Snijders-Oomen Nonverbal Intelligence Test: useful for the elderly?

The feasibility of the SON-R 5 1/2-17, a non-verbal intelligence test for deaf children, was investigated in a group of older adults, with a view to the future use of the test in older neurological patients. In a group of 58 healthy elderly persons intelligence was measured with the SON, the Raven Progressive Matrices and a Dutch reading test. The subjects were also asked for their subjective judgements of the tests. The SON-R 5 1/2-17 appears to be a user-friendly test. The high correlations between the subtests, and between the SON and other measures of intelligence suggest that the SON is a valid test for measuring fluid intelligence in elderly persons. The existing norms are not suitable when the SON is used in elderly people, new norms for adults should therefore be developed.     

Cognitive impairments among older drivers: medical examination and driving test

The aim of this study was to gain insight in the prevalence of cognitive impairments among active older drivers and in driving performance of cognitively impaired ones. The study was implemented in the existing Dutch relicensing procedure for older drivers and consisted of three evaluation moments: a medical screening (for all subjects), a neuropsychological assessment and a test-drive (for candidates with cognitive impairments). In total, 2992 drivers were medically evaluated. In 4% of cases indications for impaired cognitive functioning were observed that could be evaluated and confirmed with neuropsychological tests. Eighty subjects performed an on-road test. Of these subjects, 57% were allowed to renew their driver's license, while in the remaining 43% no new licenses or restricted licenses were issued. During the test-drive, slow reactions and attention deficits were the most important causes for impaired fitness to drive.     

Memory tests in healthy elderly: age factors and norms

The study aimed to assess the strength of age effects on both standard laboratory and ecological memory tests and the psychometric qualities of these tests. Furthermore, norm data are constructed. Memory performance was assessed in a random group of older adults (mean age 62 years, range 46-89) and a group of older adults having memory complaints who applied for memory training (mean age 63 years, range 45-85). Age effects were found on almost all memory tests, whether artificial laboratory or more ecological tests were used. Age effects remained generally present after correction for educational level. Retest reliabilities of the ecological memory tests did not differ systematically from those of standard laboratory tests. However, not all tests showed satisfactory retest reliabilities, this was even true for tests often used in clinical settings. For tests with retest reliabilities above r = .65 norms corrected for age and educational level were provided. The group of older adults having memory complaints performed on average better than the random group of older adults from the population. In the first group, higher performance thresholds should be employed in assessing whether memory performance is deviant.     

Communication and data-intensive science in the beginning of the 21st century

The advent of data-intensive science has sharpened our need for better communication within and between the fields of science and technology, to name a few. No one mind can encompass all that is necessary to be successful in controlling and analyzing the data deluge we are experiencing. Therefore, we must bring together diverse fields, communicate clearly, and build crossdisciplinary methods and tools to realize its potential. This article is a summary of the communication issues and challenges as discussed in the Data-Intensive Science (DIS) workshop in Seattle, September 19-20, 2010.     

HNF1B and endometrial cancer risk: results from the PAGE study

We examined the association between HNF1B variants identified in a recent genome-wide association study and endometrial cancer in two large case-control studies nested in prospective cohorts: the Multiethnic Cohort Study (MEC) and the Women's Health Initiative (WHI) as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. A total of 1,357 incident cases of invasive endometrial cancer and 7,609 controls were included in the analysis (MEC: 426 cases/3,854 controls; WHI: 931 cases/3,755 controls). The majority of women in the WHI were European American, while the MEC included sizable numbers of African Americans, Japanese and Latinos. We estimated the odds ratios (ORs) per allele and 95% confidence intervals (CIs) of each SNP using unconditional logistic regression adjusting for age, body mass index, and four principal components of ancestry informative markers. The combined ORs were estimated using fixed effect models. Rs4430796 and rs7501939 were associated with endometrial cancer risk in MEC and WHI with no heterogeneity observed across racial/ethnic groups (P ≥ 0.21) or between studies (P ≥ 0.70). The OR(per allele) was 0.82 (95% CI: 0.75, 0.89; P = 5.63 × 10(-6)) for rs4430796 (G allele) and 0.79 (95% CI: 0.73, 0.87; P = 3.77 × 10(-7)) for rs7501939 (A allele). The associations with the risk of Type I and Type II tumors were similar (P ≥ 0.19). Adjustment for additional endometrial cancer risk factors such as parity, oral contraceptive use, menopausal hormone use, and smoking status had little effect on the results. In conclusion, HNF1B SNPs are associated with risk of endometrial cancer and that the associated relative risks are similar for Type I and Type II tumors.     

Attenuation of Renovascular Damage in Zucker Diabetic Fatty Rat by NWT-03, an Egg Protein Hydrolysate with ACE- and DPP4-Inhibitory Activity

Background

Dipeptidyl peptidase 4 (DPP4) and angiotensin-converting enzyme (ACE) are important target enzymes in glycemic control and renovascular protection. Here, we studied the effect of NWT-03, an egg protein hydrolysate with DPP4- and ACE-inhibitory activity, on renovascular damage in Zucker diabetic fatty (ZDF) rats. Comparisons were made to rats treated with vildagliptin (VIL), included as a positive control for the effect of DPP4 inhibition.

Methods

ZDF rats received NWT-03 (1 g/kg/day) or VIL (3 mg/kg/day) from 10 to 25 weeks of age. Metabolic and renal functions were assessed; the kidney was removed for histological analysis of glomerulosclerosis and expression of pro-inflammatory/fibrotic markers (RT-PCR and Western blotting); and the aorta was removed for studies of endothelium-dependent relaxation (EDR).

Findings

Hyperinsulinemic ZDF rats typically developed signs of type-2 diabetes and renovascular damage, as evidenced by albuminuria, glomerulosclerosis, and impaired EDR. Neither NWT-03 nor VIL improved metabolic parameters; for VIL, this was despite a 5-fold increase in glucagon-like peptide (GLP)-1 levels. NWT-03 and VIL both reduced renal interleukin (Il)-1β/Il-13 mRNA expression and glomerulosclerosis. However, only NWT-03 additionally decreased renal tumor necrosis factor (TNF)-α mRNA and P22^phox protein expression, reduced albuminuria, and restored aortic EDR. Indomethacin added to the organ bath instantly improved aortic EDR, indicating a role for cyclooxygenase (COX)-derived contractile prostanoids in opposing relaxation in ZDF rats. This indomethacin effect was reduced by NWT-03, but not by VIL, and coincided with decreased renal COX-1/2 protein expression.

Conclusion and Interpretation

Long-term supplementation with the egg protein hydrolysate NWT-03 attenuated renovascular damage in this preclinical rat model of type 2 diabetes. A comparison to the DPP4-inhibitor VIL suggests that the effects of NWT-03 were related to both ACE- and DPP4-inhibitory properties. The development of protein hydrolysates with a multiple-targeting strategy may be of benefit to functional food formulations.     

Intracellular angiotensin II inhibits heterologous receptor stimulated Ca2+ entry.

Recent studies show that angiotensin II (AngII) can act from within the cell, possibly via intracellular receptors pharmacologically different from typical plasma membrane AngII receptors. The role of this intracellular AngII (AngIIi) is unclear. Besides direct effects of AngIIi on cellular processes one could hypothesise a possible role of AngIIi in modulation of cellular responses induced after heterologous receptor stimulation. We therefore examined if AngIIi influences [Ca+]i in A7r5 smooth muscle cells after serotonin (5HT) or UTP receptor stimulation. Application of AngIIi using liposomes, markedly inhibited 45Ca2+ influx after receptor stimulation with 5HT or UTP. This inhibition was reversible by intracellular administration of the AT1-antagonist losartan and not influenced by the AT2-antagonist PD123319. Similar results were obtained in single cell [Ca2+]i measurements, showing that AngIIi predominantly influences Ca2+ influx and not Ca2+ release via AT1-like receptors. It is concluded that AngIIi modulates signal transduction activated by heterologous receptor stimulation.     

Memory strategies of elderly: training efficacy

Does memory strategy training improve the quantity and quality of reported strategy use of normal older adults (N = 111, mean age 63 years, range 46-85 years) in daily life? Three strategy training conditions, remembering names (N = 26), intentions (N = 20) and verbal information (N = 20) and an educational training (N = 23) were compared to a test-retest control group (N = 22). Strategy use was assessed with a Strategy Frequency Questionnaire (investigating the reported frequency of strategy use on five scales: encoding, retrieval, general, external and no strategies) and a Memory Situations Questionnaire (investigating the preference of strategies in specific situations). Three months after training, the frequency of strategy use as assessed by the scale scores had not increased more in the strategy training conditions than in the control condition. No demographic or psychological characteristics were identified that could predict which individuals were most likely to change their strategy use. When strategies were analyzed separately, only after names training a specific effect was demonstrated, indicating that subjects more frequently used the strategy for remembering names (association) at follow-up. With regard to changes in the strategies used in specific situations, subjects in the names and intention training conditions reported an increase in the use of the trained strategies on names and prospective situations respectively. Moreover, there was some evidence of a generalization of training to strategies that were not directly dealt with during training. The control group showed that repeated practice with memory tests may result in changes in strategy use in specific situations, which are not always for the better, how-ever.     

Local drug and gene delivery through microbubbles and ultrasound

Although gene therapy has great potential as a treatment for diseases, clinical trials are slowed down by the development of a safe and efficient gene delivery system. In this review, we will give an overview of the viral and nonviral vehicles used for drug and gene delivery, and the different nonviral delivery techniques, thereby focusing on delivery through ultrasound contrast agents.The development of ultrasound contrast agents containing encapsulated microbubbles has increased the possibilities not only for diagnostic imaging, but for therapy as well. Microbubbles have been shown to be able to carry drugs and genes, and destruction of the bubbles by ultrasound will result in local release of their contents. Furthermore, ligands can be attached so that they can be targeted to a specific target tissue. The recent advances of microbubbles as vehicles for delivery of drugs and genes will be highlighted.