Long-term efficacy of orthokeratology contact lens wear in controlling the progression of childhood myopia

Purpose: The primary outcome of this study is to compare the axial length growth of white European myopic children wearing orthokeratology contact lenses (OK) to a control group (CT) over a 7-year period. Methods: Subjects 6–12 years of age with myopia −0.75 to −4.00DS and astigmatism ≤1.00DC were prospectively allocated OK or distance single-vision spectacles (SV) correction. Measurements of axial length (Zeiss IOLMaster), corneal topography, and cycloplegic refraction were taken at 6-month intervals over a 2-year period. Subjects were invited to return to the clinic approximately 5 years later (i.e., 7 years after the beginning of the study) for assessment of their ocular refractive and biometric components. The CT consisted of 4 SV and 12 subjects who switched from SV to soft contact lens wear after the initial 2 years of SV lens wear. Changes in axial length relative to baseline over a 7-year period were compared between groups. Results: Fourteen and 16 subjects from the OK and CT groups, respectively, were examined 6.7 ± 0.5 years after the beginning of the study. Statistically significant changes in the axial length were found over time and between groups (both p <0.001), but not for the time*group interaction (p = 0.125). The change in the axial length for the OK group was 22% (p = 0.328), 42% (p = 0.007), 40% (p = 0.020), 41% (p = 0.013), and 33% (p = 0.062) lower than the CT group following 6, 12, 18, 24, and 84 months of lens wear, respectively. Conclusion: A trend toward a reduction in the rate of axial elongation of the order of 33% was found in the OK group in comparison to the CT group following 7 years of lens wear

Double Dissociation of Amygdala and Hippocampal Contributions to Trace and Delay Fear Conditioning

A key finding in studies of the neurobiology of learning memory is that the amygdala is critically involved in Pavlovian fear conditioning. This is well established in delay-cued and contextual fear conditioning; however, surprisingly little is known of the role of the amygdala in trace conditioning. Trace fear conditioning, in which the CS and US are separated in time by a trace interval, requires the hippocampus and prefrontal cortex. It is possible that recruitment of cortical structures by trace conditioning alters the role of the amygdala compared to delay fear conditioning, where the CS and US overlap. To investigate this, we inactivated the amygdala of male C57BL/6 mice with GABA A agonist muscimol prior to 2-pairing trace or delay fear conditioning. Amygdala inactivation produced deficits in contextual and delay conditioning, but had no effect on trace conditioning. As controls, we demonstrate that dorsal hippocampal inactivation produced deficits in trace and contextual, but not delay fear conditioning. Further, pre- and post-training amygdala inactivation disrupted the contextual but the not cued component of trace conditioning, as did muscimol infusion prior to 1- or 4-pairing trace conditioning. These findings demonstrate that insertion of a temporal gap between the CS and US can generate amygdala-independent fear conditioning. We discuss the implications of this surprising finding for current models of the neural circuitry involved in fear conditioning

Dopaminergic modulation of appetitive trace conditioning: the role of D1 receptors in medial prefrontal cortex

Rationale: Trace conditioning may provide a behavioural model suitable to examine the maintenance of ‘on line’ information and its underlying neural substrates. Objectives: Experiment la was run to establish trace conditioning in a shortened procedure which would be suitable to test the effects of dopamine (DA) D1 receptor agents administered by microinjection directly into the brain. Experiment lb examined the effects of the DA D1 agonist SKF81297 and the DA D1 antagonist SCH23390 following systemic administration in pre-trained animals. Experiment 2 went on to test the effects of systemically administered SKF81297 on the acquisition of trace conditioning. In experiment 3, SKF81297 was administered directly in prelimbic (PL) and infralimbic (IL) sub-regions of medial prefrontal cortex (mPFC) to compare the role of different mPFC sub-regions. Results: Whilst treatment with SCH23390 impaired motor responding and/or motivation, SKF81297 had relatively little effect in the pre-trained animals tested in experiment 1b. However, systemic SKF81297 depressed the acquisition function at the 2-s trace interval in experiment 2. Similarly, in experiment 3, SKF81297 (0.1 μg in 1.0 μl) microinjected into either PL or IL mPFC impaired appetitive conditioning at the 2-s trace interval. Conclusions: Impaired trace conditioning under SKF81297 is likely to be mediated in part (but not exclusively) within the IL and PL mPFC sub-regions. The finding that trace conditioning was impaired rather than enhanced under SKF81297 provides further evidence for the inverse U-function which has been suggested to be characteristic of mPFC DA function

Computed Tomography Measurement of Rib Cage Morphometry in Emphysema

Background: Factors determining the shape of the human rib cage are not completely understood. We aimed to quantify the contribution of anthropometric and COPD-related changes to rib cage variability in adult cigarette smokers. Methods: Rib cage diameters and areas (calculated from the inner surface of the rib cage) in 816 smokers with or without COPD, were evaluated at three anatomical levels using computed tomography (CT). CTs were analyzed with software, which allows quantification of total emphysema (emphysema%). The relationship between rib cage measurements and anthropometric factors, lung function indices, and %emphysema were tested using linear regression models. Results: A model that included gender, age, BMI, emphysema%, forced expiratory volume in one second (FEV1)%, and forced vital capacity (FVC)% fit best with the rib cage measurements (R2  = 64% for the rib cage area variation at the lower anatomical level). Gender had the biggest impact on rib cage diameter and area (105.3 cm2; 95% CI: 111.7 to 98.8 for male lower area). Emphysema% was responsible for an increase in size of upper and middle CT areas (up to 5.4 cm2; 95% CI: 3.0 to 7.8 for an emphysema increase of 5%). Lower rib cage areas decreased as FVC% decreased (5.1 cm2; 95% CI: 2.5 to 7.6 for 10 percentage points of FVC variation). Conclusions: This study demonstrates that simple CT measurements can predict rib cage morphometric variability and also highlight relationships between rib cage morphometry and emphysema

Review: The increasing importance of carbon nanotubes and nanostructured conducting polymers in biosensors

The growing need for analytical devices requiring smaller sample volumes, decreased power consumption and improved performance have been driving forces behind the rapid growth in nanomaterials research. Due to their dimensions, nanostructured materials display unique properties not traditionally observed in bulk materials. Characteristics such as increased surface area along with enhanced electrical/optical properties make them suitable for numerous applications such as nanoelectronics, photovoltaics and chemical/biological sensing. In this review we examine the potential that exists to use nanostructured materials for biosensor devices. By incorporating nanomaterials, it is possible to achieve enhanced sensitivity, improved response time and smaller size. Here we report some of the success that has been achieved in this area. Many nanoparticle and nanofibre geometries are particularly relevant, but in this paper we specifically focus on organic nanostructures, reviewing conducting polymer nanostructures and carbon nanotubes

Primula vulgaris (primrose) genome assembly, annotation and gene expression, with comparative genomics on the heterostyly supergene

Primula vulgaris (primrose) exhibits heterostyly: plants produce self-incompatible pin- or thrum-form flowers, with anthers and stigma at reciprocal heights. Darwin concluded that this arrangement promotes insect-mediated cross-pollination; later studies revealed control by a cluster of genes, or supergene, known as the S (Style length) locus. The P. vulgaris S locus is absent from pin plants and hemizygous in thrum plants (thrum-specific); mutation of S locus genes produces self-fertile homostyle flowers with anthers and stigma at equal heights. Here, we present a 411 Mb P. vulgaris genome assembly of a homozygous inbred long homostyle, representing ~87% of the genome. We annotate over 24,000 P. vulgaris genes, and reveal more genes up-regulated in thrum than pin flowers. We show reduced genomic read coverage across the S locus in other Primula species, including P. veris, where we define the conserved structure and expression of the S locus genes in thrum. Further analysis reveals the S locus has elevated repeat content (64%) compared to the wider genome (37%). Our studies suggest conservation of S locus genetic architecture in Primula, and provide a platform for identification and evolutionary analysis of the S locus and downstream targets that regulate heterostyly in diverse heterostylous species

Selective synaptic remodeling of amygdalocortical connections associated with fear memory

Neural circuits underlying auditory fear conditioning have been extensively studied. Here we identified a previously unexplored pathway from the lateral amygdala (LA) to the auditory cortex (ACx) and found that selective silencing of this pathway using chemo- and optogenetic approaches impaired fear memory retrieval. Dual-color in vivo two-photon imaging of mouse ACx showed pathway-specific increases in the formation of LA axon boutons, dendritic spines of ACx layer 5 pyramidal cells, and putative LA-ACx synaptic pairs after auditory fear conditioning. Furthermore, joint imaging of pre- and postsynaptic structures showed that essentially all new synaptic contacts were made by adding new partners to existing synaptic elements. Together, these findings identify an amygdalocortical projection that is important to fear memory expression and is selectively modified by associative fear learning, and unravel a distinct architectural rule for synapse formation in the adult brain