Refinement and preliminary evaluation of two tablet-based tests of real-world visual function

PURPOSE: To describe, refine, evaluate, and provide normative control data for two freely available tablet-based tests of real-world visual function, using a cohort of young, normally-sighted adults. METHODS: Fifty young (18-40 years), normally-sighted adults completed tablet-based assessments of (1) face discrimination and (2) visual search. Each test was performed twice, to assess test-retest repeatability. Post-hoc analyses were performed to determine the number of trials required to obtain stable estimates of performance. Distributions were fitted to the normative data to determine the 99% population-boundary for normally sighted observers. Participants were also asked to rate their comprehension of each test. RESULTS: Both tests provided stable estimates in around 20 trials (~1-4 min), with only a further reduction of 14%-17% in the 95% Coefficient of Repeatability (CoR95 ) when an additional 40 trials were included. When using only ~20 trials: median durations for the first run of each test were 191 s (Faces) and 51 s (Search); test-retest CoR95 were 0.27 d (Faces) and 0.84 s (Search); and normative 99% population-limits were 3.50 d (Faces) and 3.1 s (Search). No participants exhibited any difficulties completing either test (100% completion rate), and ratings of task-understanding were high (Faces: 9.6 out of 10; Search: 9.7 out of 10). CONCLUSIONS: This preliminary assessment indicated that both tablet-based tests are able to provide simple, quick, and easy-to-administer measures of real-world visual function in normally-sighted young adults. Further work is required to assess their accuracy and utility in older people and individuals with visual impairment. Potential applications are discussed, including their use in clinic waiting rooms, and as an objective complement to Patient Reported Outcome Measures (PROMs)

Refinement and preliminary evaluation of two tablet-based tests of real-world visual function

PURPOSE To describe, refine, evaluate, and provide normative control data for two freely available tablet‐based tests of real‐world visual function, using a cohort of young, normally‐sighted adults. METHODS Fifty young (18–40 years), normally‐sighted adults completed tablet‐based assessments of (1) face discrimination and (2) visual search. Each test was performed twice, to assess test‐retest repeatability. Post‐hoc analyses were performed to determine the number of trials required to obtain stable estimates of performance. Distributions were fitted to the normative data to determine the 99% population‐boundary for normally sighted observers. Participants were also asked to rate their comprehension of each test. RESULTS Both tests provided stable estimates in around 20 trials (~1–4 min), with only a further reduction of 14%–17% in the 95% Coefficient of Repeatability (CoR95) when an additional 40 trials were included. When using only ~20 trials: median durations for the first run of each test were 191 s (Faces) and 51 s (Search); test‐retest CoR95 were 0.27 d (Faces) and 0.84 s (Search); and normative 99% population‐limits were 3.50 d (Faces) and 3.1 s (Search). No participants exhibited any difficulties completing either test (100% completion rate), and ratings of task‐understanding were high (Faces: 9.6 out of 10; Search: 9.7 out of 10). CONCLUSIONS This preliminary assessment indicated that both tablet‐based tests are able to provide simple, quick, and easy‐to‐administer measures of real‐world visual function in normally‐sighted young adults. Further work is required to assess their accuracy and utility in older people and individuals with visual impairment. Potential applications are discussed, including their use in clinic waiting rooms, and as an objective complement to Patient Reported Outcome Measures (PROMs)

Hypertrophy induced KIF5B controls mitochondrial localization and function in neonatal rat cardiomyocytes

AbstractCardiac hypertrophy is associated with growth and functional changes of cardiomyocytes, including mitochondrial alterations, but the latter are still poorly understood. Here we investigated mitochondrial function and dynamic localization in neonatal rat ventricular cardiomyocytes (NRVCs) stimulated with insulin like growth factor 1 (IGF1) or phenylephrine (PE), mimicking physiological and pathological hypertrophic responses, respectively.A decreased activity of the mitochondrial electron transport chain (ETC) (state 3) was observed in permeabilized NRVCs stimulated with PE, whereas this was improved in IGF1 stimulated NRVCs. In contrast, in intact NRVCs, mitochondrial oxygen consumption rate (OCR) was increased in PE stimulated NRVCs, but remained constant in IGF1 stimulated NRVCs. After stimulation with PE, mitochondria were localized to the periphery of the cell. To study the differences in more detail, we performed gene array studies. IGF1 and PE stimulated NRVCs did not reveal major differences in gene expression of mitochondrial encoding proteins, but we identified a gene encoding a motor protein implicated in mitochondrial localization, kinesin family member 5b (Kif5b), which was clearly elevated in PE stimulated NRVCs but not in IGF1 stimulated NRVCs. We confirmed that Kif5b gene and protein expression were elevated in animal models with pathological cardiac hypertrophy. Silencing of Kif5b reverted the peripheral mitochondrial localization in PE stimulated NRVCs and diminished PE induced increases in mitochondrial OCR, indicating that KIF5B dependent localization affects cellular responses to PE stimulated NRVCs.These results indicate that KIF5B contributes to mitochondrial localization and function in cardiomyocytes and may play a role in pathological hypertrophic responses in vivo

The social gradient in adolescent mental health: mediated or moderated by belief in a just world?

PURPOSE: A social gradient in adolescent mental health exists: adolescents with higher socioeconomic status (SES) have fewer mental health problems than their peers with lower SES. Little is known about whether adolescents' societal beliefs play a role in this social gradient. Belief in a just world (BJW) may be a mediator or moderator of the social gradient in adolescent mental health. METHODS: Using data from 848 adolescents (Mage = 17) in the Netherlands, path analyses examined whether two indicators of BJW (general and personal) mediated or moderated the associations between two indicators of SES (family affluence and perceived family wealth), and four indicators of adolescent mental health problems (emotional symptoms, conduct problems, hyperactivity, and peer problems). RESULTS: Adolescents with lower family affluence and lower perceived family wealth reported more emotional symptoms, and the association between perceived family wealth and emotional symptoms was mediated by lower personal and general BJW. Furthermore, higher personal BJW amplified the negative association between SES and peer problems. CONCLUSION: This study suggests BJW may both mediate and amplify the social gradient in adolescent mental health. Adolescents' beliefs about society may be important to include in research aimed at understanding this social gradient

In EXOG-depleted cardiomyocytes cell death is marked by a decreased mitochondrial reserve capacity of the electron transport chain

Depletion ofmitochondrial endo/exonuclease G-like (EXOG) in cultured neonatal cardiomyocytes stimulates mitochondrial oxygen consumption rate (OCR) and induces hypertrophy via reactive oxygen species (ROS). Here, we show that neurohormonal stress triggers cell death in endo/exonuclease G-like-depleted cells, and this is marked by a decrease in mitochondrial reserve capacity. Neurohormonal stimulation with phenylephrine (PE) did not have an additive effect on the hypertrophic response induced by endo/exonuclease G-like depletion. Interestingly, PE-induced atrial natriuretic peptide (ANP) gene expression was completely abolished in endo/exonuclease G-like-depleted cells, suggesting a reverse signaling function of endo/exonuclease G-like. Endo/exonuclease G-like depletion initially resulted in increased mitochondrial OCR, but this declined upon PE stimulation. In particular, the reserve capacity of the mitochondrial respiratory chain and maximal respiration were the first indicators of perturbations in mitochondrial respiration, and these marked the subsequent decline in mitochondrial function. Although pathological stimulation accelerated these processes, prolonged EXOG depletion also resulted in a decline in mitochondrial function. At early stages of endo/exonuclease G-like depletion, mitochondrial ROS production was increased, but this did not affect mitochondrial DNA (mtDNA) integrity. After prolonged depletion, ROS levels returned to control values, despite hyperpolarization of the mitochondrial membrane. The mitochondrial dysfunction finally resulted in cell death, which appears to be mainly a form of necrosis. In conclusion, endo/exonuclease G-like plays an essential role in cardiomyocyte physiology. Loss of endo/exonuclease G-like results in diminished adaptation to pathological stress. The decline in maximal respiration and reserve capacity is the first sign of mitochondrial dysfunction that determines subsequent cell death

Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids

Rationale: Evidence suggests that the gut microbiome is involved in the development of cardiovascular disease, with the host–microbe interaction regulating immune and metabolic pathways. However, there was no firm evidence for associations between microbiota and metabolic risk factors for cardiovascular disease from large-scale studies in humans. In particular, there was no strong evidence for association between cardiovascular disease and aberrant blood lipid levels. Objectives: To identify intestinal bacteria taxa, whose proportions correlate with body mass index and lipid levels, and to determine whether lipid variance can be explained by microbiota relative to age, sex, and host genetics. Methods and Results: We studied 893 subjects from the LifeLines-DEEP population cohort. After correcting for age and sex, we identified 34 bacterial taxa associated with body mass index and blood lipids; most are novel associations. Cross-validation analysis revealed that microbiota explain 4.5% of the variance in body mass index, 6% in triglycerides, and 4% in high-density lipoproteins, independent of age, sex, and genetic risk factors. A novel risk model, including the gut microbiome explained ≤25.9% of high-density lipoprotein variance, significantly outperforming the risk model without microbiome. Strikingly, the microbiome had little effect on low-density lipoproteins or total cholesterol. Conclusions: Our studies suggest that the gut microbiome may play an important role in the variation in body mass index and blood lipid levels, independent of age, sex, and host genetics. Our findings support the potential of therapies altering the gut microbiome to control body mass, triglycerides, and high-density lipoproteins