Light-induced charge generation in polymeric nanoparticles restores vision in advanced-stage retinitis pigmentosa rats.

Retinal dystrophies such as Retinitis pigmentosa are among the most prevalent causes of inherited legal blindness, for which treatments are in demand. Retinal prostheses have been developed to stimulate the inner retinal network that, initially spared by degeneration, deteriorates in the late stages of the disease. We recently reported that conjugated polymer nanoparticles persistently rescue visual activities after a single subretinal injection in the Royal College of Surgeons rat model of Retinitis pigmentosa. Here we demonstrate that conjugated polymer nanoparticles can reinstate physiological signals at the cortical level and visually driven activities when microinjected in 10-months-old Royal College of Surgeons rats bearing fully light-insensitive retinas. The extent of visual restoration positively correlates with the nanoparticle density and hybrid contacts with second-order retinal neurons. The results establish the functional role of organic photovoltaic nanoparticles in restoring visual activities in fully degenerate retinas with intense inner retina rewiring, a stage of the disease in which patients are subjected to prosthetic interventions.

Network-based Responses to the Psychomotor Vigilance Task during Lapses in Adolescents after Short and Extended Sleep.

Neuroimaging studies of the Psychomotor Vigilance Task (PVT) have revealed brain regions involved in attention lapses in sleep-deprived and well-rested adults. Those studies have focused on individual brain regions, rather than integrated brain networks, and have overlooked adolescence, a period of ongoing brain development and endemic short sleep. This study used functional MRI (fMRI) and a contemporary analytic approach to assess time-resolved peri-stimulus response of key brain networks when adolescents complete the PVT, and test for differences across attentive versus inattentive periods and after short sleep versus well-rested states. Healthy 14-17-year-olds underwent a within-subjects randomized protocol including 5-night spans of extended versus short sleep. PVT was performed during fMRI the morning after each sleep condition. Event-related independent component analysis (eICA) identified coactivating functional networks and corresponding time courses. Analysis of salient time course characteristics tested the effects of sleep condition, lapses, and their interaction. Seven eICA networks were identified supporting attention, executive control, motor, visual, and default-mode functions. Attention lapses, after either sleep manipulation, were accompanied by broadly increased response magnitudes post-stimulus and delayed peak responses in some networks. Well-circumscribed networks respond during the PVT in adolescents, with timing and intensity impacted by attentional lapses regardless of experimentally shortened or extended sleep.

Childhood-onset lupus with clinical neurocognitive dysfunction shows lower streamline density and pairwise connectivity on diffusion tensor imaging.

OBJECTIVES: The objective of this report is to use diffusion-tensor imaging (DTI) for investigating white-matter connectivity changes associated with neurocognitive dysfunction in childhood-onset lupus (cSLE-NCD) as measured by formal neuropsychological testing. METHODS: DTI was performed in six individuals with (cSLE-NCD) and nine without neurocognitive dysfunction (cSLE-noNCD) as well as 14 healthy controls. Presence of neurocognitive deficits was identified by formal neuropsychological testing. The brain was divided into 116 regions, and pairwise connectivity (defined as the number of streamlines with an endpoint in each of those regions) and streamline density (defined as the number of streamlines passing through a region regardless of endpoints) were evaluated. Group comparisons were made for regional and global measures of streamline density and pairwise connectivity. RESULTS: A significant decrease in global streamline density was observed in the cSLE-NCD vs. control group (1189 vs. 1305 p = 0.002) and vs. cSLE-noNCD (1189 vs 1320 p = 0.001). The cSLE-noNCD and control groups had similar streamline density. A similar pattern for pairwise connectivity was observed with a significant decrease in the cSLE-NCD group (217) versus the cSLE-noNCD (236; p = 0.013) and control group (238; p = 0.004). Regional measures of pairwise connectivity displayed mixed results. CONCLUSIONS: The analysis of DTI in this pilot study shows cSLE-NCD is associated with global loss of streamline density and pairwise connectivity, suggesting breakdown of the structural network. These results complement previously reported functional and volumetric findings that suggest cSLE-NCD is associated with measurable changes in gray and white matter. If confirmed in larger cohorts, DTI abnormalities could be used as imaging biomarkers of cSLE-NCD.

Transmission of Lawsonia intracellularis to weanling foals using feces from experimentally infected rabbits.

The aim of this study was to investigate whether feces from rabbits experimentally infected with Lawsonia intracellularis were infectious to foals. Two rabbits were infected with L. intracellularis, while two rabbits served as controls. Eight foals received daily feces from either the infected or the control rabbits. All rabbits and foals were monitored daily for clinical signs for the entire study period (21days for rabbits, 42days for foals). Feces and blood were collected for the PCR detection of L. intracellularis and serologic analysis, respectively. None of the infected rabbits or foals developed clinical signs compatible with proliferative enteropathy. All infected rabbits and foals shed L. intracellularis in their feces and all seroconverted. The results support the role of rabbits as asymptomatic amplifiers of L. intracellularis and their role as sources of infection for susceptible foals.

Oral infection of weanling foals with an equine isolate of Lawsonia intracellularis, agent of equine proliferative enteropathy.

BACKGROUND: Equine proliferative enteropathy (EPE) is an emerging disease of weanling foals. OBJECTIVES: Describe clinical, hematologic, biochemical, serologic, molecular, and ultrasonographic findings in foals experimentally infected with Lawsonia intracellularis. ANIMALS: Eight foals. METHODS: Recently weaned foals were assigned to either the challenge (n = 3), the sentinel (n = 3), or the control (n = 2) group. Foals were experimentally challenged via intragastric inoculation of 3 x 10(10)L. intracellularis organisms grown in culture. Each experimentally infected foal was housed with a sentinel foal in order to assess feco-oral transmission. All foals were monitored daily for the development of clinical abnormalities and were weighed once weekly for the duration of the study (90 days). Abdominal ultrasound examination was performed weekly. Feces were collected every other day for 60 days, then weekly for an additional 30 days for the quantitative molecular detection of L. intracellularis. Blood was collected weekly for hematologic, biochemical, and serologic analysis. RESULTS: Only challenged foals developed transient clinical signs of EPE consisting of anorexia, lethargy, fever, loose feces, and peripheral edema. Two challenged foals developed transient hypoalbuminemia. Fecal shedding of L. intracellularis was first detected in the challenged foals between days 12 and 18 postinoculation and lasted for 7-21 days. Seroconversion was documented in all challenged foals and in 1 sentinel foal. The remaining sentinel and control foals remained unaffected. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical EPE of variable severity was induced in all foals infected with L. intracellularis. Furthermore, L. intracellularis can be transmitted via the feco-oral route to susceptible herdmates.

Comparison of SNR and CNR for in vivo mouse brain imaging at 3 and 7 T using well matched scanner configurations.

Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for magnetic resonance microimaging were measured using two nearly identical magnetic resonance imaging (MRI) scanners operating at field strengths of 3 and 7 T. Six mice were scanned using two imaging protocols commonly applied for in vivo imaging of small animal brain: RARE and FLASH. An accounting was made of the field dependence of relaxation times as well as a small number of hardware disparities between scanner systems. Standard methods for relaxometry were utilized to measure T1 and T2 for two white matter (WM) and two gray matter (GM) regions in the mouse brain. An average increase in T1 between 3 and 7 T of 28% was observed in the brain. T2 was found to decrease by 27% at 7 T in agreement with theoretical models. The SNR was found to be uniform throughout the mouse brain, increasing at higher field by a factor statistically indistinguishable from the ratio of Larmor frequencies when imaging with either method. The CNR between GM and WM structures was found to adhere to the expected field dependence for the RARE imaging sequence. Improvement in the CNR for the FLASH imaging sequence between 3 and 7 T was observed to be greater than the Larmor ratio, reflecting a greater susceptibility to partial volume effects at the lower SNR values at 3 T. Imaging at 7 T versus 3 T in small animals clearly provides advantages with respect to the CNR, even beyond the Larmor ratio, especially in lower SNR regimes. This careful multifaceted assessment of the benefits of higher static field is instructive for those newly embarking on small animal imaging. Currently the number of 7 T MRI scanners in use for research in human subjects is increasing at a rapid pace with approximately 30 systems deployed worldwide in 2008. The data presented in this article verify that if system performance and radio frequency uniformity is optimized at 7 T, it should be possible to realize the expected improvements in the CNR and SNR compared with MRI at 3 T.

A targeted, single-dose azithromycin strategy for trachoma.

OBJECTIVE: To evaluate the impact of treating children with acute trachoma and their contacts with oral azithromycin. DESIGN: Open, uncontrolled, prospective evaluation of a community-based treatment strategy. SETTING: Central Australian semi-desert Aboriginal community (1995-1996). PARTICIPANTS: 216 school- and pre-schoolchildren aged 6 months and up to 15 years. INTERVENTION: All children with acute trachoma and their contacts (co-resident siblings aged between 6 months and 15 years) received single-dose oral azithromycin suspension (20 mg/kg, to a maximum of 1000 mg). MAIN OUTCOME MEASURE: Prevalence of acute trachoma (World Health Organization trachoma diagnostic criteria). RESULTS: Trachoma prevalence at baseline was 42% (71/169) and 55% (18/33) for schoolchildren and pre-schoolchildren, respectively: 103 schoolchildren and 21 pre-schoolchildren, comprising 77 with follicular trachoma and their 47 contacts, were treated with azithromycin over an 8-week period. Acute trachoma prevalence in schoolchildren fell to 22% at 6-8 months (P < 0.0001) and was 31% at 12 months (P < 0.05 compared with baseline). Pre-schoolchildren were followed up for 6 months after treatment, and their trachoma prevalence fell from 55% to 25% (P < 0.05). Further treatment was given to children with trachoma at 12 months, and the point prevalence of trachoma for schoolchildren at 24 months was 34%. CONCLUSIONS: In contrast to mass-treatment strategies, significant reductions in trachoma prevalence at 6 months were achieved by screening 35% of community members (216) and treating 20% (124). The subsequent prevalence increases support the need for more comprehensive treatment programs, including health promotion and efforts to improve living conditions.