PLGA microspheres are loaded with protein antigens under aqueous conditions with minimal impact on their antigenicity and immunogenicity. In this report, we show that mice immunized with self-encapsulating PLGA microspheres in a prime-boost regimen generated significantly enhanced antigen-specific CD8α+ T cell and antibody responses, compared with mice immunized with free, soluble protein admixed with calcium phosphate gel, a widely used adjuvant. Furthermore, a single-dose of microspheres designed for >40 day sustained antigen release elicited robust cellular and humoral immune responses as efficiently as the prime-boost vaccinations with calcium phosphate gel. Overall, these results suggest excellent potential of our self-encapsulating PLGA microspheres as a vaccine platform for multiple-dose as well as single-dose vaccinations.

Compositional Variation and Bioactivity of the Leaf Essential Oil of Montanoa guatemalensis from Monteverde, Costa Rica: A Preliminary Investigation.

BACKGROUND: Montanoa guatemalensis is a small to medium-sized tree in the Asteraceae that grows in Central America from Mexico south through Costa Rica. There have been no previous investigations on the essential oil of this tree. METHODS: The leaf essential oils of M. guatemalensis were obtained from different individual trees growing in Monteverde, Costa Rica, in two different years, and were analyzed by gas chromatography-mass spectrometry. RESULTS: The leaf oils from 2008 were rich in sesquiterpenoids, dominated by α-selinene, ß-selinene, and cyclocolorenone, with lesser amounts of the monoterpenes α-pinene and limonene. In contrast, the samples from 2009 showed no α- or ß-selinene, but large concentrations of trans-muurola-4(14),5-diene, ß-cadinene, and cyclocolorenone, along with greater concentrations of α-pinene and limonene. The leaf oils were screened for cytotoxic and antimicrobial activities and did show selective cytotoxic activity on MDA-MB-231 breast tumor cells. CONCLUSION: M. guatemalensis leaf oil, rich in cyclocolorenone, α-selinene, and ß-selinene, showed selective in vitro cytotoxic activity to MDA-MB-231 cells. The plant may be a good source of cyclocolorenone.

Injectable controlled release depots for large molecules.

Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few "real world" biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LARproducts, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development.