Immune-epithelial cell cross-talk enhances antiviral responsiveness to SARS-CoV-2 in children.

The risk of developing severe COVID-19 rises dramatically with age. Schoolchildren are significantly less likely than older people to die from SARS-CoV-2 infection, but the molecular mechanisms underlying this age-dependence are unknown. In primary infections, innate immunity is critical due to the lack of immune memory. Children, in particular, have a significantly stronger interferon response due to a primed state of their airway epithelium. In single-cell transcriptomes of nasal turbinates, we find increased frequencies of immune cells and stronger cytokine-mediated interactions with epithelial cells, resulting in increased epithelial expression of viral sensors (RIG-I, MDA5) via IRF1. In vitro, adolescent peripheral blood mononuclear cells produce more cytokines, priming A549 cells for stronger interferon responses to SARS-CoV-2. Taken together, our findings suggest that increased numbers of immune cells in the airways of children and enhanced cytokine-based interactions with epithelial cells tune the setpoint of the epithelial antiviral system. Our findings shed light on the molecular basis of children's remarkable resistance to COVID-19 and may suggest a novel concept for immunoprophylactic treatments.

Adapting to a new environment: postnatal maturation of the human cardiomyocyte.

The postnatal mammalian heart undergoes remarkable developmental changes, which are stimulated by the transition from the intrauterine to extrauterine environment. With birth, increased oxygen levels promote metabolic, structural and biophysical maturation of cardiomyocytes, resulting in mature muscle with increased efficiency, contractility and electrical conduction. In this Topical Review article, we highlight key studies that inform our current understanding of human cardiomyocyte maturation. Collectively, these studies suggest that human atrial and ventricular myocytes evolve quickly within the first year but might not reach a fully mature adult phenotype until nearly the first decade of life. However, it is important to note that fetal, neonatal and paediatric cardiac physiology studies are hindered by a number of limitations, including the scarcity of human tissue, small sample size and a heavy reliance on diseased tissue samples, often without age-matched healthy controls. Future developmental studies are warranted to expand our understanding of normal cardiac physiology/pathophysiology and inform age-appropriate treatment strategies for cardiac disease.

Childhood to adulthood: Accounting for age dependence in healthy-reference distributions in 129 Xe gas-exchange MRI.

PURPOSE: Xenon-129 (129 Xe) gas-exchange MRI is a pulmonary-imaging technique that provides quantitative metrics for lung structure and function and is often compared to pulmonary-function tests. Unlike such tests, it does not normalize to predictive values based on demographic variables such as age. Many sites have alluded to an age dependence in gas-exchange metrics; however, a procedure for normalizing metrics has not yet been introduced. THEORY: We model healthy reference values for 129 Xe gas-exchange MRI against age using generalized additive models for location, scale, and shape (GAMLSS). GAMLSS takes signal data from an aggregated heathy-reference cohort and fits a distribution with flexible median, variation, skewness, and kurtosis to predict age-dependent centiles. This approach mirrors methods by the Global Lung Function Initiative for modeling pulmonary-function test data and applies it to binning methods widely used by the 129 Xe MRI community to interpret and quantify gas-exchange data. METHODS: Ventilation, membrane-uptake, red blood cell transfer, and red blood cell:membrane gas-exchange metrics were collected on 30 healthy subjects over an age range of 5 to 68 years. A GAMLSS model was fit against age and compared against widely used linear and generalized-linear binning 129 Xe MRI analysis schemes. RESULTS: All 4 gas-exchange metrics had significant skewness, and membrane-uptake had significant kurtosis compared to a normal distribution. Age has significant impact on distribution parameters. GAMLSS-binning produced narrower bins compared to the linear and generalized-linear binning schemes and distributed signal data closer to a normal distribution. CONCLUSION: The proposed "proof-of-concept" GAMLSS-binning approach can improve diagnostic accuracy of 129 Xe gas-exchange MRI by providing a means of modeling voxel distribution data against age.

Age-specific effects of density and weather on body condition and birth rates in a large herbivore, the Przewalski's horse.

Reproduction in young females can show a particularly sensitive response to environmental challenges, although empirical support from individual-based long-term studies is scarce. Based on a 20-year data set from a free-roaming Przewalski's horse population (Equus ferus przewalskii), we studied effects of large-herbivore density (horses + cattle) and weather conditions experienced during different life stages on females' annual birth rates. Foaling probability was very low in 2-year-olds, reaching maximum values in 5 to 10-year-olds, followed by a decrease in older females indicating reproductive senescence. Mother's previous reproductive investment affected her current reproduction; young and old mothers (as opposed to middle-aged ones), which had nursed a foal for at least 60 days during the previous year, reproduced with a lower probability. Foaling probability and body condition of young females were lower when large-herbivore density was high. Reproduction was also influenced by interactive weather effects during different life stages. Low late-summer precipitation during the females' year of birth was associated with a pronounced decrease in foaling probability in response to harsh late-winter temperatures prior to the mating season. In turn, increased amounts of late-summer rain during this early age together with more late-summer rain during the females' current pregnancy led to an increased reproductive probability in 2-3-year-olds. These results were corroborated by the ameliorating effects of late-summer rain on body condition in such females. In conclusion, our findings highlight the interactive importance of weather conditions experienced during early life, and of density and weather during current pregnancy on foaling probability, particularly in young females.

Variation in generation time reveals density regulation as an important driver of pace of life in a bird metapopulation.

Generation time determines the pace of key demographic and evolutionary processes. Quantified as the weighted mean age at reproduction, it can be studied as a life-history trait that varies within and among populations and may evolve in response to ecological conditions. We combined quantitative genetic analyses with age- and density-dependent models to study generation time variation in a bird metapopulation. Generation time was heritable, and males had longer generation times than females. Individuals with longer generation times had greater lifetime reproductive success but not a higher expected population growth rate. Density regulation acted on recruit production, suggesting that longer generation times should be favoured when populations are closer to carrying capacity. Furthermore, generation times were shorter when populations were growing and longer when populations were closer to equilibrium or declining. These results support classic theory predicting that density regulation is an important driver of the pace of life-history strategies.

Looking at breast cancer through the ethnic and racial lens𠄄One size definitely does not fit all.

LAY SUMMARY: Breast cancer cases are elevated in younger women in minority cohorts in the United States. Much of this is due to their younger age distributions, particularly for Hispanic women, but beyond this there are elevated risks in younger Black and Asian women. Disparities increase further for minority women when being diagnosed with more advanced disease or dying of breast cancer before the age of 50 years is considered. Strategies for culturally appropriate education about breast cancer, better access to screening, and prompt treatment must be implemented.

Effects of motion and retrospective motion correction on the visualization and quantification of perivascular spaces in ultrahigh resolution T2-weighted images at 7T.

PURPOSE: Motion can strongly affect MRI image quality and derived imaging measures. We studied the effects of motion and retrospective motion correction (MC) on the visualization and quantitative measures of the perivascular space and penetrating vessel (PVSV) complex, an essential part of the glymphatic system, on high-resolution T2 -weighted MRI images at 7T. METHODS: MC was achieved by adjusting k-space data based on head positions measured using fat navigator images. PVSV visibility and quantitative measures including diameter, volume fraction (VF), count, and contrast were compared between images with and without MC. RESULTS: Without MC, VF, and count decreased significantly with increasing head rotation. MC improved PVSV visualization in all cases with severe motion artifacts. MC decreased diameter in white matter (WM) and increased VF, count, and contrast in basal ganglia and WM. The changes of VF, count, and contrast after MC strongly correlated with motion severity. MC eliminated the significant dependences of VF and count on rotation and reduced the inter-subject variations of VF and count. The effect sizes of age and breathing gas effects on VF and count, and contrast increased in most cases after MC, while those on diameter exhibited inconsistent behavior. CONCLUSIONS: Motion affects PVSV quantification without MC. MC improves PVSV visibility and increases the statistical power of detecting physiological PVSV VF, count, and contrast changes but may have limited benefits for increasing the power for detecting diameter changes.

Mitochondrial polymorphism shapes intrapopulation behavioural variation in wild Drosophila.

Intrapopulation variation in behaviour, including activity, boldness and aggressiveness, is becoming more widely recognized and is hypothesized to substantially affect ecological and evolutionary dynamics. Although previous studies used candidate-gene approaches and genome-wide association analyses to identify genes correlated with variations in activity and aggressiveness, behavioural variation may not be fully captured in the nuclear genome, as it does not account for mitochondrial genomes. Mitochondrial genes encode products that are key regulators of the cellular energy-producing pathways in metabolic processes and are thought to play a significant role in life-history and reproductive traits. In this study, we considered many isofemale lines of Drosophila immigrans established from two wild populations to investigate whether intrapopulation variation in the mitochondrial genome affected activity level within this species. We identified two major haplogroups in these populations, and activity levels in both larvae and adults differed significantly between the two haplogroups. This result indicated that intrapopulation variation in activity level may be partially controlled by mitochondrial genes, along with the interaction between nuclear and mitochondrial genes and the age of individual organisms.

Individual variation in age-dependent reproduction: Fast explorers live fast but senesce young?

Adaptive integration of life history and behaviour is expected to result in variation in the pace-of-life. Previous work focused on whether 'risky' phenotypes live fast but die young, but reported conflicting support. We posit that individuals exhibiting risky phenotypes may alternatively invest heavily in early-life reproduction but consequently suffer greater reproductive senescence. We used a 7-year longitudinal dataset with >1,200 breeding records of >800 female great tits assayed annually for exploratory behaviour to test whether within-individual age dependency of reproduction varied with exploratory behaviour. We controlled for biasing effects of selective (dis)appearance and within-individual behavioural plasticity. Slower and faster explorers produced moderate-sized clutches when young; faster explorers subsequently showed an increase in clutch size that diminished with age (with moderate support for declines when old), whereas slower explorers produced moderate-sized clutches throughout their lives. There was some evidence that the same pattern characterized annual fledgling success, if so, unpredictable environmental effects diluted personality-related differences in this downstream reproductive trait. Support for age-related selective appearance was apparent, but only when failing to appreciate within-individual plasticity in reproduction and behaviour. Our study identifies within-individual age-dependent reproduction, and reproductive senescence, as key components of life-history strategies that vary between individuals differing in risky behaviour. Future research should thus incorporate age-dependent reproduction in pace-of-life studies.

Quantitative phase contrast MRI of penetrating arteries in centrum semiovale at 7T.

Pathological changes of penetrating arteries (PA) within the centrum semiovale is an important contributing factor of cerebral small vessel disease (SVD). However, quantitative characterization of the PAs remains challenging due to their sub-voxel sizes. Here, we proposed a Model-based Analysis of Complex Difference images (MACD) of phase contrast MRI capable of measuring the mean velocities (vmean), diameters (D), and volume flow rates (VFR) of PAs without contamination from neighboring static tissues at 7 T. Simulation, phantom and in vivo studies were performed to evaluate the reproducibility and errors of the proposed method. For comparison, a Model-based Analysis of Phase difference images (MAP) was also carried out in the simulation. The proposed MACD analysis approach was applied in vivo to study the age dependence of PA properties in healthy subjects between 21 and 55 years old. Simulation showed that our proposed MACD approach yielded smaller errors than MAP, with errors increasing at lower velocities and diameters for both methods. In the phantom study, errors of the MACD-derived vmean, D, and VFR were ≤20% of their true values when vmean≥1cm/s and similar at different spatial resolutions. On the other hand, errors of the uncorrected apparent velocities were 24-60% and depended strongly on voxel size. The MACD errors linearly increased with the angle (α) between the vessel and slice normal direction at α ≤ 2° but remained almost constant at larger α. Results of the in vivo studies showed that the coefficients of repeatability for vmean, D, and VFR for PAs with α = 0° were 0.67 cm/s, 0.060 mm, and 0.067 mm3/s, respectively. No significant age dependence was found for the number, vmean, D, and VFR of PAs. The mean vmean, D, and VFR over all PAs with α = 0° were 1.79 ±â€¯0.62 cm/s, 0.17 ±â€¯0.05 mm, and 0.36 ±â€¯0.18 mm3/s, respectively. Quantitative measurements of PAs with the MACD method may serve as a useful tool for illuminating the vascular pathology in cerebral SVD.

Fine-scale spatial climate variation and drought mediate the likelihood of reburning.

In many forested ecosystems, it is increasingly recognized that the probability of burning is substantially reduced within the footprint of previously burned areas. This self-limiting effect of wildland fire is considered a fundamental emergent property of ecosystems and is partly responsible for structuring landscape heterogeneity (i.e., mosaics of different age classes), thereby reducing the likelihood of uncharacteristically large fires in regions with active fire regimes. However, the strength and longevity of this self-limiting phenomenon is not well understood in most fire-prone ecosystems. In this study, we quantify the self-limiting effect in terms of its strength and longevity for five fire-prone study areas in western North America and investigate how each measure varies along a spatial climatic gradient and according to temporal (i.e., annual) climatic variation. Results indicate that the longevity (i.e., number of years) of the self-limiting effect ranges between 15 yr in the warm and dry study area in the southwestern United States to 33 yr in the cold, northern study areas in located in northwestern Montana and the boreal forest of Canada. We also found that spatial climatic variation has a strong influence on wildland fire's self-limiting capacity. Specifically, the self-limiting effect within each study area was stronger and lasted longer in areas with low mean moisture deficit (i.e., wetter and cooler settings) compared to areas with high mean moisture deficit (warmer and drier settings). Last, our findings show that annual climatic variation influences wildland fire's self-limiting effect: drought conditions weakened the strength and longevity of the self-limiting effect in all study areas, albeit at varying magnitudes. Overall, our study provides support for the idea that wildland fire contributes to spatial heterogeneity in fuel ages that subsequently mediate future fire sizes and effects. However, our findings show that the strength and longevity of the self-limiting effect varies considerably according to spatial and temporal climatic variation, providing land and fire managers relevant information for effective planning and management of fire and highlighting that fire itself is an important factor contributing to fire-free intervals.

Sex-Related Aspects of Biomarkers in Cardiac Disease.

Biomarkers play an important role in the clinical management of cardiac care. In particular, cardiac troponins (cTn) and natriuretic peptides are the cornerstones for the diagnosis of acute myocardial infarction (AMI) and for the diagnosis of heart failure (HF), respectively. Current guidelines do not make a distinction between women and men. However, the commonly used "one size fits all" algorithms are topic of debate to improve assessment of prognosis, particularly in women. Due to the high-sensitivity assays (hs-cTn), lower cTn levels (and 99th percentile upper reference limits) were observed in women as compared with men. Sex-specific diagnostic thresholds may improve the diagnosis of AMI in women, though clinical relevance remains controversial and more trials are needed. Also other diagnostic aspects are under investigation, like combined biomarkers approach and rapid measurement strategies. For the natriuretic peptides, previous studies observed higher concentrations in women than in men, especially in premenopausal women who might benefit from the cardioprotective actions. Contrary to hs-cTn, natriuretic peptides are particularly incorporated in the ruling-out algorithms for the diagnosis of HF and not ruling-in. Clinical relevance of sex differences here seems marginal, as clinical research has shown that negative predictive values for ruling-out HF were hardly effected when applying a universal diagnostic threshold that is independent from sex or other risk factors. Apart from the diagnostic issues of AMI in women, we believe that in the future most sex-specific benefits of cardiac biomarkers can be obtained in patient follow-up (guiding therapy) and prognostic applications, fitting modern ideas on preventive and personalized medicine.

Effect of dietary cereal type, crude protein and butyrate supplementation on metabolic parameters of broilers.

This study investigates the metabolic effects of maize- or wheat-based diets with normal (NP) and lowered (LP) dietary crude protein level [the latter supplemented with limiting amino acids and sodium (n-)butyrate at 1.5 g/kg diet] at different phases of broiler fattening. Blood samples of Ross 308 broilers were tested at the age of 1, 3 and 6 weeks. Total protein (TP) concentration increased in wheat-based and decreased in LP groups in week 3, while butyrate reduced albumin/TP ratio in week 1. Uric acid level was elevated by wheat-based diet in week 1 and by wheat-based diet and butyrate in week 3, but decreased in LP groups in weeks 3 and 6. Aspartate aminotransferase activity was increased by wheat-based diet in week 3, and creatine kinase activity was intensified by LP in weeks 3 and 6. Blood glucose level decreased in wheat-based groups in week 3; however, triglyceride concentration was augmented in the same groups in week 3. No change of glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide and insulin concentration was observed. In conclusion, an age-dependent responsiveness of broilers to dietary factors was found, dietary cereal type was a potent modulator of metabolism, and a low crude protein diet supplemented with limiting amino acids might have a beneficial impact on the growth of chickens.

Neurogenesis upregulation on the healthy hemisphere after stroke enhances compensation for age-dependent decrease of basal neurogenesis.

Stroke is a leading cause of death and disability worldwide with no treatment for the chronic phase available. Interestingly, an endogenous repair program comprising inflammation and neurogenesis is known to modulate stroke outcome. Several studies have shown that neurogenesis decreases with age but the therapeutic importance of endogenous neurogenesis for recovery from cerebral diseases has been indicated as its ablation leads to stroke aggravation and worsened outcome. A detailed characterization of the neurogenic response after stroke related to ageing would help to develop novel and targeted therapies. In an innovative approach, we used the DCX-Luc mouse, a transgenic model expressing luciferase in doublecortin-positive neuroblasts, to monitor the neurogenic response following middle cerebral artery occlusion over three weeks in three age groups (2, 6, 12months) by optical imaging while the stroke lesion was monitored by quantitative MRI. The individual longitudinal and noninvasive time profiles provided exclusive insight into age-dependent decrease in basal neurogenesis and neurogenic upregulation in response to stroke which are not accessible by conventional BrdU-based measures of cell proliferation. For cortico-striatal strokes the maximal upregulation occurred at 4days post stroke followed by a continuous decrease to basal levels by three weeks post stroke. Older animals effectively compensated for reduced basal neurogenesis by an enhanced sensitivity to the cerebral lesion, resulting in upregulated neurogenesis levels approaching those measured in young mice. In middle aged and older mice, but not in the youngest ones, additional upregulation of neurogenesis was observed in the contralateral healthy hemisphere. This further substantiates the increased propensity of older brains to respond to lesion situation. Our results clearly support the therapeutic relevance of endogenous neurogenesis for stroke recovery and particularly in older brains.

Suitable reference tissues for quantitative susceptibility mapping of the brain.

PURPOSE: Since quantitative susceptibility mapping (QSM) quantifies magnetic susceptibility relative to a reference value, a suitable reference tissue has to be available to compare different subjects and stages of disease. METHODS: To find such a suitable reference tissue for QSM of the brain, melanoma patients with and without brain metastases were measured. Twelve reference regions were chosen and assessed for stability of susceptibility values with respect to multiple intra-individual and inter-individual measurements, age, and stage of disease. RESULTS: Cerebrospinal fluid (CSF), the internal capsule and one region in the splenium of the corpus callosum are the regions with the smallest standard deviations of the mean susceptibility value. The mean susceptibility is 0.010 ± 0.014 ppm for CSF in the atrium of the lateral ventricles (csfpost ), -0.060 ± 0.019 ppm for the posterior limb of the internal capsule (ci2), and -0.008 ± 0.019 ppm for the splenium of the corpus callosum. csfpost and ci2 show nearly no dependence on age or stage of disease, whereas some other regions, e.g., the red nucleus, show moderate dependence on age or disease. CONCLUSION: The internal capsule and CSF appear to be the most suitable reference regions for QSM of the brain in the melanoma patients studied. Both showed virtually no dependence on age or disease and small variations among patients. Magn Reson Med 78:204-214, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Diffusion tensor spectroscopic imaging of the human brain in children and adults.

PURPOSE: We developed diffusion tensor spectroscopic imaging (DTSI), based on proton-echo-planar-spectroscopic imaging (PEPSI), and evaluated the feasibility of mapping brain metabolite diffusion in adults and children. METHODS: PRESS prelocalized DTSI at 3 Tesla (T) was performed using navigator-based correction of movement-related phase errors and cardiac gating with compensation for repetition time (TR) related variability in T1 saturation. Mean diffusivity (MD) and fractional anisotropy (FA) of total N-acetyl-aspartate (tNAA), total creatine (tCr), and total choline (tCho) were measured in eight adults (17-60 years) and 10 children (3-24 months) using bmax = 1734 s/mm2 , 1 cc and 4.5 cc voxel sizes, with nominal scan times of 17 min and 8:24 min. Residual movement-related phase encoding ghosting (PEG) was used as a regressor across scans to correct overestimation of MD. RESULTS: After correction for PEG, metabolite slice-averaged MD estimated at 20% PEG were lower (P < 0.042) for adults (0.17/0.20/0.18 × 10-3 mm2 /s) than for children (0.26/0.27/0.24 × 10-3 mm2 /s). Extrapolated to 0% PEG, the MD estimates decreased further (0.09/0.11/0.11 × 10-3 mm2 /s versus 0.15/0.16/0.15 × 10-3 mm2 /s). Slice-averaged FA of tNAA (P = 0.049), tCr (P = 0.067), and tCho (P = 0.003) were higher in children. CONCLUSION: This high-speed DTSI approach with PEG regression allows for estimation of metabolite MD and FA with improved tolerance to movement. Our preliminary data suggesting age-related changes support DTSI as a sensitive technique for investigating intracellular markers of biological processes. Magn Reson Med 78:1246-1256, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

The effect of age on the homotopic motor cortical long-term potentiation-like effect induced by quadripulse stimulation.

The reduction of plasticity with age has been shown by many previous papers in animal experiments. This issue can be studied in humans because several non-invasive brain stimulation techniques induce synaptic plasticity in the human brain. We investigated the influence of individuals' age on the responder rate of the long-term potentiation (LTP)-like effect induced by quadripulse magnetic stimulation (QPS). The participants were 107 healthy volunteers: 53 older participants (Mean ± SD 65.0 ± 1.5 years) and 54 younger participants (37.2 ± 8.7). The quadripulse stimulation with 5-ms inter-pulse interval (QPS5) was applied over the primary motor cortex (M1). We measured motor evoked potentials (MEPs) before QPS, and at five time points after QPS for up to 25 min. In each participant, average MEP amplitude (size) ratios were quantified. We first classified participants as responders and non-responders simply by comparing the size ratio with 1.0 for consistency with previous studies, then as "significant responders", "non-responders", and "opposite responders" for more detailed analysis by comparing the size ratio with the mean and standard deviation of the MEP size ratios of the sham condition. The degree of LTP-like effects induced by QPS5 was significantly smaller in the older group compared to the younger group. Also, the rates of responders and significant responders were lower in the older group (58 and 47%, respectively) compared to the younger group (80 and 76%, respectively). The age of the participants significantly affected the LTP-like effect induced by QPS5, which suggests that brain plasticity decreases with age.

Influence of maternal and sociodemographic characteristics on the accumulation of organohalogen compounds in Argentinian women. The EMASAR study.

The occurrence of organohalogen compounds in venous serum from post-partum mothers from two Argentinian cities, Salta and Ushuaia, has been investigated (n = 698). 4,4'-DDE was the most abundant compound in these cities, with geometric means of 33 and 67ng/g lipid weight, respectively. City of residence, age and parity were the main determinants of the accumulation of these compounds. Hexachlorobenzene (HCB) was the second most abundant pollutant in Ushuaia, 8.7ng/g lipid, and ß-hexachlorocyclohexane (ß-HCH) in Salta, 7.8ng/g lipid. Decabromodiphenyl ether was higher in Ushuaia than Salta, 8.2 and 4.1ng/g lipid, respectively. The predominance of ß-HCH, 4,4'-DDE and 4,4'-DDT in Salta was related with higher use of pesticides for agricultural applications. The observed higher concentrations of 4,4'-DDE and 4,4'-DDT in the mothers from rural+semi-urban sites than in urban areas were consistent with this agricultural origin. In addition, the most volatile organochlorine compounds included in this study, HCB and α-HCH, were mainly found in Ushuaia. The concentrations of the studied organohalogen pollutants in Argentina were lower than those found in other similar studies which is consistent with the location of these cities in the southern hemisphere. Age, mainly for 4,4'-DDE and polychlorobiphenyl (PCB) congeners 138, 153 and 180, and parity, mainly for HCB, ß-HCH, 4,4'-DDT and PCB congener 118, were the second main determinants of the concentrations of these compounds. Gestational weight gain also influenced on the maternal levels of HCB, ß-HCH, 4,4'-DDT and PCB congeners 118, 138 and 153. Higher weight accumulation during pregnancy involved dilution of these persistent pollutants. Body mass index (BMI) was a statistically significant determinant for 4,4'-DDT, α-HCH and PCB congeners 153 and 180. The observed direct correspondence between higher BMI and 4,4'-DDT concentrations was in agreement with the above reported inputs related with agricultural applications. The reverse correspondence of BMI with α-HCH and the PCB congeners indicated higher dilution at higher weight increase.

The age dependence of T2 relaxation times of N-acetyl aspartate, creatine and choline in the human brain at 3 and 4T.

Knowledge of the T2 age dependence is of importance for MRS clinical studies involving subject groups with a wide age range. A number of studies have focused on the age dependence of T2 values in the human brain, with rather conflicting results. The aim of this study was to analyze the age dependence of T2 values of N-acetyl aspartate (NAA), creatine (Cr) and choline (Cho) in the human brain using data acquired at 3T and 4T and to assess the influence of the macromolecule (MM) baseline handling on the obtained results. Two distinct groups of young and elderly controls have been measured at 3T (TE = 30-540 ms, 9 young and 11 elderly subjects) and 4T (TE = 10-180 ms, 18 young and 14 elderly subjects) using single-voxel spectroscopy. In addition, MM spectra were measured from two subjects using the inversion-recovery technique at 4T. All spectra were processed with LCModel using basis sets with different MM signals (measured or simulated) and also with MM signals included for a different TE range. Individual estimated T2 values were statistically analyzed using the R programming language for the age dependence of T2 values as well as the influence of the MM baseline handling. A significant decrease of T2 values of NAA and Cr in elderly subjects compared with young subjects was confirmed. The same trend was observed for Cho. Significantly higher T2 values calculated using the measured MM baseline for all studied metabolites at 4T were observed for both young and elderly subjects. To conclude, while the handling of MM and lipid signals may have a significant effect on estimated T2 values, we confirmed the age dependence of T2 values of NAA and Cr and the same trend for Cho in the human brain. Copyright © 2016 John Wiley & Sons, Ltd.

Reference intervals of plasma matrix metalloproteinases 2, 3, and 9 and serum asymmetric dimethylarginine levels.

OBJECTIVE: The present study aimed to verify the reference intervals of plasma matrix metalloproteinases (MMPs) 2, 3, and 9 and serum asymmetric dimethylarginine (ADMA) in a healthy population with an average age corresponding to that of patients with cardiovascular diseases. METHODS: The study included 180 healthy volunteers. Plasma MMP-2, MMP-3, MMP-9, and serum ADMA levels were determined using an enzyme-linked immunosorbent assay. These levels were analyzed for association with age and gender. The Cbstat5, R software, and NCSS 2007 programs were used for statistical analysis. RESULTS: The average volunteer age was 47.4 years in the group in which MMP-3 and ADMA were analyzed, 40.3 years in the MMP-9 group, and 47.8 years for the MMP-2 group. Serum ADMA levels were determined to be independent of age and gender. Plasma MMP-2 levels were significantly correlated with age (p = 0.001), with lower levels detected in persons ≤ 49 years of age. Plasma MMP-3 was significantly associated with both age (p < 0.0001) and gender, with lower levels detected in persons of ≤ 47 years of age and among women. Plasma MMP-9 levels were not age dependent, but were associated with gender (p = 0.014), showing lower levels in women. CONCLUSIONS: Reference intervals of heparin-plasma MMP-2, MMP-3, and MMP-9 and serum ADMA levels were determined. MMP-2 and MMP-3 levels were found to be age dependent, and MMP-3 and MMP-9 levels were gender dependent.