Lack of clear understanding remains on the overlapping atrophy patterns of aging and early Alzheimer disease (AD) pathology in gray matter (GM) of the brain in vivo.
To evaluate the independent and ...overlapping patterns of GM atrophy in normal aging and AD.
A total of 169 cognitively normal subjects and 33 persons with probable AD enrolled in the longitudinal Cardiovascular Health Study-Cognition Study underwent 3-dimensional volumetric MRI scans. Controls remained cognitively normal for at least 5 years after their MRI scans and the probable AD subjects were relatively early in their clinical course with an average modified Mini-Mental State Examination score of 76/100. The scans were analyzed using voxel-based morphometry adjusting for total intracranial volume, gender, education, and race.
With older age, GM volume was lower in the sensorimotor and heteromodal association areas in frontal, temporal, occipital, and parietal lobes, as well as in the cerebellum (false discovery rate p = 0.05). Additional atrophy was observed in the posterior hippocampus, thalamus, and middle cingulate gyrus. By contrast, atrophy was seen in subjects with AD in the anterior hippocampal/parahippocampal regions and the precuneus. Normal aging and AD overlapped in the hippocampal body and the entorhinal cortex.
Brain atrophy with aging was observed in supratentorial and infratentorial areas, as well in primary motor, sensory, and heteromodal association regions. Age and Alzheimer disease exert independent gray matter atrophy patterns but these effects overlapped substantially in the hippocampus and entorhinal cortex.
Today obesity and type 2 diabetes (T2D) have both reached epidemic proportions. However, our current understanding of the primary mechanisms leading to these diseases is still limited due to the ...complex multifactorial nature of the underlying phenomena. We hypothesize that the levels of specific cytokines and miRNAs vary across the diabetes spectrum and unique signatures associated with them may serve as early biomarkers of the disease and provide insights into respective pathogenetic mechanisms. In this study, we measured the circulating levels of cytokines and microRNAs (miRNAs) in lean and obese humans with prediabetes (
n
= 21), T2D (
n
= 17), and healthy controls (
n
= 20) (ORIGINS trial, NCT02226640). Data were analyzed by fitting linear models adjusted for confounding variables (BMI, age, and gender in the diabetes context and age, gender, and diabetes status in the obesity context) and implementing nonparametric randomization-based tests for statistical inference. Group differences and correlations (
r
> 0.3) between variables with
P
< 0.05 were considered significant. False discovery rates (FDR) correcting for multiple testing were calculated using the Benjamini-Hochberg correction. We found a number of circulating cytokines and miRNAs deregulated in subjects with obesity, prediabetes, and T2D. Specifically, cytokines IL-6, IL-8, IL-10, IL-12, and SFRP4, as well as miRNAs miR-21, miR-24.1, miR-27a, miR-28-3p, miR-29b, miR-30d, miR-34a, miR-93, miR-126, miR-146a, miR-148, miR-150, miR-155, and miR-223, significantly changed across the diabetes spectrum, and were associated with measures of pancreatic islet β cell function and glycemic control, among others. Notably, SFRP4 was the only studied cytokine that was significantly associated with obesity, prediabetes, and T2D, which underscores the important role of this molecule during disease development and progression. Our data suggest that changes in circulating miRNAs and cytokines may have clinical utility as biomarkers of prediabetes.
Today obesity and type 2 diabetes (T2D) have both reached epidemic proportions.
Chronic illnesses like obesity, type 2 diabetes (T2D) and cardiovascular diseases, are worldwide major causes of morbidity and mortality. These pathological conditions involve interactions between ...environmental, genetic, and epigenetic factors. Recent advances in nutriepigenomics are contributing to clarify the role of some nutritional factors, including dietary fatty acids in gene expression regulation. This systematic review assesses currently available information concerning the role of the different fatty acids on epigenetic mechanisms that affect the development of chronic diseases or induce protective effects on metabolic alterations.
A targeted search was conducted in the PubMed/Medline databases using the keywords "fatty acids and epigenetic". The data were analyzed according to the PRISMA-P guidelines.
Consumption fatty acids like n-3 PUFA: EPA and DHA, and MUFA: oleic and palmitoleic acid was associated with an improvement of metabolic alterations. On the other hand, fatty acids that have been associated with the presence or development of obesity, T2D, pro-inflammatory profile, atherosclerosis and IR were n-6 PUFA, saturated fatty acids (stearic and palmitic), and trans fatty acids (elaidic), have been also linked with epigenetic changes.
Fatty acids can regulate gene expression by modifying epigenetic mechanisms and consequently result in positive or negative impacts on metabolic outcomes.
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Roux-en-Y gastric bypass (RYGB) surgery improves insulin sensitivity (S
) and β-cell function in obese non-diabetic subjects. Exercise also improves S
and may be an effective adjunct therapy to RYGB ...surgery. However, the mechanisms by which exercise or weight loss improve peripheral S
after RYGB surgery are unclear. We hypothesized that microRNAs (miRNAs) mediate at least some of the regulatory processes driving such mechanisms. Consequently, this work aimed at profiling plasma miRNAs in participants of the Physical Activity Following Surgery Induced Weight Loss study (clinicaltrials.gov identifier: NCT00692367), to assess whether miRNA levels track with improvements in S
and cardiometabolic risk factors.
Ninety-four miRNAs implicated in metabolism were profiled in plasma samples from 22 severely obese subjects who were recruited 1-3 months after RYGB surgery and followed for 6 months of RYGB surgery-induced weight loss, with (exercise program (EX), N=11) or without (CON, N=11) an exercise training intervention. The subjects were selected, considering a priori sample size calculations, among the participants in the parent study. Mixed-effect modeling for repeated measures and partial correlation analysis was implemented in the R environment for statistical analysis.
Mirroring results in the parent trial, both groups experienced significant weight loss and improvements in cardiometabolic risk. In the CON group, weight loss significantly altered the pattern of circulating miR-7, miR-15a, miR-34a, miR-106a, miR-122 and miR-221. In the EX group, a distinct miRNA signature was altered: miR-15a, miR-34a, miR-122, miR-135b, miR-144, miR-149 and miR-206. Several miRNAs were significantly associated with improvements in acute insulin response, S
, and other cardiometabolic risk factors.
These findings present novel insights into the RYGB surgery-induced molecular changes and the effects of mild exercise to facilitate and/or maintain the benefits of a 'comprehensive' weight-loss intervention with concomitant improvements in cardiometabolic functions. Notably, we show a predictive value for miR-7, miR-15a, miR-106b and miR-135b.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aunque la industria avícola colombiana ha crecido casi el doble en producción durante la última década, el diagnóstico de agentes infecciosos y caracterización de estos aún es escasa, y es poca la ...información acerca de las cepas virales circulantes en el país. Dentro de estos agentes se encuentra el Virus de la Enfermedad de Marek (VEM), el cual es un patógeno inmunosupresor que puede causar mortalidad elevada y graves pérdidas en la producción. Aunque es poco probable que ocurran casos clínicos de la enfermedad causada por el VEM, debido a los programas de vacunación generalizada con GaHV-2 (serotipo I) y HVT (serotipo III), la inmunosupresión que causan las infecciones subclínicas puede estar causando pérdidas considerables en la producción avícola nacional. El objetivo de esta revisión es describir brevemente la enfermedad de Marek y el estado actual del estudio de la infección en Colombia.
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The Little Ice Age in Iberian mountains Oliva, M.; Ruiz-Fernández, J.; Barriendos, M. ...
Earth-science reviews,
February 2018, 2018-02-00, Volume:
177
Journal Article
Peer reviewed
The Little Ice Age (LIA) is known as one of the coldest stages of the Holocene. Most records from the Northern Hemisphere show evidence of significantly colder conditions during the LIA, which in ...some cases had substantial socio-economic consequences. In this study we investigated the magnitude and timing of climate variability during the LIA in the mountains of the Iberian Peninsula, based on a wide range of natural records (including from glacial, periglacial, and lacustrine/peatland areas; fluvial/alluvial deposits; speleothems; and tree rings), historical documents, and early instrument data. The onset of the LIA commenced in approximately CE1300, and cold conditions with alternating moisture regimes persisted until approximately CE1850; the environmental responses ranged from rapid (e.g. tree rings) to delayed (e.g. glaciers). The colder climate of the LIA was accompanied by severe droughts, floods, and cold/heat waves that showed significant spatio-temporal variation across the Iberian mountains. Several phases within the LIA have been detected, including (a) 1300–1480: increasing cooling with moderate climate oscillations; (b) 1480–1570: relatively warmer conditions; (c) 1570–1620: gradual cooling; (d) 1620–1715: coldest climate period of the LIA, particularly during the Maunder Minimum, with temperatures approximately 2°C below those at present; (e) 1715–1760: warmer temperatures and a low frequency of extreme events; (f) 1760–1800: climate deterioration and more climate extremes (i.e. cold and heat waves, floods and droughts); (g) 1800–1850: highly variable climate conditions alternating with stability (1800–1815), extreme events (1815–1835), and a slight trend of warming associated with intense hydrometeorological events (1835–1850); (h) since 1850: a gradual staggered increase in temperature of approximately 1°C. Post-LIA warming has led to substantial changes in geo-ecological dynamics, mainly through shrinking of the spatial domain affected by cold climate processes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The mechanism of corrosion inhibition of AA2024-T3 by sodium molybdate was investigated using various electrochemical, microscopic and spectroscopic techniques. Polarization curves in ...naturally-aerated solution showed that molybdate provided mixed inhibition in near-neutral pH solution and at a threshold concentration of 0.1 M. The largest effect was a 250 mV increase in the breakdown potential associated with pitting and a 350 mV decrease in the open-circuit potential (OCP). In addition, electrochemical impedance indicated that the corrosion inhibition mechanism is oxygen-dependent owing to the protection afforded by Mo(VI) species. It is proposed that the corrosion inhibition of AA2024-T3 by molybdate may occur following a two-step process whereby molybdate is rapidly reduced to MoO·(OH)2 over the intermetallic particles and is subsequently oxidized to intermediate molybdenum oxides (e.g. Mo4O11) in the presence of oxygen.
Physical activity (PA) has been hypothesized to spare gray matter volume in late adulthood, but longitudinal data testing an association has been lacking. Here we tested whether PA would be ...associated with greater gray matter volume after a 9-year follow-up, a threshold could be identified for the amount of walking necessary to spare gray matter volume, and greater gray matter volume associated with PA would be associated with a reduced risk for cognitive impairment 13 years after the PA evaluation.
In 299 adults (mean age 78 years) from the Cardiovascular Health Cognition Study, we examined the association between gray matter volume, PA, and cognitive impairment. Physical activity was quantified as the number of blocks walked over 1 week. High-resolution brain scans were acquired 9 years after the PA assessment on cognitively normal adults. White matter hyperintensities, ventricular grade, and other health variables at baseline were used as covariates. Clinical adjudication for cognitive impairment occurred 13 years after baseline.
Walking amounts ranged from 0 to 300 blocks (mean 56.3; SD 69.7). Greater PA predicted greater volumes of frontal, occipital, entorhinal, and hippocampal regions 9 years later. Walking 72 blocks was necessary to detect increased gray matter volume but walking more than 72 blocks did not spare additional volume. Greater gray matter volume with PA reduced the risk for cognitive impairment 2-fold.
Greater amounts of walking are associated with greater gray matter volume, which is in turn associated with a reduced risk of cognitive impairment.
To develop a late-life dementia risk index that can accurately stratify older adults into those with a low, moderate, or high risk of developing dementia within 6 years.
Subjects were 3,375 ...participants in the Cardiovascular Health Cognition Study without evidence of dementia at baseline. We used logistic regression to identify those factors most predictive of developing incident dementia within 6 years and developed a point system based on the logistic regression coefficients.
Subjects had a mean age of 76 years at baseline; 59% were women and 15% were African American. Fourteen percent (n = 480) developed dementia within 6 years. The final late-life dementia risk index included older age (1-2 points), poor cognitive test performance (2-4 points), body mass index <18.5 (2 points), > or =1 apolipoprotein E epsilon4 alleles (1 point), cerebral MRI findings of white matter disease (1 point) or ventricular enlargement (1 point), internal carotid artery thickening on ultrasound (1 point), history of bypass surgery (1 point), slow physical performance (1 point), and lack of alcohol consumption (1 point) (c statistic, 0.81; 95% confidence interval, 0.79-0.83). Four percent of subjects with low scores developed dementia over 6 years compared with 23% of subjects with moderate scores and 56% of subjects with high scores.
The late-life dementia risk index accurately stratified older adults into those with low, moderate, and high risk of developing dementia. This tool could be used in clinical or research settings to target prevention and intervention strategies toward high-risk individuals.
The clinical presentation of diabetes sometimes overlaps, contributing to ambiguity in the diagnosis. Thus, circulating pancreatic islet-enriched microRNAs (miRNAs) might be useful biomarkers of ...β-cell injury/dysfunction that would allow more accurate subtyping of diabetes. We measured plasma levels of selected miRNAs in subjects with prediabetes (n = 12), type 2 diabetes (T2D, n = 31), latent autoimmune diabetes of adults (LADA, n = 6) and type 1 diabetes (T1D, n = 16) and compared them to levels in healthy control subjects (n = 27). The study was conducted at the Translational Research Institute for Metabolism and Diabetes (TRI-MD), Florida Hospital. MiRNAs including miR-375 (linked to β-cell injury), miR-21 (associated with islet inflammation), miR-24.1, miR-30d, miR-34a, miR-126, miR-146, and miR-148a were significantly elevated in subjects with various forms of diabetes compared to healthy controls. Levels of several miRNAs were significantly correlated with glucose responses during oral glucose tolerance testing, HbA1c, β-cell function, and insulin resistance in healthy controls, prediabetes, and T2D. These data suggest that miRNAs linked to β-cell injury and islet inflammation might be useful biomarkers to distinguish between subtypes of diabetes. This information could be used to predict progression of the disease, guide selection of optimal therapy and monitor responses to interventions, thus improving outcomes in patients with diabetes.
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