Zinc intake, status and indices of cognitive function in adults and children: a systematic review and meta-analysis

In developing countries, deficiencies of micronutrients are thought to have a major impact on child development; however, a consensus on the specific relationship between dietary zinc intake and cognitive function remains elusive. The aim of this systematic review was to examine the relationship between zinc intake, status and indices of cognitive function in children and adults. A systematic literature search was conducted using EMBASE, MEDLINE and Cochrane Library databases from inception to March 2014. Included studies were those that supplied zinc as supplements or measured dietary zinc intake. A meta-analysis of the extracted data was performed where sufficient data were available. Of all of the potentially relevant papers, 18 studies met the inclusion criteria, 12 of which were randomised controlled trials (RCTs; 11 in children and 1 in adults) and 6 were observational studies (2 in children and 4 in adults). Nine of the 18 studies reported a positive association between zinc intake or status with one or more measure of cognitive function. Meta-analysis of data from the adult’s studies was not possible because of limited number of studies. A meta-analysis of data from the six RCTs conducted in children revealed that there was no significant overall effect of zinc intake on any indices of cognitive function: intelligence, standard mean difference of <0.001 (95% confidence interval (CI) –0.12, 0.13) P=0.95; executive function, standard mean difference of 0.08 (95% CI, –0.06, 022) P=0.26; and motor skills standard mean difference of 0.11 (95% CI –0.17, 0.39) P=0.43. Heterogeneity in the study designs was a major limitation, hence only a small number (n=6) of studies could be included in the meta-analyses. Meta-analysis failed to show a significant effect of zinc supplementation on cognitive functioning in children though, taken as a whole, there were some small indicators of improvement on aspects of executive function and motor development following supplementation but high-quality RCTs are necessary to investigate this further

Accurate Visuomotor Control below the Perceptual Threshold of Size Discrimination

Background: Human resolution for object size is typically determined by psychophysical methods that are based on conscious perception. In contrast, grasping of the same objects might be less conscious. It is suggested that grasping is mediated by mechanisms other than those mediating conscious perception. In this study, we compared the visual resolution for object size of the visuomotor and the perceptual system. Methodology/Principal Findings: In Experiment 1, participants discriminated the size of pairs of objects once through perceptual judgments and once by grasping movements toward the objects. Notably, the actual size differences were set below the Just Noticeable Difference (JND). We found that grasping trajectories reflected the actual size differences between the objects regardless of the JND. This pattern was observed even in trials in which the perceptual judgments were erroneous. The results of an additional control experiment showed that these findings were not confounded by task demands. Participants were not aware, therefore, that their size discrimination via grasp was veridical. Conclusions/Significance: We conclude that human resolution is not fully tapped by perceptually determined thresholds

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Distinct Neurobehavioural Effects of Cannabidiol in Transmembrane Domain Neuregulin 1 Mutant Mice

The cannabis constituent cannabidiol (CBD) possesses anxiolytic and antipsychotic properties. We have previously shown that transmembrane domain neuregulin 1 mutant (Nrg1 TM HET) mice display altered neurobehavioural responses to the main psychoactive constituent of cannabis, Δ9-tetrahydrocannabinol. Here we investigated whether Nrg1 TM HET mice respond differently to CBD and whether CBD reverses schizophrenia-related phenotypes expressed by these mice. Adult male Nrg1 TM HET and wild type-like littermates (WT) received vehicle or CBD (1, 50 or 100 mg/kg i.p.) for 21 days. During treatment and 48 h after withdrawal we measured behaviour, whole blood CBD concentrations and autoradiographic receptor binding. Nrg1 HET mice displayed locomotor hyperactivity, PPI deficits and reduced 5-HT2A receptor binding density in the substantia nigra, but these phenotypes were not reversed by CBD. However, long-term CBD (50 and 100 mg/kg) selectively enhanced social interaction in Nrg1 TM HET mice. Furthermore, acute CBD (100 mg/kg) selectively increased PPI in Nrg1 TM HET mice, although tolerance to this effect was manifest upon repeated CBD administration. Long-term CBD (50 mg/kg) also selectively increased GABAA receptor binding in the granular retrosplenial cortex in Nrg1 TM HET mice and reduced 5-HT2A binding in the substantia nigra in WT mice. Nrg1 appears necessary for CBD-induced anxiolysis since only WT mice developed decreased anxiety-related behaviour with repeated CBD treatment. Altered pharmacokinetics in mutant mice could not explain our findings since no genotype differences existed in CBD blood concentrations. Here we demonstrate that Nrg1 modulates acute and long-term neurobehavioural effects of CBD, which does not reverse the schizophrenia-relevant phenotypes

Grasping isoluminant stimuli

We used a virtual reality setup to let participants grasp discs, which differed in luminance, chromaticity and size. Current theories on perception and action propose a division of labor in the brain into a color proficient perception pathway and a less color-capable action pathway. In this study, we addressed the question whether isoluminant stimuli, which provide only a chromatic but no luminance contrast for action planning, are harder to grasp than stimuli providing luminance contrast or both kinds of contrast. Although we found that grasps of isoluminant stimuli had a slightly steeper slope relating the maximum grip aperture to disc size, all other measures of grip quality were unaffected. Overall, our results do not support the view that isoluminance of stimulus and background impedes the planning of a grasping movement

First Data Release of the COSMOS Ly alpha Mapping and Tomography Observations: 3D Ly alpha Forest Tomography at 2.05 < z < 2.55

Faint star-forming galaxies at z ~ 2–3 can be used as alternative background sources to probe the Lyα forest in addition to quasars, yielding high sightline densities that enable 3D tomographic reconstruction of the foreground absorption field. Here, we present the first data release from the COSMOS Lyα Mapping And Tomography Observations (CLAMATO) Survey, which was conducted with the LRIS spectrograph on the Keck I telescope. Over an observational footprint of 0.157 deg2 within the COSMOS field, we used 240 galaxies and quasars at 2.17 < z < 3.00, with a mean comoving transverse separation of $2.37\,{h}^{-1}\,\mathrm{Mpc}$, as background sources probing the foreground Lyα forest absorption at 2.05 < z < 2.55. The Lyα forest data was then used to create a Wiener-filtered tomographic reconstruction over a comoving volume of $3.15\,\times {10}^{5}\,{h}^{-3}\,{\mathrm{Mpc}}^{3}$ with an effective smoothing scale of $2.5\,{h}^{-1}\,\mathrm{Mpc}$. In addition to traditional figures, this map is also presented as a virtual-reality visualization and manipulable interactive figure. We see large overdensities and underdensities that visually agree with the distribution of coeval galaxies from spectroscopic redshift surveys in the same field, including overdensities associated with several recently discovered galaxy protoclusters in the volume. Quantitatively, the map signal-to-noise is ${\rm{S}}/{{\rm{N}}}^{\mathrm{wiener}}\approx 3.4$ over a 3 h −1Mpc top-hat kernel based on the variances estimated from the Wiener filter. This data release includes the redshift catalog, reduced spectra, extracted Lyα forest pixel data, and reconstructed tomographic map of the absorption. These can be downloaded from Zenodo (10.5281/zenodo.1292459)

Trends in modeling Biomedical Complex Systems

In this paper we provide an introduction to the techniques for multi-scale complex biological systems, from the single bio-molecule to the cell, combining theoretical modeling, experiments, informatics tools and technologies suitable for biological and biomedical research, which are becoming increasingly multidisciplinary, multidimensional and information-driven. The most important concepts on mathematical modeling methodologies and statistical inference, bioinformatics and standards tools to investigate complex biomedical systems are discussed and the prominent literature useful to both the practitioner and the theoretician are presented

Sex-differential genetic effect of phosphodiesterase 4D (PDE4D) on carotid atherosclerosis

<p>Abstract</p> <p>Background</p> <p>The phosphodiesterase 4D (PDE4D) gene was reported as a susceptibility gene to stroke. The genetic effect might be attributed to its role in modulating the atherogenic process in the carotid arteries. Using carotid intima-media thickness (IMT) and plaque index as phenotypes, the present study sought to determine the influence of this gene on subclinical atherosclerosis.</p> <p>Methods</p> <p>Carotid ultrasonography was performed on 1013 stroke-free subjects who participated in the health screening programs (age 52.6 ± 12.2; 47.6% men). Genotype distribution was compared among the high-risk (plaque index ≥ 4), low-risk (index = 1-3), and reference (index = 0) groups. We analyzed continuous IMT data and further dichotomized IMT data using mean plus one standard deviation as the cutoff level. Because the plaque prevalence and IMT values displayed a notable difference between men and women, we carried out sex-specific analyses in addition to analyzing the overall data. Rs702553 at the PDE4D gene was selected because it conferred a risk for young stroke in our previous report. Previous young stroke data (190 cases and 211 controls) with an additional 532 control subjects without ultrasonic data were shown as a cross-validation for the genetic effect.</p> <p>Results</p> <p>In the overall analyses, the rare homozygote of rs702553 led to an OR of 3.1 (p = 0.034) for a plaque index ≥ 4. When subjects were stratified by sex, the genetic effect was only evident in men but not in women. Comparing male subjects with plaque index ≥ 4 and those with plaque index = 0, the TT genotype was over-represented (27.6% vs. 13.4%, p = 0.008). For dichotomized IMT data in men, the TT genotype had an OR of 2.1 (p = 0.032) for a thicker IMT at the common carotid artery compared with the (AA + AT) genotypes. In women, neither IMT nor plaque index was associated with rs702553. Similarly, SNP rs702553 was only significant in young stroke men (OR = 1.8, p = 0.025) but not in women (p = 0.27).</p> <p>Conclusions</p> <p>The present study demonstrates a sex-differential effect of PDE4D on IMT, plaque index and stroke, which highlights its influence on various aspects of atherogenesis.</p

Serum IL-6: a candidate biomarker for intracranial pressure elevation following isolated traumatic brain injury

<p>Abstract</p> <p>Background</p> <p>Increased intracranial pressure (ICP) is a serious, life-threatening, secondary event following traumatic brain injury (TBI). In many cases, ICP rises in a delayed fashion, reaching a maximal level 48-96 hours after the initial insult. While pressure catheters can be implanted to monitor ICP, there is no clinically proven method for determining a patient's risk for developing this pathology.</p> <p>Methods</p> <p>In the present study, we employed antibody array and Luminex-based screening methods to interrogate the levels of inflammatory cytokines in the serum of healthy volunteers and in severe TBI patients (GCS≤8) with or without incidence of elevated intracranial pressure (ICP). De-identified samples and ELISAs were used to confirm the sensitivity and specificity of IL-6 as a prognostic marker of elevated ICP in both isolated TBI patients, and polytrauma patients with TBI.</p> <p>Results</p> <p>Consistent with previous reports, we observed sustained increases in IL-6 levels in TBI patients irrespective of their ICP status. However, the group of patients who subsequently experienced ICP ≥ 25 mm Hg had significantly higher IL-6 levels within the first 17 hours of injury as compared to the patients whose ICP remained ≤20 mm Hg. When blinded samples (n = 22) were assessed, a serum IL-6 cut-off of <5 pg/ml correctly identified 100% of all the healthy volunteers, a cut-off of >128 pg/ml correctly identified 85% of isolated TBI patients who subsequently developed elevated ICP, and values between these cut-off values correctly identified 75% of all patients whose ICP remained ≤20 mm Hg throughout the study period. In contrast, the marker had no prognostic value in predicting elevated ICP in polytrauma patients with TBI. When the levels of serum IL-6 were assessed in patients with orthopedic injury (n = 7) in the absence of TBI, a significant increase was found in these patients compared to healthy volunteers, albeit lower than that observed in TBI patients.</p> <p>Conclusions</p> <p>Our results suggest that serum IL-6 can be used for the differential diagnosis of elevated ICP in isolated TBI.</p

Patient satisfaction with antiretroviral services at primary health-care facilities in the Free State, South Africa – a two-year study using four waves of cross-sectional data

<p>Abstract</p> <p>Background</p> <p>The study's first objective was to determine the levels of patient satisfaction with services at antiretroviral treatment (ART) assessment sites. Differences in patient satisfaction with several aspects of service over time and among health districts were measured. The second objective was to examine the association between human resource shortages and levels of patient satisfaction with services.</p> <p>Methods</p> <p>Four cross-sectional waves of data were collected from a random sample of 975 patients enrolled in the Free State's public-sector ART programme. One-way analysis of variance (ANOVA) with the Bonferroni adjustment for multiple comparisons was used to assess the differences in patient satisfaction among the Province's five districts and among the four waves of data. Correlation coefficient analysis using Pearson's <it>r </it>was used to assess the association between ART nurse vacancy rates and patient satisfaction with the services provided by nurses over time.</p> <p>Results</p> <p>With respect to both general services and the services provided by nurses, our results indicate high overall satisfaction among Free State patients receiving public-sector ART. However, our data present a less positive picture of patient satisfaction with waiting times. Patients in Fezile Dabi District were generally slightly dissatisfied with the waiting times at their assessment sites. In fact, waiting times at assessment sites were the most important predictor of discontent among ART patients. Significant geographical (<it>P </it>< 0.001) and temporal differences (<it>P </it>< 0.005) were observed in these three aspects of patient satisfaction. Patients were most satisfied in Thabo Mofutsanyana District and least satisfied in Motheo District. Patients in Fezile Dabi District were generally slightly dissatisfied with the waiting times at their assessment sites. Finally, our analysis revealed a strong negative association (<it>r </it>= -0.438, <it>P </it>< 0.001) between nurse vacancy rates and mean satisfaction levels with services performed by nurses at baseline. Patients attending facilities with high professional nurse vacancy rates reported significantly less satisfaction with nurses' services than did those attending facilities with fewer vacant nursing posts.</p> <p>Conclusion</p> <p>Collectively, our findings show high levels of patient satisfaction with ART-related services, but also confirm claims by other studies, which have identified human resource shortages as the most important obstacle to a successful South African AIDS strategy.</p