Categorical perception and influence of attention on neural consistency in response to speech sounds in adults with dyslexia.

Developmental dyslexia is a common neurodevelopmental disorder that is associated with alterations in the behavioral and neural processing of speech sounds, but the scope and nature of that association is uncertain. It has been proposed that more variable auditory processing could underlie some of the core deficits in this disorder. In the current study, magnetoencephalography (MEG) data were acquired from adults with and without dyslexia while they passively listened to or actively categorized tokens from a /ba/-/da/ consonant continuum. We observed no significant group difference in active categorical perception of this continuum in either of our two behavioral assessments. During passive listening, adults with dyslexia exhibited neural responses that were as consistent as those of typically reading adults in six cortical regions associated with auditory perception, language, and reading. However, they exhibited significantly less consistency in the left supramarginal gyrus, where greater inconsistency correlated significantly with worse decoding skills in the group with dyslexia. The group difference in the left supramarginal gyrus was evident only when neural data were binned with a high temporal resolution and was only significant during the passive condition. Interestingly, consistency significantly improved in both groups during active categorization versus passive listening. These findings suggest that adults with dyslexia exhibit typical levels of neural consistency in response to speech sounds with the exception of the left supramarginal gyrus and that this consistency increases during active versus passive perception of speech sounds similarly in the two groups.

Induction of specific brain oscillations may restore neural circuits and be used for the treatment of Alzheimer's disease.

Brain oscillations underlie the function of our brains, dictating how we both think and react to the world around us. The synchronous activity of neurons generates these rhythms, which allow different parts of the brain to communicate and orchestrate responses to internal and external stimuli. Perturbations of cognitive rhythms and the underlying oscillator neurons that synchronize different parts of the brain contribute to the pathophysiology of diseases including Alzheimer's disease, (AD), Parkinson's disease (PD), epilepsy and other diseases of rhythm that have been studied extensively by Gyorgy Buzsaki. In this review, we discuss how neurologists manipulate brain oscillations with neuromodulation to treat diseases and how this can be leveraged to improve cognition and pathology underlying AD. While multiple modalities of neuromodulation are currently clinically indicated for some disorders, nothing is yet approved for improving memory in AD. Recent investigations into novel methods of neuromodulation show potential for improving cognition in memory disorders. Here, we demonstrate that neuronal stimulation using audiovisual sensory stimulation that generated 40-HZ gamma waves reduced AD-specific pathology and improved performance in behavioural tests in mouse models of AD, making this new mode of neuromodulation a promising new avenue for developing a new therapeutic intervention for the treatment of dementia.

A simple, rapid, interpretable, actionable and implementable digital PCR based mortality index.

Mortality assessments are conducted for both civil and commercial purposes. Recent advances in epigenetics have resulted in DNA methylation tools to assess risk and aid in this task. However, widely available array-based algorithms are not readily translatable into clinical tools and do not provide a good foundation for clinical recommendations. Further, recent work shows evidence of heritability and possible racial bias in these indices. Using a publicly available array data set, the Framingham Heart Study (FHS), we develop and test a five-locus mortality-risk algorithm using only previously validated methylation biomarkers that have been shown to be free of racial bias, and that provide specific assessments of smoking, alcohol consumption, diabetes and heart disease. We show that a model using age, sex and methylation measurements at these five loci outperforms the 513 probe Levine index and approximates the predictive power of the 1030 probe GrimAge index. We then show each of the five loci in our algorithm can be assessed using a more powerful, reference-free digital PCR approach, further demonstrating that it is readily clinically translatable. Finally, we show the loci do not reflect ethnically specific variation. We conclude that this algorithm is a simple, yet powerful tool for assessing mortality risk. We further suggest that the output from this or similarly derived algorithms using either array or digital PCR can be used to provide powerful feedback to patients, guide recommendations for additional medical assessments, and help monitor the effect of public health prevention interventions.

Distinct neural substrates of individual differences in components of reading comprehension in adults with or without dyslexia.

Reading comprehension is a complex task that depends on multiple cognitive and linguistic processes. According to the updated Simple View of Reading framework, in adults, individual variation in reading comprehension can be largely explained by combined variance in three component abilities: (1) decoding accuracy, (2) fluency, and (3) language comprehension. Here we asked whether the neural correlates of the three components are different in adults with dyslexia as compared to typically-reading adults and whether the relative contribution of these correlates to reading comprehension is similar in the two groups. We employed a novel naturalistic fMRI reading task to identify the neural correlates of individual differences in the three components using whole-brain and literature-driven regions-of-interest approaches. Across all participants, as predicted by the Simple View framework, we found distinct patterns of associations with linguistic and domain-general regions for the three components, and that the left-hemispheric neural correlates of language comprehension in the angular and posterior temporal gyri made the largest contributions to explaining out-of-scanner reading comprehension performance. These patterns differed between the two groups. In typical adult readers, better fluency was associated with greater activation of left occipitotemporal regions, better comprehension with lesser activation in prefrontal and posterior parietal regions, and there were no significant associations with decoding. In adults with dyslexia, better fluency was associated with greater activation of bilateral inferior parietal regions, better comprehension was associated with greater activation in some prefrontal clusters and lower in others, and better decoding skills were associated with lesser activation of bilateral prefrontal and posterior parietal regions. Extending the behavioral findings of skill-level differences in the relative contribution of the three components to reading comprehension, the relative contributions of the neural correlates to reading comprehension differed based on dyslexia status. These findings reveal some of the neural correlates of individual differences in the three components and the underlying mechanisms of reading comprehension deficits in adults with dyslexia.

Impact of patient decision aids on appropriate and timely access to hip or knee arthroplasty for osteoarthritis: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of patient decision aids (PtDA) compared to usual education on appropriate and timely access to total joint arthroplasty in patients with osteoarthritis. METHOD: A randomized controlled trial (RCT) with patients undergoing orthopedic screening. Control and intervention arms received usual education; intervention arm also received a PtDA and a surgeon preference report. Wait times (primary outcome) were described using stratified Kaplan-Meier survival curves with patients censored at the time of death or loss to follow-up, and multivariable Cox proportional hazards regression. Secondary outcomes were compared using stratified Cochran-Mantel-Haenszel chi-squared tests. RESULTS: 343 patients were randomized to intervention (n = 174) or control (n = 169). The typical patient was 66 years old, retired, living with someone, and 51% had high school education or less. The intervention was associated with a trend towards reduction in wait time (hazard ratio (HR) 1.25, 95% confidence interval (CI) 0.99-1.60, P = 0.0653). Median wait times were 3 weeks shorter in intervention than in control at the community site with no difference at the academic site. Good decision quality was reached by 56.1% intervention and 44.5% control (Relative risk (RR) 1.25; 95% CI 1.00-1.56, P = 0.050). Surgery rates were 73.2% intervention and 80.5% controls (RR 0.91: 95% CI 0.81-1.03) with 12 intervention (7.3%) and eight control participants (4.9%) returning to have surgery within 2 years (P = 0.791). CONCLUSION: Compared to controls, decision aid recipients had shorter wait times at one site, fewer surgeries, and were more likely to reach good decision quality, but overall effect was not statistically significant. TRIALS REGISTRATION: The full trial protocol is available at ClinicalTrials.Gov (NCT00911638).

Application of low-background gamma-ray spectrometry to monitor radioactivity in the environment and food.

The results are described of an upgrade of the low-background gamma-ray spectrometry laboratory at New York State Department of Health by acquiring sensitivity to low-energy gamma rays. Tuning of the spectrometer and its low-energy response characteristics are described. The spectrometer has been applied to monitor the environment by measuring aerosols and water in New York State contaminated by the 2011 Fukushima accident plume. In addition, the spectrometer has been used to monitor radioactivity in food by performing a study of cesium in Florida milk.

A cross-platform genome-wide comparison of the relationship of promoter DNA methylation to gene expression.

Peripheral mononuclear cell preparations are commonly used as proxies for other tissues in studies of the role of gene expression and methylation in human disease. Whether changes in peripheral DNA methylation are associated with changes in peripheral blood or brain gene expression is not clear. In order to test the former hypothesis and determine which genome-wide methylation platform was most suitable for our studies of peripheral blood cells, we compared the results from two commercially available genome-wide methylation arrays with respect to genome-wide gene expression using lymphoblast DNA and RNA from eight individuals at the promoters of 5619 genes. We found that methylation signatures at these gene promoters were significantly correlated with one another across platforms and with genome-wide gene expression, but the extent of that relationship is dependent on choice of platform and degree of methylation. Taken in context with data from other studies, these data demonstrate that peripheral blood cell methylation is associated with gene expression and that further studies to clarify the extent of this relationship, and the relationship between central and peripheral DNA methylation are in order.

Snail is a repressor of RKIP transcription in metastatic prostate cancer cells.

Diminished expression of the metastasis suppressor protein RKIP was previously reported in a number of cancers. The underlying mechanism remains unknown. Here, we show that the expression of RKIP negatively correlates with that of Snail zinc-transcriptional repressor, a key modulator of normal and neoplastic epithelial-mesenchymal transition (EMT) program. With a combination of loss-of-function and gain-of-function approaches, we showed that Snail repressed the expression of RKIP in metastatic prostate cancer cell lines. The effect of Snail on RKIP was on the level of transcriptional initiation and mediated by a proximal E-box on the RKIP promoter. Our results therefore suggest that RKIP is a novel component of the Snail transcriptional regulatory network important for the progression and metastasis of cancer.

The 5' Third of Cauliflower mosaic virus Gene VI Conditions Resistance Breakage in Arabidopsis Ecotype Tsu-0.

ABSTRACT Arabidopsis thaliana ecotypes vary in their responses to viruses. In this study, we analyzed the variation in response of A. thaliana ecotype Tsu-0 to Cauliflower mosaic virus (CaMV). This ecotype was previously reported to be resistant to two CaMV isolates (CM1841 and CM4-184), but susceptible to W260. In this study, we show that Tsu-0 is resistant to four additional CaMV isolates. CaMV propagated within the rosette leaves of Tsu-0 plants, but did not appear to spread systemically into the inflorescence. However, virus viability in rosette leaves of Tsu-0 plants apparently was not compromised because infectious CaMV could be recovered from these organs. W260 overcomes Tsu-0 resistance by a passive mechanism (i.e., this virus avoids activating plant defenses). The portion of the viral genome responsible for W260 resistance breakage was mapped to the 5' third of gene VI, which we have termed RBR-1. This region is also responsible for controlling the ability of CaMV to infect different types of solanaceous plants. Hence, the pathways by which plants of different families interact with CaMV may be conserved through evolution.

Disease status in African American single mothers with HIV: the role of depressive symptoms.

The association between depressive symptoms and 2 measures of HIV disease status in 73 African American single mothers was examined. Hierarchical multiple regression analyses revealed that clinician-rated depressive symptoms predicted subjective, but not objective, parameters of disease status 12 to 14 months later. More symptoms of depression at the 1st assessment predicted an increase in physical complaints over the course of the study. Results suggest that researchers and clinicians interested in enhancing quality of life among African American single mothers with HIV infection, an understudied population within the HIV-AIDS literature, should consider both subjective and objective measures of the disease.

Task independence, safety, and adequacy among nondisabled and osteoarthritis-disabled older women.

OBJECTIVE: To examine the constructs of task independence, safety, and adequacy. METHOD: Fifty-seven nondisabled (ND) and 56 osteoarthritis-disabled (OAK) women were observed performing daily tasks. RESULTS: Intercorrelations among the constructs of independence and adequacy were uniformly high, while the relationship of safety to these constructs was moderate and more variable, although stronger in the OAK group. Task performance of the OAK group was consistently less adequate and independent than that of the ND group; however, the groups were generally equivalent in safety. For individual tasks, adequacy best differentiated between the groups. In both groups, those who performed independently also performed safely, but fewer independent OAK participants also performed totally adequately. CONCLUSION: The majority of older women who perform tasks independently also perform them safely and adequately; for a clinically significant minority, independence is not always synonymous with safe and adequate performance. Patients may be placed at risk if independence is the only construct used to determine disability.

HIV infection and depressive symptoms: an investigation of African American single mothers.

Risk for depressive symptoms among HIV-infected African American single mothers (n = 96), relative to demographically matched non-infected single mothers (n = 120), was examined, using both self-report and clinician-rated scales of depression. Assessment of depressive symptoms occurred at two points separated by one year. Findings revealed that HIV-infected mothers were at greater risk for depressive symptoms at both assessments, regardless of method of assessment. Moreover, HIV-infected mothers remained at greater risk when analyses were limited to cognitive and affective symptoms of depression, decreasing the likelihood that the difference between the two groups was due to greater endorsement of somatic symptoms of depression by the HIV-infected group.

Involvement in caregiving and adjustment to death of a spouse: findings from the caregiver health effects study.

CONTEXT: Most deaths in the United States occur among older persons who have 1 or more disabling conditions. As a result, many deaths are preceded by an extended period during which family members provide care to their disabled relative. OBJECTIVE: To better understand the effect of bereavement on family caregivers by examining predeath vs postdeath changes in self-reported and objective health outcomes among elderly persons providing varying levels of care prior to their spouse's death. DESIGN AND SETTING: Prospective, population-based cohort study conducted in 4 US communities between 1993 and 1998. PARTICIPANTS: One hundred twenty-nine individuals aged 66 to 96 years whose spouse died during an average 4-year follow-up. Individuals were classified as noncaregivers (n = 40), caregivers who reported no strain (n = 37), or strained caregivers (n = 52). MAIN OUTCOME MEASURES: Changes in depression symptoms (assessed by the 10-item Center for Epidemiological Studies-Depression [CES-D] scale), antidepressant medication use, 6 health risk behaviors, and weight among the 3 groups of participants. RESULTS: Controlling for age, sex, race, education, prevalent cardiovascular disease at baseline, and interval between predeath and postdeath assessments, CES-D scores remained high but did not change among strained caregivers (9.44 vs 9.19; P =.76), while these scores increased for both noncaregivers (4.74 vs 8.25; F(1,116) = 14.33; P<.001) and nonstrained caregivers (4.94 vs 7.13; F(1,116) = 4.35; P =.04). Noncaregivers were significantly more likely to be using nontricyclic antidepressant medications following the death than the nonstrained caregiver group (odds ratio [OR], 12.85; 95% confidence interval [CI], 1.02-162.13; P =.05). The strained caregiver group experienced significant improvement in health risk behaviors following the death of their spouse (1.47 vs 0.66 behaviors; F(1,118) = 20.23; P<.001), while the noncaregiver and nonstrained caregiver groups showed little change (0.27 vs 0.27 [P =.99] and 0.46 vs 0.27 [P =.39] behaviors, respectively). Noncaregivers experienced significant weight loss following the death (149.1 vs 145.3 lb [67.1 vs 65.4 kg]; F(1,101) = 8.12; P =.005), while the strained and nonstrained caregiving groups did not show significant weight change (156.2 vs 155.2 lb [70.3 vs 69.8 kg] [P =.41] and 156.2 vs 154.0 lb [70.3 vs 69.3 kg] [P =.12], respectively). CONCLUSIONS: These data indicate that the impact of losing one's spouse among older persons varies as a function of the caregiving experiences that precede the death. Among individuals who are already strained prior to the death of their spouse, the death itself does not increase their level of distress. Instead, they show reductions in health risk behaviors. Among noncaregivers, losing one's spouse results in increased depression and weight loss.

Attributions in marriage: examining the entailment model in dyadic context.

The entailment model of attributions is examined for the first time using a dyadic approach and longitudinal data. In a sample of 229 married partners with children, causal attributions were distinguished empirically from responsibility attributions and, consistent with the entailment model, the effect of causal attributions on conflict was mediated through attributions of responsibility. Only 1 path was influenced by spouse gender. Examination of cross-spouse effects revealed significant effects and provided a better fit than a model with no cross-spouse effects. The importance of including cross-spouse effects in attributional models is discussed.

Maternal and paternal parenting during adolescence: forecasting early adult psychosocial adjustment.

This study investigated the relationship of maternal and paternal parenting behavior (acceptance and firm control) during adolescence to four domains of early adult functioning (internalizing problems, externalizing problems, prosocial competence, and cognitive competence). Twenty-one females and 29 males from intact families, along with their mothers and fathers, participated. Assessments were conducted in adolescence and early adulthood, separated by approximately five and one-half years. Higher levels of maternal firm control during adolescence were associated with more secure early adult romantic attachment and lower levels of educational achievement. There were no main effects for fathers, but paternal parenting behavior interacted with maternal parenting behavior to predict both early adult romantic attachment and delinquency. Clinical implications and directions for future research are discussed.

Individual and crossover effects of stress on adjustment in medical student marriages.

High-stress individuals may benefit from social support, although their support providers may be adversely affected via stress crossover effects. Individual and crossover effects of perceived stress within medical student marriages (n = 30) were investigated. Perceived spousal support was positively associated with individuals' own marital and emotional adjustment, attenuating stress effects. With regard to crossover effects, medical students' perceived stress was significantly associated with their spouses' emotional adjustment. Further, medical students' own emotional adjustment fully mediated this crossover effect. Results suggest that the contagion of negative affect may serve as a key mechanism through which stress crossover effects operate in marriage.

The nature and correlates of underachievement among elementary schoolchildren in Hong Kong.

This study investigated for the first time several characteristics of underachievement in a large sample of Hong Kong elementary schoolchildren. More males were identified as underachievers than females, but the ratio was substantially less than the two-to-one rate typically found in the American literature. The stability and persistence of underachievement increased during the elementary school years, and the stability of underachievement tended to be higher in subject matter that was relatively more difficult, which varied with gender. Underachievement became more specific to particular academic subjects rather than more general across the elementary grades. Parents and teachers, but not the children themselves, perceived that underachievers were more capable than same-grade nonunderachievers (who score lower on ability tests), although this awareness is more likely directed at male than female underachievers, which has been observed in other samples. In grades 1-4, teachers provided extra mentoring, communications, and support to underachievers. Thereafter, underachievers became more disruptive, impatient, and aggressive in school and perhaps at home. At that point, teachers became less supportive, offered less extra mentoring, and applied greater behavioral control over underachievers. Underachieving children also perceived that their parents became less supportive and used more discipline in grades 5-6 relative to grades 3-4. These correlates of underachievement suggests the existence of a syndrome of underachievement that separates underachievers from children who have the same grades but lower mental ability.

Negative and positive health effects of caring for a disabled spouse: longitudinal findings from the caregiver health effects study.

Data from the first 2 waves of the Caregiver Health Effects Study (n = 680) were analyzed to examine the effects of changes in caregiving involvement on changes in caregiver health-related outcomes in a population-based sample of elders caring for a disabled spouse. Caregiving involvement was indexed by levels of (a) spouse physical impairment, (b) help provided to the spouse, and (c) strain associated with providing help. Health-related outcomes included perceived health, health-risk behaviors, anxiety symptoms, and depression symptoms. Increases in spouse impairment and caregiver strain were generally related to poorer outcomes over time (poorer perceived health, increased health-risk behaviors, and increased anxiety and depression), whereas increased helping was related to better outcomes (decreased anxiety and depression). Results suggest that caring for a disabled spouse is a complex phenomenon that can have both deleterious and beneficial consequences.

Association between depression and mortality in older adults: the Cardiovascular Health Study.

BACKGROUND: Studies of the association between depressive symptoms and mortality in elderly populations have yielded contradictory findings. To address these discrepancies, we test this association using the most extensive array of sociodemographic and physical health control variables ever studied, to our knowledge, in a large population-based sample of elderly individuals. OBJECTIVE: To examine the relation between baseline depressive symptoms and 6-year all-cause mortality in older persons, systematically controlling for sociodemographic factors, clinical disease, subclinical disease, and health risk factors. METHODS: A total of 5201 men and women aged 65 years and older from 4 US communities participated in the study. Depressive symptoms and 4 categories of covariates were assessed at baseline. The primary outcome measure was 6-year mortality. RESULTS: Of the 5201 participants, 984 (18.9%) died within 6 years. High baseline depressive symptoms were associated with a higher mortality rate (23.9%) than low baseline depression scores (17.7%) (unadjusted relative risk [RR], 1.41; 95% confidence interval [CI], 1.22-1.63). Depression was also an independent predictor of mortality when controlling for sociodemographic factors (RR, 1.43; 95% CI, 1.23-1.66), prevalent clinical disease (RR, 1.25; 95% CI, 1.07-1.45), subclinical disease indicators (RR, 1.35; 95% CI, 1.15-1.58), or biological or behavioral risk factors (RR, 1.42; 95% CI, 1.22-1.65). When the best predictors from all 4 classes of variables were included as covariates, high depressive symptoms remained an independent predictor of mortality (RR, 1.24; 95% CI, 1.06-1.46). CONCLUSIONS: High levels of depressive symptoms are an independent risk factor for mortality in community-residing older adults. Motivational depletion may be a key underlying mechanism for the depression-mortality effect.