Visual Performance, and it\u27s Response to Intervention, in Subjects with Age-Related Macular Degeneration.

Abstract Objectives: 1. To explore visual performance status through a range of psychophysical methods beyond corrected distance visual acuity (CDVA), in subjects with age-related macular degeneration (AMD). 2. To investigate the effects on these visual performance parameters in subjects with neovascular age-related macular degeneration (nv-AMD) and in subjects with early AMD undergoing anti-VEGF (vascular endothelial growth factor) therapy and macular carotenoid supplementation, respectively. 3. To understand the role of a supplement containing meso-zeaxanthin (MZ; the third, and currently least explored, macular carotenoid) on the augmentation of macular pigment (MP), on visual performance and on disease progression (graded according to the AREDS [Age-Related Eye Disease Study] criteria), in subjects with early AMD. 4. To explore the impact of macular carotenoid supplementation on vision in subjects presenting with atypical macular pigment optical density (MPOD) spatial profiles at baseline. Outcomes: This study has shown that CDVA is not the most appropriate measure of visual function and does not reflect retinal morphology in cases of early AMD or in cases of nv-AMD. Retinotopic ocular sensitivity (ROS), however, appears to be a more reflective measure of disease severity, where it correlates well with AMD-severity grade (in cases of early AMD) and also with mean foveal thickness (MFT; in cases of nv-AMD). In eyes with nv-AMD undergoing monthly intravitreal ranibizumab injections, there have been demonstrable improvements in a range of parameters of visual function, namely, contrast sensitivity (CS), glare disability (GD), and ROS but no significant change in CDVA, despite a reduction in MFT. MP can be augmented, and CS enhanced, in subjects with early AMD who receive supplemental macular carotenoids. Subjects with low baseline central MPOD had the greatest increases in MPOD and the greatest improvements in CS, when compared with subjects with medium or high baseline MPOD, suggesting that the 4 optimisation of CS (and putatively visual performance in general) is somewhat dependent on central MP levels. The literature review has concluded that supplementation with the macular carotenoids offers the best means of fortifying the antioxidant defenses of the macula, thus putatively reducing the risk of AMD and/or its progression, and of optimising visual performance. Conclusions: The findings of this work suggest the incorporation of tests, complimentary to CDVA, such as CS, GD, and particularly ROS, when attempting to understand disease severity in cases of AMD. In terms of monitoring change over time, the results of this study do seem to indicate that measures of ROS may be particularly useful in monitoring subjects with nv-AMD, while measures of CS and GD may be more apt in monitoring change in subjects with early AMD. Macular carotenoid supplementation can enhance visual performance in subjects with early AMD

The integration of size and weight cues for perception and action: evidence for a weight-size illusion

Humans routinely estimate the size and weight of objects. Yet, when lifting two objects of equal weight but different size, they often perceive the smaller object as being heavier. This size-weight illusion (SWI) is known to have a lesser effect on motor control of object lifting. How the nervous system combines "weight” and "size” cues with prior experience and whether these cues are differentially integrated for perception and sensorimotor action is still not fully understood. Therefore, we assessed not only whether the experience of size biases weight perception, but also if experience of weight biases the size perception of objects. Further, to investigate differences between perceptual and motor systems for cue-experience integration, participants haptically explored the weight of an object with one hand and then shaped the aperture of their other hand to indicate its perceived size. Results—First, next to a SWI, healthy adults (N=21) perceived lighter objects as being smaller and heavier objects as being larger, demonstrating a weight-size illusion (WSI). Second, participants were more susceptible to either the SWI or WSI. Third, aperture of the non-exploring hand was scaled to perceived weight and not to physical size. Hand openings were consistently smaller than physical size, with SWI-sensitive participants being significantly more affected than WSI-sensitive subjects. We conclude: first, both size and weight perceptions are biased by prior experience. Weight perception is biased by expectations of size, while size perception is influenced by the expectancy of weight. Second, humans have the tendency to use one cue predominantly for both types of perception. Third, combining perceived weight with expected size influenced hand motor control, while online haptic feedback was largely ignored. Finally, we present a processing model underlying the size-weight cue integration for the perceptual and motor syste

The molecular pathology of pathogenic mitochondrial tRNA variants

Mitochondrial diseases are clinically and genetically heterogeneous disorders, caused by pathogenic variants in either the nuclear or mitochondrial genome. This heterogeneity is particularly striking for disease caused by variants in mitochondrial DNA-encoded tRNA (mt-tRNA) genes, posing challenges for both the treatment of patients and understanding the molecular pathology. In this review, we consider disease caused by the two most common pathogenic mt-tRNA variants: m.3243A>G (within MT-TL1, encoding mt-tRNA(Leu(UUR))) and m.8344A>G (within MT-TK, encoding mt-tRNA(Lys)), which together account for the vast majority of all mt-tRNA-related disease. We compare and contrast the clinical disease they are associated with, as well as their molecular pathologies, and consider what is known about the likely molecular mechanisms of disease. Finally, we discuss the role of mitochondrial-nuclear crosstalk in the manifestation of mt-tRNA-associated disease and how research in this area not only has the potential to uncover molecular mechanisms responsible for the vast clinical heterogeneity associated with these variants but also pave the way to develop treatment options for these devastating diseases.Peer reviewe

Strata-bound vein array in the basal Pierre Shale, Lake Francis Case, South Dakota, U.S.A

A distinctive strata-bound vein array occurs in the basal Pierre Shale exposed along the shores of Lake Francis Case, a reservoir on the Missouri River in south-central South Dakota. Typically 2–4 meters in thickness, the array consistently outcrops over a \u3e50-km distance, a significant areal footprint. Ash layers define the upper and lower bounds of the vein array. Two, suborthogonal, preferred directions of vertical veins (northeast and southeast strike) define a regional pattern. By volume, vertical veins comprise 1–2% of the rock. Thinner, more discontinuous, and irregular horizontal veins also occur. Comparisons between array orientations and the joint/vein pattern in the immediately underlying marls of the top of the Niobrara Chalk identify distinct differences. Traverse data suggest that the vein arrays are characterized by uniform horizontal extension. Vertical veins in the array are typically 1–2 centimeters thick and contain massive jarosite, selenite, and fibrous gypsum. The abundance of jarosite and fibrous gypsum distinctly correlates with position in the weathering profile, and these phases are interpreted as due to replacement of original selenite during modern weathering. However, for initial vein array formation, the following suggests that they are not related to modern weathering and formed at depth: (1) a lack of correlation of vein width/frequency with position in the weathering profile; (2) the regional extent; (3) the consistent preferred orientations; (4) the uniform horizontal extension; and (5) the coarse-grained character of the selenite. The consistent strike pattern suggests influence of a regional stress field. The mechanism/timing of vein array formation is unclear. Formation due to diagenetic processes, which are especially significant in mud rocks, would explain the strata-bound character and isotropic horizontal strain and is considered most likely. Formation during glacial loading is one intriguing possibility. Localization of the vein array may be due to the organic-rich character of the host Burning Brule Member of the Sharon Springs Formation

Visual Performance in Patients with Neovascular Age Related Macular Degeneration Undergoing Treatment With Intravitreal Ranibizumab

Purpose. To assess visual function and its response to serial intravitreal ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (nv-AMD). Methods. Forty-seven eyes of 47 patients with nv-AMD, and corrected distance visual acuity (CDVA) logMAR 0.7 or better, undergoing intravitreal injections of ranibizumab, were enrolled into this prospective study. Visual function was assessed using a range of psychophysical tests, while mean foveal thickness (MFT) was determined by optical coherence tomography (OCT). Results. Groupmean (±sd)MFT reduced significantly frombaseline (233±59)) to exit (205±40)) (p = 0.001). CDVA exhibited no change between baseline and exit visits (p = 0.48 and p = 0.31 resp.). Measures of visual function that did exhibit statistically significant improvements (p \u3c 0.05 for all) included reading acuity, reading speed, mesopic and photopic contrast sensitivity (CS), mesopic and photopic glare disability (GD), and retinotopic ocular sensitivity (ROS) at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal ranibizumab injections exhibit improvements in many parameters of visual function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not only be considered in the design of studies investigating nv-AMD, but also in treatment and retreatment strategies for patients with the condition

The Effects of Caring for Young Children with Developmental Disabilities on Mothers’ Health and Healthcare Use : Analysis of Primary Care Data in the Born in Bradford Cohort

We explored the association between caregiving for preschool children with developmental disabilities and maternal health and healthcare use using linked primary care and Born in Bradford birth cohort data. Adjusting for prenatal health, healthcare use and socioeconomic status, mothers who were caregivers were more likely than other mothers to have symptoms of psychological distress (odds ratio 1.24; 95% CI 1.01, 1.53), exhaustion (1.42; 1.12, 1.80) and possibly head and musculoskeletal pain (1.18; 0.97, 1.43). Despite the higher prevalence of symptoms, they did not access healthcare services more and may seek healthcare for psychological distress less often (0.64; 0.40, 1.02). In general, socioeconomic disadvantage was associated with worse health. Pakistani ethnicity (versus white British) and prenatal consultation were strongly associated with higher postnatal consultation rates. Prenatal ill health, healthcare use and socioeconomic status are important factors in the detection of postnatal ill health via primary care services. If caregiver burden and the risk of under-detecting (and thus under treating) caregiver ill health is not addressed during the preschool period health inequalities between caregivers and other mothers and their families may persist and grow. The health of mothers of young disabled children, in particular their unmet health needs, warrants attention in research and clinical practice

Attitudes to E-Cigarettes and Cessation Support for Pregnant Women from English Stop Smoking Services: A Mixed Methods Study

Smoking in pregnancy remains a public health problem. In the UK e-cigarettes are the most popular aid to quitting smoking outside of pregnancy, but we don’t know the extent of e-cigarette use in pregnancy or how English Stop Smoking Services (SSS) respond to pregnant women who vape. In 2015 we surveyed SSS managers about cessation support for pregnant women and responses to clients who vaped. Subsequently we interviewed a sub-sample of managers to seek explanations for the SSS’ position on e-cigarettes; interviews were thematically analysed. Survey response rate was 67.8% (72/106); overall managers reported 2.2% (range 1.4–4.3%) of pregnant clients were using e-cigarettes. Most SSS reported supporting pregnant women who already vaped, but would not recommend e-cigarette use; for women that were still smoking and not using e-cigarettes, 8.3% of SSS were likely/very likely to advise using e-cigarettes, with 56.9% of SSS unlikely/very unlikely to advise using them. Fifteen respondents were interviewed; interviewees were generally positive about the potential of e-cigarettes for cessation in pregnancy although concerns about perceived lack of evidence for safety were expressed and most wanted research on this. Clear guidance on e-cigarette use informed by pregnancy specific research will assist SSS to provide consistent evidence-based support