Executive functioning of 4 children with hyperphenylalaninemia from childhood to adolescence

Hyperphenylalaninemia is a variant of phenylketonuria, and debate remains as to what, if any, active management of this condition is required to preserve cognitive function and psychological well-being. This study is the first to examine longitudinally the executive function (EF) in adolescents with hyperphenylalaninemia. Two sibling pairs with mild hyperphenylalaninemia underwent neuropsychological examination in early childhood and again in adolescence using EF tests that were highly sensitive to phenylalanine exposure. By early adolescence, none of the 4 children demonstrated EF impairment. The children demonstrated a typical developmental trajectory of EF from childhood to adolescence, given phenylalanine exposure consistent with their condition.

The role of resilience and mTBI as predictors of postconcussional disorder symptomatology

Objective Resilience is 1 of several factors that are thought to contribute to outcome following mild traumatic brain injury (mTBI). This study explored the predictors of the postconcussional syndrome (PCS) symptoms that can occur following mTBI. We hypothesized that a reported recent mTBI and lower psychological resilience would predict worse reported PCS symptomatology. Method 233 participants completed the Neurobehavioral Symptom Inventory (NSI) and the Brief Resilience Scale (BRS). Three NSI scores were used to define PCS symptomatology. A total of 35 participants reported an mTBI (as operationally defined by the World Health Organization) that was sustained between 1 and 6 months prior to their participation (positive mTBI history); the remainder reported having never had an mTBI. Results Regression analyses revealed that a positive reported recent mTBI history and lower psychological resilience were significant independent predictors of reported PCS symptomatology. These results were found for the 3 PCS scores from the NSI, including using a stringent caseness criterion, p < .05. Demographic variables (age and gender) were not related to outcome, with the exception of education in some analyses. Conclusion The results demonstrate that: (a) both perceived psychological resilience and mTBI history play a role in whether or not PCS symptoms are experienced, even when demographic variables are considered, and; (b) of these 2 variables, lower perceived psychological resilience was the strongest predictor of PCS-like symptomatology.

Estimating the burden of disease attributable to lead exposure in South Africa in 2000

Objectives To estimate the burden of disease attributable to lead exposure in South Africa in 2000. Design World Health Organization comparative risk assessment (CRA) methodology was followed. Recent community studies were used to derive mean blood lead concentrations in adults and children in urban and rural areas. Population-attributable fractions were calculated and applied to revised burden of disease estimates for the relevant disease categories for South Africa in the year 2000. Monte Carlo simulation-modelling techniques were used for the uncertainty analysis. Setting South Africa. Subjects Children under 5 and adults 30 years and older. Outcome measures Cardiovascular mortality and disability-adjusted life years (DALYs) in adults 30 years and older and mild mental disability DALYs in children under 5 years. Results Lead exposure was estimated to cause 1 428 deaths (95% uncertainty interval 1 086-1 772) or 0.27% (95% uncertainty interval: 0.21 - 0.34%) of all deaths in South Africa in 2000. Burden of disease attributed to lead exposure was dominated by mild mental disability in young children, accounting for 75% of the total 58 939 (95% uncertainty interval 55 413 - 62 500) attributable DALYs. Cardiovascular disease in adults accounted for the remainder of the burden. Conclusions Even with the phasing out of leaded petrol, exposure to lead from its ongoing addition to paint, paraoccupational exposure and its use in backyard 'cottage industries' will continue to be an important public health hazard in South Africa for decades. Young children, especially those from disadvantaged communities, remain particularly vulnerable to lead exposure and poisoning.

Common values in assessing health outcomes from disease and injury: Disability weights measurement study for the Global Burden of Disease Study 2010

BACKGROUND Measurement of the global burden of disease with disability-adjusted life-years (DALYs) requires disability weights that quantify health losses for all non-fatal consequences of disease and injury. There has been extensive debate about a range of conceptual and methodological issues concerning the definition and measurement of these weights. Our primary objective was a comprehensive re-estimation of disability weights for the Global Burden of Disease Study 2010 through a large-scale empirical investigation in which judgments about health losses associated with many causes of disease and injury were elicited from the general public in diverse communities through a new, standardised approach. METHODS We surveyed respondents in two ways: household surveys of adults aged 18 years or older (face-to-face interviews in Bangladesh, Indonesia, Peru, and Tanzania; telephone interviews in the USA) between Oct 28, 2009, and June 23, 2010; and an open-access web-based survey between July 26, 2010, and May 16, 2011. The surveys used paired comparison questions, in which respondents considered two hypothetical individuals with different, randomly selected health states and indicated which person they regarded as healthier. The web survey added questions about population health equivalence, which compared the overall health benefits of different life-saving or disease-prevention programmes. We analysed paired comparison responses with probit regression analysis on all 220 unique states in the study. We used results from the population health equivalence responses to anchor the results from the paired comparisons on the disability weight scale from 0 (implying no loss of health) to 1 (implying a health loss equivalent to death). Additionally, we compared new disability weights with those used in WHO's most recent update of the Global Burden of Disease Study for 2004. FINDINGS 13,902 individuals participated in household surveys and 16,328 in the web survey. Analysis of paired comparison responses indicated a high degree of consistency across surveys: correlations between individual survey results and results from analysis of the pooled dataset were 0·9 or higher in all surveys except in Bangladesh (r=0·75). Most of the 220 disability weights were located on the mild end of the severity scale, with 58 (26%) having weights below 0·05. Five (11%) states had weights below 0·01, such as mild anaemia, mild hearing or vision loss, and secondary infertility. The health states with the highest disability weights were acute schizophrenia (0·76) and severe multiple sclerosis (0·71). We identified a broad pattern of agreement between the old and new weights (r=0·70), particularly in the moderate-to-severe range. However, in the mild range below 0·2, many states had significantly lower weights in our study than previously. INTERPRETATION This study represents the most extensive empirical effort as yet to measure disability weights. By contrast with the popular hypothesis that disability assessments vary widely across samples with different cultural environments, we have reported strong evidence of highly consistent results.

Single step purification of plasmid DNA using peptide ligand affinity chromatography

Single step affinity chromatography was employed for the purification of plasmid DNA (pDNA), thus eliminating several steps compared with current commercial purification methods for pDNA. Significant reduction in pDNA production time and cost was obtained. This chromatographic operation employed a peptide-monolith construct to isolate pDNA from Escherichia coli (E. coli) impurities present in a clarified lysate feedstock. Mild conditions were applied to avoid any degradation of pDNA. The effect of some important parameters on pDNA yield was also evaluated with the aim of optimising the affinity purification of pDNA. The results demonstrate that 81% of pDNA was recovered and contaminating gDNA, RNA and protein were removed below detectable levels. © 2008 Elsevier B.V. All rights reserved.

A neuronal topography of visual and acoustic fear conditioning within the amygdala

The lateral amygdala (LA) receives information from auditory and visual sensory modalities, and uses this information to encode lasting memories that predict threat. One unresolved question about the amygdala is how multiple memories, derived from different sensory modalities, are organized at the level of neuronal ensembles. We previously showed that fear conditioning using an auditory conditioned stimulus (CS) was spatially allocated to a stable topography of neurons within the dorsolateral amygdala (LAd) (Bergstrom et al, 2011). Here, we asked how fear conditioning using a visual CS is topographically organized within the amygdala. To induce a lasting fear memory trace we paired either an auditory (2 khz, 55 dB, 20 s) or visual (1 Hz, 0.5 s on/0.5 s off, 35 lux, 20 s) CS with a mild foot shock unconditioned stimulus (0.6 mA, 0.5 s). To detect learning-induced plasticity in amygdala neurons, we used immunohistochemistry with an antibody for phosphorylated mitogen-activated protein kinase (pMAPK). Using a principal components analysis-based approach to extract and visualize spatial patterns, we uncovered two unique spatial patterns of activated neurons in the LA that were associated with auditory and visual fear conditioning. The first spatial pattern was specific to auditory cued fear conditioning and consisted of activated neurons topographically organized throughout the LAd and ventrolateral nuclei (LAvl) of the LA. The second spatial pattern overlapped for auditory and visual fear conditioning and was comprised of activated neurons located mainly within the LAvl. Overall, the density of pMAPK labeled cells throughout the LA was greatest in the auditory CS group, even though freezing in response to the visual and auditory CS was equivalent. There were no differences detected in the number of pMAPK activated neurons within the basal amygdala nuclei. Together, these results provide the first basic knowledge about the organizational structure of two different fear engrams within the amygdala and suggest they are dissociable at the level of neuronal ensembles within the LA

Single voxel Magnetic Resonance Spectroscopic (1H-MRS) analysis of deep brain structures after traumatic prefrontal brain injury (TBI) in rat

Chronic difficulties arising from mild brain injury (TBI) are difficult to predict because the processes underlying changes after TBI are poorly understood. In mild brain injury the extent of neuropsychiatric and cognitive symptoms correspond poorly to overt tissue loss (Barth 1983; Liu 2010). Cellular, immune and hormonal cascades occurring after injury and continuing during the healing process may impact uninjured brain regions sensitive to the effects of physiological and emotional stress, which receive projections from the injury site. Changes in these most basic properties due to injury or disease have profound implications for virtually every aspect of brain function through disruption of neurotransmitter, neuroendocrine and metabolic systems. In order to screen for changes in transmitter and metabolic activity, in this study we developed Single voxel proton Magnetic Resonance Spectroscopy (1H-MRS) for use in both injured and control animals. We first evaluated if 1H-MRS could be used to evaluate in vivo, alterations in brain metabolism and catabolism of the prefrontal cortex, amygdala and ventral hippocampus in both control and injured animals after controlled cortical impact injury to the rat prefrontal cortex. We found that metabolite measurements for Myo-Inositol, Choline, creatine, Glutamate+Glutamine, and N-acetyl-acetate are attainable in deep brain structures in vivo in injured and controls rats. We next seek to evaluate longitudinally, in vivo, alterations in brain metabolism and catabolism of the prefrontal cortex, amygdala and ventral hippocampus during the first month after controlled cortical impact injury to the rat prefrontal cortex. These ongoing studies will provide data on the changes in transmitters and metabolites over time in injured and non-injured subjects. These studies address some of the fundamental questions about how mild brain injury has such diverse effects on overall brain health and function.

Co-optimisation of indoor environmental quality and energy consumption within urban office buildings

This study aimed to develop a multi-component model that can be used to maximise indoor environmental quality inside mechanically ventilated office buildings, while minimising energy usage. The integrated model, which was developed and validated from fieldwork data, was employed to assess the potential improvement of indoor air quality and energy saving under different ventilation conditions in typical air-conditioned office buildings in the subtropical city of Brisbane, Australia. When operating the ventilation system under predicted optimal conditions of indoor environmental quality and energy conservation and using outdoor air filtration, average indoor particle number (PN) concentration decreased by as much as 77%, while indoor CO2 concentration and energy consumption were not significantly different compared to the normal summer time operating conditions. Benefits of operating the system with this algorithm were most pronounced during the Brisbane’s mild winter. In terms of indoor air quality, average indoor PN and CO2 concentrations decreased by 48% and 24%, respectively, while potential energy savings due to free cooling went as high as 108% of the normal winter time operating conditions. The application of such a model to the operation of ventilation systems can help to significantly improve indoor air quality and energy conservation in air-conditioned office buildings.

Addressing barriers to help-seeking behaviour through M-mental health services : a social marketing perspective

Although seeking help for mental ill-health is beneficial, the majority of persons afflicted do not access available help services. Young adults (16-24 years old) in particular have the highest prevalence of mental health problems and the lowest rate of help-seeking behaviour. Key barriers to help-seeking for young adults, including cost, privacy concerns, inconvenience, access to health professionals and interpersonal interaction, appear to derive from the face-to-face method of service delivery traditionally used to distribute mental health services. Social marketing employs the principle of value exchange, whereby consumers will choose a behaviour in exchange for receiving valued benefits and/or a reduction in key barriers, to achieve behavioural goals for social good. The appropriation of mobile digital technology to deliver self-help mental health services may reduce the current barriers to help seeking, however, extant literature offers no empirical support for this proposition. Our research addresses this gap by examining the perceptions of young adults regarding M-mental health services. Depth interviews were undertaken with 15 young adults (18-24 years old), who had self-reported mild-moderate stress, anxiety or depression. The data were thematically analysed with the assistance of Nvivo. The findings reveal M-mental health services reduce the barriers to accessing face-to-face help services to a large extent. However, they also present their own barriers to help-seeking that must be considered by social marketers, including negligible cost expectations and service efficacy concerns. Overall, this study highlights the potential of M-mental health services to encourage early intervention and help-seeking behaviour as part of a social marketing strategy to address mental illness in young adults.

Estimating the burden of disease attributable to iron deficiency anaemia in South Africa in 2000

OBJECTIVES To estimate the extent of iron deficiency anaemia (IDA) among children aged 0 - 4 years and pregnant women aged 15 - 49 years, and the burden of disease attributed to IDA in South Africa in 2000. DESIGN The comparative risk assessment (CRA) methodology of the World Health Organization (WHO) was followed using local prevalence and burden estimates. IDA prevalence came from re-analysis of the South African Vitamin A Consultative Group study in the case of the children, and from a pooled estimate from several studies in the case of the pregnant women (haemoglobin level < 11 g/dl and ferritin level < 12 microg/l). Monte Carlo simulation-modelling was used for the uncertainty analysis. SETTING South Africa. SUBJECTS Children under 5 years and pregnant women 15 - 49 years. OUTCOME MEASURES Direct sequelae of IDA, maternal and perinatal deaths and disability-adjusted life years (DALYs) from mild mental disability related to IDA. Results. It is estimated that 5.1% of children and 9 - 12% of pregnant women had IDA and that about 7.3% of perinatal deaths and 4.9% of maternal deaths were attributed to IDA in 2000. Overall, about 174,976 (95% uncertainty interval 150,344 - 203,961) healthy years of life lost (YLLs), or between 0.9% and 1.3% of all DALYs in South Africa in 2000, were attributable to IDA. CONCLUSIONS This first study in South Africa to quantify the burden from IDA suggests that it is a less serious public health problem in South Africa than in many other developing countries. Nevertheless, this burden is preventable, and the study highlights the need to disseminate the food-based dietary guidelines formulated by the National Department of Health to people who need them and to monitor the impact of the food fortification programme.

Increasing enjoyable activities to treat depression in nursing home residents with dementia: A pilot study

This pilot study aimed to assess the feasibility and acceptability of a Behavioral Activities intervention (BE-ACTIV) in Australian nursing homes. BE-ACTIV was developed by researchers at the University of Louisville, USA, to improve mood and quality of life (QOL) in nursing home residents with mild to moderate dementia. An 8-week trial was conducted and 10 residents with mild to moderate dementia received the BE-ACTIV intervention while 8 residents received a Walking and Talking intervention. Measures of depression (GDS–12R), and QOL (QOL-AD-NH) were administered prior to and following the interventions. Qualitative feedback indicated residents benefited from BE-ACTIV, evident by improved mood, although no statistically significant treatment effect was found. Moreover, the intervention was found to be feasible and acceptable to Australian nursing home staff and our findings highlight the importance of individualizing activities for people with dementia, of which 1:1 staff attention was a key component.

Relationships between biophysical and psychosocial outcomes following minor stroke

This descriptive correlational study examined relationships between mild stroke functional and psychosocial outcomes over the early post-discharge period among dyads of mild stroke patients (n=38) and their spousal caregivers (n=38). We measured patients' functional scores using the modified Rankin Scale; patients' and caregivers' quality of life (QoL) using Stroke Impact Scale and Short-Form 36 respectively, mood using the Beck Depression Inventory-II, and marital function scores using the Family Assessment Device. Spousal caregivers also completed the Bakas Caregiving Outcomes Scale as a measure of caregiver strain. The average age of stroke patients was 64 years and of spousal caregivers 58 years. All stroke patients were male; all spousal caregivers female. At three months post discharge, patient functional status scores had significantly improved from discharge (p=0.026) with a corresponding increase in QoL scores (p=0.012). Functional status was significantly correlated with patient perceptions of QoL at three months (r=.014, p=0.024) and spousal caregiver perceptions of physical domain QoL (r=.-.397, p=0.014). Spousal caregivers' mood at three months post discharge was strongly correlated with their perceptions of marital satisfaction (r=.578, p=0.000) and caregiver strain (r=-.620, p=0.000). In preparing patients for discharge following mild stroke, nurses must consider the psychological and social implications of the recovery process over time for both the patient with stroke and their spousal caregivers.

Hemi-orolingual angioedema and ACE inhibition after alteplase treatment of stroke

One hundred seventy-six consecutive patients treated with IV tissue plasminogen activator (tPA) for acute ischemic stroke were examined prospectively, and orolingual angioedema was found in nine (5.1%; 95% CI 2.3 to 9.5). The reaction was typically mild, transient, and contralateral to the ischemic hemisphere. Risk of angioedema was associated with angiotensin-converting enzyme inhibitors (relative risk [RR] 13.6; 95% CI 3.0 to 62.7) and signs on initial CT of ischemia in the insular and frontal cortex (RR 9.1; 95% CI 1.4 to 30.0).

Quantitative and qualitative impairments in semantic fluency, but not phonetic fluency, as a potential risk factor for Alzheimer's disease

Qualitative aspects of verbal fluency may be more useful in discerning the precise cause of any quantitative deficits in phonetic or category fluency, especially in the case of mild cognitive impairment (MCI), a possible intermediate stage between normal performance and Alzheimer's disease (AD). The aim of this study was to use both quantitative and qualitative (switches and clusters) methods to compare the phonetic and category verbal fluency performance of elderly adults with no cognitive impairment (n = 51), significant memory impairment (n = 16), and AD (n = 16). As expected, the AD group displayed impairments in all quantitative and qualitative measures of the two fluency tasks relative to their age- and education-matched peers. By contrast, the amnestic MCI group produced fewer animal names on the semantic fluency task than controls and showed normal performance on the phonetic fluency task. The MCI group's inferior category fluency performance was associated with a deficit in their category-switching rate rather than word cluster size. Overall, the results indicate that a semantic measure such as category fluency when used in conjunction with a test of episodic memory may increase the sensitivity for detecting preclinical AD. Future research using external cues and other measures of set shifting capacity may assist in clarifying the origin of the amnestic MCI-specific category-switching deficiency. Copyright

Progressive dysgraphia in a case of posterior cortical atrophy

Dysgraphia (agraphia) is a common feature of posterior cortical atrophy (PCA). However, detailed analyses of these spelling and writing impairments are infrequently conducted. LM is a 59-year-old woman with dysgraphia associated with PCA. She presented with a two-year history of decline in her writing and dressmaking skills. A 3D T1-weighted MRI scan confirmed selective bi-parietal atrophy, with relative sparing of the hippocampi and other cortical regions. Analyses of LM's preserved and impaired spelling abilities indicated mild physical letter distortions and a significant spelling deficit characterised by letter substitutions, insertions, omissions, and transpositions that was systematically sensitive to word length while insensitive to real word versus nonword category, word frequency, regularity, imagery, grammatical class and ambiguity. Our findings suggest a primary graphemic buffer disorder underlies LM's spelling errors, possibly originating from disruption to the operation of a fronto-parietal network implicated in verbal working memory.