Principal Component Analyses and Scalp Distribution of the Auditory P150–250 and N250–550 to Speech Contrasts in Mexican and American Infants

We report a Principal Component Analysis (PCA) and the scalp distribution of the normalized peak amplitude values for speech-related auditory Event-related Potentials (ERP) P150–250 and N250–550 in 7-, 11-, and 20-month-old American infants learning English and in 10–13-month-old Mexican infants learning Spanish. After assessing the infant auditory ERP P-N complex using PCA, we evaluated the topographic distribution of each of the discriminatory phases to native and non-native CV-syllabic contrasts used in Spanish and English. We found that the first two Principal Components for each contrast type across ages showing a maximization of differences between the P150–250 and the N250–550 waves, explain more than 70% of the variance. The scalp distributions of the P150–250 and N250–550 components also differed, the P150–250 showing a frontal and anterior temporal distribution, and the N250–550 a more posterior distribution. The older infants showed a broader distribution of responses, particularly for the N250–550. There were no differences in the topographies of the components between same-aged Mexican and American infants. We discuss the perceptual/linguistic functions that each component may reflect during development and across the two cultures.     

Interhemisphere Power Ratios of Cortical Potentials in the 1–60 Hz Band during the Formation and Testing of a Cognitive Set to a Facial Expression

Interhemisphere cortical potential power ratios were studied in the 1–60 Hz band during the prestimulus period at the stages of formation and testing of a cognitive set to a facial expression. Different topographies in the patterns of asymmetry in subjects with different levels of set expression were demonstrated. At the formation stage, the group of subjects without actualization of the set (n = 11) showed significantly higher power levels at gamma frequencies (21–40 and 41–60 Hz) in the frontal areas of the right hemisphere and at frequencies at 2–7 and 8–13 Hz, also in the frontal areas, but in the left hemisphere. At the set testing stage, the main topographic asymmetry pattern in these subjects persisted. In subjects with marked set actualization (n = 18), formation was characterized by a different topographical asymmetry pattern, with significantly higher power levels at gamma frequencies seen in the posterior temporal and occipital areas of the left hemisphere at frequencies of 2–7, 8–13, and 14–20 Hz, also in the posterior areas, but in the right hemisphere. At the set testing stage, the phenomenon of interhemisphere asymmetry in the power of cortical potentials was not seen.     

Blood lipids and lipoproteins in relation to incidence and mortality risks for CVD and cancer in the prospective EPIC–Heidelberg cohort

Background

Circulating concentrations of lipid biomarkers are associated with risk of cardiovascular diseases (CVD). The evidence for a relationship with cancer risk, however, is not entirely consistent. This study aims to assess the relationships of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein (a) (apo(a)), apoB-100, and lipoprotein(a) (Lp(a)) with risk of common cancer forms and total cancer mortality in comparison to incidence and mortality of CVD.

Methods

We selected a case-cohort sample out of the prospective EPIC–Heidelberg study, including a random subcohort (n?=?2739), and cases of cancer (n?=?1632), cancer mortality (n?=?761), CVD (n?=?1070), and CVD mortality (n?=?381). Concentrations of lipid biomarkers were measured in pre-diagnostic blood samples. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Prentice-weighted Cox regression models.

Results

High levels of circulating apoB-100 and TG were inversely associated and high HDL-C levels were positively associated with breast cancer risk (highest vs. lowest quartile (Q4 vs. Q1), HR_apoB 0.71, 95% CI 0.52–0.98; HR_TG 0.65, 0.46–0.92; and HR_HDL 1.39, 1.01–1.93). Higher levels of Lp(a) were associated with an increase in prostate cancer risk (Q4 vs. Q1, HR_Lp(a) 1.43, 1.02–2.03) and high levels of apo(a) were associated with a decrease in lung cancer risk (Q4 vs. Q1, HR_apo(a) 0.52, 0.30–0.91). High TC, HDL-C, apo(a), and Lp(a) levels were associated with a reduction in total cancer mortality (Q4 vs. Q1, HR_TC 0.71, 0.54–0.94; HR_HDL 0.67, 0.50–0.91; HR_apo(a) 0.71, 0.54–0.93; and HR_Lp(a) 0.74, 0.57–0.98). All lipid biomarkers were associated with risk of myocardial infarction, whereby TC, apoB-100, TG, and Lp(a) were positively and HLD-C and apo(a) inversely associated with risk. Only high levels of TG were associated with an increased risk of stroke. None of the lipids were associated with risk of colorectal cancer and with risk of CVD mortality after multivariable adjustments.

Conclusions

This prospective study demonstrates inverse associations of lipid biomarkers with cancer incidence and mortality, with the exception of positive associations of HDL-C and Lp(a) with breast and prostate cancer risk, respectively. Thus, the observed cancer risk pattern clearly differs from the CVD risk pattern.

     

An acid-labile temperature-responsive sol–gel reversible polymer for enhanced gene delivery to the myocardium and skeletal muscle cells

The work demonstrates the development of acid-labile temperature-responsive sol–gel reversible polymer for enhanced in vivo myocardium and skeletal muscle gene delivery. In this report, multi-block copolymers (MBCPs) synthesized from pluronic^® and di-(ethylene glycol) divinyl ether (DEGDVE) were used as a delivery vehicle for controlled and sustained release of plasmid DNA (pDNA) in in vitro as well as in vivo experiments. The non-ionic MBCP/pDNA complex showed remarkable transfection efficiencies against the myocardium cells as well as muscle cells in vivo, which is otherwise very difficult to achieve by using cationic polymers. In in vitro experimental settings, this intelligent stimuli-responsive polymer is shown to improve the transfection efficiency of branched polyethylenimine (BPEI)/pDNA complex when used together. The effect of MBCP on the surface charge and particle size of its various complexes with pDNA and BPEI was also studied. The release profile of pDNA from the MBCP gel was investigated and pH of the degraded polymer was also monitored to ascertain its non-cytotoxicity arising due to the increased acidity as observed with other PLGA-based polymers. The rapid sol–gel transition of MBCP under thermal stimuli with concomitant release of pDNA under acidic stimulation has potential for site specific, efficient and controlled transfection of therapeutic gene. In short, MBCP provides the silver lining in combat against the hurdles encountered in transfection to myocardial or other muscle cells.     

To Go or not to Go, that is the question: Do the N2 and P3 reflect stimulus- or response-related conflict?

Several studies have linked increases in the N2 and P3 components to response conflict, evoked when multiple incompatible responses are simultaneously activated. However, these studies confound a change of response with a change of stimulus identity, and often a change in stimulus probability also. In two experiments, additional trial types were presented, which signified a change of stimulus, but still demanded the expected response. RT costs were observed when participants changed a planned response to a different one, and when they activated an unplanned response, but RT was not substantially increased for stimulus mismatch trials when these were clearly linked to the required response. N2 results were mixed and did not clearly favour a stimulus mismatch or response conflict interpretation. For the P3 component, stimulus-related differences were small but significant, with large increases in positivity when participants cancelled the planned response. Further experiments are required to determine the relative contribution of stimulus- and response-related conflict to N2.     

Lipid–calcium phosphate nanoparticles for delivery to the lymphatic system and SPECT/CT imaging of lymph node metastases

A lipid/calcium/phosphate (LCP) nanoparticle (NP) formulation (particle diameter ∼25 nm) with superior siRNA delivery efficiency was developed and reported previously. Here, we describe the successful formulation of ¹¹¹In into LCP for SPECT/CT imaging. Imaging and biodistribution studies showed that, polyethylene glycol grafted ¹¹¹In-LCP preferentially accumulated in the lymph nodes at ∼70% ID/g in both C57BL/6 and nude mice when the improved surface coating method was used. Both the liver and spleen accumulated only ∼25% ID/g. Larger LCP (diameter ∼67 nm) was less lymphotropic. These results indicate that 25 nm LCP was able to penetrate into tissues, enter the lymphatic system, and accumulate in the lymph nodes via lymphatic drainage due to 1) small size, 2) a well-PEGylated lipid surface, and 3) a slightly negative surface charge. The capability of intravenously injected ¹¹¹In-LCP to visualize an enlarged, tumor-loaded sentinel lymph node was demonstrated using a 4T1 breast cancer lymph node metastasis model. Systemic gene delivery to the lymph nodes after IV injection was demonstrated by the expression of red fluorescent protein cDNA. The potential of using LCP for lymphatic drug delivery is discussed.     

An aptamer that binds efficiently to the hemagglutinins of highly pathogenic avian influenza viruses (H5N1 and H7N7) and inhibits hemagglutinin–glycan interactions

Highly pathogenic avian influenza (HPAI) H5 and H7 viruses have ravaged the poultry industry in numerous countries in Asia, Europe, Africa and the Middle East, and have resulted in the deaths of millions of birds. Although HPAI H5N1 viruses currently remain avian viruses, they are continuously evolving and have the potential to become pandemic-type viruses capable of human–human transmission. To develop specific reagents to allow better preparedness against this threat, we selected an aptamer (8-3) from a completely random RNA pool that binds with high affinity (∼K_D 170 pM) to the hemagglutinins (HAs) derived from HPAI H5N1 (A/H5N1/Vietnam/1194/2004 and A/H5N1/Indonesia/05/2005) and H7N7 (A/H7N7/Netherlands/219/2003) influenza A viruses. Aptamer 8-3 was able to efficiently distinguish HAs derived from subtypes of influenza A virus other than H5 and H7. Aptamer 8-3 was analyzed further to assess its ability to interfere with HA–glycan interactions using our previously established SPR-based competitive assay, and we found that aptamer 8-3 efficiently interferes with HA–glycan binding (EC₅₀ ∼ 25 nM). To derive shorter variants for other applications, aptamer 8-3 was shortened to a 44-mer by deletion analyses. The shortened aptamer, 8-3S, retains the full-length aptamer’s affinity and specificity for its cognate Has, and also interferes with HA–glycan interactions. These studies suggest that aptamer 8-3S should be studied further to explore its potential applications not only in surveillance and diagnosis, but also in the development of H5N1- and H7N7-specific virucidal products that interfere with virus–host interactions to contain future H5N1 and H7N7 pandemics.     

Brain–heart coupling at the P300 latency is linked to anterior cingulate cortex and insula—A cardio-electroencephalographic covariance tracing study

Prior work on the coupling of cortical and cardiac responses to feedback demonstrated that feedback-evoked single-trial EEG magnitudes 300 ms post-stimulus predict the degree of subsequent cardiac acceleration. The main goal of the current study was to explore the neural sources of this phenomenon using (a) independent component analysis in conjunction with dipole fitting and (b) low resolution electromagnetic tomography (LORETA) in N = 14 participants who performed a gambling task with feedback presented after each trial. It was shown that independent components localized near anterior cingulate cortex produced robust within-subjects correlations with feedback-evoked heart-period, suggesting that anterior cingulate cortex activity 300 ms after feedback presentation predicts the strength of subsequent cardiac acceleration. Moreover, interindividual differences in evoked left insular cortex LORETA-estimated activity at around 300 ms moderated within-subjects EEG–heart period correlations. These results suggest that key regions of central autonomic control are involved in cortico-cardiac coupling evoked by feedback stimuli.     

Test–retest stability,convergent validity,and sensitivity to change for the Goal-Based Outcome tool for adolescents: Analysis of data from a randomized controlled trial

Objective(s)

To examine the psychometric properties of the idiographic Goal-Based Outcome (GBO) tool for young people: test–retest stability, convergent validity, and sensitivity to an intervention.

Methods

This measure validation study used data from a randomized controlled trial of school-based humanistic counseling. We used multilevel analyses to assess test–retest stability, convergent validity of the GBO tool against nomothetic measures of mental wellbeing, and sensitivity to an intervention.

Results

The GBO tool showed acceptable stability over a 6–24 week period; moderate convergent validity with nomothetic measures of mental well-being, self-esteem, and depression; and greater sensitivity to an intervention than a measure of psychological distress.

Conclusions

The GBO tool shows evidence of having acceptable psychometric properties and is suitable for monitoring change on individual goals. It may also have the capacity to function as a population-level indicator of outcomes in conjunction with the use of other measures of mental health and wellbeing.     

Log-linear models for assessing gene–age interaction and their application to case-control studies of the apolipoprotein E (apoE) gene in Alzheimer's disease

Case-control studies provide a powerful approach for detecting disease-susceptibility genes or assessing gene–environment interactions. We investigated the situation in which the gene being studied plays a role in several diseases, and the allele frequency among subjects free of the disease of interest consequently decreases with age as subjects die from other diseases. The logistic model is one approach frequently used for analyzing case-control data, but it cannot accommodate this dependence of genotype and age. Using a log-linear model, we therefore proposed a hierarchical procedure that could be used as a valid method for assessing interactions in such situations. We then applied this procedure to observed data on Alzheimer's disease and the apolipoprotein E gene in Japan. We were able to derive an appropriate inference on whether the interaction was a gene–age interaction or merely a bias due to death from other diseases.     

The Ornstein–Uhlenbeck third-order Gaussian process (OUGP) applied directly to the un-resampled heart rate variability (HRV) tachogram for detrending and low-pass filtering

The heart rate variability signal derived from the ECG is a beat-to-beat record of RR-intervals and is, as a time series, irregularly sampled. It is common engineering practice to resample this record, typically at 4 Hz, onto a regular time axis for conventional analysis using IIR and FIR filters, and power spectral estimators, in the time and frequency domain, respectively. However, such interpolative resampling introduces noise into the signal and the information quality is compromised. Here, the Ornstein-Uhlenbeck third-order band-pass filter is presented which operates on data sampled at arbitrary time and preserves fidelity. The algorithm is available as open source code for MATLAB(?) (MathWorks? Inc.) and supported by an interactive website at http://clinengnhs.liv.ac.uk/OUGP.htm.     

Refinement of the locus for autosomal recessive cone–rod dystrophy (CORD8) linked to chromosome 1q23–q24 in a Pakistani family and exclusion of candidate genes

Cone–rod retinal dystrophy (CORD) characteristically leads to early impairment of vision due to the simultaneous involvement of both cone and rod photoreceptor cells. Several loci/genes have been identified for CORD, including the cone–rod dystrophy (CORD8) locus [OMIM#605549] identified for a Pakistani family. All members of this family underwent detailed clinical re-examination to determine the nature of the dystrophy. All affected individuals suffered from bilateral CORD8 with an autosomal recessive mode of inheritance. The CORD8 locus, mapped on chromosome 1q12–q24, consisted of a very large critical disease region of 21 cM. Analysis with more recently available microsatellite markers within the reported region showed heterozygosity with some of the new markers, and the crossovers lead to a refinement of the disease region from 21 to 11.53 cM. Mutation screening has excluded some of the candidate genes in the region. The disease phenotype of this family could be due to a mutation in a novel gene located within the refined CORD8 locus.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at .Khalid Anwar: Deceased