Domain-specific deficits in self-awareness and relationship to psychosocial outcomes after severe traumatic brain injury.

Purpose: To investigate the evidence for domain-specific deficits in self-awareness on the Patient Competency Rating Scale (PCRS) and the relationship to psychosocial outcomes after severe traumatic brain injury (TBI).Methods: Fifty-six adults with severe TBI (75% males, M age =36.96, SD = 12.96), and 50 age- and gender-matched controls (72% male, M age =34.12, SD = 11.43) were administered the PCRS self-report form, and the Depression, Anxiety, Stress Scales. Relatives of TBI and control participants completed the PCRS informant version. Relatives of the TBI group also completed the Sydney Psychosocial Rating Scale.Results: A within-group analysis indicated that self-awareness varied according to PCRS domain (p <.01). Relative to their own profile, TBI participants displayed significantly poorer self-awareness on the activities of daily living (ADLs) domain than on the interpersonal and emotional domains (p < 0.01). Further, TBI participants displayed significantly poorer self-awareness of ADLs than controls (p < 0.001), but there were no significant between-group differences in other domains. Hierarchical regression analyses revealed that poorer self-awareness of cognitive difficulties was related to lower occupational functioning (p = 0.01), whereas poorer self-awareness of difficulties with ADLs was related to lower independent living skills (p < 0.001).Conclusions: The results provide only limited support for domain-specific deficits in self-awareness after severe TBI, with impairment most evident for ADLs. Poorer self-awareness in the ADLs and cognitive domains were associated with lower independence and occupational functioning, respectively. The findings highlight the potential benefits of targeting self-awareness related to difficulties with ADLs in the rehabilitation of people with severe TBI.Implications for rehabilitationPeople with severe traumatic brain injury had poorest self-awareness of difficulties regarding activities of daily living, which was related to less independenceDifficulties with complex activities of daily living were more likely to be under-reported than difficulties with basic self-careIt may be beneficial to target self-awareness of difficulties relating to complex activities of daily living in rehabilitation.

Transduction of photoreceptors with equine infectious anemia virus lentiviral vectors: safety and biodistribution of StarGen for Stargardt disease.

PURPOSE: StarGen is an equine infectious anemia virus (EIAV)-based lentiviral vector that expresses the photoreceptor-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) protein that is mutated in Stargardt disease (STGD1), a juvenile macular dystrophy. EIAV vectors are able to efficiently transduce rod and cone photoreceptors in addition to retinal pigment epithelium in the adult macaque and rabbit retina following subretinal delivery. The safety and biodistribution of StarGen following subretinal delivery in macaques and rabbits was assessed. METHODS: Regular ophthalmic examinations, IOP measurements, ERG responses, and histopathology were carried out in both species to compare control and vector-treated eyes. Tissue and fluid samples were obtained to evaluate the persistence, biodistribution, and shedding of the vector following subretinal delivery. RESULTS: Ophthalmic examinations revealed a slightly higher level of inflammation in StarGen compared with control treated eyes in both species. However, inflammation was transient and no overt toxicity was observed in StarGen treated eyes and there were no abnormal clinical findings. There was no StarGen-associated rise in IOP or abnormal ERG response in either rabbits or macaques. Histopathologic examination of the eyes did not reveal any detrimental changes resulting from subretinal administration of StarGen. Although antibodies to StarGen vector components were detected in rabbit but not macaque serum, this immunologic response did not result in any long-term toxicity. Biodistribution analysis demonstrated that the StarGen vector was restricted to the ocular compartment. CONCLUSIONS: In summary, these studies demonstrate StarGen to be well tolerated and localized following subretinal administration.