Intermittent enzyme replacement therapy with recombinant human ß-galactosidase prevents neuraminidase 1 deficiency

Mutations in the galactosidase ß 1 (GLB1) gene cause lysosomal ß-galactosidase (ß-Gal) deficiency and clinical onset of the neurodegenerative lysosomal storage disease, GM1 gangliosidosis. ß-Gal and neuraminidase 1 (NEU1) form a multienzyme complex in lysosomes along with the molecular chaperone, protective protein cathepsin A (PPCA). NEU1 is deficient in the neurodegenerative lysosomal storage disease sialidosis, and its targeting to and stability in lysosomes strictly depend on PPCA. In contrast, ß-Gal only partially depends on PPCA, prompting us to investigate the role that ß-Gal plays in the multienzyme complex. Here, we demonstrate that ß-Gal negatively regulates NEU1 levels in lysosomes by competitively displacing this labile sialidase from PPCA. Chronic cellular uptake of purified recombinant human ß-Gal (rhß-Gal) or chronic lentiviral-mediated GLB1 overexpression in GM1 gangliosidosis patient fibroblasts coincides with profound secondary NEU1 deficiency. A regimen of intermittent enzyme replacement therapy dosing with rhß-Gal, followed by enzyme withdrawal, is sufficient to augment ß-Gal activity levels in GM1 gangliosidosis patient fibroblasts without promoting NEU1 deficiency. In the absence of ß-Gal, NEU1 levels are elevated in the GM1 gangliosidosis mouse brain, which are restored to normal levels following weekly intracerebroventricular dosing with rhß-Gal. Collectively, our results highlight the need to carefully titrate the dose and dosing frequency of ß-Gal augmentation therapy for GM1 gangliosidosis. They further suggest that intermittent intracerebroventricular enzyme replacement therapy dosing with rhß-Gal is a tunable approach that can safely augment ß-Gal levels while maintaining NEU1 at physiological levels in the GM1 gangliosidosis brain.

Exploring the Social Capital of Adolescents Who Are Deaf or Hard of Hearing and Their Parents: A Preliminary Investigation.

The study explored the social capital of Australian adolescents who were deaf or hard of hearing (DHH) and their parents, and investigated the relationship between social capital and individual characteristics, language, literacy, and psychosocial outcomes. Sixteen adolescents (ages 11-14 years) and 24 parents enrolled in the Longitudinal Outcomes of Children with Hearing Impairment (LOCHI) study completed an online questionnaire on social capital and psychosocial outcomes. Information about demographics, language, and literacy was retrieved from the LOCHI study database. On average, parent-rated social capital was positively related to adolescent-rated social capital, but not to child outcomes. Aspects of adolescent-reported social capital were significantly related to the adolescents' language and reading skills, but not to psychosocial outcomes. This study gives support to the promotion of social capital in adolescents who are DHH and their families, and considers how social capital promotion could be applied in interventions.

Psychosocial development of 5-year-old children with hearing loss: Risks and protective factors.

OBJECTIVE: The aims of this paper were to report on the global psychosocial functioning of 5-year-old DHH children and examine the risk and protective factors that predict outcomes. DESIGN: A cross-sectional analysis of data collected from a prospective, population-based longitudinal study. STUDY SAMPLE: Parents/caregivers of 356 children completed questionnaires on psychosocial development (CDI, SDQ), functional communication (PEACH) and demographic information. Children completed standardized assessments of non-verbal cognitive ability (WNV) and language (PLS-4). RESULTS: On average, global psychosocial functioning was within the range of typically developing children; however, variability was high and 12% of children had scores that were more than 2 SDs below the norm. Non-verbal cognitive ability, presence of additional disabilities, language and functional communication significantly predicted outcomes. In contrast, type of hearing device, severity of hearing loss and age at intervention did not. CONCLUSION: The global psychosocial functioning of this cohort of 5-year-old DHH children fell within the range of typically developing children. The findings suggest that spoken language ability and functional communication skills are vital for healthy psychosocial development.

Psychosocial Development in 5-Year-Old Children With Hearing Loss Using Hearing Aids or Cochlear Implants.

This article reports on the psychosocial development and factors influencing outcomes of 5-year-old children with cochlear implants (CIs) or hearing aids (HAs). It further examines differences between children with CIs and HAs with similar levels of hearing loss. Data were collected as part of the Longitudinal Outcomes of Children with Hearing Impairment study-a prospective, population-based study. Parents/caregivers of children completed the Strengths and Difficulties Questionnaire ( n = 333), the Social Skills subscale from the Child Development Inventory ( n = 317), and questionnaires on functional auditory behavior (Parents' Evaluation of Aural/oral performance of Children), and demographics. Children completed assessments of nonverbal cognitive ability (Wechsler Non-verbal Scale of Ability) and language (Preschool Language Scale - fourth edition). On average, parent-rated Strengths and Difficulties Questionnaire scores on emotional or behavioral difficulties were within 1 SD of the normative mean; however, Child Development Inventory scores on social skills were more than 1 SD below the norm. Children with severe-to-profound hearing losses using HAs had significantly more behavioral problems than children with CIs. Regression analyses showed that non-verbal cognitive ability, language, and functional auditory behavior were significantly associated with psychosocial outcomes for children with HAs, whereas outcomes for children with CIs were associated with functional auditory behavior and the presence of additional disabilities. Age at hearing intervention, severity of hearing loss, and communication mode were not associated with outcomes. The results suggest that even children who develop good language ability with the help of a HA or CI may have psychosocial problems if they exhibit difficulties with listening and communicating in everyday environments. The findings have implications for developing interventions for young children with hearing loss.

Can personality close the intention-behavior gap for healthy eating? An examination with the HEXACO personality traits.

The aim of this study was to investigate the predictive and moderating effects of HEXACO personality factors, in addition to theory of planned behavior (TPB) variables, on fruit and vegetable consumption. American college students (N = 1036) from 24 institutions were administered the TPB, HEXACO and a self-reported fruit and vegetable consumption measure. The TPB predicted 11-17% of variance in fruit and vegetable consumption, with greater variance accounted for in healthy weight compared to overweight individuals. Personality did not significantly improve the prediction of behavior above TPB constructs; however, conscientiousness was a significant incremental predictor of intention in both healthy weight and overweight/obese groups. While support was found for the TPB as an important predictor of fruit and vegetable consumption in students, little support was found for personality factors. Such findings have implications for interventions designed to target students at risk of chronic disease.

Visual field asymmetries in object individuation.

Repetition blindness (RB) is a failure to detect both instances of two identical stimuli presented in close temporal proximity. It is due to an inability to form separate episodic tokens for a repeated stimulus, resulting in a single conscious representation. In three experiments, participants identified two targets presented simultaneously in different spatial locations. These stimuli were either the same or different. In two experiments the targets occurred on either side of fixation, and in a third experiment both were in the same hemifield. In all experiments, RB was more pronounced for stimuli in the right hemifield. In addition, there was a left hemifield advantage for both repeated and non-repeated stimuli when the two stimuli occurred in opposite visual fields and, thus, were processed by different hemispheres. These findings suggest that the right hemisphere plays a dominant role in attentional selection and in creating conscious representations of visual events.

An examination of the demographic predictors of adolescent breakfast consumption, content, and context.

BACKGROUND: Breakfast consumption is important to health; however, adolescents often skip breakfast, and an increased understanding of the breakfast consumption patterns of adolescents is needed. The purpose of this study was to identify the predictors of breakfast eating, including the content and context, in an adolescent sample from Australia and England. METHODS: Four-hundred and eighty-one students completed an online questionnaire measuring breakfast skipping, and breakfast content (what was eaten) and context (who they ate with, involvement in preparation). Logistic regression was conducted to investigate the predictors of skipping breakfast, breakfast context, and consumption of the ten most commonly consumed foods. Chi-square analyses were used to examine differences in breakfast content according to context. RESULTS: Most students (88%) had consumed breakfast on the day of the survey; breakfast skipping was more common in England (18%) than in Australia (8%). Country, gender, socioeconomic status, and body mass index (BMI) were all predictors of breakfast content and context. Whether adolescents ate with others and/or were involved in breakfast preparation predicted the content of breakfast consumed. CONCLUSIONS: This study provides a comprehensive examination of the factors underlying breakfast consumption (content and context) and has important implications for the development of evidence-based interventions to improve rates of breakfast consumption and the quality of food consumed amongst adolescents.

Predicting adolescent breakfast consumption in the UK and Australia using an extended theory of planned behaviour.

The aim of this study was to investigate whether the theory of planned behaviour (TPB) with the addition of risk awareness could predict breakfast consumption in a sample of adolescents from the UK and Australia. It was hypothesised that the TPB variables of attitudes, subjective norm and perceived behavioural control (PBC) would significantly predict intentions, and that inclusion of risk perception would increase the proportion of variance explained. Secondly it was hypothesised that intention and PBC would predict behaviour. Participants were recruited from secondary schools in Australia and the UK. A total of 613 participants completed the study (448 females, 165 males; mean=14years ±1.1). The TPB predicted 42.2% of the variance in intentions to eat breakfast. All variables significantly predicted intention with PBC as the strongest component. The addition of risk made a small but significant contribution to the prediction of intention. Together intention and PBC predicted 57.8% of the variance in breakfast consumption.

The function of the anterior temporal lobe: a review of the empirical evidence.

Recent work on the anterior temporal lobe (ATL) has lead to substantively different theoretical branches, of its putative functions, that have in some part developed independently of one another. The ATL has dense connectivity with a number of sensory modalities. This has resulted in empirical evidence that supports different functionality dependent upon the variables under investigation. The main bodies of evidence have implicated the ATL as a domain-general semantic hub, whilst other evidence points to a domain-specific role in social or 'person-related' processing. A third body of evidence suggests that the ATLs underlie processing of unique entities. Primarily, research of the ATL has been based on lesion studies and from clinical populations such as semantic dementia or temporal lobe epilepsy patients. Although important, this neuropsychological evidence has a number of confounds, therefore techniques such as functional neuroimaging on healthy participants and the relatively novel use of non-invasive brain stimulation may be more useful to isolate specific variables that can discriminate between these different theories concerning 'normal' function. This review focuses on these latter types of studies and considers the empirical evidence for each perspective. The overall literature is integrated in an attempt to formulate a unifying theory and the functional sub-regions within the ATL are explored. It is concluded that a holistic integration of the theories is feasible in that the ATLs could process domain-general semantic knowledge but with a bias towards social information or stimuli that is personally relevant. Thus, it may be the importance of social/emotional information that gives it priority of processing in the ATL not an inherent property of the structure itself.

Evidence for a social function of the anterior temporal lobes: low-frequency rTMS reduces implicit gender stereotypes.

By nature, stereotypes require processes of categorization or semantic association, including social information about groups of people. There is empirical evidence that the anterior temporal lobe (ATL) processes domain-general semantic information, and supports social knowledge. A recent study showed that inhibitory repetitive transcranial magnetic stimulation (rTMS) to the ATL reduced racial stereotypes on an implicit association test (IAT). However, it was not determined whether this was caused by changes to specific social, or general semantic processing, or both. The current study addresses these theoretical issues. The design investigated the effect of rTMS to the left or right ATL, or a sham stimulation, on a social IAT (gender stereotypes), a non-social IAT (living versus non-living associations), and a non-semantic control (Stroop) task. The results showed that low-frequency rTMS to both left and right ATL significantly reduced D-scores on the gender IAT compared to the sham group; however, there were no differences on the non-social IAT or the Stroop. The findings show the ATL has a role in mediating stereotypes, and the decrease of bias after stimulation could be due to weakening of social stereotypical associations either within the ATL or via a network of brain regions connected with the ATL.

The role of executive function in bridging the intention-behaviour gap for binge-drinking in university students.

BACKGROUND: Alcohol consumption contributes to a significant proportion of disease and the high prevalence amongst young adults is a worldwide health concern. PURPOSE: To determine which aspects of executive function (EF) distinguish binge-drinkers from non binge-drinkers and to establish the role of EF in predicting behaviour. METHODS: Self-report questionnaires, four tests of self-regulation and a behaviour measure were administered to 153 students. RESULTS: The Theory of Planned Behaviour model was significant in predicting both intentions and behaviour. Although binge-drinkers and non binge-drinkers were found to differ on three of the four measures of EF, none predicted additional variance in behaviour. Planning ability and inhibition control moderated the relationship between intention and behaviour such that for individuals who intended to binge-drink, those with high planning ability or high inhibitory control were more likely to avoid doing so. CONCLUSIONS: Interventions targeting binge-drinking behaviour should aim to develop planning skills and inhibitory control.

Noninvasive brain stimulation reduces prejudice scores on an implicit association test.

OBJECTIVE: Inhibiting the anterior temporal lobe (ATL) via repetitive transcranial magnetic stimulation (rTMS) appears to have deleterious effects on people's semantic conceptualization, and left ATL damage is associated with semantic dementia. However, little research has investigated whether rTMS can inhibit conceptual schemata that have potentially negative consequences. Our aim was to investigate whether rTMS to the ATLs could reduce scores on a standard measure of prejudice (implicit association test, IAT). METHOD: Forty (17 female; mean age 20.6) neurologically normal, right-handed undergraduates participated. Participants were randomly allocated into one of four rTMS stimulation conditions-left ATL, right ATL, control site (motor cortex, Cz), and sham stimulation. All participants completed a modified IAT, where "good" and "bad" words were replaced with "terrorist" and "law-abider" words, and, "Black" and "White" were replaced with "Arab" and "Non-Arab" words. Participants were then given 15 min of rTMS stimulation. Afterward, participants completed a parallel form of the IAT. RESULTS: To investigate the effects of rTMS on IAT scores, a one-way ANOVA on the difference between pre- and postscores was carried out revealing that there were significant between group differences (F3,36 = 3.57; p = .02). Planned contrasts revealed that both left and right ATL stimulation significantly reduced IAT scores poststimulation, indicating lower prejudice. CONCLUSION: We show that prejudice scores can be significantly reduced by inhibitory rTMS delivered to the bilateral ATLs. This may implicate this area in conceptual associations that lead to overgeneralization and stereotyping of social groups.

Low-frequency repetitive transcranial magnetic stimulation of the anterior temporal lobes does not dissociate social versus nonsocial semantic knowledge.

Social conceptual knowledge is imperative to communicate with, interact with, and interpret human society; however, little is known about the neural basis of social concepts. Previous research has predominantly suggested that the right anterior temporal lobe (ATL) may specifically represent social conceptual knowledge, whereas the left ATL is necessary for general semantic processing. However, this view has not always been supported by empirical studies. Employing a lateralized design and two different semantic tasks and a nonsemantic control task, we aimed to clarify some of these ambiguities by potentially dissociating left from right functionality and social from nonsocial concepts, using inhibitory repetitive transcranial magnetic stimulation (rTMS) coupled with a sham and control site stimulation (N = 56). The results showed that stimulation of the left ATL led to overall faster processing times without affecting accuracy, whilst the right ATL and control groups did not significantly change in reaction times or accuracy. No difference occurred between social and nonsocial concepts after stimulation. This study is the first to show that inhibition of the left temporal lobe may improve performance on a semantic task and provides evidence that the ATLs may be lateralized in conceptual processing. The results do not confirm that the right temporal lobe is crucial for social conceptual processing, as inhibition did not significantly affect performance for social concepts.

Hygienic food handling behaviours. An application of the Theory of Planned Behaviour.

It is estimated that 5.4 million Australians get sick annually from eating contaminated food and that up to 20% of this illness results from food handling behaviour. A study was undertaken to investigate the efficacy of the Theory of Planned Behaviour (TPB) including past behaviour in predicting safe food handling intention and behaviour. One hundred and nine participants completed questionnaires regarding their attitudes, perceived behavioural control (PBC), subjective norm, intentions and past behaviour. Behaviour was measured 4 weeks later. The TPB predicted a high proportion of variance in both intentions and behaviour, and past behaviour/habit was found to be the strongest predictor of behaviour. The results of the present study suggest interventions aimed at increasing safe food handling intentions should focus on the impact of normative influences and perceptions of control over their food handling environment; whereas interventions to change actual behaviour should attempt to increase hygienic food handling as a habitual behaviour.

Predicting breakfast consumption: an application of the theory of planned behaviour and the investigation of past behaviour and executive function.

OBJECTIVES: The objective of the current study is to examine the determinants of breakfast consumption with the application of the Theory of Planned Behaviour (TPB; 1991) and investigate the additional variables of past behaviour and executive function. DESIGN: A prospective 1-week study investigating the predictive ability of TPB variables, past behaviour and executive function was utilized. METHODS: Ninety-six participants were administered two measures of executive function (response inhibition and planning) and completed self-report questionnaires regarding their attitudes, subjective norms, perceived control, intentions and past behaviour of breakfast consumption. One week later, participants returned a follow-up questionnaire on their behaviour. RESULTS: The result of the study showed that the TPB significantly predicted intentions and prospective behaviour of breakfast consumption, however, past behaviour was found to be the strongest predictor of future behaviour. Considering executive function, response inhibition was not found to predict behaviour, however, planning ability explained unique variance in behaviour and moderated the association between intention and behaviour. CONCLUSIONS: The findings support the use of the TPB in explaining breakfast eating habits, and suggest that executive function of planning may be somewhat useful to predict this behaviour. The significance of past behaviour also suggests that breakfast consumption may commonly be a stable, habitual behaviour that may undermine the need for self-regulation. Implications for creating behavioural-change interventions are discussed.