Improving effects of huperzine A on spatial working memory in aged monkeys and young adult monkeys with experimental cognitive impairment

Our previous studies demonstrated that huperzine A, a reversible and selective acetylcholinesterase inhibitor, exerts beneficial effects on memory deficits in various rodent models of amnesia. To extend the antiamnesic action of huperzine A to nonhuman primates, huperzine A was evaluated for its ability to reverse the deficits in spatial memory produced by scopolamine in young adult monkeys or those that are naturally occurring in aged monkeys using a delayed-response task. Scopolamine, a muscarinic receptor antagonist, dose dependently impaired performance with the highest dose (0.03 mg/kg, i.m.) producing a significant reduction in choice accuracy in young adult monkeys. The delayed performance changed from an average of 26.8/30 trials correct on saline control to an average of 20.2/30 trials correct after scopolamine administration. Huperzine A (0.01-0.1 mg/kg, i.m.) significantly reversed deficits induced by scopolamine in young adult monkeys on a delayed-response task; performance after an optimal dose (0.1 mg/kg) averaged 25.0/30 correct. In four aged monkeys, huperzine A (0.001-0.01 mg/kg, i.m.) significantly increased choice accuracy from 20.5/30 on saline control to 25.2/30 at the optimal dose (0.001 mg/kg for two monkeys and 0.01 mg/kg for the other two monkeys). The beneficial effects of huperzine A on delayed-response performance were long lasting; monkeys remained improved for about 24 h after a single injection of huperzine A. This study extended the findings that huperzine A improves the mnemonic performance requiring working memory in monkeys, and suggests that huperzine A may be a promising agent for clinical therapy of cognitive impairments in patients with Alzheimer's disease.

Established cardiovascular disease and CVD risk factors in a primary care population of middle-aged Irish men and women

Contemporary Irish data on the prevalence of major cardiovascular disease (CVD) risk factors are sparse. The primary aims of this study were (1) to estimate the prevalence of major cardiovascular disease risk factors, including Type 2 Diabetes Mellitus, in the general population of men and women between the ages of 50 and 69 years; and (2) to estimate the proportion of individuals in this age group at high absolute risk of cardiovascular disease events on the basis of pre-existing cardiovascular disease or as defined by the Framingham equation. Participants were drawn from the practice lists of 17 general practices in Cork and Kerry using stratified random sampling. A total of 1018 people attended for screening (490 men, 48%) from 1473 who were invited, a response rate of 69.1%. Cardiovascular disease risk factors and glucose intolerance are common in the population of men and women aged between 50 and 69 years. Almost half the participants were overweight and a further quarter met current international criteria for obesity, one of the highest recorded prevalence rates for obesity in a European population sample. Forty per cent of the population reported minimal levels of physical activity and 19% were current cigarette smokers. Approximately half the sample had blood pressure readings consistent with international criteria for the diagnosis of hypertension, but only 38% of these individuals were known to be hypertensive. Eighty per cent of the population sample had a cholesterol concentration in excess of 5 mmol/l. Almost 4% of the population had Type 2 Diabetes Mellitus, of whom 30% were previously undiagnosed. A total of 137 participants (13.5%) had a history or ECG findings consistent with established cardiovascular disease. Of the remaining 881 individuals in the primary prevention population, a total of 20 high-risk individuals (19 male) had a risk of a coronary heart disease event 30% over ten years according to the Framingham risk equation, giving an overall population prevalence of 2.0% (95% CI 1.3 - 3.0). At a risk level 20% over ten years, an additional 91 individuals (8.9%) were identified. Thus a total of 24.4% of the population were at risk either through pre-existing CVD (13.5%) or an estimated 10-year risk exceeding 20% according to the Framingham risk equation (10.9%). Thus a substantial proportion of middle-aged men are at high risk of CVD. The findings emphasise the scale of the CVD epidemic in Ireland and the need for ongoing monitoring of risk factors at the population level and the need to develop preventive strategies at both the clinical and societal level.

Enhanced toxicity of ‘bulk' titanium dioxide compared to ‘fresh' and ‘aged' nano-TiO2in marine mussels (Mytilus galloprovincialis)

Marine bivalves (Mytilus galloprovincialis) were exposed to titanium dioxide (10 mg L-1) either as engineered nanoparticles (nTiO(2); fresh, or aged under simulated sunlight for 7 days) or the bulk equivalent. Inductively coupled plasma-optical emission spectrometry analyses of mussel tissues showed higher Ti accumulation (>10-fold) in the digestive gland compared to gills. Nano-sized TiO2 showed greater accumulation than bulk, irrespective of ageing, particularly in digestive gland (>sixfold higher). Despite this, transcriptional expression of metallothionein genes, histology and histochemical analysis suggested that the bulk material was more toxic. Haemocytes showed significantly enhanced DNA damage, determined by the modified comet assay, for all treatments compared to the control, but no significant differences between the treatments. Our integrated study suggests that for this ecologically relevant organism photocatalytic ageing of nTiO(2) does not significantly alter toxicity, and that bulk TiO2 may be less ecotoxicologically inert than previously assumed.

Self-reported quality of life of 8-12 year old children with cerebral palsy: a cross-sectional European Study

Background

Little is known about the quality of life (QoL) of disabled children. We describe self-reported QoL of children with cerebral palsy, factors that influence it, and how it compares with QoL of the general population.

Methods

1174 children aged 8–12 years were randomly selected from eight population-based registers of children with cerebral palsy in six European countries and 743 (63%) agreed to participate; one further region recruited 75 children from multiple sources. Researchers visited these 818 children. 318 (39%) with severe intellectual impairment could not self-report; 500 (61%) reported their QoL using KIDSCREEN, an instrument with scores in ten domains, each with SD=10. Multivariable regression was used to relate QoL to impairments, pain, and sociodemographic characteristics. Comparisons were made with QoL data from the general population.

Findings

Impairments were not significantly associated with six KIDSCREEN domains. Comparison of least and most able groups showed that severely limited self-mobility was significantly associated with reduced mean score for physical wellbeing (7·6, 95% CI 2·7–12·4); intellectual impairment with reduced mean for moods and emotions (3·7, 1·5–5·9) and autonomy (3·3, 0·9–5·7); and speech difficulties with reduced mean for relationships with parents (4·5, 1·9–7·1). Pain was common and associated with lower QoL on all domains. Impairments and pain explained up to 3% and 7%, respectively, of variation in QoL. Children with cerebral palsy had similar QoL to children in the general population in all domains except schooling, in which evidence was equivocal, and physical wellbeing, in which comparison was not possible.

Interpretation

Parents can be reassured that most children aged 8–12 years with cerebral palsy will have similar QoL to other children. This finding should guide social and educational policy to ensure that disabled children participate fully in society. Because of its association with QoL, children's pain should be carefully assessed.

Incidence of Type 1 Diabetes in Sweden Among Individuals Aged 0–34 Years, 1983–2007:An analysis of time trends

OBJECTIVE: To clarify whether the increase in childhood type 1 diabetes is mirrored by a decrease in older age-groups, resulting in younger age at diagnosis.
RESEARCH DESIGN AND METHODS: We used data from two prospective research registers, the Swedish Childhood Diabetes Register, which included case subjects aged 0-14.9 years at diagnosis, and the Diabetes in Sweden Study, which included case subjects aged 15-34.9 years at diagnosis, covering birth cohorts between 1948 and 2007. The total database included 20,249 individuals with diabetes diagnosed between 1983 and 2007. Incidence rates over time were analyzed using Poisson regression models.
RESULTS: The overall yearly incidence rose to a peak of 42.3 per 100,000 person-years in male subjects aged 10-14 years and to a peak of 37.1 per 100,000 person-years in female subjects aged 5-9 years and decreased thereafter. There was a significant increase by calendar year in both sexes in the three age-groups <15 years; however, there were significant decreases in the older age-groups (25- to 29-years and 30- to 34-years age-groups). Poisson regression analyses showed that a cohort effect seemed to dominate over a time-period effect.
CONCLUSIONS: Twenty-five years of prospective nationwide incidence registration demonstrates a clear shift to younger age at onset rather than a uniform increase in incidence rates across all age-groups. The dominance of cohort effects over period effects suggests that exposures affecting young children may be responsible for the increasing incidence in the younger age-groups.

Motor Skills in Children Aged 7–10 Years, Diagnosed with Autism Spectrum Disorder

This study used the Movement Assessment Battery for Children (M-ABC2) to assess the level of motor skill in children aged 7-10 years with autism (n=18) and compared their performance to two groups of age-matched typically developing children; a receptive vocabulary matched group (n=19) and a nonverbal IQ matched group (n=22). Although the results support previous work, as indicated by a significant general motor impairment in the group with autism, a sub-analysis of the M-ABC2 revealed that there were only 2 out of 8 subcomponent skills which showed universally significant specific deficits for the autism group; namely catching a ball and static balance. These results suggest that motor skill deficits associated with autism may not be pervasive but more apparent in activities demanding complex, interceptive actions or core balance ability.

Restorative justice conferencing for reducing recidivism in young offenders (aged 7 to 21)

Background
Restorative justice is “a process whereby parties with a stake in a specific offence resolve collectively how to deal with the aftermath of the offence and its implications for the future” (Marshall 2003). Despite the increasing use of restorative justice programmes as an alternative to court proceedings, no systematic review has been undertaken of the available evidence on the effectiveness of these programmes with young offenders. Recidivism in young offenders is a particularly worrying problem, as recent surveys have indicated
the frequency of re-offences for young offenders has ranged from 40.2% in 2000 to 37.8% in 2007 (Ministry of Justice 2009)

Objectives
To evaluate the effects of restorative justice conferencing programmes for reducing recidivism in young offenders.

Search methods
We searched the following databases up to May 2012: CENTRAL, 2012 Issue 5, MEDLINE (1978 to current), Bibliography of Nordic Criminology (1999 to current), Index to Theses (1716 to current), PsycINFO (1887 to current), Social Sciences Citation Index (1970 to current), Sociological Abstracts (1952 to current), Social Care Online (1985 to current), Restorative Justice Online (1975 to current), Scopus (1823 to current), Science Direct (1823 to current), LILACS (1982 to current), ERIC (1966 to current), Restorative Justice Online (4May 2012),WorldCat (9May 2012), ClinicalTrials.gov (19May 2012) and ICTRP (19May 2012). ASSIA,National Criminal Justice Reference Service and Social Services Abstracts were searched up to May 2011. Relevant bibliographies, conference programmes and journals were also searched.

Selection criteria
Randomised controlled trials (RCTs) or quasi-RCTs of restorative justice conferencing versus management as usual, in young offenders.

Data collection and analysis
Two authors independently assessed the risk of bias of included trials and extracted the data. Where necessary, original investigators were contacted to obtain missing information.

Main results
Four trials including a total of 1447 young offenders were included in the review. Results failed to find a significant effect for restorative justice conferencing over normal court procedures for any of the main analyses, including number re-arrested (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.59 to 1.71; P = 0.99), monthly rate of reoffending (standardised mean difference (SMD) -0.06, 95% CI -0.28 to 0.16; P = 0.61), young person’s remorse following conference (OR 1.73, 95% CI 0.97 to 3.10; P = 0.06), young person’s recognition of wrongdoing following conference (OR 1.97, 95% CI 0.81 to 4.80; P = 0.14), young person’s self-perception following conference (OR 0.95, 95% CI 0.55 to 1.63; P = 0.85), young person’s satisfaction following conference (OR 0.42, 95% CI 0.04 to 4.07; P = 0.45) and victim’s satisfaction following conference (OR 4.05, 95%CI 0.56 to 29.04; P = 0.16). A small number of sensitivity analyses did indicate significant effects, although all are to be interpreted with caution.

Authors’ conclusions
There is currently a lack of high quality evidence regarding the effectiveness of restorative justice conferencing for young offenders. Caution is urged in interpreting the results of this review considering the small number of included studies, subsequent low power and high risk of bias. The effects may potentially be more evident for victims than offenders. The need for further research in this area is highlighted.

The incidences of trisomy 8, trisomy 9 and D20S108 deletion in polycythaemia vera: an analysis of blood granulocytes using interphase fluorescence in situ hybridization:an analysis of blood granulocytes using interphase fluorescence in situ hybridization

We have used interphase fluorescence in situ hybridization (IFISH) to detect trisomy 8, trisomy 9 and 20q deletion in circulating granulocytes from patients with polycythaemia vera (PV). Out of 64 PV patients, 15 (23%) exhibited an abnormality. Two patients had trisomy 9, three had trisomy 8 and 10 patients had hemizygous deletion of D20S108 (a locus in the 20q common deleted region). Aberrant nuclei ranged from 10% to 80% in these 15 cases. There was no correlation between the presence of a marker and sex, age, interval between presentation and IFISH analysis, neutrophil or platelet count or therapy. Conventional marrow cytogenetic karyotype results were available in 23 cases and there was concurrence between these and blood IFISH in 16 cases (13 normal and three with 20q/D20S108 deletion by both methods). Three patients with D20S108 deletion by IFISH were normal by previous marrow cytogenetic testing and four cases with 20q deletion by previous marrow cytogenetics had normal blood granulocytes according to IFISH. Thus, we confirm that trisomies 8 and 9 and deletion of 20q are diagnostically useful markers of PV. IFISH analysis of blood granulocytes is a practical method for detecting these markers, but as an adjunct to, not as a substitute for, conventional marrow cytogenetics.

Up close and personal: A qualitative study exploring the lived experience of older carers. Mental Health and Learning Disabilities Research. 8 (1). Pp.15-29.

This study explored the experiences of informal carers who were aged 65 years and over. It has been estimated that 15 per cent of those aged 65 or over provide some form of informal care in England. Despite a growing literature on the involvement of older people in research, there is a paucity of literature on the involvement of older carers. In this study, older carers were identified via a General Practice (GP) register in one urban medical practice. Data was collected through a series of focus groups, which were transcribed and analysed using
thematic analysis. Every carer aged 55 or over and registered with the medical practice was invited to take part in the study. Four female carers and one male carer took part in the study (age range 65-83). Themes that emerged during data analysis included, 1) managing things in an emergency, 2) feeling valued because they took part in the research and 3) the day-to-day reality of living with social exclusion. GP registers provide a valuable tool for identifying older
carers who may otherwise be difficult to engage in research. However, persuading GPs to engage with qualitative research may be a challenge.

Any versus long-term prescribing of high risk medications in older people using 2012 Beers Criteria: results from three cross-sectional samples of primary care records for 2003/4, 2007/8 and 2011/12

Background: High risk medications are commonly prescribed to older US patients. Currently, less is known about high risk medication prescribing in other Western Countries, including the UK. We measured trends and correlates of high risk medication prescribing in a subset of the older UK population (community/institutionalized) to inform harm minimization efforts. Methods: Three cross-sectional samples from primary care electronic clinical records (UK Clinical Practice Research Datalink, CPRD) in fiscal years 2003/04, 2007/08 and 2011/12 were taken. This yielded a sample of 13,900 people aged 65 years or over from 504 UK general practices. High risk medications were defined by 2012 Beers Criteria adapted for the UK. Using descriptive statistical methods and regression modelling, prevalence of ‘any’ (drugs prescribed at least once per year) and ‘long-term’ (drugs prescribed all quarters of year) high risk medication prescribing and correlates were determined. Results: While polypharmacy rates have risen sharply, high risk medication prevalence has remained stable across a decade. A third of older (65+) people are exposed to high risk medications, but only half of the total prevalence was long-term (any = 38.4 % [95 % CI: 36.3, 40.5]; long-term = 17.4 % [15.9, 19.9] in 2011/12). Long-term but not any high risk medication exposure was associated with older ages (85 years or over). Women and people with higher polypharmacy burden were at greater risk of exposure; lower socio-economic status was not associated. Ten drugs/drug classes accounted for most of high risk medication prescribing in 2011/12. Conclusions: High risk medication prescribing has not increased over time against a background of increasing polypharmacy in the UK. Half of patients receiving high risk medications do so for less than a year. Reducing or optimising the use of a limited number of drugs could dramatically reduce high risk medications in older people. Further research is needed to investigate why the oldest old and women are at greater risk. Interventions to reduce high risk medications may need to target shorter and long-term use separately.

Correction of moderate myopia is associated with improvement in self-reported visual functioning among Mexican school-aged children.

PURPOSE: To quantify the impact on self-reported visual functioning of spectacle provision for school-aged children in Oaxaca, Mexico. METHODS: The Refractive Status Vision Profile (RSVP), a previously validated tool to measure the impact of refractive correction on visual functioning, was adapted for use in rural children and administered at baseline and 4 weeks (27.3 +/- 4.4 days) after the provision of free spectacles. Visual acuity with and without correction, age, sex, and spherical equivalent refraction were recorded at the time of follow-up. RESULTS: Among 88 children (mean age, 12 years; 55.7% girls), the median presenting acuity (uncorrected or with original spectacles), tested 4 weeks after the provision of free spectacles, was 6/9 (range, 6/6-6/120). Significant improvements in the following subscales of the RSVP were seen for the group as a whole after the provision of free spectacles: function, 11.2 points (P = 0.0001); symptoms, 14.3 points (P < 0.0001); total score, 10.3 points (P = 0.0001). After stratification by presenting vision in the better-seeing eye, children with 6/6 acuity (n = 22) did not have significant improvement in any subscale; those with acuity of 6/7.5 to 6/9 (n = 34) improved only on function (P = 0.02), symptoms (P = 0.005), and total score (P = 0.003); and those with acuity of 6/12 or worse improved on total score (P < 0.0001) and all subscales. Subjects (n = 31) with uncorrected myopia of -1.25 D or more had a mean improvement in total score of 15.9 points (P < 0.0001), whereas those with uncorrected myopia between -0.50 and -1.00 D inclusive (n = 53) had a mean improvement of 8 points (P = 0.01). CONCLUSIONS: Provision of spectacles to children in this setting had a significant impact on self-reported function, even at modest levels of baseline visual disability. The correlation between presenting vision/refraction and improvement and the failure of children 6/6 at baseline to improve offer evidence for a real effect.

Step based physical activity guidelines for preschool-aged children

Objective Public health organizations recommend that preschool-aged children accumulate at least 3 h of physical activity (PA) daily. Objective monitoring using pedometers offers an opportunity to measure preschooler's PA and assess compliance with this recommendation. The purpose of this study was to derive step-based recommendations consistent with the 3 h PA recommendation for preschool-aged children. Method The study sample comprised 916 preschool-aged children, aged 3 to 6 years (mean age = 5.0 ± 0.8 years). Children were recruited from kindergartens located in Portugal, between 2009 and 2013. Children wore an ActiGraph GT1M accelerometer that measured PA intensity and steps per day simultaneously over a 7-day monitoring period. Receiver operating characteristic (ROC) curve analysis was used to identify the daily step count threshold associated with meeting the daily 3 hour PA recommendation. Results A significant correlation was observed between minutes of total PA and steps per day (r = 0.76, p < 0.001). The optimal step count for ≥ 3 h of total PA was 9099 steps per day (sensitivity (90%) and specificity (66%)) with area under the ROC curve = 0.86 (95% CI: 0.84 to 0.88). Conclusion Preschool-aged children who accumulate less than 9000 steps per day may be considered Insufficiently Active.