Are changes in self-rated health associated with memory decline in older adults?

OBJECTIVE: The association between patterns of change in self-rated health (SRH) and memory trajectories in older adults was examined using a systematic approach. METHOD: Data from the Health and Retirement Study (n = 6,016) and the English Longitudinal Study of Ageing (n = 734) were analyzed. Individuals were grouped into five categories according to their pattern of change in SRH over 8 years: stable excellent/very good/good, stable fair/poor, improvement, decline, and fluctuating pattern without a trend. Memory was measured using immediate and delayed recall tests. Kruskal–Wallis, chi-squares tests, and linear mixed models were used to examine the association. RESULTS: Different rates of decline in memory can be identified in the different patterns of change in SRH. Those who had a stable excellent/very good/good pattern had the slowest rate of decline. DISCUSSION: Our findings suggest that SRH status and patterns of change could be used as a marker of cognitive decline in prevention screening programs

Comparison of the procedures of Fleishman and Ramberg et al. for generating non normal data in simulation studies

Simulation techniques must be able to generate the types of distributions most commonly encountered in real data, for example, non-normal distributions. Two recognized procedures for generating non-normal data are Fleishman's linear transformation method and the method proposed by Ramberg et al. that is based on generalization of the Tukey lambda distribution. This study compares these procedures in terms of the extent to which the distributions they generate fit their respective theoretical models, and it also examines the number of simulations needed to achieve this fit. To this end, the paper considers, in addition to the normal distribution, a series of non-normal distributions that are commonly found in real data, and then analyses fit according to the extent to which normality is violated and the number of simulations performed. The results show that the two data generation procedures behave similarly. As the degree of contamination of the theoretical distribution increases, so does the number of simulations required to ensure a good fit to the generated data. The two procedures generate more accurate normal and non-normal distributions when at least 7000 simulations are performed, although when the degree of contamination is severe (with values of skewness and kurtosis of 2 and 6, respectively) it is advisable to perform 15000 simulations

The effect of skewness and kurtosis on the Kenward-Roger approximation when group distributions differ

This study examined the independent effect of skewness and kurtosis on the robustness of the linear mixed model (LMM), with the Kenward-Roger (KR) procedure, when group distributions are different, sample sizes are small, and sphericity cannot be assumed. Methods: A Monte Carlo simulation study considering a split-plot design involving three groups and four repeated measures was performed. Results: The results showed that when group distributions are different, the effect of skewness on KR robustness is greater than that of kurtosis for the corresponding values. Furthermore, the pairings of skewness and kurtosis with group size were found to be relevant variables when applying this procedure. Conclusions: With sample sizes of 45 and 60, KR is a suitable option for analyzing data when the distributions are: (a) mesokurtic and not highly or extremely skewed, and (b) symmetric with different degrees of kurtosis. With total sample sizes of 30, it is adequate when group sizes are equal and the distributions are: (a) mesokurtic and slightly or moderately skewed, and sphericity is assumed; and (b) symmetric with a moderate or high/extreme violation of kurtosis. Alternative analyses should be considered when the distributions are highly or extremely skewed and samples sizes are small

NO NORMALIDAD Y HETEROGENEIDAD DE VARIANZA EN EL MODELO LINEALMIXTO (MLM) EN DISEÑOS SPLIT-PLOTCON MUESTRAS PEQUEÑAS

Los datos provenientes de investigaciones de tipo longitudinal en psicología suelen reflejar condiciones características de este ámbito de estudio, como son los tamaños muestrales reducidos, distribuciones no normales, violaciones de los supuestos de esfericidad y homogeneidad de varianza. Actualmente, el modelo lineal mixto (MLM) es uno de los procedimientos más recomendados cuando los supuestos en los que se basan los procedimientos tradicionales no se cumplen. Cuando los tamaños muestrales son reducidos se suele utilizar algún procedimiento de ajuste de los grados de libertad que mejore las propiedades del MLM, como el propuesto por Kenward y Roger (KR; 1997). El objetivo de este estudio fue ampliar el estudio realizado por Arnau et al. (2011) evaluando la robustez de KR con diseños split-plot de muestras pequeñas ante violaciones de la normalidad en diferente grado en los distintos grupos, violaciones de la esfericidad y de la homogeneidad de varianza. Se realiza un estudio de simulación Monte Carlo considerando un diseño split-plot con 3 grupos y 4 ocasiones de medidas repetidas, con tamaños muestrales totales de 36 y 42 individuos, asumiendo una matriz de covarianza no estructurada en la generación de datos. Se han manipulado las siguientes condiciones: a) con grupos balanceados y no balanceados; b) homogeneidad y heterogeneidad de la matriz de covarianza; c) emparejamiento nulo, positivo o negativo entre el tamaño de grupo y la matriz de covarianza y d) esfericidad de 0,57 ó 0,75. Los resultados muestran que KR es robusto cuando los diseños son equilibrados, independientemente de la violación de los supuestos de esfericidad y/o de homogeneidad de varianza. Sin embargo, cuando los diseños no son equilibrados, se halla una tendencia a la liberalidad, especialmente cuando el emparejamiento de las matrices de covarianza y el tamaño de los grupos es negativo. Los resultados de este estudio van en la línea con los obtenidos en estudios previos.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Proyecto de Investigación PSI2012-32662 Ministerio Economía y Competitividad

Microglial activation decreases retention of the protease inhibitor saquinavir: implications for HIV treatment

Background Active HIV infection within the central nervous system (CNS) is confined primarily to microglia. The glial cell compartment acts as a viral reservoir behind the blood-brain barrier. It provides an additional roadblock to effective pharmacological treatment via expression of multiple drug efflux transporters, including P-glycoprotein. HIV/AIDS patients frequently suffer bacterial and viral co-infections, leading to deregulation of glial cell function and release of pro-inflammatory mediators including cytokines, chemokines, and nitric oxide. Methods To better define the role of inflammation in decreased HIV drug accumulation into CNS targets, accumulation of the antiretroviral saquinavir was examined in purified cultures of rodent microglia exposed to the prototypical inflammatory mediator lipopolysaccharide (LPS). Results [3H]-Saquinavir accumulation by microglia was rapid, and was increased up to two-fold in the presence of the specific P-glycoprotein inhibitor, PSC833. After six or 24 hours of exposure to 10 ng/ml LPS, saquinavir accumulation was decreased by up to 45%. LPS did not directly inhibit saquinavir transport, and did not affect P-glycoprotein protein expression. LPS exposure did not alter RNA and/or protein expression of other transporters including multidrug resistance-associated protein 1 and several solute carrier uptake transporters. Conclusions The decrease in saquinavir accumulation in microglia following treatment with LPS is likely multi-factorial, since drug accumulation was attenuated by inhibitors of NF-κβ and the MEK1/2 pathway in the microglia cell line HAPI, and in primary microglia cultures from toll-like receptor 4 deficient mice. These data provide new pharmacological insights into why microglia act as a difficult-to-treat viral sanctuary site

Spanish version of the Phubbing Scale:Internet addiction, Facebook intrusion, and fear of missing out as correlates

BACKGROUND:Phubbing is an increasingly common behavior that involves using a smartphone in a social setting of two or more people and interacting with the phone rather than with the other people. Research to date on phubbing has measured it using different scales or single questions, and therefore standard measures with appropriate psychometric properties are needed to improve its assessment. The aim of our study was to develop a Spanish version of the Phubbing Scale and to examine its psychometric properties: factor structure, reliability, and concurrent validity.METHOD:Participants were 759 Spanish adults between 18 and 68 years of age. They completed an online survey.RESULTS:The results support a structure that is consistent with the original validation study, with two factors: Communication Disturbance and Phone Obsession. Internal consistency was found to be adequate. Evidence of concurrent validity was provided via a hierarchical regression model that showed positive associations with measures of internet addiction, Facebook intrusion, and fear of missing out.CONCLUSIONS:These results indicate that the Spanish version of the Phubbing Scale exhibits appropriate psychometric properties

Uptake and transport of novel amphiphilic polyelectrolyte-insulin nanocomplexes by caco-2 cells - towards oral insulin

“The original publication is available at www.springerlink.com”. Copyright SpringerPurpose: The influence of polymer architecture on cellular uptake and transport across Caco-2 cells of novel amphiphilic polyelectrolyte-insulin nanocomplexes was investigated. Method: Polyallylamine (PAA) (15 kDa) was grafted with palmitoyl chains (Pa) and subsequently modified with quaternary ammonium moieties (QPa). These two amphiphilic polyelectrolytes (APs) were tagged with rhodamine and their uptake by Caco-2 cells or their polyelectrolyte complexes (PECs) with fluorescein isothiocyanate-insulin (FITC-insulin) uptake were investigated using fluorescence microscopy. The integrity of the monolayer was determined by measurement of transepithelial electrical resistance (TEER). Insulin transport through Caco-2 monolayers was determined during TEER experiments. Result: Pa and insulin were co-localised in the cell membranes while QPa complexes were found within the cytoplasm. QPa complex uptake was not affected by calcium, cytochalasin D or nocodazole. Uptake was reduced by co-incubation with sodium azide, an active transport inhibitor. Both polymers opened tight junctions reversibly where the TEER values fell by up to 35 % within 30 minutes incubation with Caco-2 cells. Insulin transport through monolayers increased when QPa was used (0.27 ngmL-1 of insulin in basal compartment) compared to Pa (0.14 ngmL-1 of insulin in basal compartment) after 2 hours. Conclusion: These APs have been shown to be taken up by Caco-2 cells and reversibly open tight cell junctions. Further work is required to optimise these formulations with a view to maximising their potential to facilitate oral delivery of insulin.Peer reviewe

Circulating Glycated Albumin and Glomerular Anionic Charges

Aiming to discern the mechanisms by which circulating glycated albumin alters the glomerular filtration properties that lead to glomerular dysfunction in diabetes, the authors studied the distribution and densities of anionic charges through the rat glomerular wall upon intravascular infusion of Amadori products, as well as in various conditions of increased glomerular permselectivity. Polylysine-gold was used as the probe to reveal the anionic charges. The study was carried on renal tissue sections of bovine serum albumin (BSA)- and glycated BSA–injected, normoglycemic animals. Results were generated through morphometrical evaluations of the gold labeling. Changes in glomerular anionic distribution were corroborated on renal tissue sections of short- and long-term diabetic rats and of normal newborn rats, situations known for abnormal glomerular filtration. Altered renal function in these conditions was clearly associated with changes in glomerular anionic charges. On the other hand, the infusion of glycated albumin in the circulation of normal rats, though altering glomerular filtration properties, did not modify the distribution and density of the polylysine-gold labeling through the glomerular basement membrane. Thus, anionic charges seem not to be the factor involved in the early changes of glomerular permeability induced by circulating glycated albumin

Multimorbidity patterns and memory trajectories in older adults: Evidence from the English Longitudinal Study of Ageing

Background: We aimed to examine the multimorbidity patterns within a representative sample of UK older adults and their association with concurrent and subsequent memory. Methods: Our sample consisted of 11,449 respondents (mean age at baseline was 65.02) from the English Longitudinal Study of Ageing (ELSA). We used fourteen health conditions and immediate and delayed recall scores (IMRC and DLRC) over 7 waves (14 years of follow up). Latent class analyses were performed to identify the multimorbidity patterns and linear mixed models were estimated to explore their association with their memory trajectories. Models were adjusted by socio-demographics, BMI and health behaviors. Results: Results showed 8 classes: Class 1:Heart Disease/Stroke (26%), Class 2:Asthma/Lung Disease (16%), Class 3:Arthritis/Hypertension (13%), Class 4:Depression/Arthritis (12%), Class 5:Hypertension/Cataracts/Diabetes (10%), Class 6:Psychiatric Problems/Depression (10%), Class 7:Cancer (7%) and Class 8:Arthritis/Cataracts (6%). At baseline, Class 4 was found to have lower IMRC and DLRC scores and Class 5 in DLRC, compared to the no multimorbidity group (n=6380, 55.72% of total cohort). For both tasks, in unadjusted models, we found an accelerated decline in Classes 1, 3 and 8; and, for DLRC, also in Classes 2 and 5. However, it was fully attenuated after adjustments. Conclusions: These findings suggest that individuals with certain combinations of health conditions are more likely to have lower levels of memory compared those with no multimorbidity and their memory scores tend to differ between combinations. Socio-demographics and health behaviours have a key role to understand who is more likely to be at risk of an accelerated decline