Amblyopia: A review of unmet needs, current treatment options, and emerging therapies.

Amblyopia is a global public health issue with extensive, multifaceted impacts on vision and quality of life (QoL) for both patients and families. Geographical variation exists in the management of amblyopia, with traditional mainstay treatments, optical correction, and fellow eye occlusion most successful when implemented at an early age. In recent years, however, studies demonstrating meaningful improvements in older children and adults have challenged the concept of a complete loss of visual processing plasticity beyond the critical period of visual development, with growing evidence supporting the potential efficacy of emerging, more engaging, binocular therapies in both adults and children. Binocular approaches aim to restore deficits in amblyopia that extend beyond monocular visual acuity impairment, including binocular fusion and visuomotor skills. In view of this, incorporating outcome measures that evaluate the visual performance and functional ability of individuals with amblyopia will provide a clearer understanding of the effect of amblyopia on QoL and a more comprehensive evaluation of amblyopia therapies.

Economic burden and loss of quality of life from dry eye disease in Canada.

OBJECTIVE: To describe the direct and indirect cost estimates of dry eye disease (DED), stratified by disease severity, and the impact of DED on quality of life (QoL) in Canadian patients. METHODS AND ANALYSIS: A prospective, multicentre, observational, cross-sectional study was conducted at six sites across Canada. Eligible patients completed a 20 min survey on demography, general health, disease severity, QoL and direct (resource utilisation and out-of-pocket expenses for the past 3-24 months) and indirect costs (absenteeism and presenteeism based on Work Productivity and Activity Impairment questionnaire responses). Subgroup analyses were performed according to DED severity and presence of Sjögren's syndrome. RESULTS: Responses from 146 of 151 participants were included in the analysis. DED was rated as moderate or severe by 19.2% and 69.2% of patients, respectively. Total mean annual costs of DED were $C24 331 (Canadian dollars) per patient and increased with patient-reported disease severity. Mean (standard deviation [SD]) indirect costs for mild, moderate and severe disease were $C5961 ($C6275), $C16 525 ($C11 607), and $C25 485 ($C22,879), respectively. Mean (SD) direct costs were $C958 ($C1216), $C1303 ($C1574) and $C2766 ($C7161), respectively. QoL scores were lowest in patients with Sjögren's syndrome (8.2% of cohort) and those with severe DED. CONCLUSION: This study provides important insights into the negative impact of DED in a Canadian setting. Severe DED was associated with higher direct and indirect costs and lower QoL compared with those with mild or moderate disease. Increased costs and poorer QoL were also evident for patients with DED plus Sjögren's syndrome versus DED alone.

A survey of adult referrals to specialist attention-deficit/hyperactivity disorder clinics in Canada.

BACKGROUND: Canadian guidelines encourage family physicians to diagnose/manage adults with uncomplicated attention-deficit/hyperactivity disorder (ADHD); specialist referral is recommended only for complex cases. This retrospective case review investigated adults referred to Canadian ADHD clinics. METHODS: Adult ADHD specialists reviewed referral letters/charts of patients (aged ≥18 years and no family history/known/expressed childhood ADHD) from family physicians/psychiatrists over 2 years. RESULTS: Data on 515 referrals (mean age 33 years, 60% males) were collected (December 2014 to September 2015); 472/515 (92%) were made by family physicians. No psychiatric comorbid symptoms were noted in 344/515 (67%) referrals. ADHD was confirmed by a specialist in 483/515 (94%) cases, whether comorbid symptoms were noted at referral (155/171 [91%]) or not (328/344 [95%]). ADHD was reported to impact "work" (251/317 [79%]), "school" (121/166 [73%]), "social/friends" (260/483 [54%]), and "spouse/family" (231/483 [48%]). Overall, 335/483 (69%) patients had more than or equal to one comorbid symptom (diagnosed by referring physician or specialist). Stimulant monotherapy was recommended for 383/483 (79%) patients, non-stimulant monotherapy for 41/483 (8%) patients, and stimulant plus non-stimulant monotherapy for 39/483 (8%) patients. Almost half of patients were returned for referring physician's follow-up, either before treatment initiation (102/483 [21%]) or after treatment stabilization (99/483 [20%]). Follow-up was by a specialist for 282/483 (58%) patients. CONCLUSION: ADHD diagnosis was specialist confirmed in most cases. Although most referrals (67%) noted no psychiatric comorbid symptoms, 69% of patients had ≥1 such symptom (diagnosed by a referring physician or specialist), so comorbid symptoms although not always noted at referral, may have contributed to the decision to refer. ADHD has a wide-ranging impact on patients' daily lives. It is possible that greater confidence of family physicians to diagnose and treat adult ADHD could help to meet patients' needs.

Social environment influences performance in a cognitive task in natural variants of the foraging gene.

In Drosophila melanogaster, natural genetic variation in the foraging gene affects the foraging behaviour of larval and adult flies, larval reward learning, adult visual learning, and adult aversive training tasks. Sitters (for(s)) are more sedentary and aggregate within food patches whereas rovers (for(R)) have greater movement within and between food patches, suggesting that these natural variants are likely to experience different social environments. We hypothesized that social context would differentially influence rover and sitter behaviour in a cognitive task. We measured adult rover and sitter performance in a classical olfactory training test in groups and alone. All flies were reared in groups, but fly training and testing were done alone and in groups. Sitters trained and tested in a group had significantly higher learning performances compared to sitters trained and tested alone. Rovers performed similarly when trained and tested alone and in a group. In other words, rovers learning ability is independent of group training and testing. This suggests that sitters may be more sensitive to the social context than rovers. These differences in learning performance can be altered by pharmacological manipulations of PKG activity levels, the foraging (for) gene's gene product. Learning and memory is also affected by the type of social interaction (being in a group of the same strain or in a group of a different strain) in rovers, but not in sitters. These results suggest that for mediates social learning and memory in D. melanogaster.

Costs of memory: lessons from 'mini' brains.

Variation in learning and memory abilities among closely related species, or even among populations of the same species, has opened research into the relationship between cognition, ecological context and the fitness costs, and benefits of learning and memory. Such research programmes have long been dominated by vertebrate studies and by the assumption of a relationship between cognitive abilities, brain size and metabolic costs. Research on these 'large brained' organisms has provided important insights into the understanding of cognitive functions and their adaptive value. In the present review, we discuss some aspects of the fitness costs of learning and memory by focusing on 'mini-brain' studies. Research on learning and memory in insects has challenged some traditional positions and is pushing the boundaries of our understanding of the evolution of learning and memory.

Use of spatial information and search strategies in a water maze analog in Drosophila melanogaster.

Learning the spatial organization of the environment is crucial to fitness in most animal species. Understanding proximate and ultimate factors underpinning spatial memory is thus a major goal in the study of animal behavior. Despite considerable interest in various aspects of its behavior and biology, the model species Drosophila melanogaster lacks a standardized apparatus to investigate spatial learning and memory. We propose here a novel apparatus, the heat maze, conceptually based on the Morris water maze used in rodents. Using the heat maze, we demonstrate that D. melanogaster flies are able to use either proximal or distal visual cues to increase their performance in navigating to a safe zone. We also show that flies are actively using the orientation of distal visual cues when relevant in targeting the safe zone, i.e., Drosophila display spatial learning. Parameter-based classification of search strategies demonstrated the progressive use of spatially precise search strategies during learning. We discuss the opportunity to unravel the mechanistic and evolutionary bases of spatial learning in Drosophila using the heat maze.

Transgenerational memory effect of ageing in Drosophila.

Children born to older parents tend to have lower intelligence and are at higher risk for disorders such as schizophrenia and autism. Such observations of ageing damage being passed on from parents to offspring are not often considered within the evolutionary theory of ageing. Here, we show the 25% memory impairment in Drosophila melanogaster offspring solely dependent on the age of the parents and also passed on to the F2 generation. Furthermore, this parental age effect was not attributed to a generalized reduction in condition of the offspring but was specific to short-term memory. We also provide evidence implicating oxidative stress as a causal factor by showing that lines selected for resistance to oxidative stress did not display a memory impairment in offspring of old parents. The identification of the parental age-related memory impairment in a model system should stimulate integration between mechanistic studies of age-related mortality risk and functional studies of parental age effects on the fitness of future generations.

The validity of three tests of temperament in guppies (Poecilia reticulata).

Differences in temperament (consistent differences among individuals in behavior) can have important effects on fitness-related activities such as dispersal and competition. However, evolutionary ecologists have put limited effort into validating their tests of temperament. This article attempts to validate three standard tests of temperament in guppies: the open-field test, emergence test, and novel-object test. Through multiple reliability trials, and comparison of results between different types of test, this study establishes the confidence that can be placed in these temperament tests. The open-field test is shown to be a good test of boldness and exploratory behavior; the open-field test was reliable when tested in multiple ways. There were problems with the emergence test and novel-object test, which leads one to conclude that the protocols used in this study should not be considered valid tests for this species.

The birds, the bees, and the virtual flowers: can pollinator behavior drive ecological speciation in flowering plants?

Biologists have long assumed that pollinator behavior is an important force in angiosperm speciation, yet there is surprisingly little direct evidence that floral preferences in pollinators can drive floral divergence and the evolution of reproductive (ethological) isolation between incipient plant species. In this study, we expose computer-generated plant populations with a wide variation in flower color to selection by live and virtual hummingbirds and bumblebees and track evolutionary changes in flower color over multiple generations. Flower color, which was derived from the known genetic architecture and phenotypic variance of naturally occurring plant species pollinated by both groups, evolved in simulations through a genetic algorithm in which pollinator preference determined changes in flower color between generations. The observed preferences of live hummingbirds and bumblebees were strong enough to cause adaptive divergence in flower color between plant populations but did not lead to ethological isolation. However, stronger preferences assigned to virtual pollinators in sympatric and allopatric scenarios rapidly produced ethological isolation. Pollinators can thus drive ecological speciation in flowering plants, but more rigorous and comprehensive behavioral studies are required to specify conditions that produce sufficient preference levels in pollinators.

A consideration of patterns of virulence arising from host-parasite coevolution.

In this article we explore how host survival and fecundity are affected by host-parasite coevolution. We examine a situation in which hosts upon being infected can mount a defensive response to clear the infection, but in which there is a fecundity cost to such immunological up-regulation. We also suppose that the parasite exploits the host and thereby causes an elevated host mortality rate. We determine the coevolutionary stable strategies of the parasite's level of exploitation and the host's level of up-regulation, and illustrate the patterns of reduced host fitness (i.e., virulence) that these produce. We find that counterintuitive patterns of virulence are often expected to arise as a result of the interaction between coevolved host and parasite strategies. In particular, despite the fact that the parasite imposes only a mortality cost on the host, coevolution by the host results in a pattern whereby infected hosts always have the same probability of death from infection, but they vary in the extent to which their fecundity is reduced. This contrasts with previous results and arises from our inclusion of two important factors absent from previous theory: costs of immunological up-regulation and a more suitable measure of parasite-induced mortality.