Stability and change in etiological factors for alcohol use disorder and major depression.

PubMed

Torvik, Fartein Ask; Rosenström, Tom Henrik; Ystrom, Eivind; Tambs, Kristian; Røysamb, Espen; Czajkowski, Nikolai; Gillespie, Nathan; Knudsen, Gun Peggy; Kendler, Kenneth S; Reichborn-Kjennerud, Ted

2017-08-01

Alcohol use disorder (AUD) and major depressive disorder (MDD) are often comorbid. It is not understood how genetic risk factors for these disorders relate to each other over time and to what degree they are stable. Age-dependent characteristics of the disorders indicate that different genetic factors could be relevant at different stages of life, and MDD may become increasingly correlated with AUD over time. DSM-IV diagnoses of AUD and MDD were assessed by interviews of 2,801 young adult twins between 1999 and 2004 (T1) and 2,284 of the same twins between 2010 and 2011 (T2). Stability, change, and covariation were investigated in longitudinal biometric models. New genetic factors explained 56.4% of the genetic variance in AUD at T2. For MDD, there was full overlap between genetic influences at T1 and T2. Genetic risk factors for MDD were related to AUD, but their association with AUD did not increase over time. Thus, genetic risk factors for AUD, but not MDD, vary with age, suggesting that AUD has age-dependent heritable etiologies. Molecular genetic studies of AUD may therefore benefit from stratifying by age. The new genetic factors in AUD were not related to MDD. Environmental influences on the 2 disorders were correlated in middle, but not in young adulthood. The environmental components for AUD correlated over time (r = .27), but not for MDD. Environmental influences on AUD can have long-lasting effects, and the effects of preventive efforts may be enduring. Environment influences seem to be largely transient. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Relationship between T2* magnetic resonance imaging-derived liver and heart iron content and serum ferritin levels in transfusion-dependent thalassemic children

PubMed Central

Suthar, Kiran; Goyal, Vishnu Kumar; Sharma, Pramod; Deopa, Bindu; Rathore, Pradeep Singh; Bishnoi, Rama Krishan

2018-01-01

CONTEXT: T2* magnetic resonance imaging (MRI) is being increasingly used for the assessment of organ iron content in thalassemics, but cost is a major prohibitive factor for repeated measurements. If serum ferritin correlates well with the T2* MRI liver and heart, it will be economical and more simple tool to assess organ iron deposition. AIMS: The aim of this study was to find out the relationship between serum ferritin level and T2* MRI-derived liver and heart iron content in transfusion-dependent thalassemic children SETTINGS: Thalassemia day-care center of a teaching hospital DESIGN: This was a cross-sectional study SUBJECTS AND METHODS: Seventy-three transfusion-dependent beta thalassemic children belonging to 2–18 years of age were subjected to T2* MRI of heart and liver to assess their iron content. Values obtained here were related to serum ferritin. STATISTICAL ANALYSIS USED: Keeping the correlation between serum ferritin and T2* MRI as primary outcome, spearman's correlation coefficient was calculated. RESULTS: We found poor (negative) correlation between serum ferritin level and T2* MRI liver (r = -0.448, P = 0.000) but no correlation between serum ferritin and T2*MRI heart (r = -0.221, P = 0.060). Conclusions: Serum ferritin cannot reliably predict the liver and heart iron content in Indian children with β thalassemia. PMID:29563679

Evaluation of dexterity in insulin-treated patients with type 1 and type 2 diabetes mellitus.

PubMed

Pfützner, Julia; Hellhammer, Juliane; Musholt, Petra; Pfützner, Anke H; Böhnke, Jan; Torsten, Hero; Amann-Zalan, Ildiko; Ganz, Manfred; Forst, Thomas; Pfützner, Andreas

2011-01-01

Daily routine for insulin-treated patients with diabetes mellitus requires correct performance of self-monitoring of blood glucose and insulin injections several times a day. Dexterity skills may play an important role in the performance efficacy of these procedures. We collected data of insulin-treated (>10 years) patients with different age ranges [healthy controls, 14 female/11 male, age (mean ± standard deviation) 55 ± 7 years; type 1 diabetes mellitus (T1DM) patients, 12/13, 45 ± 9 years, disease duration 23.9 ± 6.5 years; T2DM patients, 8/17, 64 ± 6 years, 16.2 ± 6.9 years; T2DM patients (>70 years of age), 9/16, 75 ± 4 years, 19.7 ± 7.0 years]. After assessment of neuropathy (temperature, pain, and vibration perception), the patients participated in two dexterity test batteries [Jebsen-Taylor hand-function test (JHFT) and motoric performance series (MPS)]. Patients with type 2 diabetes showed disturbed vibration perception as compared to the other groups. The dexterity results were influenced by age to a large extent. Older T2DM patients performed worst in the majority of the subtests (e.g., JHFT, writing nondominant hand: control, 40.8 ± 11.7 s; T1DM, 46.3 ± 50.9 s, not significant versus control; old T2DM, 68.1 ± 29.5 s, p < .05; young T2DM, 52.5 ± 26.2 s, p < .05). Patients with type 1 diabetes showed similar JHFT and MPS results than the 10-year-older control subjects and performed outside of the age-dependent normal reference range. Manual skills and dexterity differed between the groups, and age-corrected reduced skills were common in both T1DM and T2DM patients in this study. Our findings underline the importance of considering dexterity and manual skills when designing medical devices for patients with diabetes mellitus. © 2010 Diabetes Technology Society.

Effects of Age, Gender and Hemispheric Location on T2 Hypointensity in the Pulvinar at 3T.

PubMed

White, Matthew L; Zhang, Yan; Helvey, Jason T; Yu, Fang; Omojola, Matthew F

2014-12-01

Pulvinar signal intensity decrease on T2-weighted images has been reported in some neurological abnormalities. We aimed to define the normal T2 signal hypointensity pattern present in the pulvinar to avoid erroneous radiological interpretation. One hundred and forty-two subjects (54 men and 88 women; age range 9-91 years) with unremarkable brain 3T MR findings were enrolled. MR images were analyzed with regard to signal intensity of the pulvinar relative to the thalamus on fluid attenuated inversion recovery images. Effects of age, gender and hemispheric location on the degree of T2 hypointensity were statistically analyzed. The statistical association was measured between the pattern of signal changes in the pulvinar region and that in the putamen and the globus pallidus. We detected a linear signal decrease in the pulvinar region with age. The male subjects had a more rapid decrease of signal with age than female subjects. The right pulvinar region had a higher chance of hypointensity compared to the left. A positive linear association was found when signal change from the pulvinar region was compared with signal in the putamen and globus pallidus. We detected a linear signal decrease with age in the pulvinar. The physiological signal features of the pulvinar also depend on gender and hemispheric lateralization. The pattern of signal change in the pulvinar is similar to but not the same as that in the putamen and globus pallidus.

Cognitive Training Sustainably Improves Executive Functioning in Middle-Aged Industry Workers Assessed by Task Switching: A Randomized Controlled ERP Study

PubMed Central

Gajewski, Patrick D.; Freude, Gabriele; Falkenstein, Michael

2017-01-01

Recently, we reported results of a cross-sectional study investigating executive functions in dependence of aging and type of work. That study showed deficits in performance and electrophysiological activity in middle-aged workers with long-term repetitive and unchallenging work. Based on these findings, we conducted a longitudinal study that aimed at ameliorating these cognitive deficits by means of a trainer-guided cognitive training (CT) in 57 further middle-aged workers with repetitive type of work from the same factory. This study was designed as a randomized controlled trail with pre- (t1), post- (t2), and a 3-month follow-up (t3) measure. The waiting control group was trained between t2 and t3. The training lasted 3 months (20 sessions) and was evaluated with the same task switching paradigm used in the previous cross-sectional study. The CT improved performance in accuracy at the behavioral level and affected the electrophysiological correlates of retrieval of stimulus-response sets (P2), response selection (N2), and error detection (Ne), thus unveiling the neuronal background of the behavioral effects. The same training effects were observed in the waiting control group after CT at t3. Moreover, at t3, most of the behavioral and electrophysiological training-induced changes were found stable. Hence, CT appears to be an important intervention for compensating cognitive deficits in executive functions in middle-aged employees with cognitively unchallenging work. PMID:28275347

Ghrelin augments murine T-cell proliferation by activation of the phosphatidylinositol-3-kinase, extracellular signal-regulated kinase and protein kinase C signaling pathways

PubMed Central

Lee, Jun Ho; Patel, Kalpesh; Tae, Hyun Jin; Lustig, Ana; Kim, Jie Wan; Mattson, Mark P.; Taub, Dennis D.

2014-01-01

Thymic atrophy occurs during normal aging, and is accelerated by exposure to chronic stressors that elevate glucocorticoid levelsand impair the naïve T cell output. The orexigenic hormone ghrelin was recently shown to attenuate age-associated thymic atrophy. Here, we report that ghrelin enhances the proliferation of murine CD4+ primary T cells and a CD4+ T-cell line. Ghrelin induced activation of the ERK1/2 and Akt signaling pathways, via upstream activation of phosphatidylinositol-3-kinase and protein kinase C, to enhance T-cell proliferation. Moreover, ghrelin induced expression of the cell cycle proteins cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2) and retinoblastoma phosphorylation. Finally, ghrelin activated the above-mentioned signaling pathways and stimulated thymocyte proliferation in young and older mice in vivo. PMID:25447526

Expression levels of the PiT-2 receptor explain, in part, the gestational age-dependent alterations in transduction efficiency after in utero retroviral-mediated gene transfer

PubMed Central

Ozturk, Ferhat; Park, Paul J.; Tellez, Joseph; Colletti, Evan; Eiden, Maribeth V.; Almeida-Porada, Graça; Porada, Christopher D.

2014-01-01

Background A fundamental obstacle to using retroviral-mediated gene transfer (GT) to treat human diseases is the relatively low transduction levels that have been achieved in clinically relevant human cells. We previously showed that performing GT in utero overcomes this obstacle and results in significant levels of transduction within multiple fetal organs, with different tissues exhibiting optimal transduction at different developmental stages. We undertook the present study aiming to elucidate the mechanism for this age-dependent transduction, testing the two factors that we hypothesized could be responsible: (i) the proliferative status of the tissue at the time of GT and (ii) the expression level of the amphotropic PiT-2 receptor. Methods Immunofluorescence was performed on tissues from sheep of varying developmental stages to assess the proliferative status of the predominant cells within each organ as a function of age. After developing an enzyme-linked immunosorbent assay (ELISA) and a quantitative reverse transcription chain reaction (qRT-PCR) assay, we then quantified PiT-2 expression at the protein and mRNA levels, respectively. Results The results obtained indicate that the proliferative status of organs at the time of fetal GT is not the major determinant governing transduction efficiency. By contrast, our ELISA and qRT-PCR analyses demonstrated that PiT-2 mRNA and protein levels vary with gestational age, correlating with the observed differences in transduction efficiency. Conclusions The findings of the present study explain the age-related differences that we previously observed in transduction efficiency after in utero GT. They also suggest it may be possible to achieve relatively selective GT to specific tissues by performing in utero GT when levels of PiT-2 are maximal in the desired target organ. PMID:22262359

T2 Relaxometry MRI Predicts Cerebral Palsy in Preterm Infants.

PubMed

Chen, L-W; Wang, S-T; Huang, C-C; Tu, Y-F; Tsai, Y-S

2018-01-18

T2-relaxometry brain MR imaging enables objective measurement of brain maturation based on the water-macromolecule ratio in white matter, but the outcome correlation is not established in preterm infants. Our study aimed to predict neurodevelopment with T2-relaxation values of brain MR imaging among preterm infants. From January 1, 2012, to May 31, 2015, preterm infants who underwent both T2-relaxometry brain MR imaging and neurodevelopmental follow-up were retrospectively reviewed. T2-relaxation values were measured over the periventricular white matter, including sections through the frontal horns, midbody of the lateral ventricles, and centrum semiovale. Periventricular T2 relaxometry in relation to corrected age was analyzed with restricted cubic spline regression. Prediction of cerebral palsy was examined with the receiver operating characteristic curve. Thirty-eight preterm infants were enrolled for analysis. Twenty patients (52.6%) had neurodevelopmental abnormalities, including 8 (21%) with developmental delay without cerebral palsy and 12 (31.6%) with cerebral palsy. The periventricular T2-relaxation values in relation to age were curvilinear in preterm infants with normal development, linear in those with developmental delay without cerebral palsy, and flat in those with cerebral palsy. When MR imaging was performed at >1 month corrected age, cerebral palsy could be predicted with T2 relaxometry of the periventricular white matter on sections through the midbody of the lateral ventricles (area under the receiver operating characteristic curve = 0.738; cutoff value of >217.4 with 63.6% sensitivity and 100.0% specificity). T2-relaxometry brain MR imaging could provide prognostic prediction of neurodevelopmental outcomes in premature infants. Age-dependent and area-selective interpretation in preterm brains should be emphasized. © 2018 by American Journal of Neuroradiology.

Kcne2 deletion impairs insulin secretion and causes type 2 diabetes mellitus.

PubMed

Lee, Soo Min; Baik, Jasmine; Nguyen, Dara; Nguyen, Victoria; Liu, Shiwei; Hu, Zhaoyang; Abbott, Geoffrey W

2017-06-01

Type 2 diabetes mellitus (T2DM) represents a rapidly increasing threat to global public health. T2DM arises largely from obesity, poor diet, and lack of exercise, but it also involves genetic predisposition. Here we report that the KCNE2 potassium channel transmembrane regulatory subunit is expressed in human and mouse pancreatic β cells. Kcne2 deletion in mice impaired glucose tolerance as early as 5 wk of age in pups fed a Western diet, ultimately causing diabetes. In adult mice fed normal chow, skeletal muscle expression of insulin receptor β and insulin receptor substrate 1 were down-regulated 2-fold by Kcne2 deletion, characteristic of T2DM. Kcne2 deletion also caused extensive pancreatic transcriptome changes consistent with facets of T2DM, including endoplasmic reticulum stress, inflammation, and hyperproliferation. Kcne2 deletion impaired β-cell insulin secretion in vitro up to 8-fold and diminished β-cell peak outward K + current at positive membrane potentials, but also left-shifted its voltage dependence and slowed inactivation. Interestingly, we also observed an aging-dependent reduction in β-cell outward currents in both Kcne2 +/+ and Kcne2 - / - mice. Our results demonstrate that KCNE2 is required for normal β-cell electrical activity and insulin secretion, and that Kcne2 deletion causes T2DM. KCNE2 may regulate multiple K + channels in β cells, including the T2DM-linked KCNQ1 potassium channel α subunit.-Lee, S. M., Baik, J., Nguyen, D., Nguyen, V., Liu, S., Hu, Z., Abbott, G. W. Kcne2 deletion impairs insulin secretion and causes type 2 diabetes mellitus. © FASEB.

Improved sample preparation and counting techniques for enhanced tritium measurement sensitivity

NASA Astrophysics Data System (ADS)

Moran, J.; Aalseth, C.; Bailey, V. L.; Mace, E. K.; Overman, C.; Seifert, A.; Wilcox Freeburg, E. D.

2015-12-01

Tritium (T) measurements offer insight to a wealth of environmental applications including hydrologic tracking, discerning ocean circulation patterns, and aging ice formations. However, the relatively short half-life of T (12.3 years) limits its effective age dating range. Compounding this limitation is the decrease in atmospheric T content by over two orders of magnitude (from 1000-2000 TU in 1962 to < 10 TU currently) since the cessation of above ground nuclear testing in the 1960's. We are developing sample preparation methods coupled to direct counting of T via ultra-low background proportional counters which, when combined, offer improved T measurement sensitivity (~4.5 mmoles of H2 equivalent) and will help expand the application of T age dating to smaller sample sizes linked to persistent environmental questions despite the limitations above. For instance, this approach can be used to T date ~ 2.2 mmoles of CH4 collected from sample-limited systems including microbial communities, soils, or subsurface aquifers and can be combined with radiocarbon dating to distinguish the methane's formation age from C age in a system. This approach can also expand investigations into soil organic C where the improved sensitivity will permit resolution of soil C into more descriptive fractions and provide direct assessments of the stability of specific classes of organic matter in soils environments. We are employing a multiple step sample preparation system whereby organic samples are first combusted with resulting CO2 and H2O being used as a feedstock to synthesize CH4. This CH4 is mixed with Ar and loaded directly into an ultra-low background proportional counter for measurement of T β decay in a shallow underground laboratory. Analysis of water samples requires only the addition of geologic CO2 feedstock with the sample for methane synthesis. The chemical nature of the preparation techniques enable high sample throughput with only the final measurement requiring T decay with total sample analysis time ranging from 2 -5 weeks depending on T content.

Processor-Based Strong Physical Unclonable Functions with Aging-Based Response Tuning (Preprint)

DTIC Science & Technology

2013-01-01

NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON GARRET S. ROSE a. REPORT U b . ABSTRACT U c. THIS PAGE U 19b. TELEPHONE NUMBER (Include area code...generated by quad-tree process variation model [1]. The number in the right side of the figures means Z value of Gaussian distribution. B . Delay model To...and B are technology dependent constants. As shown in Equation 2, the Vth shift heavily depends on temperature (T ) and stress time (t). By applying

[Investigation of exciting light and plant leaves age effects on chlorophyll fluorescense of radish plants].

PubMed

Nesterenko, T V; Tikhomirov, A A; Shikhov, V N

2012-01-01

The effect of exciting light intensity and leaves age on characteristics of slow stage of chlorophyll fluorescence induction (CFI) of radish leaves has been investigated. Light dependence of the relationship of maximum fluorescence intensity in the peak P and the stationary fluorescence level (F(P)/F(S)) and also light dependence of temporal characteristics of CFI (T0.5 - half decrease of chlorophyll fluorescence intensity during slow stage of fluorescence induction and tmin - summarized CFI characteristics derived by calculating via integral proportional to variable part of illuminated in the result of chlorophyll fluorescence energy during slow stage of CFI) have been studied. Plants were grown in controlled conditions of light culture at 100 Wt/m2 of photosynthetic active radiation (PAR). It has been shown that variability of the characteristics under study, associated with the effect of leaves age, significantly decreases at exciting light intensity equal to 40 Wt/m2 of PAR and more. The lowest effect of leaves age on the value of fluorescence characteristics for T0.5 and tmin and also for F(P)/F(S) ratio was observed at the intensity of exciting fluorescence light of 60 Wt/m2 of PAR. In the researched range of light intensities the temporal characteristics of T0.5 and tmin for uneven-aged radish leaves appeared to be by an order less responsive to the intensity changes of exciting fluorescence light as compared with F(P)/F(S) ratio.

β-Cell Ca(2+) dynamics and function are compromised in aging.

PubMed

Barker, Christopher J; Li, Luosheng; Köhler, Martin; Berggren, Per-Olof

2015-01-01

Defects in pancreatic β-cell function and survival are key components in type 2 diabetes (T2D). An age-dependent deterioration in β-cell function has also been observed, but little is known about the molecular mechanisms behind this phenomenon. Our previous studies indicate that the regulation of cytoplasmic free Ca(2+) concentration ([Ca(2+)]i) may be critical and that this is dependent on the proper function of the mitochondria. The [Ca(2+)]i dynamics of the pancreatic β-cell are driven by an interplay between glucose-induced influx of extracellular Ca(2+) via voltage-dependent Ca(2+) channels and the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-mediated liberation of Ca(2+) from intracellular stores. Our previous work has indicated a direct relationship between disruption of Ins(1,4,5)P3-mediated Ca(2+) regulation and loss of β-cell function, including disturbed [Ca(2+)]i dynamics and compromised insulin secretion. To investigate these processes in aging we used three mouse models, a premature aging mitochondrial mutator mouse, a mature aging phenotype (C57BL/6) and an aging-resistant phenotype (129). Our data suggest that age-dependent impairment in mitochondrial function leads to modest changes in [Ca(2+)]i dynamics in mouse β-cells, particularly in the pattern of [Ca(2+)]i oscillations. These changes are driven by modifications in both PLC/Ins(1,4,5)P3-mediated Ca(2+) mobilization from intracellular stores and decreased β-cell Ca(2+) influx over the plasma membrane. Our findings underscore an important concept, namely that even relatively small, time-dependent changes in β-cell signal-transduction result in compromised insulin release and in a diabetic phenotype. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cerebral white matter maturation patterns in preterm infants: an MRI T2 relaxation anisotropy and diffusion tensor imaging study

PubMed Central

Knight, Michael J.; Smith-Collins, Adam; Newell, Sarah; Denbow, Mark; Kauppinen, Risto A.

2017-01-01

Background and Purpose Preterm birth is associated with worse neurodevelopmental outcome, but brain maturation in preterm infants is poorly characterised with standard methods. We evaluated white matter (WM) of infant brains at term-equivalent age, as a function of gestational age at birth, using multi-modal MRI. Methods Infants born very pre-term (< 32 weeks gestation) and late pre-term (33-36 weeks gestation) were scanned at 3T at term-equivalent age using diffusion tensor imaging (DTI) and T2 relaxometry. MRI data were analysed using tract-based spatial statistics, and anisotropy of T2 relaxation was also determined. Principal component analysis and linear discriminant analysis were applied to seek the variables best distinguishing very pre-term and late pre-term groups. Results Across widespread regions of WM, T2 is longer in very pre-term infants than in late pre-term ones. These effects are more prevalent in regions of WM which myelinate earlier and faster. Similar effects are obtained from DTI, showing that fractional anisotropy (FA) is lower and radial diffusivity higher in the very pre-term group, with a bias towards earlier myelinating regions. Discriminant analysis shows high sensitivity and specificity of combined T2 relaxometry and DTI for the detection of a distinct WM development pathway in very preterm infants. T2 relaxation is anisotropic, depending on the angle between WM fibre and magnetic field, and this effect is modulated by FA. Conclusions Combined T2 relaxometry and DTI characterises specific patterns of retarded WM maturation, at term equivalent age, in infants born very pre-term relative to late pre-term. PMID:29205635

Peer victimization and social phobia: a follow-up study among adolescents.

PubMed

Ranta, Klaus; Kaltiala-Heino, Riittakerttu; Fröjd, Sari; Marttunen, Mauri

2013-04-01

This study examined longitudinal associations between direct and relational peer victimization (DV/RV) and self-reported social phobia (SP) among adolescents from 15 to 17 years of age, controlling for depression and family socioeconomic covariates. A total of 3,278 Finnish adolescents with a mean age of 15.5 years were surveyed at baseline (T1), and followed up 2 years afterwards (T2) their mean age being 17.6 years. In all, 2,070 adolescents were reached for the follow-up. Both types of victimization were assessed with structured questions, SP with the Social Phobia Inventory, and depression with the 13-item Beck Depression Inventory. Socioeconomic covariates were assessed with items from the Life Events Checklist. Frequency of victimization and SP were assessed at T1 and T2, and incidence and persistence from T1 to T2. Longitudinal associations between victimization and SP were examined with three logistic regression analyses with depression and socioeconomic covariates controlled for, with SP, DV, and RV in turn as the dependent endpoint (T2) variables. Among boys a bidirectional association between DV and SP was found with DV both predicting SP [Odds Ratio (OR) 2.6] and being predicted by SP (OR 3.9). Among girls RV predicted SP (OR 2.8), but not vice versa, while depression in turn predicted DV (OR 4.3). Direct victimization and SP have a bidirectional association among boys, while among girls RV increases the risk of subsequent SP.

Determining the amount of physical activity needed for long-term weight control

NASA Technical Reports Server (NTRS)

Wier, L. T.; Ayers, G. W.; Jackson, A. S.; Rossum, A. C.; Poston, W. S.; Foreyt, J. P.

2001-01-01

OBJECTIVE: To evaluate prospectively the influence of habitual physical activity on body weight of men and women and to develop a model that defines the role of physical activity on longitudinal weight change. DESIGN AND SETTING: Occupational cohort study conducted for a mean of 5.5 y. SUBJECTS: A total of 496 (341 male and 155 female) NASA/Johnson Space Center employees who completed the 3 month education component of the employee health-related fitness program and remained involved for a minimum of 2 y. MEASUREMENTS: Body weights were measured at baseline (T1) and follow-up (T2), and habitual physical activity was obtained from the mean of multiple ratings of the 11-point (0-10) NASA Activity Scale (NAS) recorded quarterly between T1 and T2. Other measures included age, gender, VO(2 max) obtained from maximal treadmill testing, body mass index (BMI), and body fat percentage. RESULTS: Multiple regression demonstrated that mean NAS, T1 weight, aging and gender all influence long-term T2 weight. T1 age was significant for the men only. Independently, each increase in mean NAS significantly (P<0.01) reduced T2 weight in men (b=-0.91 kg; 95% CI:-1.4 to-0.42 kg) and women (b=-2.14 kg; 95% CI:-2.93 to-1.35 kg). Mean NAS had a greater effect on T2 weight as T1 weight increased, and the relationship was dose-dependent. CONCLUSIONS: Habitual physical activity is a significant source of long-term weight change. The use of self-reported activity level is helpful in predicting long-term weight changes and may be used by health care professionals when counseling patients about the value of physical activity for weight control.

Friend or foe: the dichotomous impact of T cells on neuro-de/re-generation during aging.

PubMed

Coder, Brandon; Wang, Weikan; Wang, Liefeng; Wu, Zhongdao; Zhuge, Qichuan; Su, Dong-Ming

2017-01-24

The interaction between T cells and the central nervous system (CNS) in homeostasis and injury has been recognized being both pathogenic (CD4+ T-helper 1 - Th1, Th17 and γδT) and ameliorative (Th2 and regulatory T cells - Tregs). However, in-depth studies aimed to elucidate the precise in the aged microenvironment and the dichotomous role of Tregs have just begun and many aspects remain unclear. This is due, not only to a mutual dependency and reciprocal causation of alterations and diseases between the nervous and T cell immune systems, but also to an inconsistent aging of the two systems, which dynamically changes with CNS injury/recovery and/or aging process. Cellular immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution - sources of chronic inflammation in the elderly (termed inflammaging), potentially induces an acceleration of brain aging and memory loss. In turn, aging of the brain via neuro-endocrine-immune network drives total body systemic aging, including that of the immune system. Therefore, immunotherapeutics including vaccination and "protective autoimmunity" provide promising means to rejuvenate neuro-inflammatory disorders and repair CNS acute injury and chronic neuro-degeneration. We review the current understanding and recent discoveries linking the aging immune system with CNS injury and neuro-degeneration. Additionally, we discuss potential recovery and rejuvenation strategies, focusing on targeting the aging T cell immune system in an effort to alleviate acute brain injury and chronic neuro-degeneration during aging, via the "thymus-inflammaging-neurodegeneration axis".

Friend or foe: the dichotomous impact of T cells on neuro-de/re-generation during aging

PubMed Central

Wang, Liefeng; Wu, Zhongdao; Zhuge, Qichuan; Su, Dong-Ming

2017-01-01

The interaction between T cells and the central nervous system (CNS) in homeostasis and injury has been recognized being both pathogenic (CD4+ T-helper 1 - Th1, Th17 and γδT) and ameliorative (Th2 and regulatory T cells - Tregs). However, in-depth studies aimed to elucidate the precise in the aged microenvironment and the dichotomous role of Tregs have just begun and many aspects remain unclear. This is due, not only to a mutual dependency and reciprocal causation of alterations and diseases between the nervous and T cell immune systems, but also to an inconsistent aging of the two systems, which dynamically changes with CNS injury/recovery and/or aging process. Cellular immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution - sources of chronic inflammation in the elderly (termed inflammaging), potentially induces an acceleration of brain aging and memory loss. In turn, aging of the brain via neuro-endocrine-immune network drives total body systemic aging, including that of the immune system. Therefore, immunotherapeutics including vaccination and “protective autoimmunity” provide promising means to rejuvenate neuro-inflammatory disorders and repair CNS acute injury and chronic neuro-degeneration. We review the current understanding and recent discoveries linking the aging immune system with CNS injury and neuro-degeneration. Additionally, we discuss potential recovery and rejuvenation strategies, focusing on targeting the aging T cell immune system in an effort to alleviate acute brain injury and chronic neuro-degeneration during aging, via the “thymus-inflammaging-neurodegeneration axis”. PMID:27738345

The concentration of N-acetyl aspartate, creatine + phosphocreatine, and choline in different parts of the brain in adulthood and senium.

PubMed

Christiansen, P; Toft, P; Larsson, H B; Stubgaard, M; Henriksen, O

1993-01-01

The fully relaxed water signal was used as an internal standard in a STEAM experiment to calculate the concentrations of the metabolites: N-acetyl aspartate (NAA), creatine + phosphocreatine (Cr + PCr), and choline (Cho) containing compounds in four different parts of the brain in two age groups of healthy volunteers (20-30 yr, n = 8) and (60-80 yr, n = 8). Furthermore, T1 and T2 relaxation time of the metabolites and signal ratios: NAA/Cho, NAA/Cr + PCr, and Cho/Cr + PCr at TE = 272 msec were calculated. The experiments were carried out using a Siemens Helicon SP 63/84 wholebody MR-scanner at 1.5 T. In the younger age group, the concentration of NAA was significantly higher in the occipital part than in the other three parts of the brain. No significant regional variation was found for any other metabolite concentration. There was a significantly higher concentration of NAA in the occipital part of the brain in the younger age group compared to the older one. No significant regional or age dependent variation was found concerning the T1 and T2 relaxation times.

Detection of Normal Aging Effects on Human Brain Metabolite Concentrations and Microstructure with Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging.

PubMed

Eylers, V V; Maudsley, A A; Bronzlik, P; Dellani, P R; Lanfermann, H; Ding, X-Q

2016-03-01

Knowledge of age-related physiological changes in the human brain is a prerequisite to identify neurodegenerative diseases. Therefore, in this study whole-brain (1)H-MRS was used in combination with quantitative MR imaging to study the effects of normal aging on healthy human brain metabolites and microstructure. Sixty healthy volunteers, 21-70 years of age, were studied. Brain maps of the metabolites NAA, creatine and phosphocreatine, and Cho and the tissue irreversible and reversible transverse relaxation times T2 and T2' were derived from the datasets. The relative metabolite concentrations and the values of relaxation times were measured with ROIs placed within the frontal and parietal WM, centrum semiovale, splenium of the corpus callosum, hand motor area, occipital GM, putamen, thalamus, pons ventral/dorsal, and cerebellar white matter and posterior lobe. Linear regression analysis and Pearson correlation tests were used to analyze the data. Aging resulted in decreased NAA concentrations in the occipital GM, putamen, splenium of the corpus callosum, and pons ventral and decreased creatine and phosphocreatine concentrations in the pons dorsal and putamen. Cho concentrations did not change significantly in selected brain regions. T2 increased in the cerebellar white matter and decreased in the splenium of the corpus callosum with aging, while the T2' decreased in the occipital GM, hand motor area, and putamen, and increased in the splenium of the corpus callosum. Correlations were found between NAA concentrations and T2' in the occipital GM and putamen and between creatine and phosphocreatine concentrations and T2' in the putamen. The effects of normal aging on brain metabolites and microstructure are region-dependent. Correlations between both processes are evident in the gray matter. The obtained data could be used as references for future studies on patients. © 2016 by American Journal of Neuroradiology.

Volumetric brain differences in children with periventricular T2-signal hyperintensities: a grouping by gestational age at birth.

PubMed

Panigrahy, A; Barnes, P D; Robertson, R L; Back, S A; Sleeper, L A; Sayre, J W; Kinney, H C; Volpe, J J

2001-09-01

The purpose of this study was to compare both the volumes of the lateral ventricles and the cerebral white matter with gestational age at birth of children with periventricular white matter (PVWM) T2-signal hyperintensities on MR images. The spectrum of neuromotor abnormalities associated with these hyperintensities was also determined. We retrospectively reviewed the MR images of 70 patients who were between the ages of 1 and 5 years and whose images showed PVWM T2-signal hyperintensities. The patients were divided into premature (n = 35 children) and term (n = 35) groups depending on their gestational age at birth. Volumetric analysis was performed on four standardized axial sections using T2-weighted images. Volumes of interest were digitized on the basis of gray-scale densities of signal intensities to define the hemispheric cerebral white matter and lateral ventricles. Age-adjusted comparisons of volumetric measurements between the premature and term groups were performed using analysis of covariance. The volume of the cerebral white matter was smaller in the premature group (54 +/- 2 cm(3)) than in the term group (79 +/- 3 cm(3), p < 0.0001). The volume of the lateral ventricles was greater among the patients in the premature group (30 +/- 2 cm(3)) than among those in the term group (13 +/- 1 cm(3), p < 0.0001). Fifty percent of all the premature children had spastic diplegia or quadriplegia. Thirty-two percent of all the term children had hypotonia. There were patients in both groups whose PVWM T2-signal hyperintensities did not correlate with any neuromotor abnormalities but were associated with seizures or developmental delays. The differences in volumetric measurements of cerebral white matter and lateral ventricles in children with PVWM T2-signal hyperintensities are related to their gestational age at birth. Several neurologic motor abnormalities are found in children with such hyperintensities.

Aging Wiener-Khinchin theorem and critical exponents of 1/f^{β} noise.

PubMed

Leibovich, N; Dechant, A; Lutz, E; Barkai, E

2016-11-01

The power spectrum of a stationary process may be calculated in terms of the autocorrelation function using the Wiener-Khinchin theorem. We here generalize the Wiener-Khinchin theorem for nonstationary processes and introduce a time-dependent power spectrum 〈S_{t_{m}}(ω)〉 where t_{m} is the measurement time. For processes with an aging autocorrelation function of the form 〈I(t)I(t+τ)〉=t^{Υ}ϕ_{EA}(τ/t), where ϕ_{EA}(x) is a nonanalytic function when x is small, we find aging 1/f^{β} noise. Aging 1/f^{β} noise is characterized by five critical exponents. We derive the relations between the scaled autocorrelation function and these exponents. We show that our definition of the time-dependent spectrum retains its interpretation as a density of Fourier modes and discuss the relation to the apparent infrared divergence of 1/f^{β} noise. We illustrate our results for blinking-quantum-dot models, single-file diffusion, and Brownian motion in a logarithmic potential.

Geographical variation in the progression of type 2 diabetes in Peru: The CRONICAS Cohort Study

PubMed Central

Bernabé-Ortiz, Antonio; Carrillo-Larco, Rodrigo M.; Gilman, Robert H.; Miele, Catherine H.; Checkley, William; Wells, Jonathan C.; Smeeth, Liam; Miranda, J. Jaime

2016-01-01

Background The study aims were to estimate the incidence and risk factors for T2D in four settings with different degree of urbanization and altitude in Peru. Methods Prospective cohort study conducted in urban, semi-urban, and rural areas in Peru. An age- and sex-stratified random sample of participants was taken from the most updated census. T2D was defined as fasting blood glucose ⩾7.0 mmol/L or taking anti-diabetes medication. Exposures were divided into two groups: geographical variables (urbanization and altitude), and modifiable risk factors. Incidence, relative risks (RR), 95% confidence intervals (95%CI), and population attributable fractions (PAF) were estimated. Results Data from 3135 participants, 48.8% males, mean age 55.6 years, was analyzed. Overall baseline prevalence of T2D was 7.1% (95%CI 6.2–8.0%). At follow-up, including 6207 person-years of follow-up, a total of 121 new T2D cases were accrued, equating to an incidence of 1.95 (95%CI 1.63–2.33) per 100 person-years. There was no urban to rural gradient in the T2D incidence; however, compared to sea level sites, participants living in high altitude had a higher incidence of diabetes (RR = 1.58; 95%CI 1.01–2.48). Obesity had the highest attributable risk for developing T2D, although results varied by setting, ranging from 14% to 80% depending on urbanization and altitude. Conclusions Our results suggest that the incidence of T2D was greater in high altitude sites. New cases of diabetes were largely attributed to obesity, but with substantial variation in the contribution of obesity depending on the environment. These findings can inform appropriate context-specific strategies to reduce the incidence of diabetes. PMID:27710820

Geographical variation in the progression of type 2 diabetes in Peru: The CRONICAS Cohort Study.

PubMed

Bernabé-Ortiz, Antonio; Carrillo-Larco, Rodrigo M; Gilman, Robert H; Miele, Catherine H; Checkley, William; Wells, Jonathan C; Smeeth, Liam; Miranda, J Jaime

2016-11-01

The study aims were to estimate the incidence and risk factors for T2D in four settings with different degree of urbanization and altitude in Peru. Prospective cohort study conducted in urban, semi-urban, and rural areas in Peru. An age- and sex-stratified random sample of participants was taken from the most updated census. T2D was defined as fasting blood glucose ⩾7.0mmol/L or taking anti-diabetes medication. Exposures were divided into two groups: geographical variables (urbanization and altitude), and modifiable risk factors. Incidence, relative risks (RR), 95% confidence intervals (95%CI), and population attributable fractions (PAF) were estimated. Data from 3135 participants, 48.8% males, mean age 55.6years, was analyzed. Overall baseline prevalence of T2D was 7.1% (95%CI 6.2-8.0%). At follow-up, including 6207 person-years of follow-up, a total of 121 new T2D cases were accrued, equating to an incidence of 1.95 (95%CI 1.63-2.33) per 100 person-years. There was no urban to rural gradient in the T2D incidence; however, compared to sea level sites, participants living in high altitude had a higher incidence of diabetes (RR=1.58; 95%CI 1.01-2.48). Obesity had the highest attributable risk for developing T2D, although results varied by setting, ranging from 14% to 80% depending on urbanization and altitude. Our results suggest that the incidence of T2D was greater in high altitude sites. New cases of diabetes were largely attributed to obesity, but with substantial variation in the contribution of obesity depending on the environment. These findings can inform appropriate context-specific strategies to reduce the incidence of diabetes. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Correlated Time-Variation of Asphalt Rheology and Bulk Microstructure

NASA Astrophysics Data System (ADS)

Ramm, Adam; Nazmus, Sakib; Bhasin, Amit; Downer, Michael

We use noncontact optical microscopy and optical scattering in the visible and near-infrared spectrum on Performance Grade (PG) asphalt binder to confirm the existence of microstructures in the bulk. The number of visible microstructures increases linearly as penetration depth of the incident radiation increases, which verifies a uniform volume distribution of microstructures. We use dark field optical scatter in the near-infrared to measure the temperature dependent behavior of the bulk microstructures and compare this behavior with Dynamic Shear Rheometer (DSR) measurements of the bulk complex shear modulus | G* (T) | . The main findings are: (1) After reaching thermal equilibrium, both temperature dependent optical scatter intensity (I (T)) and bulk shear modulus (| G* (T) |) continue to change appreciably for times much greater than thermal equilibration times. (2) The hysteresis behavior during a complete temperature cycle seen in previous work derives from a larger time dependence in the cooling step compared with the heating step. (3) Different binder aging conditions show different thermal time-variations for both I (T) and | G* (T) | .

Role of Type 2 Diabetes in Determining Retinal, Renal, and Cardiovascular Outcomes in Women With Previous Gestational Diabetes Mellitus.

PubMed

Retnakaran, Ravi; Shah, Baiju R

2017-01-01

Women who have gestational diabetes mellitus (GDM) have elevated lifetime risks for the development of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), compared with their peers. However, it is not known whether their risk of CVD is dependent upon the development of T2DM. Thus, we sought to evaluate the role of T2DM in determining vascular outcomes in women with previous GDM. All women in Ontario, Canada, with a live-birth pregnancy between April 1994 and March 2014 (n = 1,515,079) were stratified into the following four groups: women with GDM in whom T2DM subsequently developed (n = 15,585, median age 32 years); those with GDM in whom T2DM did not develop (n = 41,299; median age 32 years); women who did not have GDM but in whom T2DM developed (n = 49,397; median age 31 years); and those with neither GDM nor T2DM (n = 1,408,798; median age 30 years). Women were followed over a median time of 10.0 years for the development of microvascular and macrovascular outcomes. Among women who had GDM, only those in whom T2DM developed had an increased risk of vitrectomy/photocoagulation (hazard ratio [HR] 4.49, 95% CI 3.90-5.17), renal dialysis (HR 7.52, 5.24-10.81), and hospitalization for foot infection (HR 4.32, 3.42-5.46) (all P < 0.0001). However, for macrovascular outcomes, both women with GDM in whom T2DM developed and those in whom T2DM did not develop had increased risks of CVD (HR 2.82; 2.41-3.30; P < 0.0001; and HR 1.30; 1.07-1.59; P = 0.008, respectively) and coronary artery disease (HR 3.54; 2.96-4.23; P < 0.0001; and HR 1.41; 1.11-1.80; P = 0.005, respectively), although absolute event rates were very low. Women with GDM have an elevated risk of cardiovascular outcomes, even in the absence of T2DM. In contrast, microvascular risk emerges only in those in whom T2DM develops. © 2017 by the American Diabetes Association.

Mathematical modelling the age dependence of Epstein-Barr virus associated infectious mononucleosis.

PubMed

Huynh, Giao T; Adler, Frederick R

2012-09-01

Most people get Epstein-Barr virus (EBV) infection at young age and are asymptomatic. Primary EBV infection in adolescents and young adults, however, often leads to infectious mononucleosis (IM) with symptoms including fever, fatigue and sore throat that can persist for months. Expansion in the number of CD8(+) T cells, especially against EBV lytic proteins, are the main cause of these symptoms. We propose a mathematical model for the regulation of EBV infection within a host to address the dependence of IM on age. This model tracks the number of virus, infected B cell and epithelial cell and CD8(+) T-cell responses to the infection. We use this model to investigate three hypotheses for the high incidence of IM in teenagers and young adults: saliva and antibody effects that increase with age, high cross-reactive T-cell responses and a high initial viral load. The model supports the first two of these hypotheses and suggests that variation in host antibody responses and the complexity of the pre-existing cross-reactive T-cell repertoire, both of which depend on age, may play important roles in the etiology of IM.

Heterogeneity in recent-onset type 1 diabetes - a clinical trial perspective.

PubMed

Bollyky, Jennifer B; Xu, Ping; Butte, Atul J; Wilson, Darrell M; Beam, Craig A; Greenbaum, Carla J

2015-09-01

Type 1 diabetes (T1D) TrialNet is a National Institutes of Health-sponsored clinical trial network aimed at altering the disease course of T1D. The purpose of this study is to evaluate age-dependent heterogeneity in clinical, metabolic and immunologic characteristics of individuals with recent-onset T1D, to identify cohorts of interest and to aid in planning of future studies. Eight hundred eighty-three individuals with recent-onset T1D involved in five TrialNet studies were categorized by age as follows: ≥18 years, 12-17 years, 8-12 years and <8 years. Data were compared with healthy age-matched subjects in the National Health and Nutrition Examination Survey. Only 2.0% of the individuals overall were excluded from trial participation because of insufficient C-peptide values (<0.2 pmol/mL). A disproportionate number of these subjects were <8 years old. Leukopenia was present in 21.2% of individuals and lymphopenia in 11.6%; these frequencies were markedly higher than age-matched healthy National Health and Nutrition Examination Survey population. Of the cohort, 24.5% were overweight or obese. Neither high-risk human leukocyte antigen type DR3 nor DR4 was present in 31% of adults and 21% of children. The ability of recent-onset T1D patients to meet key entry criteria for TrialNet studies, including C-peptide >0.2 pmol/mL, varies by age. Lower C-peptide level requirements for younger participants and other aspects of heterogeneity of recent-onset T1D patients, such as white blood cell count abnormalities and body mass index should be considered in the design of future clinical studies. Copyright © 2015 John Wiley & Sons, Ltd.

THE RELATIONSHIP BETWEEN IMPULSIVITY, -TAKING PROPENSITY AND NICOTINE DEPENDENCE AMONG OLDER ADOLESCENT SMOKERS

PubMed Central

Ryan, Katherine K.; MacKillop, James; Carpenter, Matthew J.

2012-01-01

Impulsivity and risk-taking propensity are neurobehavioral traits that reliably distinguish between smoking and non-smoking adults. However, how these traits relate to smoking quantity and nicotine dependence among older adolescent smokers is unclear. The current study examined impulsivity and risk-taking propensity in relation to smoking behavior and nicotine dependence among current older adolescent smokers (age 16–20 years; N = 107). Participants completed the Barratt Impulsiveness Scale–11 (BIS-11), the Balloon Analogue Risk Task (BART), and self-report measures of smoking behavior and nicotine dependence. Results indicated a significant positive relationship between nicotine dependence and the Attention subscale (β =.20, t = 2.07, p <.05) and the Non-planning subscale (β =.19, t=1.92, p<.06) of the BIS-11. Contrary to expectation, the results also indicated a significant negative relationship between performance on the BART and nicotine dependence (β = −.19, t=−2.18, p <.05), such that greater risk-taking propensity was associated with less dependence. These data suggest that impulsivity and risk-taking propensity are related to older adolescent smoking but are separable traits with distinguishable associations to nicotine dependence among adolescents. These findings support the notion that impulsivity is related to heightened nicotine dependence, but suggest the relationship between risk-taking propensity and nicotine dependence is more ambiguous and warrants further investigation. PMID:23006247

Impact of beverage consumption, age, and site dependency on dual energy X-ray absorptiometry (DEXA) measurements in perimenopausal women: a prospective study.

PubMed

Lo, Huan-Chu; Kuo, Duen-Pang; Chen, Yen-Lin

2017-08-01

The aim of this study was to determine the best site for bone mineral density (BMD) measurements based on T -scores, age, and beverage consumption. In this prospective study, 271 women stratified by age (average age: 61.9 years) underwent dual energy X-ray absorptiometry (DEXA) scanning of their lumbar spine, hips, and forearms. Osteoporosis was defined as a BMD of 2.5 standard deviations or more below the mean peak bone mass based on a reference population of adult women (translated as a T -score ≤ -2.5), as measured by DEXA. Participants were also evaluated regarding alcohol and caffeine consumption by a semiquantitative questionnaire. A significant discrepancy was observed in the classification of osteoporosis at different locations, with hip and forearm showing the best correlation (Pearson's r = 0.627, p < 0.001). In addition, for participants over 50 years of age, hip and forearm showed the best correlation. Significant correlations were also noted between forearm T -scores and caffeine consumed and, to a lesser extent, the level of alcohol consumption. In the group ≤ 50 years of age, lumbar spine and forearm T -scores were only associated with alcohol consumption. In the group over 50 years of age, hip and forearm T -scores were only associated with caffeine consumption. Bone mineral density measurements at the hip and forearm correlated with caffeine consumption in elderly Taiwanese women. This is an important finding since age and caffeine consumption are known risk factors for osteoporosis.

A major role for Bim in regulatory T cell homeostasis.

PubMed

Chougnet, Claire A; Tripathi, Pulak; Lages, Celine S; Raynor, Jana; Sholl, Allyson; Fink, Pamela; Plas, David R; Hildeman, David A

2011-01-01

We have previously shown that regulatory T cells (Treg) accumulate dramatically in aged animals and negatively impact the ability to control persistent infection. However, the mechanisms underlying the age-dependent accrual of Treg remain unclear. In this study, we show that Treg accumulation with age is progressive and likely not the result of increased thymic output, increased peripheral proliferation, or from enhanced peripheral conversion. Instead, we found that Treg from aged mice are more resistant to apoptosis than Treg from young mice. Although Treg from aged mice had increased expression of functional IL-7Rα, we found that IL-7R signaling was not required for maintenance of Treg in vivo. Notably, aged Treg exhibit decreased expression of the proapoptotic molecule Bim compared with Treg from young mice. Furthermore, in the absence of Bim, Treg accumulate rapidly, accounting for >25% of the CD4(+) T cell compartment by 6 mo of age. Additionally, accumulation of Treg in Bim-deficient mice occurred after the cells left the transitional recent thymic emigrant compartment. Mechanistically, we show that IL-2 drives preferential proliferation and accumulation of Bim(lo) Treg. Collectively, our data suggest that chronic stimulation by IL-2 leads to preferential expansion of Treg having low expression of Bim, which favors their survival and accumulation in aged hosts.

A major role for Bim in regulatory T cell homeostasis1

PubMed Central

Chougnet, Claire A.; Tripathi, Pulak; Lages, Celine S.; Raynor, Jana; Sholl, Allyson; Fink, Pamela; Plas, David R.; Hildeman, David A.

2011-01-01

We have previously shown that regulatory T cells (Treg) accumulate dramatically in aged animals and negatively impact the ability to control persistent infection. However, the mechanism(s) underlying the age-dependent accrual of Treg remain unclear. Here, we show that Treg accumulation with age is progressive and likely not the result of increased thymic output, increased peripheral proliferation, nor from enhanced peripheral conversion. Instead, we found that Treg from aged mice are more resistant to apoptosis than Treg from young mice. Although Treg from aged mice had increased expression of functional IL-7Rα, we found that IL-7R-signaling was not required for maintenance of Treg in vivo. Notably, aged Treg exhibit decreased expression of the pro-apoptotic molecule Bim compared to Treg from young mice. Further, in the absence of Bim, Treg accumulate rapidly, accounting for more than 25% of the CD4+ T cell compartment by 6 months of age. In addition, accumulation of Treg in Bim-deficient mice occurred after the cells left the transitional recent thymic emigrant compartment. Mechanistically, we show that IL-2 drives preferential proliferation and accumulation of Bimlo Treg. Combined, our data suggest that chronic stimulation by IL-2 leads to preferential expansion of Treg having low expression of Bim, which favors their survival and accumulation in aged hosts. PMID:21098226

Resistance to age-dependent thymic atrophy in long-lived mice that are deficient in pregnancy-associated plasma protein A

PubMed Central

Vallejo, Abbe N.; Michel, Joshua J.; Bale, Laurie K.; Lemster, Bonnie H.; Borghesi, Lisa; Conover, Cheryl A.

2009-01-01

Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase that controls the tissue availability of insulin-like growth factor (IGF). Homozygous deletion of PAPPA in mice leads to lifespan extension. Since immune function is an important determinant of individual fitness, we examined the natural immune ecology of PAPPA−/− mice and their wild-type littermates reared under specific pathogen-free condition with aging. Whereas wild-type mice exhibit classic age-dependent thymic atrophy, 18-month-old PAPPA−/− mice maintain discrete thymic cortex and medulla densely populated by CD4+CD8+ thymocytes that are capable of differentiating into single-positive CD4 and CD8 T cells. Old PAPPA−/− mice have high levels of T cell receptor excision circles, and have bone marrows enriched for subsets of thymus-seeding progenitors. PAPPA−/− mice have an overall larger pool of naive T cells, and also exhibit an age-dependent accumulation of CD44+CD43+ memory T cells similar to wild-type mice. However, CD43+ T cell subsets of old PAPPA−/− mice have significantly lower prevalence of 1B11 and S7, glycosylation isoforms known to inhibit T cell activation with normal aging. In bioassays of cell activation, splenic T cells of old PAPPA−/− mice have high levels of activation antigens and cytokine production, and also elicit Ig production by autologous B cells at levels equivalent to young wild-type mice. These data suggest an IGF-immune axis of healthy longevity. Controlling the availability of IGF in the thymus by targeted manipulation of PAPPA could be a way to maintain immune homeostasis during postnatal development and aging. PMID:19549878

Identification of Dynapenia in Older Adults Through the Use of Grip Strength T-Scores

PubMed Central

Bohannon, Richard W; Magasi, Susan

2014-01-01

Objective To generate reference values and t-scores (1.0 to 2.5 standard deviations below average) for grip strength for healthy young adults and to examine the utility of t-scores from this group for the identification of dynapenia in older adults. Design Secondary analysis of cross-sectional grip strength data from the NIH Toolbox norming sample. Setting Population-based general community sample. Participants Community dwelling adults, between the ages 20 and 40 years (n=558); and 60 to 85 years (n=390) Main Outcomes Measures Grip strength measured with a Jamar plus dynamometer. Results Maximum grip strengths were consistent over the 20–40 year age span. For men they were 108.0 lbs (S.D. 22.6). For women, they were 65.8 lbs (S.D. 14.6) Comparison of older participant grip strengths to those of the younger reference group revealed (depending on age strata) that 46.2–87.1% of older men and 50.0–82.4% of older women could be designated as dynapenic on the basis of t-scores. Conclusion The use of reference value t-scores from younger adults is a promising method for determining dynapenia in older adults. PMID:24729356

Identification of dynapenia in older adults through the use of grip strength t-scores.

PubMed

Bohannon, Richard W; Magasi, Susan

2015-01-01

The aim of this study was to generate reference values and t-scores (1.0-2.5 standard deviations below average) for grip strength for healthy young adults and to examine the utility of t-scores from this group for the identification of dynapenia in older adults. Our investigation was a population-based, general community secondary analysis of cross-sectional grip strength data utilizing the NIH Toolbox Assessment norming sample. Participants consisted of community-dwelling adults, with age ranges of 20-40 years (n = 558) and 60-85 years (n = 390). The main outcome measure was grip strength using a Jamar plus dynamometer. Maximum grip strengths were consistent over the 20-40-year age group [men 108.0 (SD 22.6) pounds, women 65.8 (SD 14.6) pounds]. Comparison of older group grip strengths to those of the younger reference group revealed (depending on age strata) that 46.2-87.1% of older men and 50.0-82.4% of older women could be designated as dynapenic on the basis of t-scores. The use of reference value t-scores from younger adults is a promising method for determining dynapenia in older adults. © 2014 Wiley Periodicals, Inc.

Correlation between liver iron concentration determined by magnetic resonance imaging and serum ferritin in adolescents with thalassaemia disease.

PubMed

Chuansumrit, Ampaiwan; Laothamathat, Jiraporn; Sirachainan, Nongnuch; Sungkarat, Witaya; Wongwerawattanakoon, Pakawan; Kumkrua, Patrapop

2016-08-01

MRI imaging is an alternative to serum ferritin for assessing iron overload in patients with thalassaemia disease. To correlate liver iron concentration (LIC) determined by MRI and clinical and biochemical parameters. An MRI study using cardiovascular magnetic resonance (CMR) tools to determine cardiac and liver iron was undertaken in adolescents with thalassaemia disease. Eighty-nine patients (48 males) with thalassaemia disease were enrolled. Seventy patients had been transfusion-dependent since a mean (SD) age of 3.8 (3.0) years, and 19 patients were not transfusiondependent. Mean (SD) haematocrit was 27.3 (2.9)%. Twenty-eight patients were splenectomized. Mean (SD) serum ferritin was 1673 (1506) μg/L. All transfusion-dependent patients received iron chelation at the mean (SD) age of 8.4 (3.5) years with either monotherapy of desferrioxamine, deferiprone, deferasirox or combined therapy of desferrioxamine and deferiprone, while only 5 of 19 patients who were not transfusion-dependent received oral chelation. The 89 patients underwent an MRI scan at the mean (SD) age of 14.8 (3.2) years. No patients had myocardial iron overload, but nine had severe liver iron overload, 27 had moderate liver iron overload, and 36 had mild liver iron overload. A significant correlation between liver T2* and serum ferritin was expressed as the equation: T2* (ms) = 28.080-7.629 log ferritin (μg/L) (r(2) 0.424, P = 0.0001). Patients with serum ferritin of >1000 to >2500 μg/L risked moderate and severe liver iron loading with the odds ratio ranging from 6.8 to 13.3 (95% CI 2.5-50.8). In thalassaemia, MRI is an alternative means of assessing iron stores, but when it is not available serum ferritin can be used to estimate liver T2*.

Distribution of Salivary Testosterone in Men and Women in a British General Population-Based Sample: The Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

PubMed Central

Clifton, Soazig; Tanton, Clare; Macdowall, Wendy; Copas, Andrew J.; Lee, David; Field, Nigel; Mitchell, Kirstin R.; Sonnenberg, Pam; Bancroft, John; Mercer, Cath H.; Johnson, Anne M.; Wellings, Kaye; Wu, Frederick C. W.

2017-01-01

Introduction: Measurement of salivary testosterone (Sal-T) to assess androgen status offers important potential advantages in epidemiological research. The utility of the method depends on the interpretation of the results against robustly determined population distributions, which are currently lacking. Aim: To determine age-specific Sal-T population distributions for men and women. Methods: Morning saliva samples were obtained from participants in the third National Survey of Sexual Attitudes and Lifestyles, a probability sample survey of the British general population. Sal-T was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Linear and quantile regression analyses were used to determine the age-specific 2.5th and 97.5th percentiles for the general population (1675 men and 2453 women) and the population with health exclusions (1145 men and 1276 women). Results: In the general population, the mean Sal-T level in men decreased from 322.6 pmol/L at 18 years of age to 153.9 pmol/L at 69 years of age. In women, the decrease in the geometric mean Sal-T level was from 39.8 pmol/L at 18 years of age to 19.5 pmol/L at 74 years of age. The annual decrease varied with age, with an average of 1.0% to 1.4% in men and 1.3% to 1.5% in women. For women, the 2.5th percentile fell below the detection limit (<6.5 pmol/L) from age 52 years onward. The mean Sal-T level was approximately 6 times greater in men than in women, and this remained constant over the age range. The Sal-T level was lowest for men and highest for women in the summer. The results were similar for the general population with exclusions. Conclusions: To our knowledge, this is the first study to describe the sex- and age-specific distributions for Sal-T in a large representative population using a specific and sensitive LC-MS/MS technique. The present data can inform future population research by facilitating the interpretation of Sal-T results as a marker of androgen status. PMID:29264442

Ontogeny of con A and PHA responses of chicken blood cells in MHC-compatible lines 6(3) and 7(2).

PubMed

Fredericksen, T L; Gilmour, D G

1983-06-01

The development of T cell responsiveness to Con A and PHA was examined in two MHC-compatible inbred chicken lines, RPRL 6(3) and 7(2), at ages 2 to 118 days posthatching. These lines are respectively resistant or susceptible to Marek's disease, a naturally occurring, virally induced T cell lymphoma. Between-line comparisons were made of optimal in vitro responses of diluted serum-free blood cells to each mitogen in two groups of chicks tested over ages 2 to 63 and 41 to 118 days. Over 2 to 63 days, Con A responses increased with age at the same rate in each line, but 7(2) responses averaged 2.3 times higher than 6(3). The increase with age was dependent on blood lymphocyte counts, which also increased with age in parallel in both lines. In contrast, the between-line difference in responsiveness was dependent on intrinsic reactivity of cells as well as lymphocyte counts. Covariance analysis was used to estimate that line 7(2) was 1.4 times higher than 6(3) in intrinsic cell reactivity, after accounting for the effect of the twofold higher blood lymphocyte counts in 7(2), and that this intrinsic difference contributed almost one-half the total difference. Over 41 to 118 days Con A responses no longer increased with age, although lymphocyte counts were still increasing, and the line difference (2.6 times) was now almost entirely contributed by a 2.3-fold superiority of 7(2) blood cells in intrinsic reactivity. The line difference in PHA responses was the reverse of the above in young chicks, with 6(3) responses greater than 7(2) in spite of lower lymphocyte counts. In additional chicks tested over 5 to 26 days, intrinsic reactivity of 6(3) cells to PHA averaged 4.5 times higher than 7(2). There was an abrupt decline in intrinsic reactivity of line 6(3) blood cells between 26 and 41 days to a level equal with 7(2). After this age, line 7(2) responses were 1.8 times greater than those of 6(3), and this difference was dependent solely on lymphocyte count differences. The results suggest that different gene systems mediate blood cell responses to PHA as compared with Con A. The pattern of developmental differences between inbred lines indicates the existence of distinct or partly overlapping T cell subsets with different reactivities to PHA or Con A, and of higher suppressor activity of adherent cells in line 6(3) blood. Both these differences may be related to line 6(3) inherited resistance to Marek's disease.

Spatial working memory impairment in primary onset middle-age type 2 diabetes mellitus: An ethology and BOLD-fMRI study.

PubMed

Huang, Ran-Ran; Jia, Bao-Hui; Xie, Lei; Ma, Shu-Hua; Yin, Jing-Jing; Sun, Zong-Bo; Le, Hong-Bo; Xu, Wen-Can; Huang, Jin-Zhuang; Luo, Dong-Xue

2016-01-01

To explore mild cognitive dysfunction and/or spatial working memory impairment in patients with primary onset middle-age type 2 diabetes mellitus (T2DM] using ethology (behavior tests) and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). Eighteen primary onset T2DM patients and 18 matched subjects with normal blood glucose levels were all tested using the Montreal cognitive assessment scale test, the Wechsler Memory Scale Chinese-revised test, and scanned using BOLD-fMRI (1.5T, EPI sequence) while performing the n-back task to find the activation intensity of some cognition-related areas. The ethology results showed that T2DM patients had a mild cognitive impairment and memory dysfunction (P < 0.05). The fMRI scan identified a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), bilateral parietal lobe (PA), and anterior cingulate cortex (ACC) / supplementary motor area (SMA) that was activated during the n-back task, with right hemisphere dominance. However, only the right PA and ACC/SMA showed a load effect via quantitative analysis in the T2DM group; the activation intensity of most working memory-related brain areas for the T2DM group were lower than for the control group under three memory loads. Furthermore, we found that the activation intensity of some cognition-related areas, including the right insular lobe, left caudate nucleus, and bilateral hippocampus/parahippocampal gyrus were lower than the control group under the memory loads. Diabetes-related brain damage of primary onset middle-age T2DM patients with right DLPFC-posterior parietal lobe and parahippocampal gyrus default network causes impairment of spatial working memory and mild cognitive dysfunction. © 2015 Wiley Periodicals, Inc.

Age- and gender-specific associations of napping duration with type 2 diabetes mellitus in a Chinese rural population: the RuralDiab study.

PubMed

Liu, Ruihua; Li, Yuqian; Wang, Fang; Liu, Xiaotian; Zhou, Hao; Wang, Panpan; Fan, Jingjing; Xu, Fei; Yang, Kaili; Hu, Dongsheng; Bie, Ronghai; Wang, Chongjian

2017-05-01

The consistency and strength of the relationship between napping duration and type 2 diabetes mellitus (T2DM) remained uncertain, especially in the rural population. The purpose of this study was to explore the relationship between napping duration and T2DM in a Chinese rural population. A total of 12663 participants (4365 males and 8298 females) were derived from the RuralDiab study in China. Napping duration was obtained through a standardized questionnaire, and was divided into five categories: no napping (reference), 1∼, 31∼, 61∼, and ≥91 min. Fasting blood glucose was measured. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A meta-analysis including seven studies was conducted to validate the result of the RuralDiab study. The crude and age-standardized prevalence of T2DM were 10.31% and 8.14%, respectively. Compared with no napping, the adjusted OR (95%CI) for napping duration ≥91 min was 1.23 (1.05-1.45). A similar relationship was found only in females aged 45-54 years, but not in males and other age group females. In addition, napping duration was associated with T2DM in a positive dose-dependent manner among females aged 45-54 years (P for trend <0.05). The meta-analysis demonstrated this association, and the pooled OR (95%CI) for the longest napping duration compared with no napping was 1.28 (1.22-1.35). Longer napping duration is associated with higher risk of T2DM in the Chinese rural population, and this association varies across gender and age. Further multi-center prospective researches are needed to confirm the relationship and reveal underlying mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues.

PubMed

Padron, Alvaro Souto; Neto, Ruy Andrade Louzada; Pantaleão, Thiago Urgal; de Souza dos Santos, Maria Carolina; Araujo, Renata Lopes; de Andrade, Bruno Moulin; da Silva Leandro, Monique; de Castro, João Pedro Saar Werneck; Ferreira, Andrea Claudia Freitas; de Carvalho, Denise Pires

2014-06-01

In general, 3,5-diiodothyronine (3,5-T2) increases the resting metabolic rate and oxygen consumption, exerting short-term beneficial metabolic effects on rats subjected to a high-fat diet. Our aim was to evaluate the effects of chronic 3,5-T2 administration on the hypothalamus-pituitary-thyroid axis, body mass gain, adipose tissue mass, and body oxygen consumption in Wistar rats from 3 to 6 months of age. The rats were treated daily with 3,5-T2 (25, 50, or 75 μg/100 g body weight, s.c.) for 90 days between the ages of 3 and 6 months. The administration of 3,5-T2 suppressed thyroid function, reducing not only thyroid iodide uptake but also thyroperoxidase, NADPH oxidase 4 (NOX4), and thyroid type 1 iodothyronine deiodinase (D1 (DIO1)) activities and expression levels, whereas the expression of the TSH receptor and dual oxidase (DUOX) were increased. Serum TSH, 3,3',5-triiodothyronine, and thyroxine were reduced in a 3,5-T2 dose-dependent manner, whereas oxygen consumption increased in these animals, indicating the direct action of 3,5-T2 on this physiological variable. Type 2 deiodinase activity increased in both the hypothalamus and the pituitary, and D1 activities in the liver and kidney were also increased in groups treated with 3,5-T2. Moreover, after 3 months of 3,5-T2 administration, body mass and retroperitoneal fat pad mass were significantly reduced, whereas the heart rate and mass were unchanged. Thus, 3,5-T2 acts as a direct stimulator of energy expenditure and reduces body mass gain; however, TSH suppression may develop secondary to 3,5-T2 administration. © 2014 The authors.

Insulin Storage and Glucose Homeostasis in Mice Null for the Granule Zinc Transporter ZnT8 and Studies of the Type 2 Diabetes–Associated Variants

PubMed Central

Nicolson, Tamara J.; Bellomo, Elisa A.; Wijesekara, Nadeeja; Loder, Merewyn K.; Baldwin, Jocelyn M.; Gyulkhandanyan, Armen V.; Koshkin, Vasilij; Tarasov, Andrei I.; Carzaniga, Raffaella; Kronenberger, Katrin; Taneja, Tarvinder K.; da Silva Xavier, Gabriela; Libert, Sarah; Froguel, Philippe; Scharfmann, Raphael; Stetsyuk, Volodymir; Ravassard, Philippe; Parker, Helen; Gribble, Fiona M.; Reimann, Frank; Sladek, Robert; Hughes, Stephen J.; Johnson, Paul R.V.; Masseboeuf, Myriam; Burcelin, Remy; Baldwin, Stephen A.; Liu, Ming; Lara-Lemus, Roberto; Arvan, Peter; Schuit, Frans C.; Wheeler, Michael B.; Chimienti, Fabrice; Rutter, Guy A.

2009-01-01

OBJECTIVE Zinc ions are essential for the formation of hexameric insulin and hormone crystallization. A nonsynonymous single nucleotide polymorphism rs13266634 in the SLC30A8 gene, encoding the secretory granule zinc transporter ZnT8, is associated with type 2 diabetes. We describe the effects of deleting the ZnT8 gene in mice and explore the action of the at-risk allele. RESEARCH DESIGN AND METHODS Slc30a8 null mice were generated and backcrossed at least twice onto a C57BL/6J background. Glucose and insulin tolerance were measured by intraperitoneal injection or euglycemic clamp, respectively. Insulin secretion, electrophysiology, imaging, and the generation of adenoviruses encoding the low- (W325) or elevated- (R325) risk ZnT8 alleles were undertaken using standard protocols. RESULTS ZnT8−/− mice displayed age-, sex-, and diet-dependent abnormalities in glucose tolerance, insulin secretion, and body weight. Islets isolated from null mice had reduced granule zinc content and showed age-dependent changes in granule morphology, with markedly fewer dense cores but more rod-like crystals. Glucose-stimulated insulin secretion, granule fusion, and insulin crystal dissolution, assessed by total internal reflection fluorescence microscopy, were unchanged or enhanced in ZnT8−/− islets. Insulin processing was normal. Molecular modeling revealed that residue-325 was located at the interface between ZnT8 monomers. Correspondingly, the R325 variant displayed lower apparent Zn2+ transport activity than W325 ZnT8 by fluorescence-based assay. CONCLUSIONS ZnT8 is required for normal insulin crystallization and insulin release in vivo but not, remarkably, in vitro. Defects in the former processes in carriers of the R allele may increase type 2 diabetes risks. PMID:19542200

A PLC-γ1-independent, RasGRP1-ERK dependent pathway drives lymphoproliferative disease in LAT-Y136F mutant mice

PubMed Central

Kortum, Robert L.; Rouquette-Jazdanian, Alexandre K.; Miyaji, Michihiko; Merrill, Robert K.; Markegard, Evan; Pinski, John M.; Wesselink, Amelia; Nath, Nandan N.; Alexander, Clayton P.; Li, Wenmei; Kedei, Noemi; Roose, Jeroen P.; Blumberg, Peter M.; Samelson, Lawrence E.; Sommers, Connie L.

2012-01-01

Mice expressing a germline mutation in the PLC-γ1 binding site of LAT (linker for activation of T cells) show progressive lymphoproliferation and ultimately die at 4–6 months of age. The hyper-activated T cells in these mice show defective TCR-induced calcium flux, but enhanced Ras/ERK activation that is critical for disease progression. Despite the loss of LAT-dependent PLC-γ1 binding and activation, genetic analysis revealed RasGRP1, and not Sos1 or Sos2, to be the major RasGEF responsible for ERK activation and the lymphoproliferative phenotype in these mice. Analysis of isolated CD4+ T cells from LAT-Y136F mice showed altered proximal TCR-dependent kinase signaling, which activated a Zap70- and LAT-independent pathway. Moreover, LAT-Y136F T cells showed ERK activation that was dependent on Lck and/or Fyn, PKCθ, and RasGRP1. These data demonstrate a novel route to Ras activation in vivo in a pathological setting. PMID:23209318

Rapid high resolution T1 mapping as a marker of brain development: Normative ranges in key regions of interest.

PubMed

Eminian, Sylvain; Hajdu, Steven David; Meuli, Reto Antoine; Maeder, Philippe; Hagmann, Patric

2018-01-01

We studied in a clinical setting the age dependent T1 relaxation time as a marker of normal late brain maturation and compared it to conventional techniques, namely the apparent diffusion coefficient (ADC). Forty-two healthy subjects ranging from ages 1 year to 20 years were included in our study. T1 brain maps in which the intensity of each pixel corresponded to T1 relaxation times were generated based on MR imaging data acquired using a MP2RAGE sequence. During the same session, diffusion tensor imaging data was collected. T1 relaxation times and ADC in white matter and grey matter were measured in seven clinically relevant regions of interest and were correlated to subjects' age. In the basal ganglia, there was a small, yet significant, decrease in T1 relaxation time (-0.45 ≤R≤-0.59, p<10-2) and ADC (-0.60≤R≤-0.65, p<10-4) as a function of age. In the frontal and parietal white matter, there was a significant decrease in T1 relaxation time (-0.62≤R≤-0.68, p<10-4) and ADC (-0.81≤R≤-0.85, p<10-4) as a function of age. T1 relaxation time changes in the corpus callosum and internal capsule were less relevant for this age range. There was no significant difference between the correlation of T1 relaxation time and ADC with respect to age (p-value = 0.39). The correlation between T1 relaxation and ADC is strong in the white matter but only moderate in basal ganglia over this age period. T1 relaxation time is a marker of brain maturation or myelination during late brain development. Between the age of 1 and 20 years, T1 relaxation time decreases as a function of age in the white matter and basal ganglia. The greatest changes occur in frontal and parietal white matter. These regions are known to mature in the final stage of development and are mainly composed of association circuits. Age-correlation is not significantly different between T1 relaxation time and ADC. Therefore, T1 relaxation time does not appear to be a superior marker of brain maturation than ADC but may be considered as complementary owing the intrinsic differences in bio-physical sensitivity. This work may serve as normative ranges in clinical imaging routines.

Evolution of wavelength-dependent mass absorption cross sections of carbonaceous aerosols during the 2010 DOE CARES campaign

NASA Astrophysics Data System (ADS)

Flowers, B. A.; Dubey, M. K.; Subramanian, R.; Sedlacek, A. J.; Kelley, P.; Luke, W. T.; Jobson, B. T.; Zaveri, R. A.

2011-12-01

Predictions of aerosol radiative forcing require process level optical property models that are built on precise and accurate field observations. Evolution of aerosol optical properties for urban influenced carbonaceous aerosol undergoing transport and mixing with rural air masses was a focal point of the DOE Carbonaceous Aerosol and Radiative Effects (CARES) campaign near Sacramento, CA in summer 2010. Urban aerosol was transported from Sacramento, CA (T0) to the foothills of the Sierra Nevada Mountains to a rural site located near Cool, CA (T1). Aerosol absorption and scattering coefficients were measured at the T0 and T1 sites using integrated photoacoustic acoustic/nephelometer instruments (PASS-3 and PASS-UV) at 781, 532, 405, and 375 nm. Single particle soot photometry (SP2) instrumentation was used to monitor black carbon (BC) mass at both sites. Combining data from these sensors allows estimate of the wavelength-dependent mass absorption coefficient (MAC(λ)) and partitioning of MAC(λ) into contributions from the BC core and from enhancements from coating of BC cores. MAC(λ) measured in this way is free of artifacts associated with filter-based aerosol absorption measurements and takes advantage of the single particle sensitivity of the SP2 instrument, allowing observation of MAC(λ) on 10 minute and faster time scales. Coating was observed to enhance MAC(λ) by 20 - 30 % and different wavelength dependence for MAC(λ) was observed for urban and biomass burning aerosol. Further, T0 - T1 evolution of MAC(λ) was correlated with separately measured NO/NOy ratios and CO/CO2 ratios to understand the effects of aging & transport on MAC(λ) and the implications of aerosol processing that links air quality to radiative forcing on a regional scale. Aircraft observations made from the Gulfstream-1 during CARES are also analyzed to enhance process level understanding of the optical properties of fresh and aged carbonaceous aerosol in the urban-rural interface.

Acute loading and aging effects on myostatin pathway biomarkers in human skeletal muscle after three sequential bouts of resistance exercise.

PubMed

Dalbo, Vincent J; Roberts, Michael D; Sunderland, Kyle L; Poole, Chris N; Stout, Jeff R; Beck, Travis W; Bemben, Mike; Kerksick, Chad M

2011-08-01

To determine the influence of age and resistance exercise on myostatin pathway-related genes, younger (n = 10; 28 ± 5 years) and older (n = 10; 68 ± 6 years) men underwent four testing conditions (T1-T4). A baseline (T1) muscle sample was obtained, whereas the second and third biopsies were obtained 48 hours following the first and second training sessions (T2, T3), and a final biopsy was taken 24 hours following T3. The training sessions consisted of 3 sets of 10 repetitions (80% of one repetition maximum) on leg press, hack squat, and leg extension exercises. Follistatin (FST) messenger RNA was greater in older compared with younger men at T1 and T2 (p < .05). Follistatin-like 3 (FSTL3) messenger RNA was greater in older compared with younger men at T1 and T4 (p < .05). In older men, there was a significant decrease in myostatin (MSTN) messenger RNA at T4 (p < .05). Older men contained less active (Ser-425 phosphorylated) SMAD3 (p-SMAD3) protein than younger men at T3 and T4 (p < .05).Although it is well known that younger individuals possess a greater hypertrophic potential to resistance exercise, it appears that older individuals may paradoxically possess a more favorable resistance exercise response regarding myostatin pathway-related genes and a protein marker of pathway activity. Future research is warranted to examine the physiological significance of this age-dependent mechanism.

In vitro and in vivo effects of zinc on cytokine signalling in human T cells.

PubMed

Varin, Audrey; Larbi, Anis; Dedoussis, George V; Kanoni, Stavroula; Jajte, Jolanta; Rink, Lothar; Monti, Daniela; Malavolta, Marco; Marcellini, Fiorella; Mocchegiani, Eugenio; Herbein, Georges; Fulop, Tamas

2008-05-01

Aging is associated with changes in the immune response which are collectively called immunosenescence. The changes mainly affect the adaptive immune response and especially the T cell-mediated cellular immune response. There are a few data indicating that the cytokine signalling in T cells is altered with aging. Zinc has been specifically shown to have potent immunomodulatory effects. The aim of the present work was to study the IL-2 and IL-6 cytokine signalling and activation induced cell death (AICD) in T cells of elderly subjects of various ages and from various European countries. These experiments were performed in the frame of European Community financed project called ZINCAGE "Nutritional zinc, oxidative stress and immunosenescence: biochemical, genetic and lifestyle implications for healthy ageing", assembling 17 laboratories from 8 countries through Europe. The study was carried out in a total of 312 French and a group of 201 (26 from Italy, 63 from France, 57 from Greece, 24 from Poland and 30 from Germany) healthy non-institutionalized men and women older than 60 years of age, with available dietary data. Human peripheral blood mononuclear cells (PBMC) were obtained from heparinized blood and were stimulated in vitro by IL-2 or IL-6 for various periods and the phosphorylation of STAT3 and STAT5 was measured by FACScan. The activation induced cell death (AICD) was measured after anti-CD3 and CD28 restimulation for 48h by using the Annexin:FITC Apoptosis Kit. We found that there is an IL-2 signalling defect with aging up to 90 years of age which cannot be modulated by zinc. In contrast at 90 years and over the zinc could reverse the negative signalling effect of IL-2. There is also a signalling defect for STAT3 and STAT5 activation in T cells under IL-6 stimulation with aging and the zinc supplementation could potentiate only the STAT5 activation in the age-group 90 years and over. Studying signalling in PBL from different countries we detected less activation in T cells of subjects from France and the most changes occurred in T cells of subjects from Poland, suggesting no correlation with the plasma zinc status observed in these countries. In vivo zinc supplementation had no effect on IL-2 and IL-6-modulated STAT3 and STAT5 activation. Zinc added in vitro to these T cells even inhibited the stimulation either by IL-2 or by IL-6. Zinc supplementation improved the susceptibility of T cells to AICD in both age-groups, with more efficiency in later ages. Our results suggest that zinc can have a potent immunomodulatory effect via the modulation of cytokine signalling and AICD, however this effect depends on the function and the activation status of the T cells.

Dietary influences on cognitive function with aging: from high-fat diets to healthful eating.

PubMed

Parrott, Matthew D; Greenwood, Carol E

2007-10-01

Human epidemiologic studies provide convincing evidence that dietary patterns practiced during adulthood are important contributors to age-related cognitive decline and dementia risk. Diets high in fat, especially trans and saturated fats, adversely affect cognition, while those high in fruits, vegetables, cereals, and fish are associated with better cognitive function and lower risk of dementia. While the precise physiologic mechanisms underlying these dietary influences are not completely understood, modulation of brain insulin activity and neuroinflammation likely contribute. Not surprisingly, deficits in cognitive functions, especially those dependent on the medial temporal lobes, are apparent in type 2 diabetes mellitus (T2DM). Special care in food selection at meals should be exercised by those with T2DM since ingestion of rapidly absorbed, high-glycemic index carbohydrate foods further impairs medial temporal lobe function, with food-induced increases in oxidative stress and cytokine release likely explaining the association between food ingestion and reduction in cognitive function in those with T2DM.

Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene.

PubMed

Murovets, Vladimir O; Bachmanov, Alexander A; Zolotarev, Vasiliy A

2015-01-01

The G-protein-coupled sweet taste receptor dimer T1R2/T1R3 is expressed in taste bud cells in the oral cavity. In recent years, its involvement in membrane glucose sensing was discovered in endocrine cells regulating glucose homeostasis. We investigated importance of extraorally expressed T1R3 taste receptor protein in age-dependent control of blood glucose homeostasis in vivo, using nonfasted mice with a targeted mutation of the Tas1r3 gene that encodes the T1R3 protein. Glucose and insulin tolerance tests, as well as behavioral tests measuring taste responses to sucrose solutions, were performed with C57BL/6ByJ (Tas1r3+/+) inbred mice bearing the wild-type allele and C57BL/6J-Tas1r3tm1Rfm mice lacking the entire Tas1r3 coding region and devoid of the T1R3 protein (Tas1r3-/-). Compared with Tas1r3+/+ mice, Tas1r3-/- mice lacked attraction to sucrose in brief-access licking tests, had diminished taste preferences for sucrose solutions in the two-bottle tests, and had reduced insulin sensitivity and tolerance to glucose administered intraperitoneally or intragastrically, which suggests that these effects are due to absence of T1R3. Impairment of glucose clearance in Tas1r3-/- mice was exacerbated with age after intraperitoneal but not intragastric administration of glucose, pointing to a compensatory role of extraoral T1R3-dependent mechanisms in offsetting age-dependent decline in regulation of glucose homeostasis. Incretin effects were similar in Tas1r3+/+ and Tas1r3-/- mice, which suggests that control of blood glucose clearance is associated with effects of extraoral T1R3 in tissues other than the gastrointestinal tract. Collectively, the obtained data demonstrate that the T1R3 receptor protein plays an important role in control of glucose homeostasis not only by regulating sugar intake but also via its extraoral function, probably in the pancreas and brain.

Age-dependent systemic DNA damage in early Type 2 Diabetes mellitus.

PubMed

Rogulj, Dinko; El Aklouk, Ismail; Konjevoda, Paško; Ljubić, Spomenka; Pibernik Okanović, Mirjana; Barbir, Ante; Luburić, Marijana; Radman, Maja; Budinski, Ninoslav; Vučić Lovrenčić, Marijana

2017-01-01

Oxidative stress, capable of eliciting damage to various biomolecules including DNA, is a recognized component of diabetes mellitus and its complications. Metabolic syndrome (MetS) is associated with the development of type 2 diabetes mellitus (T2DM), as well as other unfavorable outcomes. The aim of this study was to elucidate the role of oxidative stress in the development of T2DM, by investigating association of oxidative DNA damage with metabolic parameters in subjects with MetS and early T2DM. Selected anthropometric and biochemical parameters of MetS, inflammation and oxidative DNA damage: body mass index (BMI), fatty liver index (FLI), waist circumference (WC), total cholesterol, HDL and LDL-cholesterol, gamma-glutamyl transpeptidase (GGT), uric acid, C-reactive protein (CRP), total leukocyte/neutrophil count, and urinary 8-hidroxy-deoxyguanosine (u-8-OHdG) were assessed in male subjects with MetS and both younger (≤55 years) and older (>55 years) subjects with T2DM of short duration without complications. BMI, FLI, WC, total and LDL-cholesterol and uric acid were higher, while the u-8-OHdG was lower in MetS group, when compared to older T2DM subjects. None of these parameters were different neither between MetS and younger T2DM, nor between two sub-groups of subjects with T2DM. Values of CRP, HDL-cholesterol, triglycerides, GGT, leukocytes and neutrophils were not different between all examined groups of subjects. Higher 8-OHdG in older subjects with T2DM suggests that both aging process and diabetes could contribute to the development of DNA damage. Oxidative DNA damage cannot serve as an universal early marker of T2DM.

IL-6 Production by TLR-Activated APC Broadly Enhances Aged Cognate CD4 Helper and B Cell Antibody Responses In Vivo.

PubMed

Brahmakshatriya, Vinayak; Kuang, Yi; Devarajan, Priyadharshini; Xia, Jingya; Zhang, Wenliang; Vong, Allen Minh; Swain, Susan L

2017-04-01

Naive CD4 T cell responses, especially their ability to help B cell responses, become compromised with aging. We find that using APC pretreated ex vivo with TLR agonists, polyinosinic-polycytidylic acid and CpG, to prime naive CD4 T cells in vivo, restores their ability to expand and become germinal center T follicular helpers and enhances B cell IgG Ab production. Enhanced helper responses are dependent on IL-6 production by the activated APC. Aged naive CD4 T cells respond suboptimally to IL-6 compared with young cells, such that higher doses are required to induce comparable signaling. Preactivating APC overcomes this deficiency. Responses of young CD4 T cells are also enhanced by preactivating APC with similar effects but with only partial IL-6 dependency. Strikingly, introducing just the activated APC into aged mice significantly enhances otherwise compromised Ab production to inactivated influenza vaccine. These findings reveal a central role for the production of IL-6 by APC during initial cognate interactions in the generation of effective CD4 T cell help, which becomes greater with age. Without APC activation, aging CD4 T cell responses shift toward IL-6-independent Th1 and CD4 cytotoxic Th cell responses. Thus, strategies that specifically activate and provide Ag to APC could potentially enhance Ab-mediated protection in vaccine responses. Copyright © 2017 by The American Association of Immunologists, Inc.

Stability and Predictive Validity of the Parent-Child Sleep Interactions Scale: A Longitudinal Study Among Preschoolers.

PubMed

Barrios, Chelsey S; Jay, Samantha Y; Smith, Victoria C; Alfano, Candice A; Dougherty, Lea R

2018-01-01

Little research has examined the processes underlying children's persistent sleep problems and links with later psychopathology. The current study examined the stability of parent-child sleep interactions as assessed with the parent-reported Parent-Child Sleep Interactions Scale (PSIS) and examined whether sleep interactions in preschool-age children predict sleep problems and psychiatric symptoms later in childhood. Participants included 108 preschool-age children (50% female) and their parents. Parents completed the PSIS when children were 3-5 years (T1) and again when they were 6-9 years (T2). The PSIS includes three subscales-Sleep Reinforcement (reassurance of child sleep behaviors), Sleep Conflict (parent-child conflict at bedtime), Sleep Dependence (difficulty going to sleep without parent)-and a total score. Higher scores indicate more problematic bedtime interactions. Children's sleep problems and psychiatric symptoms at T1 and T2 were assessed with a clinical interview. PSIS scores were moderately stable from T1 to T2, and the factor structure of the PSIS remained relatively consistent over time. Higher total PSIS scores at T1 predicted increases in children's sleep problems at T2. Higher PSIS Sleep Conflict scores at T1 predicted increases in oppositional defiant disorder symptoms at T2. Children with more sleep problems and higher PSIS Sleep Reinforcement scores at T1 showed increases in attention deficit/hyperactivity disorder, depressive, and anxiety symptoms at T2. These findings provide evidence for the predictive validity of the PSIS and highlight the importance of early parent-child sleep interactions in the development of sleep and psychiatric symptoms in childhood. Parent-child sleep interactions may serve as a useful target for interventions.

Long-term Isothermal Aging Effects on Weight Loss, Compression Properties, and Dimensions of T650-35 Fabric-reinforced PMR-15 Composites-data

NASA Technical Reports Server (NTRS)

Bowles, Kenneth J.; Tsuji, Luis; Kamvouris, John; Roberts, Gary D.

2003-01-01

A cooperative program was conducted with the General Electric Aircraft Engines plant in Evendale, Ohio, to study the effects of long-term isothermal aging at elevated temperatures on compression and thermal durability properties of T650 35 fabric-reinforced PMR 15 composites. This degradation study was conducted over an approximate time period of 3 1/2 yr. The aging temperatures were 204, 260, 288, 316, and 343 C. Specimens of different dimensions were evaluated. Specimens with ratios of the cut edge to total surface area of 0.03 to 0.89 were fabricated and aged. The aged and unaged specimens were tested in compression as specified in Test Method for Compressive Properties of Rigid Plastics (ASTM D695M). Thickness changes, degraded surface layer growth, weight loss, and failure modes were monitored and recorded. All property changes were thickness dependent.

Aging Effects on Cardiac and Respiratory Dynamics in Healthy Subjects across Sleep Stages

PubMed Central

Schumann, Aicko Y.; Bartsch, Ronny P.; Penzel, Thomas; Ivanov, Plamen Ch.; Kantelhardt, Jan W.

2010-01-01

Study Objectives: Respiratory and heart rate variability exhibit fractal scaling behavior on certain time scales. We studied the short-term and long-term correlation properties of heartbeat and breathing-interval data from disease-free subjects focusing on the age-dependent fractal organization. We also studied differences across sleep stages and night-time wake and investigated quasi-periodic variations associated with cardiac risk. Design: Full-night polysomnograms were recorded during 2 nights, including electrocardiogram and oronasal airflow. Setting: Data were collected in 7 laboratories in 5 European countries. Participants: 180 subjects without health complaints (85 males, 95 females) aged from 20 to 89 years. Interventions: None. Measurements and Results: Short-term correlations in heartbeat intervals measured by the detrended fluctuation analysis (DFA) exponent α1 show characteristic age dependence with a maximum around 50–60 years disregarding the dependence on sleep and wake states. Long-term correlations measured by α2 differ in NREM sleep when compared with REM sleep and wake, besides weak age dependence. Results for respiratory intervals are similar to those for α2 of heartbeat intervals. Deceleration capacity (DC) decreases with age; it is lower during REM and deep sleep (compared with light sleep and wake). Conclusion: The age dependence of α1 should be considered when using this value for diagnostic purposes in post-infarction patients. Pronounced long-term correlations (larger α2) for heartbeat and respiration during REM sleep and wake indicate an enhanced control of higher brain regions, which is absent during NREM sleep. Reduced DC possibly indicates an increased cardiovascular risk with aging and during REM and deep sleep. Citation: Schumann AY; Bartsch RP; Penzel T; Ivanov PC; Kantelhardt JW. Aging effects on cardiac and respiratory dynamics in healthy subjects across sleep stages. SLEEP 2010;33(7):943-955. PMID:20614854

Effect of low incubation temperature and low ambient temperature until 21 days of age on performance and body temperature in fast-growing chickens

PubMed Central

Nyuiadzi, D; Travel, A; Méda, B; Berri, C; Guilloteau, L A; Coustham, V; Wang, Y; Tona, J K; Collin, A

2017-01-01

Abstract Thermal manipulation during embryogenesis was previously reported to decrease the occurrence of ascites and to potentially improve cold tolerance of broilers. The objective of our study was to explore the effects of the interaction of cold incubation temperatures and cool ambient temperatures until 21 d of age on performance and body temperature. Ross 308 eggs were incubated either under control conditions I0 (37.6°C) or with cyclic cold stimulations I1 (6 h/d at 36.6°C from d 10 to 18 of incubation) or with 2 cold stimulations I2 (30 min at 15°C) at d 18 and 19 of incubation. These treatments were followed by individual rearing and postnatal exposure to either standard rearing temperature T0 (from 33°C at hatching to 21°C at d 21) or continuously lower temperature T2 (from 28°C at hatching to 21°C at d 21) or exposure to cyclically lower temperature T1 (with circadian temperature oscillations). Treatments I1 and I2 did not significantly alter hatchability compared to control incubation (with 94.8, 95.1, and 92.3%, respectively), or hatching BW and overall chick quality. Hatching body temperature (Tb) was 0.5 and 0.3°C higher in I1 than in I0 and I2 groups, respectively (P = 0.007). A doubled occurrence of health problems was observed with T2 condition, regardless of incubation or sex. At d 3, BW was 2% lower with treatment I1 than with I0 and I2 and was 3% higher in T1 and T2 groups than in T0, but these effects disappeared with age. Group T2 presented a 5% higher feed intake than the control group T0 between 3 and 21 d of age (P = 0.025). Feed conversion ratio (FCR) was affected by experimental conditions (P < 0.001), with low FCR values obtained with I2 incubation in control or cyclically cold postnatal conditions. Maximal FCR values were observed in the continuously cold postnatal conditions, in males submitted to control incubation and in females submitted to I1 incubation, revealing sex-dependent effects of the treatments on performance. PMID:29053847

T-kininogen, a cystatin-like molecule, inhibits ERK-dependent lymphocyte proliferation.

PubMed

Acuña-Castillo, Claudio; Aravena, Mauricio; Leiva-Salcedo, Elías; Pérez, Viviana; Gómez, Christian; Sabaj, Valeria; Nishimura, Sumiyo; Pérez, Claudio; Colombo, Alicia; Walter, Robin; Sierra, Felipe

2005-12-01

Plasma levels of kininogens increase with age in both rats and humans. Kininogens are inhibitors of cysteine proteinases, and filarial cysteine proteinase inhibitors (cystatins) reduce the proliferation of T cells. We evaluated whether T-kininogen (T-KG) might mimic this effect, and here we present data indicating that exposure of either rat splenocytes or Jurkat cells to purified T-KG results in inhibition of both ERK activation and [(3)H]-thymidine incorporation, both basal and in response to ConA or PHA. Interestingly, T-KG did not impair [(3)H]-thymidine incorporation in response to IL-2, which requires primarily the activation of the JNK and Jak/STAT pathways. These effects were neither the consequence of increased cell death, nor required the activity of kinin receptors. Furthermore, when T cell receptor proximal events were bypassed by the use of PMA plus Calcium ionophore, T-KG no longer inhibited ERK activation, suggesting that inhibition occurs upstream of these events, possibly at the level of membrane associated signal transduction molecules. We conclude that, like filarial cystatins, T-KG inhibits ERK-dependent T cell proliferation, and these observations suggest a possible role for T-KG in immunosenescence.

Activation of Akt by Advanced Glycation End Products (AGEs): Involvement of IGF-1 Receptor and Caveolin-1

PubMed Central

Yang, Su-Jung; Chen, Chen-Yu; Chang, Geen-Dong; Wen, Hui-Chin; Chen, Ching-Yu; Chang, Shi-Chuan; Liao, Jyh-Fei; Chang, Chung-Ho

2013-01-01

Diabetes is characterized by chronic hyperglycemia, which in turn facilitates the formation of advanced glycation end products (AGEs). AGEs activate signaling proteins such as Src, Akt and ERK1/2. However, the mechanisms by which AGEs activate these kinases remain unclear. We examined the effect of AGEs on Akt activation in 3T3-L1 preadipocytes. Addition of AGEs to 3T3-L1 cells activated Akt in a dose- and time-dependent manner. The AGEs-stimulated Akt activation was blocked by a PI3-kinase inhibitor LY 294002, Src inhibitor PP2, an antioxidant NAC, superoxide scavenger Tiron, or nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase inhibitor DPI, suggesting the involvement of Src and NAD(P)H oxidase in the activation of PI3-kinase-Akt pathway by AGEs. AGEs-stimulated Src tyrosine phosphorylation was inhibited by NAC, suggesting that Src is downstream of NAD(P)H oxidase. The AGEs-stimulated Akt activity was sensitive to Insulin-like growth factor 1 receptor (IGF-1R) kinase inhibitor AG1024. Furthermore, AGEs induced phosphorylation of IGF-1 receptorβsubunit (IGF-1Rβ) on Tyr1135/1136, which was sensitive to PP2, indicating that AGEs stimulate Akt activity by transactivating IGF-1 receptor. In addition, the AGEs-stimulated Akt activation was attenuated by β-methylcyclodextrin that abolishes the structure of caveolae, and by lowering caveolin-1 (Cav-1) levels with siRNAs. Furthermore, addition of AGEs enhanced the interaction of phospho-Cav-1 with IGF-1Rβ and transfection of 3T3-L1 cells with Cav-1 Y14F mutants inhibited the activation of Akt by AGEs. These results suggest that AGEs activate NAD(P)H oxidase and Src which in turn phosphorylates IGF-1 receptor and Cav-1 leading to activation of IGF-1 receptor and the downstream Akt in 3T3-L1 cells. AGEs treatment promoted the differentiation of 3T3-L1 preadipocytes and addition of AG1024, LY 294002 or Akt inhibitor attenuated the promoting effect of AGEs on adipogenesis, suggesting that IGF-1 receptor, PI3-Kinase and Akt are involved in the facilitation of adipogenesis by AGEs. PMID:23472139

Vertebral hemangiomas: their demographical characteristics, location along the spine and position within the vertebral body.

PubMed

Slon, Viviane; Stein, Dan; Cohen, Haim; Sella-Tunis, Tatiana; May, Hila; Hershkovitz, Israel

2015-10-01

Vertebral hemangiomas (VHs) are the most common form of benign tumors in the spine. The aim of this research was to study the prevalence of VHs in the human population, their distribution along the spine and their location in the vertebral body. The presence of VHs was assessed in full spine CT scans of 196 adults. Demographic data were gathered from medical records. VHs were present in 26.0% of the individuals studied, a rate significantly higher (χ2=43.338, p<0.001) than the prevalence reported in the literature (10.7%). Multiple VHs (≥2) appeared in 7.2% of the population studied. VHs prevalence is sex-independent, appearing in 28.6% of females and 23.5% of males (χ2=0.663, p=0.416); and age-dependent: the mean age of affected individuals (65.8 years) was significantly higher (p<0.001) than unaffected individuals (56.2 years). VH size was also age-dependent (p=0.023). No vertebra was significantly more prone to be affected by a hemangioma. T11 and T12 show the highest prevalence of VHs (3.57% of vertebrae affected). VHs were found in similar percentages in the anterior and posterior parts of the vertebral body (52.8 vs. 47.2%, respectively); and at its center and periphery (50.1 and 49.9%, respectively). VHs usually appeared at mid-height of the vertebral body or slightly higher. The reported prevalence of VHs is dependent on the demographic structure of the population studied, the size of the VHs and the method used to identify them. Overall, the phenomenon is more frequent than usually reported. VHs may appear at all vertebral levels and in all areas of the vertebral body.

IL-6-mediated environmental conditioning of defective Th1 differentiation dampens antitumour immune responses in old age.

PubMed

Tsukamoto, Hirotake; Senju, Satoru; Matsumura, Keiko; Swain, Susan L; Nishimura, Yasuharu

2015-04-07

Decline in immune function and inflammation concomitantly develop with ageing. Here we focus on the impact of this inflammatory environment on T cells, and demonstrate that in contrast to successful tumour elimination in young mice, replenishment of tumour-specific CD4(+) T cells fails to induce tumour regression in aged hosts. The impaired antitumour effect of CD4(+) T cells with their defective Th1 differentiation in an aged environment is restored by interleukin (IL)-6 blockade or IL-6 deficiency. IL-6 blockade also restores the impaired ability of CD4(+) T cells to promote CD8(+) T-cell-dependent tumour elimination in aged mice, which requires IFN-γ. Furthermore, IL-6-stimulated production of IL-4/IL-21 through c-Maf induction is responsible for impaired Th1 differentiation. IL-6 also contributes to IL-10 production from CD4(+) T cells in aged mice, causing attenuated responses of CD8(+) T cells. These findings suggest that IL-6 serves as an extrinsic factor counteracting CD4(+) T-cell-mediated immunity against tumour in old age.

Plasmacytoid DC from Aged Mice Down-Regulate CD8 T Cell Responses by Inhibiting cDC Maturation after Encephalitozoon cuniculi Infection

PubMed Central

Gigley, Jason P.; Khan, Imtiaz A.

2011-01-01

Age associated impairment of immune function results in inefficient vaccination, tumor surveillance and increased severity of infections. Several alterations in adaptive immunity have been observed and recent studies report age related declines in innate immune responses to opportunistic pathogens including Encephalitozoon cuniculi. We previously demonstrated that conventional dendritic cells (cDC) from 9-month-old animals exhibit sub-optimal response to E. cuniculi infection, suggesting that age associated immune senescence begins earlier than expected. We focused this study on how age affects plasmacytoid DC (pDC) function. More specifically how aged pDC affect cDC function as we observed that the latter are the predominant activators of CD8 T cells during this infection. Our present study demonstrates that pDC from middle-aged mice (12 months) suppress young (8 week old) cDC driven CD8 T cell priming against E. cuniculi infection. The suppressive effect of pDC from older mice decreased maturation of young cDC via cell contact. Aged mouse pDC exhibited higher expression of PD-L1 and blockade of their interaction with cDC via this molecule restored cDC maturation and T cell priming. Furthermore, the PD-L1 dependent suppression of cDC T cell priming was restricted to effector function of antigen-specific CD8 T cells not their expansion. To the best of our knowledge, the data presented here is the first report highlighting a cell contact dependent, PD-L1 regulated, age associated defect in a DC subpopulation that results in a sub-optimal immune response against E. cuniculi infection. These results have broad implications for design of immunotherapeutic approaches to enhance immunity for aging populations. PMID:21695169

Plasmacytoid DC from aged mice down-regulate CD8 T cell responses by inhibiting cDC maturation after Encephalitozoon cuniculi infection.

PubMed

Gigley, Jason P; Khan, Imtiaz A

2011-01-01

Age associated impairment of immune function results in inefficient vaccination, tumor surveillance and increased severity of infections. Several alterations in adaptive immunity have been observed and recent studies report age related declines in innate immune responses to opportunistic pathogens including Encephalitozoon cuniculi. We previously demonstrated that conventional dendritic cells (cDC) from 9-month-old animals exhibit sub-optimal response to E. cuniculi infection, suggesting that age associated immune senescence begins earlier than expected. We focused this study on how age affects plasmacytoid DC (pDC) function. More specifically how aged pDC affect cDC function as we observed that the latter are the predominant activators of CD8 T cells during this infection. Our present study demonstrates that pDC from middle-aged mice (12 months) suppress young (8 week old) cDC driven CD8 T cell priming against E. cuniculi infection. The suppressive effect of pDC from older mice decreased maturation of young cDC via cell contact. Aged mouse pDC exhibited higher expression of PD-L1 and blockade of their interaction with cDC via this molecule restored cDC maturation and T cell priming. Furthermore, the PD-L1 dependent suppression of cDC T cell priming was restricted to effector function of antigen-specific CD8 T cells not their expansion. To the best of our knowledge, the data presented here is the first report highlighting a cell contact dependent, PD-L1 regulated, age associated defect in a DC subpopulation that results in a sub-optimal immune response against E. cuniculi infection. These results have broad implications for design of immunotherapeutic approaches to enhance immunity for aging populations.

Heterogeneity in Recent Onset Type 1 Diabetes – A Clinical Trial Perspective

PubMed Central

Bollyky, Jennifer B.; Xu, Ping; Butte, Atul J.; Wilson, Darrell M.; Beam, Craig A.; Greenbaum, Carla J.

2015-01-01

Background Type 1 Diabetes TrialNet is an NIH-sponsored clinical trial network aimed at altering the disease course of type 1 diabetes. The purpose of this study is to evaluate age-dependent heterogeneity in clinical, metabolic, and immunologic characteristics of individuals with recent-onset type 1 diabetes (T1D), to identify cohorts of interest and to aid in planning of future studies. Methods 883 individuals with recent onset T1D involved in five TrialNet studies were categorized by age as: ≥ 18, age 12-17, ages 8-12, and age <8. Data was compared with healthy age-matched subjects in the National Health and Nutrition Examination Survey. Results While only 2.0 % of individuals overall were excluded due to insufficient C-peptide values (<0.2 pmol/ml), 9.0% of those < age 8 did not meet this entry criteria. Leukopenia was present in 21.2% of individuals and lymphopenia in 11.6%; these frequencies were markedly different than age-matched healthy population. 24.5% of the cohort was overweight or obese. 31.1% of adults and 21.1% of children had neither HLA DR3 nor DR4. Conclusions The ability of recent onset T1D patients to meet key entry criteria for TrialNet studies, including C-peptide >0.2 pmol/ml, varies by age. Lower C-peptide level requirements for younger participants should be considered in the design of future trials. These data also highlight subgroups of type 1 diabetes patients, such as those with abnormal WBC or who are overweight, which allow for targeted studies of etiopathology and interventions. PMID:25689602

Why and when social support predicts older adults' pain-related disability: a longitudinal study.

PubMed

Matos, Marta; Bernardes, Sónia F; Goubert, Liesbet

2017-10-01

Pain-related social support has been shown to be directly associated with pain-related disability, depending on whether it promotes functional autonomy or dependence. However, previous studies mostly relied on cross-sectional methods, precluding conclusions on the temporal relationship between pain-related social support and disability. Also, research on the behavioral and psychological processes that account for such a relationship is scarce. Therefore, this study aimed at investigating the following longitudinally: (1) direct effects of social support for functional autonomy/dependence on pain-related disability, (2) mediating role of physical functioning, pain-related self-efficacy, and fear, and (3) whether pain duration and pain intensity moderate such mediating processes. A total of 168 older adults (Mage = 78.3; SDage = 8.7) participated in a 3-month prospective design, with 3 moments of measurement, with a 6-week lag between them. Participants completed the Formal Social Support for Autonomy and Dependence in Pain Inventory, the Brief Pain Inventory, the 36-SF Health Survey, behavioral tasks from the Senior Fitness Test, the Pain Self-Efficacy Questionnaire, and the Tampa Scale for Kinesiophobia. Moderated mediation analyses showed that formal social support for functional dependence (T1) predicted an increase in pain-related disability (T3), that was mediated by self-reported physical functioning (T2) and by pain-related self-efficacy (T2) at short to moderate pain duration and at low to moderate pain intensity, but not at higher levels. Findings emphasized that social support for functional dependence is a risk factor for pain-related disability and uncovered the "why" and "when" of this relationship. Implications for the design of social support interventions aiming at promoting older adults' healthy aging despite chronic pain are drawn.

SIRT6 expression and oxidative DNA damage in individuals with prediabetes and type 2 diabetes mellitus.

PubMed

Çalışkan, Z; Mutlu, T; Güven, M; Tunçdemir, M; Niyazioğlu, M; Hacioglu, Y; Dincer, Y

2018-02-05

Sirtuins (SIRTs) is a family of NAD + dependent histone deacetylases. SIRT6 takes play in glucose homeostasis, genomic stability and DNA repair. Although increased oxidative DNA damage and decreased DNA repair activity were determined in diabetes mellitus, the possible relation between level of oxidative DNA damage and SIRT6 expression has not been investigated so far. We determined SIRT6 expression and urinary 8-hydroxy deoxyguanosine (8-OHdG) levels, marker of oxidative DNA damage, in cases with prediabetes (PreDM) and type 2 diabetes mellitus (T2DM). SIRT6 gene expression was determined in peripheral blood leukocytes of 70 patients with type 2 diabetes, 50 cases in prediabetic stage and 40 healthy subjects. SIRT6 mRNA levels were determined by quantitive real time- polymerase chain reaction. SIRT6 protein was detected by immunocytochemical staining. Urinary 8-hydroxy deoxyguanosine (8-OHdG) levels were measured by ELISA. There was no significant difference between groups for SIRT6 mRNA level. SIRT6 immunopositivity in T2DM group was lower when compared to those in preDM group (P<0.05). SIRT6 positive cell number in T2DM and preDM groups were lower in comparison to control group (P<0.01 for both), however, when study groups were subdivided into two groups according to their age, the difference between preDM and control groups disappeared in both mid-aged and old-aged groups. The urinary 8-OHdG level was found to be higher in the T2DM group in comparison to preDM group (P<0.05). When age is taken into consideration, urinary 8-OHdG level in the T2DM group was found to be higher than those in both preDM and control groups in the old-aged cases but no significant difference was determined between groups in the mid-aged cases. There was no relation between SIRT6 expression and urinary 8-OHDG excretion. It was concluded that SIRT6 may take play in development of T2DM but this effect seems to be independent from repair of oxidative DNA damage. Copyright © 2017 Elsevier B.V. All rights reserved.

Rett Syndrome Mutation MeCP2 T158A Disrupts DNA Binding, Protein Stability and ERP Responses

PubMed Central

Goffin, Darren; Allen, Megan; Zhang, Le; Amorim, Maria; Wang, I-Ting Judy; Reyes, Arith-Ruth S.; Mercado-Berton, Amy; Ong, Caroline; Cohen, Sonia; Hu, Linda; Blendy, Julie A.; Carlson, Gregory C.; Siegel, Steve J.; Greenberg, Michael E.; Zhou, Zhaolan (Joe)

2011-01-01

Mutations in the MECP2 gene cause the autism spectrum disorder Rett Syndrome (RTT). One of the most common mutations associated with RTT occurs at MeCP2 Threonine 158 converting it to Methionine (T158M) or Alanine (T158A). To understand the role of T158 mutation in the pathogenesis of RTT, we generated knockin mice recapitulating MeCP2 T158A mutation. Here we show a causal role for T158A mutation in the development of RTT-like phenotypes including developmental regression, motor dysfunction, and learning and memory deficits. These phenotypes resemble those in Mecp2-null mice and manifest through a reduction in MeCP2 binding to methylated DNA and a decrease in MeCP2 protein stability. Importantly, the age-dependent development of event-related neuronal responses are disrupted by MeCP2 mutation, suggesting that impaired neuronal circuitry underlies the pathogenesis of RTT and that assessment of event-related potentials may serve as a biomarker for RTT and treatment evaluation. PMID:22119903

Simultaneous dynamic blood oxygen level-dependent magnetic resonance imaging of foot and calf muscles: aging effects at ischemia and postocclusive hyperemia in healthy volunteers.

PubMed

Kos, Sebastian; Klarhöfer, Markus; Aschwanden, Markus; Scheffler, Klaus; Jacob, Augustinus Ludwig; Bilecen, Deniz

2009-11-01

To demonstrate the feasibility of simultaneous blood oxygen level-dependent (BOLD) magnetic resonance imaging of calf and foot muscles and investigate age-related changes of BOLD signal changes during ischemia and postocclusive hyperemia in healthy volunteers. In this study, 15 healthy elderly volunteers (mean age: 69.0 +/- 7.4 years) and 15 healthy young volunteers (mean age: 26.1 +/- 3.9 years) were enrolled. In both legs, simultaneous BOLD imaging of calf and foot muscles was performed at 1.5 Tesla. Short-term ischemia and consecutive reactive hyperemia were provoked by a cuff-compression paradigm. T2*-weighted signal time courses were obtained from foot and calf muscles simultaneously. Ischemia was assessed by T2* minimum ischemic value (MIV) and the time to half ischemic minimum (THIM). Reperfusion was assessed by the time to reach T2* half hyperemia peak (THHP). Reactive hyperemia was characterized by hyperemia peak value (HPV), time to peak (TTP), and relative T2* change from end of ischemia to HPV (deltaS). Parameter differences were assessed using a 2-sided Student t test. Dynamic BOLD measurement of foot and calf muscles was techniqually feasible and successful in all volunteers.In comparison, THIM was significantly longer in elderly than in young volunteers for calf (P < 0.01) muscles (young: 28.9 +/- 3.7 seconds; elderly: 57.8 +/- 31.4 seconds) and foot (P = 0.01) muscles (young: 36.8 +/- 25.5 seconds; elderly: 56.6 +/- 31.7 seconds). MIV relative to baseline T2*-signal was significantly (P < 0.01) lower in the elderly for calf (young: 96.0% +/- 2.6%; elderly: 91.3% +/- 4.4%) and foot (young: 95.8% +/- 2.5%; elderly: 91.1% +/- 8.2%) muscles. TTP was significantly (calf: P = 0.01; foot: P = 0.02) delayed in the elderly (elderly calf: 103.0 +/- 92.7 seconds and foot: 157.1 +/- 109.9 seconds vs. young calf: 54.8 +/- 42.1 seconds and foot: 95.1 +/- 77.6 seconds). HPV was significantly (calf: P < 0.01 and foot: P = 0.03) higher in (young calf: 114.1% +/- 7.2% and foot: 105.8% +/- 3.3% vs. elderly calf: 104.0% +/- 2.1% and foot: 103.9% +/- 3.2% seconds) young volunteers.In a muscle-group comparison, no significant differences in THIM and MIV were observed between calf and foot.THHP was significantly (P = 0.02) longer in foot muscles (foot young: 32.5 +/- 29.8 seconds and elderly: 34.1 +/- 25.0 seconds vs. calf young: 16.8 +/- 14.1 seconds and elderly: 23.6 +/- 14.1 seconds) of both age groups. TTP was significantly (P = 0.01 and 0.02) longer in foot muscles (foot young: 95.1 +/- 77.6 seconds and elderly: 157.1 +/- 109.9 seconds vs. calf young: 54.8 +/- 42.1 seconds and elderly: 103.0 +/- 92.7 seconds) of both age groups. HPV was lower (P < 0.01) in foot muscles of the young (calf: 114.1% +/- 7.2% vs. foot: 105.8 +/- 3.3%). Simultaneous BOLD-imaging of calf and foot muscles is feasible and reveals statistically significant age-related differences during ischemia and postocclusive hyperemia in healthy volunteers.

Quantification of myocardial oxygenation in heart failure using blood-oxygen-level-dependent T2* magnetic resonance imaging: Comparison with cardiopulmonary exercise test.

PubMed

Nagao, Michinobu; Yamasaki, Yuzo; Kawanami, Satoshi; Kamitani, Takeshi; Sagiyama, Koji; Higo, Taiki; Ide, Tomomi; Takemura, Atsushi; Ishizaki, Umiko; Fukushima, Kenji; Watanabe, Yuji; Honda, Hiroshi

2017-06-01

Quantification of myocardial oxygenation (MO) in heart failure (HF) has been less than satisfactory. This has necessitated the use of invasive techniques to measure MO directly or to determine the oxygen demand during exercise using the cardiopulmonary exercise (CPX) test. We propose a new quantification method for MO using blood-oxygen-level-dependent (BOLD) myocardial T2* magnetic resonance imaging (M-T2* MRI), and investigate its correlation with CPX results. Thirty patients with refractory HF who underwent cardiac MRI and CPX test for heart transplantation, and 24 healthy, age-matched volunteers as controls were enrolled. M-T2* imaging was performed using a 3-Tesla and multi-echo gradient-echo sequence. M-T2* was calculated by fitting the signal intensity data for the mid-left ventricular septum to a decay curve. M-T2* was measured under room-air (T2*-air) and after inhalation of oxygen for 10min at a flow rate of 10L/min (T2*-oxy). MO was defined as the difference between the two values (ΔT2*). Changes in M-T2* at the two conditions and ΔT2* between the two groups were compared. Correlation between ΔT2* and CPX results was analyzed using the Pearson coefficient. T2*-oxy was significantly greater than T2*-air in patients with HF (29.9±7.3ms vs. 26.7±6.0ms, p<0.001), whereas no such difference was observed in controls (25.5±4.0ms vs. 25.4±4.4ms). ΔT2* was significantly greater for patients with HF than for controls (3.2±4.5ms vs. -0.1±1.3ms, p<0.001). A significant correlation between ΔT2* and CPX results (peak VO 2 , r=-0.46, p<0.05; O 2 pulse, r=-0.54, p<0.005) was observed. ΔT2* is increased T2*-oxy is greater in patients with HF, and is correlated with oxygen metabolism during exercise as measured by the CPX test. Hence, ΔT2* can be used as a surrogate marker of MO instead of CPX test. Copyright © 2017 Elsevier Inc. All rights reserved.

On the crystallization of amorphous germanium films

NASA Astrophysics Data System (ADS)

Edelman, F.; Komem, Y.; Bendayan, M.; Beserman, R.

1993-06-01

The incubation time for crystallization of amorphous Ge (a-Ge) films, deposited by e-gun, was studied as a function of temperature between 150 and 500°C by means of both in situ transmission electron microscopy and Raman scattering spectroscopy. The temperature dependence of t0 follows an Arrhenius curve with an activation energy of 2.0 eV for free-sustained a-Ge films. In the case where the a-Ge films were on Si 3N 4 substrate, the activation energy of the incubation process was 1.3 eV.

Time-Dependent Behavior of a Graphite/Thermoplastic Composite and the Effects of Stress and Physical Aging

NASA Technical Reports Server (NTRS)

Gates, Thomas S.; Feldman, Mark

1995-01-01

Experimental studies were performed to determine the effects of stress and physical aging on the matrix dominated time dependent properties of IM7/8320 composite. Isothermal tensile creep/aging test techniques developed for polymers were adapted for testing of the composite material. Time dependent transverse and shear compliance's for an orthotropic plate were found from short term creep compliance measurements at constant, sub-T(8) temperatures. These compliance terms were shown to be affected by physical aging. Aging time shift factors and shift rates were found to be a function of temperature and applied stress.

Transient aging in fractional Brownian and Langevin-equation motion.

PubMed

Kursawe, Jochen; Schulz, Johannes; Metzler, Ralf

2013-12-01

Stochastic processes driven by stationary fractional Gaussian noise, that is, fractional Brownian motion and fractional Langevin-equation motion, are usually considered to be ergodic in the sense that, after an algebraic relaxation, time and ensemble averages of physical observables coincide. Recently it was demonstrated that fractional Brownian motion and fractional Langevin-equation motion under external confinement are transiently nonergodic-time and ensemble averages behave differently-from the moment when the particle starts to sense the confinement. Here we show that these processes also exhibit transient aging, that is, physical observables such as the time-averaged mean-squared displacement depend on the time lag between the initiation of the system at time t=0 and the start of the measurement at the aging time t(a). In particular, it turns out that for fractional Langevin-equation motion the aging dependence on t(a) is different between the cases of free and confined motion. We obtain explicit analytical expressions for the aged moments of the particle position as well as the time-averaged mean-squared displacement and present a numerical analysis of this transient aging phenomenon.

The age-dependent epigenetic and physiological changes in an Arabidopsis T87 cell suspension culture during long-term cultivation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwiatkowska, Aleksandra, E-mail: A.Kwiatkows@gmail.com; Zebrowski, Jacek; Oklejewicz, Bernadetta

2014-05-02

Highlights: • A decrease in proliferation rate during long-term cultivation of Arabidopsis cells. • Age-dependent increase in senescence-associated gene expression in Arabidopsis cells. • Age-related increase in DNA methylation, H3K9me2, and H3K27me3 in Arabidopsis cells. • High potential of photosynthetic efficiency of long-term cultured Arabidopsis cells. - Abstract: Plant cell suspension cultures represent good model systems applicable for both basic research and biotechnological purposes. Nevertheless, it is widely known that a prolonged in vitro cultivation of plant cells is associated with genetic and epigenetic instabilities, which may limit the usefulness of plant lines. In this study, the age-dependent epigenetic andmore » physiological changes in an asynchronous Arabidopsis T87 cell culture were examined. A prolonged cultivation period was found to be correlated with a decrease in the proliferation rate and a simultaneous increase in the expression of senescence-associated genes, indicating that the aging process started at the late growth phase of the culture. In addition, increases in the heterochromatin-specific epigenetic markers, i.e., global DNA methylation, H3K9 dimethylation, and H3K27 trimethylation, were observed, suggesting the onset of chromatin condensation, a hallmark of the early stages of plant senescence. Although the number of live cells decreased with an increase in the age of the culture, the remaining viable cells retained a high potential to efficiently perform photosynthesis and did not exhibit any symptoms of photosystem II damage.« less

Changes in cytogenetics and molecular genetics in acute myeloid leukemia from childhood to adult age groups.

PubMed

Creutzig, Ursula; Zimmermann, Martin; Reinhardt, Dirk; Rasche, Mareike; von Neuhoff, Christine; Alpermann, Tamara; Dworzak, Michael; Perglerová, Karolína; Zemanova, Zuzana; Tchinda, Joelle; Bradtke, Jutta; Thiede, Christian; Haferlach, Claudia

2016-12-15

To obtain better insight into the biology of acute myeloid leukemia (AML) in various age groups, this study focused on the genetic changes occurring during a lifetime. This study analyzed the relation between age and genetics from birth to 100 years in 5564 patients with de novo AML diagnosed from 1998 to 2012 (1192 patients from nationwide pediatric studies [AML Berlin-Frankfurt-Münster studies 98 and 2004] and 4372 adults registered with the Munich Leukemia Laboratory). The frequencies of cytogenetic subgroups were age-dependent. Favorable subtypes (t(8;21), inv(16)/t(16;16), and t(15;17)) decreased in general from the pediatric age group (2 to < 18 years; 33%) to the oldest groups (<5% for > 70 years; P < .0001). Unfavorable cytogenetics (-7/del(7), -5/del(5q) or 5p, inv(3)/t(3;3), t(6;9), complex karyotype, 12p, 17p, and 11q23/mixed-lineage leukemia aberrations, excluding t(9;11)) were frequent (42%) in infants (<2 years), had a low frequency in children and young adults (<22%), and increased in frequency up to 36% in patients older than 85 years (P = .01). This was even more significant for complex karyotypes (P ≤ .0001), which also showed a strong increase in the absolute age-specific incidence with age. Interestingly, the frequency of 11q23 abnormalities decreased from infants to older patients. The proportion of clinically relevant molecular aberrations of CCAAT/enhancer binding protein α, nucleophosmin (NPM1), and NPM1/fms-related tyrosine kinase 3-internal tandem duplication increased with age. Altogether, with the exclusion of infants, a significant decrease in the proportion of favorable cytogenetic subtypes and an increase in unfavorable cytogenetics were observed with increasing age. These findings indicate different mechanisms for the pathogenesis of AML; these different mechanisms also suggest directions for etiological research and contribute to the more unfavorable prognosis with increasing age. Cancer 2016;122:3821-3830. © 2016 American Cancer Society. © 2016 American Cancer Society.

Longitudinal analysis of MR spin-spin relaxation times (T2) in medial femorotibial cartilage of adolescent vs mature athletes: dependence of deep and superficial zone properties on sex and age.

PubMed

Wirth, W; Eckstein, F; Boeth, H; Diederichs, G; Hudelmaier, M; Duda, G N

2014-10-01

Cartilage spin-spin magnetic resonance imaging (MRI) relaxation time (T2) represents a promising imaging biomarker of "early" osteoarthritis (OA) known to be associated with cartilage composition (collagen integrity, orientation, and hydration). However, no longitudinal imaging studies have been conducted to examine cartilage maturation in healthy subjects thus far. Therefore, we explore T2 change in the deep and superficial cartilage layers at the end of adolescence. Twenty adolescent and 20 mature volleyball athletes were studied (each 10 men and 10 women). Multi-echo spin-echo (MESE) images were acquired at baseline and 2-year follow-up. After segmentation, cartilage T2 was calculated in the deep and superficial cartilage layers of the medial tibial (MT) and the central, weight-bearing part of the medial femoral condyle (cMF), using five echoes (TE 19.4-58.2 ms). 16 adolescent (6 men, 10 women, baseline age 15.8 ± 0.5 years) and 17 mature (nine men, eight women, age 46.5 ± 5.2 years) athletes had complete baseline and follow-up images of sufficient quality to compute T2. In adolescents, a longitudinal decrease in T2 was observed in the deep layers of MT (-2.0 ms; 95% confidence interval (CI): [-3.4, -0.6] ms; P < 0.01) and cMF (-1.3 ms; [-2.4, -0.3] ms; P < 0.05), without obvious differences between males and females. No significant change was observed in the superficial layers, or in the deep or superficial layers of the mature athletes. In this first pilot study on quantitative imaging of cartilage maturation in healthy, athletic subjects, we find evidence of cartilage compositional change in deep cartilage layers of the medial femorotibial compartment in adolescents, most likely related to organizational changes in the collagen matrix. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Earlier Age of Onset of Chronic Hypertension and Type 2 Diabetes Mellitus After a Hypertensive Disorder of Pregnancy or Gestational Diabetes Mellitus.

PubMed

Heida, Karst Y; Franx, Arie; van Rijn, Bas B; Eijkemans, Marinus J C; Boer, Jolanda M A; Verschuren, Monique W M; Oudijk, Martijn A; Bots, Michiel L; van der Schouw, Yvonne T

2015-12-01

A prospective cohort study was conducted to assess the impact of a history of hypertensive disorder of pregnancy (HDP) or gestational diabetes mellitus (GDM) on the risk and age of onset of hypertension, type 2 diabetes mellitus (T2D), and cardiovascular disease (CVD) later in life, independent of hypertension and T2D. Between 1993 and 1997, 22 265 ever-pregnant women were included from the European Prospective Investigation into Cancer and Nutrition-NL study, aged 20 to 70 years at baseline. Details on complications of pregnancy and known hypertension were obtained by questionnaire. Blood pressure was measured at enrollment. Participants were followed for the occurrence of CVD events. Data were analyzed using ANCOVA, multivariable logistic regression, and Cox proportional hazard (with HDP and GDM as time-dependent variables for T2D and CVD) models. At enrollment, women with a HDP reported diagnosis of hypertension 7.7 years earlier (95% confidence interval [CI] 6.9-8.5) and women with GDM reported diagnosis of T2D 7.7 years earlier (95% CI 5.8-9.6) than women without pregnancy complications. After adjustment for potential confounders, HDP was associated with presence of hypertension at enrollment (odds ratio 2.12, 95% CI 1.98-2.28) and onset of CVD later in life (hazard ratio 1.21, 95% CI 1.10-1.32). After including the intermediates hypertension and T2D in the model, the risk of CVD later in life decreased (hazard ratio 1.09, 95% CI 1.00-1.20). GDM was associated with an increased risk of developing T2D later in life (hazard ratio 3.68, 95% CI 2.77-4.90), but not with risk of CVD. HDP and GDM have a substantial impact on the risk of CVD and are potentially important indicators for preventive cardiovascular risk management. © 2015 American Heart Association, Inc.

The Association Between Commonly Investigated User Factors and Various Types of eHealth Use for Self-Care of Type 2 Diabetes: Case of First-Generation Immigrants From Pakistan in the Oslo Area, Norway

PubMed Central

Hammer, Hugo Lewi; Andreassen, Hege Kristin; Mirkovic, Jelena; Kjøllesdal, Marte Karoline Råberg

2017-01-01

Background Sociodemographic and health-related factors are often investigated for their association with the active use of electronic health (eHealth). The importance of such factors has been found to vary, depending on the purpose or means of eHealth and the target user groups. Pakistanis are one of the biggest immigrant groups in the Oslo area, Norway. Due to an especially high risk of developing type 2 diabetes (T2D) among this population, knowledge about their use of eHealth for T2D self-management and prevention (self-care) will be valuable for both understanding this vulnerable group and for developing effective eHealth services. Objective The aim of this study was to examine how commonly were the nine types of eHealth for T2D self-care being used among our target group, the first-generation Pakistani immigrants living in the Oslo area. The nine types of eHealth use are divided into three broad categories based on their purpose: information seeking, communication, and active self-care. We also aimed to investigate how sociodemographic factors, as well as self-assessment of health status and digital skills are associated with the use of eHealth in this group. Methods A survey was carried out in the form of individual structured interviews from September 2015 to January 2016 (N=176). For this study, dichotomous data about whether or not an informant had used each of the nine types of eHealth in the last 12 months and the total number of positive answers were used as dependent variables in a regression analysis. The independent variables were age, gender, total years of education, digital skills (represented by frequency of asking for help when using information and communication technology [ICT]), and self-assessment of health status. Principal component analyses were applied to make categories of independent variables to avoid multicollinearity. Results Principal component analysis yielded three components: knowledge, comprising total years of education and digital skills; health, comprising age and self-assessment of health status; and gender, as being a female. With the exception of closed conversation with a few specific acquaintances about self-care of T2D (negatively associated, P=.02) and the use of ICT for relevant information-seeking by using search engines (not associated, P=.18), the knowledge component was positively associated with all the other dependent variables. The health component was negatively associated with the use of ICT for closed conversation with a few specific acquaintances about self-care of T2D (P=.01) but not associated with the other dependent variables. Gender component showed no association with any of the dependent variables. Conclusions In our sample, knowledge, as a composite measure of education and digital skills, was found to be the main factor associated with eHealth use regarding T2D self-care. Enhancing digital skills would encourage and support more active use of eHealth for T2D self-care. PMID:28982646

Oceanic lithosphere and asthenosphere: The thermal and mechanical structure

NASA Technical Reports Server (NTRS)

Schubert, G.; Froidevaux, C.; Yuen, D. A.

1976-01-01

A coupled thermal and mechanical solid state model of the oceanic lithosphere and asthenosphere is presented. The model includes vertical conduction of heat with a temperature dependent thermal conductivity, horizontal and vertical advection of heat, viscous dissipation or shear heating, and linear or nonlinear deformation mechanisms with temperature and pressure dependent constitutive relations between shear stress and strain rate. A constant horizontal velocity u sub 0 and temperature t sub 0 at the surface and zero horizontal velocity and constant temperature t sub infinity at great depth are required. In addition to numerical values of the thermal and mechanical properties of the medium, only the values of u sub 0, t sub 0 and t sub infinity are specified. The model determines the depth and age dependent temperature horizontal and vertical velocity, and viscosity structures of the lithosphere and asthenosphere. In particular, ocean floor topography, oceanic heat flow, and lithosphere thickness are deduced as functions of the age of the ocean floor.

Predictors of increasing BMI during the course of diabetes in children and adolescents with type 1 diabetes: data from the German/Austrian DPV multicentre survey.

PubMed

Fröhlich-Reiterer, Elke E; Rosenbauer, Joachim; Bechtold-Dalla Pozza, Susanne; Hofer, Sabine E; Schober, Edith; Holl, Reinhard W

2014-08-01

Increased weight gain has been reported prior to disease onset (accelerator hypothesis) and as a side effect of intensified insulin therapy in type 1 diabetes (T1D). Paediatric studies are complicated by the age-dependency and gender-dependency of BMI, and also by a trend towards obesity in the general population. The aim of this study was to evaluate factors related to the increase in BMI during the course of diabetes in children and adolescents with T1D in a large multicentre survey. Within the DPV database (Diabetespatienten Verlaufsdokumentation) a standardised, prospective, computer-based documentation programme, data of 53,108 patients with T1D, aged <20 years, were recorded in 248 centres. 12,774 patients (53% male, mean age 13.4±3.9, mean diabetes duration 4.7±3.0 years and mean age at diabetes onset 8.7±4.0 years) were included in this analysis. Population-based German reference data were used to calculate BMI-SDS and define overweight and obesity. 12.5% of T1D patients were overweight and 2.8% were obese. Multiple longitudinal regression analysis revealed that female gender, low BMI at diabetes onset, intensified insulin therapy and higher insulin dose, as well as pubertal diabetes onset, long diabetes duration and onset in earlier calendar years among girls, were related to higher BMI-SDS increase during the course of diabetes (p<0.01; all). Intensified insulin regimen is associated with weight gain during T1D treatment, in addition to demographic variables. Optimisation of diabetes management, especially in females, might limit weight gain in order to reduce overweight and obesity together with comorbidities among paediatric T1D patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Age-related guanine nucleotide exchange factor, mouse Zizimin2, induces filopodia in bone marrow-derived dendritic cells

PubMed Central

2012-01-01

Background We recently isolated and identified Zizimin2 as a functional factor that is highly expressed in murine splenic germinal center B cells after immunization with T-cell-dependent antigen. Zizimin2 was revealed to be a new family member of Dock (dedicator of cytokinesis), Dock11, which is the guanine nucleotide exchange factor for Cdc42, a low-molecular-weight GTPase. However, the molecular function of Zizimin2 in acquired immunity has not been elucidated. Results In this study, we show that the protein expression of Zizimin2, which is also restricted to lymphoid tissues and lymphocytes, is reduced in aged mice. Over-expression of full-length Zizimin2 induced filopodial formation in 293T cells, whereas expression of CZH2 domain inhibited it. Stimulation of Fcγ receptor and Toll-like receptor 4 triggered Zizimin2 up-regulation and Cdc42 activation in bone marrow-derived dendritic cells. Conclusions These data suggest that Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. PMID:22494997

Associations between adolescent cannabis use and neuropsychological decline: a longitudinal co-twin control study.

PubMed

Meier, Madeline H; Caspi, Avshalom; Danese, Andrea; Fisher, Helen L; Houts, Renate; Arseneault, Louise; Moffitt, Terrie E

2018-02-01

This study tested whether adolescents who used cannabis or met criteria for cannabis dependence showed neuropsychological impairment prior to cannabis initiation and neuropsychological decline from before to after cannabis initiation. A longitudinal co-twin control study. Participants were 1989 twins from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of twins born in England and Wales from 1994 to 1995. Frequency of cannabis use and cannabis dependence were assessed at age 18. Intelligence quotient (IQ) was obtained at ages 5, 12 and 18. Executive functions were assessed at age 18. Compared with adolescents who did not use cannabis, adolescents who used cannabis had lower IQ in childhood prior to cannabis initiation and lower IQ at age 18, but there was little evidence that cannabis use was associated with IQ decline from ages 12-18. For example, adolescents with cannabis dependence had age 12 and age 18 IQ scores that were 5.61 (t = -3.11, P = 0.002) and 7.34 IQ points (t = -5.27, P < 0.001) lower than adolescents without cannabis dependence, but adolescents with cannabis dependence did not show greater IQ decline from age 12-18 (t = -1.27, P = 0.20). Moreover, adolescents who used cannabis had poorer executive functions at age 18 than adolescents who did not use cannabis, but these associations were generally not apparent within twin pairs. For example, twins who used cannabis more frequently than their co-twin performed similarly to their co-twin on five of six executive function tests (Ps > 0.10). The one exception was that twins who used cannabis more frequently than their co-twin performed worse on one working memory test (Spatial Span reversed; β = -0.07, P = 0.036). Short-term cannabis use in adolescence does not appear to cause IQ decline or impair executive functions, even when cannabis use reaches the level of dependence. Family background factors explain why adolescent cannabis users perform worse on IQ and executive function tests. © 2017 Society for the Study of Addiction.

C/EBPα is dispensable for the ontogeny of PD-1+ CD4+ memory T cells but restricts their expansion in an age-dependent manner.

PubMed

Norrie, Ida Christine; Ohlsson, Ewa; Nielsen, Olaf; Hasemann, Marie Sigurd; Porse, Bo T

2014-01-01

Ageing and cancer is often associated with altered T cell distributions and this phenomenon has been suggested to be the main driver in the development of immunosenescence. Memory phenotype PD-1+ CD4+ T cells accumulate with age and during leukemic development, and they might account for the attenuated T cell response in elderly or diseased individuals. The transcription factor C/EBPα has been suggested to be responsible for the accumulation as well as for the senescent features of these cells including impaired TCR signaling and decreased proliferation. Thus modulating the activity of C/EBPα could potentially target PD-1+ CD4+ T cells and consequently, impede the development of immunosenescence. To exploit this possibility we tested the importance of C/EBPα for the development of age-dependent PD-1+ CD4+ T cells as well as its role in the accumulation of PD-1+ CD4+ T cells during leukemic progression. In contrast to earlier suggestions, we find that loss of C/EBPα expression in the lymphoid compartment led to an increase of PD-1+ CD4+ T cells specifically in old mice, suggesting that C/EBPα repress the accumulation of these cells in elderly by inhibiting their proliferation. Furthermore, C/EBPα-deficiency in the lymphoid compartment had no effect on leukemic development and did not affect the accumulation of PD-1+ CD4+ T cells. Thus, in addition to contradict earlier suggestions of a role for C/EBPα in immunosenescence, these findings efficiently discard the potential of using C/EBPα as a target for the alleviation of ageing/cancer-associated immunosenescence.

C/EBPα Is Dispensable for the Ontogeny of PD-1+ CD4+ Memory T Cells but Restricts Their Expansion in an Age-Dependent Manner

PubMed Central

Norrie, Ida Christine; Ohlsson, Ewa; Nielsen, Olaf

2014-01-01

Ageing and cancer is often associated with altered T cell distributions and this phenomenon has been suggested to be the main driver in the development of immunosenescence. Memory phenotype PD-1+ CD4+ T cells accumulate with age and during leukemic development, and they might account for the attenuated T cell response in elderly or diseased individuals. The transcription factor C/EBPα has been suggested to be responsible for the accumulation as well as for the senescent features of these cells including impaired TCR signaling and decreased proliferation. Thus modulating the activity of C/EBPα could potentially target PD-1+ CD4+ T cells and consequently, impede the development of immunosenescence. To exploit this possibility we tested the importance of C/EBPα for the development of age-dependent PD-1+ CD4+ T cells as well as its role in the accumulation of PD-1+ CD4+ T cells during leukemic progression. In contrast to earlier suggestions, we find that loss of C/EBPα expression in the lymphoid compartment led to an increase of PD-1+ CD4+ T cells specifically in old mice, suggesting that C/EBPα repress the accumulation of these cells in elderly by inhibiting their proliferation. Furthermore, C/EBPα-deficiency in the lymphoid compartment had no effect on leukemic development and did not affect the accumulation of PD-1+ CD4+ T cells. Thus, in addition to contradict earlier suggestions of a role for C/EBPα in immunosenescence, these findings efficiently discard the potential of using C/EBPα as a target for the alleviation of ageing/cancer-associated immunosenescence. PMID:24404186

All-cause mortality in adults with and without type 2 diabetes: findings from the national health monitoring in Germany

PubMed Central

Brinks, Ralph; Baumert, Jens; Paprott, Rebecca; Du, Yong; Heidemann, Christin; Scheidt-Nave, Christa

2017-01-01

Objective To estimate age-specific and sex-specific all-cause mortality among adults with and without type 2 diabetes (T2D) in Germany. Research design and methods The German National Health Interview and Examination Survey 1998 (GNHIES98) included a mortality follow-up (median follow-up time 12.0 years) of its nationwide sample representative of the population aged 18–79 years. After exclusion of participants with type 1 diabetes, age- and sex-stratified mortality rates (MR) were calculated for 330 GNHIES98 participants with diagnosed T2D (self-reported diagnosis or antidiabetic medication), 245 with undiagnosed T2D (no diagnosed T2D, glycated hemoglobin A1c ≥6.5% (≥48 mmol/mol)), and 5975 without T2D. Mortality rate ratios (MRR) comparing MR of persons with and without T2D were estimated. Age-/sex-standardized MR and MRR were calculated including persons aged 45 years or older. MRR were used to estimate the number of years of life lost (YLL) due to diagnosed diabetes in 2010. Results Over 75 994 person-years, 73 persons with undiagnosed T2D, 103 with diagnosed T2D, and 425 persons without T2D died. MRR were significantly higher in younger age groups, except for analyses limited to women or diagnosed T2D. Age- and sex-standardized MRR (95% CI) among persons aged 45 years or older were 1.96 (1.41 to 2.71) for undiagnosed, 1.68 (1.26 to 2.23) for diagnosed, and 1.82 (1.45 to 2.28) for total (undiagnosed or diagnosed) T2D. Sex-stratified analysis revealed similar age-standardized MRR for undiagnosed (1.56 (0.79 to 3.06)) and diagnosed T2D (1.56 (1.03 to 2.37)) among women, and a higher age-standardized MRR for undiagnosed (2.06 (1.43 to 2.97)) than diagnosed T2D (1.70 (1.10 to 2.63)) among men. YLL due to diagnosed diabetes in Germany in 2010 were 164 600 (35 000 to 279 300) among women and 169 900 (28 300 to 328 300) among men. Conclusions In Germany, age- and sex-standardized all-cause mortality is almost twice as high for adults with T2D as for adults without T2D. The T2D-associated excess risk of mortality appears to be most pronounced in younger adults and among men unaware of their T2D. PMID:29435349

Strong evidences for a nonextensive behavior of the rotation period in open clusters

NASA Astrophysics Data System (ADS)

de Freitas, D. B.; Nepomuceno, M. M. F.; Soares, B. B.; Silva, J. R. P.

2014-11-01

Time-dependent nonextensivity in a stellar astrophysical scenario combines nonextensive entropic indices qK derived from the modified Kawaler's parametrization, and q, obtained from rotational velocity distribution. These q's are related through a heuristic single relation given by q≈ q0(1-Δ t/qK) , where t is the cluster age. In a nonextensive scenario, these indices are quantities that measure the degree of nonextensivity present in the system. Recent studies reveal that the index q is correlated to the formation rate of high-energy tails present in the distribution of rotation velocity. On the other hand, the index qK is determined by the stellar rotation-age relationship. This depends on the magnetic-field configuration through the expression qK=1+4aN/3 , where a and N denote the saturation level of the star magnetic field and its topology, respectively. In the present study, we show that the connection q-qK is also consistent with 548 rotation period data for single main-sequence stars in 11 open clusters aged less than 1 Gyr. The value of qK ˜ 2.5 from our unsaturated model shows that the mean magnetic-field topology of these stars is slightly more complex than a purely radial field. Our results also suggest that stellar rotational braking behavior affects the degree of anti-correlation between q and cluster age t. Finally, we suggest that stellar magnetic braking can be scaled by the entropic index q.

Effect of low incubation temperature and low ambient temperature until 21 days of age on performance and body temperature in fast-growing chickens.

PubMed

Nyuiadzi, D; Travel, A; Méda, B; Berri, C; Guilloteau, L A; Coustham, V; Wang, Y; Tona, J K; Collin, A

2017-12-01

Thermal manipulation during embryogenesis was previously reported to decrease the occurrence of ascites and to potentially improve cold tolerance of broilers. The objective of our study was to explore the effects of the interaction of cold incubation temperatures and cool ambient temperatures until 21 d of age on performance and body temperature. Ross 308 eggs were incubated either under control conditions I0 (37.6°C) or with cyclic cold stimulations I1 (6 h/d at 36.6°C from d 10 to 18 of incubation) or with 2 cold stimulations I2 (30 min at 15°C) at d 18 and 19 of incubation. These treatments were followed by individual rearing and postnatal exposure to either standard rearing temperature T0 (from 33°C at hatching to 21°C at d 21) or continuously lower temperature T2 (from 28°C at hatching to 21°C at d 21) or exposure to cyclically lower temperature T1 (with circadian temperature oscillations). Treatments I1 and I2 did not significantly alter hatchability compared to control incubation (with 94.8, 95.1, and 92.3%, respectively), or hatching BW and overall chick quality. Hatching body temperature (Tb) was 0.5 and 0.3°C higher in I1 than in I0 and I2 groups, respectively (P = 0.007). A doubled occurrence of health problems was observed with T2 condition, regardless of incubation or sex. At d 3, BW was 2% lower with treatment I1 than with I0 and I2 and was 3% higher in T1 and T2 groups than in T0, but these effects disappeared with age. Group T2 presented a 5% higher feed intake than the control group T0 between 3 and 21 d of age (P = 0.025). Feed conversion ratio (FCR) was affected by experimental conditions (P < 0.001), with low FCR values obtained with I2 incubation in control or cyclically cold postnatal conditions. Maximal FCR values were observed in the continuously cold postnatal conditions, in males submitted to control incubation and in females submitted to I1 incubation, revealing sex-dependent effects of the treatments on performance. © The Author 2017. Published by Oxford University Press on behalf of Poultry Science Association.

t10,c12-Conjugated linoleic acid stimulates mammary tumor progression in Her2/ErbB2 mice through activation of both proliferative and survival pathways

PubMed Central

Meng, Xiaojing; Shoemaker, Suzanne F.; McGee, Sibel O.; Ip, Margot M.

2008-01-01

The t10,c12 isomer of conjugated linoleic acid (CLA) inhibits rat mammary carcinogenesis, metastasis from a transplantable mouse mammary tumor and angiogenesis; however, it stimulates mammary tumorigenesis in transgenic mice overexpressing ErbB2 in the mammary epithelium (ErbB2 transgenic mice). In the current study, we report that a 4-week supplementation of the diet with 0.5% trans-10, cis-12 conjugated linoleic acid (t10,c12-CLA) stimulated the growth of established ErbB2-overexpressing mammary tumors by 30% and increased the number of new tumors from 11% to 82%. Additionally, when t10,c12-CLA supplementation of ErbB2 transgenic mice was initiated at 21 weeks of age, a time just prior to tumor appearance, overall survival was decreased from 46.4 weeks in the control to 39.0 weeks in the CLA group, and survival after detection of a palpable tumor from 7.5 to 4.6 weeks. Short-term supplementation from 10 to 14 weeks or 21 to 25 weeks of age temporarily accelerated tumor development, but over the long term, there was no significant effect on mammary tumorigenesis. Long term as well as a short 4-week supplementation increased mammary epithelial hyperplasia and lobular development, and altered the mammary stroma; this was reversible in mice returned to the control diet. t10,c12-CLA altered proliferation and apoptosis of the mammary epithelium, although this differed depending on the length of administration and/or the age of the mice. The increased tumor development with t10,c12-CLA was associated with increased phosphorylation of the IGF-I/insulin receptor, as well as increased signaling through the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways; however, neither phospho-ErbB2 nor ErbB2 was altered. PMID:18339686

Serotonin receptor 2A gene and the influence of childhood maternal nurturance on adulthood depressive symptoms.

PubMed

Jokela, Markus; Keltikangas-Järvinen, Liisa; Kivimäki, Mika; Puttonen, Sampsa; Elovainio, Marko; Rontu, Riikka; Lehtimäki, Terho

2007-03-01

Gene-environment interactions are assumed to be involved in the development of depression. To determine whether the serotonin receptor 2A (HTR2A) gene moderates the association between childhood maternal nurturance and depressive symptoms in adulthood. A 21-year, prospective, longitudinal study with 2 measurements of the independent and dependent variables. A population-based sample. A subsample of 1212 participants of the Cardiovascular Risk in Young Finns study, aged 3 to 18 years at baseline. Main Outcome Measure Depressive symptoms in adulthood. Individuals carrying the T/T or T/C genotype of the T102C polymorphism of the HTR2A gene were responsive to the protective aspects of nurturing mothering, so that in the presence of high maternal nurturance, they expressed low levels of depressive symptoms, while this was not true with the carriers of the C/C genotype. The HTR2A gene may be involved in the development of depression by influencing the ability of individuals to use environmental support.

Behavioral Characterization of A53T Mice Reveals Early and Late Stage Deficits Related to Parkinson’s Disease

PubMed Central

Paumier, Katrina L.; Sukoff Rizzo, Stacey J.; Berger, Zdenek; Chen, Yi; Gonzales, Cathleen; Kaftan, Edward; Li, Li; Lotarski, Susan; Monaghan, Michael; Shen, Wei; Stolyar, Polina; Vasilyev, Dmytro; Zaleska, Margaret; D. Hirst, Warren; Dunlop, John

2013-01-01

Parkinson's disease (PD) pathology is characterized by the formation of intra-neuronal inclusions called Lewy bodies, which are comprised of alpha-synuclein (α-syn). Duplication, triplication or genetic mutations in α-syn (A53T, A30P and E46K) are linked to autosomal dominant PD; thus implicating its role in the pathogenesis of PD. In both PD patients and mouse models, there is increasing evidence that neuronal dysfunction occurs before the accumulation of protein aggregates (i.e., α-syn) and neurodegeneration. Characterization of the timing and nature of symptomatic dysfunction is important for understanding the impact of α-syn on disease progression. Furthermore, this knowledge is essential for identifying pathways and molecular targets for therapeutic intervention. To this end, we examined various functional and morphological endpoints in the transgenic mouse model expressing the human A53T α-syn variant directed by the mouse prion promoter at specific ages relating to disease progression (2, 6 and 12 months of age). Our findings indicate A53T mice develop fine, sensorimotor, and synaptic deficits before the onset of age-related gross motor and cognitive dysfunction. Results from open field and rotarod tests show A53T mice develop age-dependent changes in locomotor activity and reduced anxiety-like behavior. Additionally, digigait analysis shows these mice develop an abnormal gait by 12 months of age. A53T mice also exhibit spatial memory deficits at 6 and 12 months, as demonstrated by Y-maze performance. In contrast to gross motor and cognitive changes, A53T mice display significant impairments in fine- and sensorimotor tasks such as grooming, nest building and acoustic startle as early as 1–2 months of age. These mice also show significant abnormalities in basal synaptic transmission, paired-pulse facilitation and long-term depression (LTD). Combined, these data indicate the A53T model exhibits early- and late-onset behavioral and synaptic impairments similar to PD patients and may provide useful endpoints for assessing novel therapeutic interventions for PD. PMID:23936403

Enhanced external counterpulsation (EECP) decreases advanced glycation end products and proinflammatory cytokines in patients with non-insulin-dependent type II diabetes mellitus for up to 6 months following treatment.

PubMed

Sardina, Paloma D; Martin, Jeffrey S; Dzieza, Wojciech K; Braith, Randy W

2016-10-01

Enhanced external counterpulsation (EECP) is a noninvasive, non-pharmacologic intervention proven to increase nitric oxide bioavailability in patients with coronary artery disease. The purpose of the present study was to evaluate the potential clinical benefits of EECP on advanced glycation end products (AGEs) and proinflammatory cytokine concentrations in patients with a clinical diagnosis of type II diabetes mellitus (T2DM). Thirty subjects (60.7 ± 1.9 years) with T2DM were randomly assigned (2:1 ratio) to receive either 35 1-h sessions of EECP (n = 20) or time-matched standard care (n = 10). AGEs, receptors for AGEs (RAGEs), soluble vascular cell adhesion molecules-1 (sVCAM-1), and 8-iso-prostaglandin 2α (8-iso-PGF2α) were evaluated before and at 48 h, 2 weeks, 3, and 6 months following EECP treatment or time-matched control. EECP significantly decreased AGEs and RAGEs at all follow-up measurement time points. AGEs and RAGEs were decreased at 48 h (-75 and -16 %), 2 weeks (-87 and -28 %), 3 months (-89 and -29 %), and 6 months (-92 and -20 %) following EECP treatment, respectively. sVCAM-1 and 8-iso-PGF2α were significantly decreased at 48 h (-30 and -49 %) and 2 weeks (-22 and -27 %) following EECP, respectively. sVCAM-1 (-27 %) remained significantly reduced at 3 months following EECP. Nitrite/nitrate (NOx) was significantly increased at 48 h (+48.4 %) and 2 weeks (+51.9 %) following EECP treatment. Our findings provide novel evidence that EECP decreases AGE/RAGE concentrations, inflammation, and oxidative stress in patients with T2DM that persist for up to 6 months following treatment.

Temperature- and Length-Dependent Energetics of Formation for Polyalanine Helices in Water: Assignment of wAla(n,T) and Temperature-Dependent CD Ellipticity Standards

PubMed Central

Job, Gabriel E.; Kennedy, Robert J.; Heitmann, Björn; Miller, Justin S.; Walker, Sharon M.; Kemp*, Daniel S.

2006-01-01

Length-dependent helical propensities wAla(n,T) at T = 10, 25, and 60 °C are assigned from t/c values and NMR 13C chemical shifts for series 1 peptides TrpLysmInp2tLeu–AlantLeuInp2LysmNH2, n = 15, 19, and 25, m = 5, in water. Van’t Hoff analysis of wAla(n,T) show that α-helix formation is primarily enthalpy-driven. For series 2 peptides Ac–Trp Lys5Inp2tLeu–βAspHel–Alan–beta–tLeuInp2Lys5NH2, n = 12 and 22, which contain exceptionally helical Alan cores, protection factor-derived fractional helicities FH are assigned in the range 10–30 °C in water and used to calibrate temperature-dependent CD ellipticities [θ]λ,H,n,T. These are applied to CD data for series 1 peptides, 12 ≤ n ≤ 45, to confirm the wAla(n,T) assignments at T = 25 and 60 °C. The [θ]λ,H,n,T are temperature dependent within the wavelength region, 222 ± 12 nm, and yield a temperature correction for calculation of FH from experimental values of [θ]222,n,T,Exp. PMID:16787087

The effects of starter microbiota and the early life feeding of medium chain triglycerides on the gastric transcriptome profile of 2- or 3-week-old cesarean delivered piglets.

PubMed

Trevisi, Paolo; Priori, Davide; Motta, Vincenzo; Luise, Diana; Jansman, Alfons J M; Koopmans, Sietse-Jan; Bosi, Paolo

2017-01-01

The stomach is an underestimated key interface between the ingesta and the digestive system, affecting the digestion and playing an important role in several endocrine functions. The quality of starter microbiota and the early life feeding of medium chain triglycerides may affect porcine gastric maturation. Two trials (T1, T2) were carried out on 12 and 24 cesarean-delivered piglets (birth, d0), divided over two microbiota treatments, but slaughtered and sampled at two or three weeks of age, respectively. All piglets were fed orally: sow serum (T1) or pasteurized sow colostrum (T2) on d0; simple starter microbiota ( Lactobacillus amylovorus , Clostridium glycolicum and Parabacteroides spp.) (d1-d3); complex microbiota inoculum (sow diluted feces, CA) or a placebo (simple association, SA) (d3-d4) and milk replacer ad libitum (d0-d4). The The T1 piglets and half of the T2 piglets were then fed a moist diet (CTRL); the remaining half of the T2 piglets were fed the CTRL diet fortified with medium chain triglycerides and 7% coconut oil (MCT). Total mRNA from the oxyntic mucosa was analyzed using Affymetrix©Porcine Gene array strips. Exploratory functional analysis of the resulting values was carried out using Gene Set Enrichment Analysis. Complex microbiota upregulated 11 gene sets in piglets of each age group vs. SA. Of these sets, 6 were upregulated at both ages, including the set of gene markers of oxyntic mucosa. In comparison with the piglets receiving SA, the CA enriched the genes in the sets related to interferon response when the CTRL diet was given while the same sets were impoverished by CA with the MCT diet. Early colonization with a complex starter microbiota promoted the functional maturation of the oxyntic mucosa in an age-dependent manner. The dietary fatty acid source may have affected the recruitment and the maturation of the immune cells, particularly when the piglets were early associated with a simplified starter microbiota.

The NLRP3 Inflammasome Promotes Age-related Thymic Demise and Immunosenescence

PubMed Central

Youm, Yun-Hee; Kanneganti, Thirumala-Devi; Vandanmagsar, Bolormaa; Zhu, Xuewei; Ravussin, Anthony; Adijiang, Ayinuer; Owen, John S.; Thomas, Michael J.; Francis, Joseph; Parks, John S.; Dixit, Vishwa Deep

2013-01-01

The collapse of thymic stromal cell microenvironment with age and resultant inability of the thymus to produce naïve T cells contributes to lower immune-surveillance in the elderly. Here we show that age-related increase in ‘lipotoxic danger signals’ such as free cholesterol (FC) and ceramides, leads to thymic caspase-1 activation via the Nlrp3 inflammasome. Elimination of Nlrp3 and Asc, a critical adaptor required for inflammasome assembly, reduces age-related thymic atrophy and results in an increase in cortical thymic epithelial cells, T cell progenitors and maintenance of T cell repertoire diversity. Using a mouse model of irradiation and hematopoietic stem cell transplantation (HSCT), we show that deletion of the Nlrp3 inflammasome accelerates T cell reconstitution and immune recovery in middle-aged animals. Collectively, these data demonstrate that lowering inflammasome-dependent caspase-1 activation increases thymic lymphopoiesis and suggest that Nlrp3 inflammasome inhibitors may aid the reestablishment of a diverse T cell repertoire in middle-aged or elderly patients undergoing HSCT. PMID:22832107

Removal of sodium inactivation and block of sodium channels by chloramine-T in crayfish and squid giant axons.

PubMed Central

Huang, J. M.; Tanguy, J.; Yeh, J. Z.

1987-01-01

Modification of sodium channels by chloramine-T was examined in voltage clamped internally perfused crayfish and squid giant axons using the double sucrose gap and axial wire technique, respectively. Freshly prepared chloramine-T solution exerted two major actions on sodium channels: (a) an irreversible removal of the fast Na inactivation, and (b) a reversible block of the Na current. Both effects were observed when chloramine-T was applied internally or externally (5-10 mM) to axons. The first effect was studied in crayfish axons. We found that the removal of the fast Na inactivation did not depend on the states of the channel since the channel could be modified by chloramine-T at holding potential (from -80 to -100 mV) or at depolarized potential of -30 mV. After removal of fast Na inactivation, the slow inactivation mechanism was still present, and more channels could undergo slow inactivation. This result indicates that in crayfish axons the transition through the fast inactivated state is not a prerequisite for the slow inactivation to occur. During chloramine-T treatment, a distinct blocking phase occurred, which recovered upon washing out the drug. This second effect of chloramine-T was studied in detail in squid axons. After 24 h, chloramine-T solution lost its ability to remove fast inactivation but retained its blocking action. After removal of the fast Na inactivation, both fresh and aged chloramine-T solutions blocked the Na currents with a similar potency and in a voltage-dependent manner, being more pronounced at lower depolarizing potentials. A similar voltage-dependent block was observed with aged chloramine-T solution in an axon with intact inactivation. In contrast to the action of the fresh solution, the aged chloramine-T solution was found to accelerate the decay of Na currents.These results suggest that chloramine-T solution contains at least two active molecular forms that act at different sites in the Na channel. PMID:2444276

Effects of Gender Difference and Caffeine Supplementation on Anaerobic Muscle Performance.

PubMed

Chen, H-Y; Wang, H-S; Tung, K; Chao, H-H

2015-11-01

The primary purpose of this study was to investigate the effects of gender difference and caffeine supplementation to maximal voluntary isometric contractions (MVIC) and submaximal voluntary isometric contractions (T(lim)). 10 male (age: 20.10 ± 2.18 years, BMI: 22.23±1.96 kg/m(2)) and 10 female (age: 19.90±0.99 years, BMI: 21.76±2.65 kg/m(2)) elite collegiate athletes were recruited. Subjects ingested caffeine (6 mg/kg) or a placebo in a randomized, double-blind, placebo-control, and counter-balanced fashion. MVIC and T(lim) were measured after supplementations. T(lim) result was calculated based on the time to exhaustion of isometric contraction with 50% MVIC. Fatigue index (FI%) referred to the MVIC tested 20 s after the cessation of T(lim) test, and was indexed by the percentage of MVIC decline. No significant interaction effect was found between the gender factor and the supplementation factor for all dependent variables. Compared to the placebo, caffeine supplementation significantly increased MVIC (5.9%) and T(lim) (15.5%) (p<0.05) whereas it had no significant effect on FI%. This study demonstrates that caffeine supplementation at a 6 mg/kg dosage facilitates performances in MVIC and T(lim). The ergogenic effect of caffeine on muscle power and muscle endurance does not show a gender bias. © Georg Thieme Verlag KG Stuttgart · New York.

Age-specific and sex-specific prevalence of cerebral β-amyloidosis, tauopathy, and neurodegeneration in cognitively unimpaired individuals aged 50-95 years: a cross-sectional study.

PubMed

Jack, Clifford R; Wiste, Heather J; Weigand, Stephen D; Therneau, Terry M; Knopman, David S; Lowe, Val; Vemuri, Prashanthi; Mielke, Michelle M; Roberts, Rosebud O; Machulda, Mary M; Senjem, Matthew L; Gunter, Jeffrey L; Rocca, Walter A; Petersen, Ronald C

2017-06-01

A new classification for biomarkers in Alzheimer's disease and cognitive ageing research is based on grouping the markers into three categories: amyloid deposition (A), tauopathy (T), and neurodegeneration or neuronal injury (N). Dichotomising these biomarkers as normal or abnormal results in eight possible profiles. We determined the clinical characteristics and prevalence of each ATN profile in cognitively unimpaired individuals aged 50 years and older. All participants were in the Mayo Clinic Study of Aging, a population-based study that uses a medical records linkage system to enumerate all individuals aged 50-89 years in Olmsted County, MN, USA. Potential participants are randomly selected, stratified by age and sex, and invited to participate in cognitive assessments; individuals without medical contraindications are invited to participate in brain imaging studies. Participants who were judged clinically as having no cognitive impairment and underwent multimodality imaging between Oct 11, 2006, and Oct 5, 2016, were included in the current study. Participants were classified as having normal (A-) or abnormal (A+) amyloid using amyloid PET, normal (T-) or abnormal (T+) tau using tau PET, and normal (N-) or abnormal (N+) neurodegeneration or neuronal injury using cortical thickness assessed by MRI. We used the cutoff points of standard uptake value ratio (SUVR) 1·42 (centiloid 19) for amyloid PET, 1·23 SUVR for tau PET, and 2·67 mm for MRI cortical thickness. Age-specific and sex-specific prevalences of the eight groups were determined using multinomial models combining data from 435 individuals with amyloid PET, tau PET, and MRI assessments, and 1113 individuals who underwent amyloid PET and MRI, but not tau PET imaging. The numbers of participants in each profile group were 165 A-T-N-, 35 A-T+N-, 63 A-T-N+, 19 A-T+N+, 44 A+T-N-, 25 A+T+N-, 35 A+T-N+, and 49 A+T+N+. Age differed by ATN group (p<0·0001), ranging from a median 58 years (IQR 55-64) in A-T-N- and 57 years (54-64) in A-T+N- to a median 80 years (75-84) in A+T-N+ and 79 years (73-87) in A+T+N+. The number of APOE ε4 carriers differed by ATN group (p=0·04), with carriers roughly twice as frequent in each A+ group versus the corresponding A- group. White matter hyperintensity volume (p<0·0001) and cognitive performance (p<0·0001) also differed by ATN group. Tau PET and neurodegeneration biomarkers were discordant in most individuals who would be categorised as stage 2 or 3 preclinical Alzheimer's disease (A+T+N-, A+T-N+, and A+T+N+; 86% at age 65 years and 51% at age 80 years) or with suspected non-Alzheimer's pathophysiology (A-T+N-, A-T-N+, and A-T+N+; 92% at age 65 years and 78% at age 80 years). From age 50 years, A-T-N- prevalence declined and A+T+N+ and A-T+N+ prevalence increased. In both men and women, A-T-N- was the most prevalent until age late 70s. After about age 80 years, A+T+N+ was most prevalent. By age 85 years, more than 90% of men and women had one or more biomarker abnormalities. Biomarkers of fibrillar tau deposition can be included with those of β-amyloidosis and neurodegeneration or neuronal injury to more fully characterise the heterogeneous pathological profiles in the population. Both amyloid- dependent and amyloid-independent pathological profiles can be identified in the cognitively unimpaired population. The prevalence of each ATN group changed substantially with age, with progression towards more biomarker abnormalities among individuals who remained cognitively unimpaired. National Institute on Aging (part of the US National Institutes of Health), the Alexander Family Professorship of Alzheimer's Disease Research, the Mayo Clinic, and the GHR Foundation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhibition of Thymic Adipogenesis by Caloric Restriction Is Coupled with Reduction in Age-Related Thymic Involution1

PubMed Central

Yang, Hyunwon; Youm, Yun-Hee; Dixit, Vishwa Deep

2009-01-01

Aging of thymus is characterized by reduction in naive T cell output together with progressive replacement of lymphostromal thymic zones with adipocytes. Determining how calorie restriction (CR), a prolongevity metabolic intervention, regulates thymic aging may allow identification of relevant mechanisms to prevent immunosenescence. Using a mouse model of chronic CR, we found that a reduction in age-related thymic adipogenic mechanism is coupled with maintenance of thymic function. The CR increased cellular density in the thymic cortex and medulla and preserved the epithelial signatures. Interestingly, CR prevented the age-related increase in epithelial-mesenchymal transition (EMT) regulators, FoxC2, and fibroblast-specific protein-1 (FSP-1), together with reduction in lipid-laden thymic fibroblasts. Additionally, CR specifically blocked the age-related elevation of thymic proadipogenic master regulator, peroxisome proliferator activated receptor γ (PPARγ), and its upstream activator xanthine-oxidoreductase (XOR). Furthermore, we found that specific inhibition of PPARγ in thymic stromal cells prevented their adipogenic transformation in an XOR-dependent mechanism. Activation of PPARγ-driven adipogenesis in OP9-DL1 stromal cells compromised their ability to support T cell development. Conversely, CR-induced reduction in EMT and thymic adipogenesis were coupled with elevated thymic output. Compared with 26-mo-old ad libitum fed mice, the T cells derived from age-matched CR animals displayed greater proliferation and higher IL-2 expression. Furthermore, CR prevented the deterioration of the peripheral TCR repertoire diversity in older animals. Collectively, our findings demonstrate that reducing proadipogenic signaling in thymus via CR may promote thymopoiesis during aging. PMID:19648267

Impact Craters of Venus with D Greater Than 5 km Classified Based on Degree of Preservation of the Associated Radar-Dark Deposits

NASA Technical Reports Server (NTRS)

Basilevsky, A. T.; Head, J. W.; Setyaeva, I. V.

2003-01-01

This is a further continuation of work, which studied craters greater than or equal to 30 km in diameter. That work subdivided craters based on character of the associated radar dark deposits. It was suggested and then confirmed that the most pristine deposits of that sort are radar-dark parabolas. Non-parabolic radar-dark halos represent the next stage of the deposit evolution and then with time they disappear. So presence and character of crater-associated dark deposit can be used for estimates of the crater age and then for dating other features. Previous work classified craters into: 1) craters with dark parabola (DP), 2) with clear dark halo (CH), 3) with faint halo (FH) and 4) with no dark halo (NH). It was found that abundances of craters superposed on regional plains (whose mean age is close to the planet mean surface age T) and belonging to DP, CH, FH and NH classes were correspondingly 15, 30, 30 and 25%. From that it was concluded that DP craters are not older than 0.1-0.15T; CH craters formed during the time interval from approx. 0.5T until 0.1-0.15T ago, and the FH and NH craters formed prior to approx. 0.5T ago. It was shown that the DP, CH, FH and NH percentages show only slight apparent dependence on the crater geographic latitudes and no noticeable dependence on the crater size. The present study analyzes a much larger population (all D greater than or equal to 5 km craters) to investigate better the latitude effect and to study if within this larger crater population the size effect exists.

Age-Dependent Changes in Resting Energy Expenditure (REE): Insights from Detailed Body Composition Analysis in Normal and Overweight Healthy Caucasians

PubMed Central

Geisler, Corinna; Braun, Wiebke; Pourhassan, Maryam; Schweitzer, Lisa; Glüer, Claus-Christian; Bosy-Westphal, Anja; Müller, Manfred J.

2016-01-01

Age-related changes in organ and tissue masses may add to changes in the relationship between resting energy expenditure (REE) and fat free mass (FFM) in normal and overweight healthy Caucasians. Secondary analysis using cross-sectional data of 714 healthy normal and overweight Caucasian subjects (age 18–83 years) with comprehensive information on FFM, organ and tissue masses (as assessed by magnetic resonance imaging (MRI)), body density (as assessed by Air Displacement Plethysmography (ADP)) and hydration (as assessed by deuterium dilution (D2O)) and REE (as assessed by indirect calorimetry). High metabolic rate organs (HMR) summarized brain, heart, liver and kidney masses. Ratios of HMR organs and muscle mass (MM) in relation to FFM were considered. REE was calculated (REEc) using organ and tissue masses times their specific metabolic rates. REE, FFM, specific metabolic rates, the REE-FFM relationship, HOMA, CRP, and thyroid hormone levels change with age. The age-related decrease in FFM explained 59.7% of decreases in REE. Mean residuals of the REE-FFM association were positive in young adults but became negative in older subjects. When compared to young adults, proportions of MM to FFM decreased with age, whereas contributions of liver and heart did not differ between age groups. HOMA, TSH and inflammation (plasma CRP-levels) explained 4.2%, 2.0% and 1.4% of the variance in the REE-FFM residuals, but age and plasma T3-levels had no effects. HMR to FFM and MM to FFM ratios together added 11.8% on to the variance of REE-FFM residuals. Differences between REE and REEc increased with age, suggesting age-related changes in specific metabolic rates of organs and tissues. This bias was partly explained by plasmaT3-levels. Age-related changes in REE are explained by (i) decreases in fat free mass; (ii) a decrease in the contributions of organ and muscle masses to FFM; and (iii) decreases in specific organ and tissue metabolic rates. Age-dependent changes in the REE-FFMassociation are explained by composition of FFM, inflammation and thyroid hormones. PMID:27258302

Combination Iron Chelation Therapy with Deferiprone and Deferasirox in Iron-Overloaded Patients with Transfusion-Dependent β-Thalassemia Major.

PubMed

Karami, Hossein; Kosaryan, Mehrnoush; Amree, Arash Hadian; Darvishi-Khezri, Hadi; Mousavi, Masoomeh

2017-01-11

There are few papers on the combination therapy of deferiprone (DFP) and deferasirox (DFX) in iron-overloaded patients with transfusion-dependent β-thalassemia major (β-TM). A total of 6 patients with β-TM (5 males and 1 female) with a mean age of 23.8±5.8 years (ranging from 17 to 31) used this treatment regimen. The mean doses of DFP and DFX were 53.9±22.2 and 29.3±6.8 mg/kg/day, respectively. The duration of treatment was 11.5±4.6 months. Their serum ferritin levels were measured to be 2800±1900 and 3400±1600 ng/mL before and after treatment, respectively (p<0.6). Their cardiac magnetic resonance imaging (MRI) T2* values were 16.69±15.35 vs 17.38±5.74 millisecond (ms) before and after treatment, respectively ( p < 0.9). Although there was no significant difference between their cardiac MRI T2* values before and after treatment statistically, the values improved after combination therapy with DFP and DFX in most of the patients. Liver MRI T2 * values were changed from 2.12±0.98 to 3.03±1.51 ms after treatment (p < 0.01); Further, their liver T2* values and liver iron concentration (LIC) were improved after treatment. Our study found that cardiac MRI T2* values, liver MRI T2* values, and LIC were improved after combination therapy with DFP and DFX in β-TM patients and that DFP and DFX combination therapy could be used to alleviate cardiac and liver iron loading.

The Association Between Commonly Investigated User Factors and Various Types of eHealth Use for Self-Care of Type 2 Diabetes: Case of First-Generation Immigrants From Pakistan in the Oslo Area, Norway.

PubMed

Tatara, Naoe; Hammer, Hugo Lewi; Andreassen, Hege Kristin; Mirkovic, Jelena; Kjøllesdal, Marte Karoline Råberg

2017-10-05

Sociodemographic and health-related factors are often investigated for their association with the active use of electronic health (eHealth). The importance of such factors has been found to vary, depending on the purpose or means of eHealth and the target user groups. Pakistanis are one of the biggest immigrant groups in the Oslo area, Norway. Due to an especially high risk of developing type 2 diabetes (T2D) among this population, knowledge about their use of eHealth for T2D self-management and prevention (self-care) will be valuable for both understanding this vulnerable group and for developing effective eHealth services. The aim of this study was to examine how commonly were the nine types of eHealth for T2D self-care being used among our target group, the first-generation Pakistani immigrants living in the Oslo area. The nine types of eHealth use are divided into three broad categories based on their purpose: information seeking, communication, and active self-care. We also aimed to investigate how sociodemographic factors, as well as self-assessment of health status and digital skills are associated with the use of eHealth in this group. A survey was carried out in the form of individual structured interviews from September 2015 to January 2016 (N=176). For this study, dichotomous data about whether or not an informant had used each of the nine types of eHealth in the last 12 months and the total number of positive answers were used as dependent variables in a regression analysis. The independent variables were age, gender, total years of education, digital skills (represented by frequency of asking for help when using information and communication technology [ICT]), and self-assessment of health status. Principal component analyses were applied to make categories of independent variables to avoid multicollinearity. Principal component analysis yielded three components: knowledge, comprising total years of education and digital skills; health, comprising age and self-assessment of health status; and gender, as being a female. With the exception of closed conversation with a few specific acquaintances about self-care of T2D (negatively associated, P=.02) and the use of ICT for relevant information-seeking by using search engines (not associated, P=.18), the knowledge component was positively associated with all the other dependent variables. The health component was negatively associated with the use of ICT for closed conversation with a few specific acquaintances about self-care of T2D (P=.01) but not associated with the other dependent variables. Gender component showed no association with any of the dependent variables. In our sample, knowledge, as a composite measure of education and digital skills, was found to be the main factor associated with eHealth use regarding T2D self-care. Enhancing digital skills would encourage and support more active use of eHealth for T2D self-care. ©Naoe Tatara, Hugo Lewi Hammer, Hege Kristin Andreassen, Jelena Mirkovic, Marte Karoline Råberg Kjøllesdal. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 05.10.2017.

Do overhead sports increase risk for rotator cuff tears in wheelchair users?

PubMed

Akbar, Michael; Brunner, Manuela; Ewerbeck, Volker; Wiedenhöfer, Bernd; Grieser, Thomas; Bruckner, Thomas; Loew, Markus; Raiss, Patric

2015-03-01

To analyze whether frequent overhead-sports activity increases the risk for rotator cuff disease in patients with spinal cord injuries (SCIs) who are wheelchair dependent. Cross-sectional study, risk analysis. Department of Orthopaedic Surgery, Trauma Surgery and Spinal Cord Injury. Patients (N=296) with SCI requiring the full-time use of a manual wheelchair were recruited for this study. The total population was divided into 2 groups (sports vs no sports), among them 103 patients playing overhead sports on a regular basis (at least 1-2 times/wk) and 193 patients involved in overhead sports less than once a week or in no sports activity at all. The mean age of the sports group was 49.1 years. The mean duration of wheelchair dependence was 26.5 years. The mean age of the no-sports group was 48 years. The mean duration of wheelchair dependence was 25.2 years. Each individual completed a questionnaire designed to identify overhead-sports activity on a regular basis and was asked about shoulder problems. Magnetic resonance imaging scans of both shoulders were performed in each patient and analyzed in a standardized fashion. None. Possible differences in continuous data between patients with and without rotator cuff tear were evaluated. The relative risk of suffering from a rotator cuff tear between patients playing overhead sports and those not playing overhead sports was calculated. One hundred three patients played overhead sports regularly and 193 did not. There was no difference between groups regarding age, sex, level of SCI, and duration of wheelchair dependence. The body mass index was significantly lower in the sports group than in the no-sports group (P<.0001). A rotator cuff tear was present in 75.7% of the patients in the sports group and in 36.3% of the patients in the no-sports group (P<.0001). Rotator cuff tears were symptomatic in 92.6% of the patients. The estimated risk increase for the sports group to develop rotator cuff tears was twice as high as for the no-sports group (95% confidence interval, 1.7-2.6; P<.001). Similar results were found for the neurological level of lesion (T2-7/

Age Dependency of Myocardial Triglyceride Content: A 3T High-Field 1H-MR Spectroscopy Study.

PubMed

Petritsch, B; Gassenmaier, T; Kunz, A S; Donhauser, J; Goltz, J P; Bley, T A; Horn, M

2015-11-01

The role of myocardial triglyceride (mTG) content in the aging human heart is not entirely understood. The aim of this study was to measure concentrations of mTG content from healthy volunteers and to determine the association between age, mTG content and systolic heart function. Furthermore, the technical stability of the (1)H-magnetic resonance spectroscopy ((1)H-MRS) and the reliability of peak evaluation at 3 T were evaluated. The total study population of 47 healthy volunteers was divided into 4 age classes, according to the age of the subjects (1(st) cohort 20 - 29 years (yrs.), n = 20; 2(nd) cohort 30 - 39 yrs., n = 10; 3(rd) cohort 40 - 49 yrs., n = 9; 4(th) cohort 50 - 60 yrs., n = 8). Cardiac MRI and double triggered (1)H-MRS of the myocardium were consecutively performed using a 3 T scanner. Each participant underwent spectroscopic measurements twice in the same investigation. mTG content increases with age. The correlation of age and mTG is minimal (r = 0.48; p < 0.001). The following age-averaged mTG content values expressed as % of mTG signal compared to the water signal were determined for each cohort: 1(st) cohort 0.25 % (± 0.17); 2(nd) cohort 0.48 % (± 0.30); 3(rd) cohort 0.48 % (± 0.18); 4(th) cohort 0.77 % (± 0.70). There was no significant correlation (r = 0.04; p = n.s.) between LV mass and mTG content in healthy volunteers. Within our cohorts, no effects of age or mTG content on systolic heart function were seen (r = - 0.01; p = n.s.). The intraclass correlation coefficient of spectroscopic measurements was high (r = 0.965; p < 0.001). Myocardial TG content increases with age. The normal age-dependent concentration ranges of myocardial lipid metabolites reported in this study may be helpful for the correction of acquired (1)H-MRS data in patients when evaluating metabolic and cardiovascular diseases in future magnetic resonance spectroscopy studies. © Georg Thieme Verlag KG Stuttgart · New York.

Age-dependent changes in autophosphorylation of alpha calcium/calmodulin dependent kinase II in hippocampus and amygdala after contextual fear conditioning.

PubMed

Fang, Ton; Kasbi, Kamillia; Rothe, Stephanie; Aziz, Wajeeha; Giese, K Peter

2017-09-01

The hippocampus and amygdala are essential brain regions responsible for contextual fear conditioning (CFC). The autophosphorylation of alpha calcium-calmodulin kinase II (αCaMKII) at threonine-286 (T286) is a critical step implicated in long-term potentiation (LTP), learning and memory. However, the changes in αCaMKII levels with aging and training in associated brain regions are not fully understood. Here, we studied how aging and training affect the levels of phosphorylated (T286) and proportion of phosphorylated:total αCaMKII in the hippocampus and amygdala. Young and aged mice, naïve (untrained) and trained in CFC, were analysed by immunohistochemistry for the levels of total and phosphorylated αCaMKII in the hippocampus and amygdala. We found that two hours after CFC training, young mice exhibited a higher level of phosphorylated and increased ratio of phosphorylated:total αCaMKII in hippocampal CA3 stratum radiatum. Furthermore, aged untrained mice showed a higher ratio of phosphorylated:total αCaMKII in the CA3 region of the hippocampus when compared to the young untrained group. No effect of training or aging were seen in the central, lateral and basolateral amygdala regions, for both phosphorylated and ratio of phosphorylated:total αCaMKII. These results show that aging impairs the training-induced upregulation of autophosphorylated (T286) αCaMKII in the CA3 stratum radiatum of the hippocampus. This indicates that distinct age-related mechanisms underlie CFC that may rely more heavily on NMDA receptor-dependent plasticity in young age. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Time to failure of oral therapy in children with type 2 diabetes: a single center retrospective chart review.

PubMed

Barnes, Nicole S; White, Perrin C; Hutchison, Michele R

2012-11-01

There are no data in children with type 2 diabetes (T2D) regarding the durability of glycemic control with oral medication. Therefore, we assessed the likelihood of and time to failure of oral therapy in children and adolescents diagnosed with T2D. Charts of patients presenting to our large tertiary-care children's hospital between January 2000 and June 2007 with a new diagnosis of diabetes (n = 1625) were reviewed to identify those with T2D (n = 184). Subjects' initial therapy, hemoglobin A1c (HbA1c), body mass index, age, gender, and antibody status were documented, as well as subsequent therapies and HbA1c values, to determine whether baseline characteristics predicted future insulin dependence. Kaplan-Meier survival curves and Cox proportional hazards analysis demonstrated time to failure of oral therapy. Eighty-nine patients remained on insulin throughout the study. Baseline characteristics that determined future insulin dependence included being placed on insulin initially, initial HbA1c and race (whites less likely to be insulin dependent at study conclusion). Patients who failed oral therapy were more often reported to be non-compliant or unable to tolerate metformin than those who continued on oral therapy. The median time to failure of oral therapy (metformin monotherapy in 84/95) was not significantly different for patients initially treated with oral therapy (42 months) and insulin (35 months). Thus, children with T2D appear to fail oral therapy more quickly than what is reported in adults. It is not yet known if improving compliance with treatment might allow more children to remain on oral medications. © 2012 John Wiley & Sons A/S.

Mediator subunit MED1 is a T3-dependent and T3-independent coactivator on the thyrotropin β gene promoter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsui, Keiji; Oda, Kasumi; Mizuta, Shumpei

2013-10-11

Highlights: •MED1 is a bona fide T3-dependent coactivator on TSHB promoter. •Mice with LxxLL-mutant MED1 have attenuated TSHβ mRNA and thyroid hormone levels. •MED1 activates TSHB promoter T3-dependently in cultured cells. •T3-dependent MED1 action is enhanced when SRC1/SRC2 or HDAC2 is downregulated. •MED1 is also a T3-independent GATA2/Pit1 coactivator on TSHB promoter. -- Abstract: The MED1 subunit of the Mediator transcriptional coregulator complex is a nuclear receptor-specific coactivator. A negative feedback mechanism of thyroid-stimulating hormone (TSH, or thyrotropin) expression in the thyrotroph in the presence of triiodothyronine (T3) is employed by liganded thyroid hormone receptor β (TRβ) on the TSHβmore » gene promoter, where conventional histone-modifying coactivators act as corepressors. We now provide evidence that MED1 is a ligand-dependent positive cofactor on this promoter. TSHβ gene transcription was attenuated in MED1 mutant mice in which the nuclear receptor-binding ability of MED1 was specifically disrupted. MED1 stimulated GATA2- and Pit1-mediated TSHβ gene promoter activity in a ligand-independent manner in cultured cells. MED1 also stimulated transcription from the TSHβ gene promoter in a T3-dependent manner. The transcription was further enhanced when the T3-dependent corepressors SRC1, SRC2, and HDAC2 were downregulated. Hence, MED1 is a T3-dependent and -independent coactivator on the TSHβ gene promoter.« less

Thermal aging effect of vanadyl acetylacetonate precursor for deposition of VO{sub 2} thin films with thermochromic properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Jung-Hoon; Nam, Sang-Hun; Kim, Donguk

Highlights: • 7 day aged VO(acac){sub 2} sol shows enhanced adhesivity on the SiO{sub 2} compared with non-aged sol. • The aging process has significantly affected the morphologies of VO{sub 2} films. • From the FT-IR spectra, thermal aging process provides the deformation of precursor. • The metal insulator transition (MIT) efficiency (ΔT{sub at2000} {sub nm}) reached a maximum value of 51% at 7 day aging. • Thermal aging process could shorten the aging time of sol solution. - Abstract: Thermochromic properties of vanadium dioxide (VO{sub 2}) have been studied extensively due to their IR reflection applications in energy smartmore » windows. In this paper, we studied the optical switching property of VO{sub 2} thin film, depending on the thermal aging time of the vanadyl acetylacetonate (VO(acac){sub 2}) precursor. We found the alteration of the IR spectra of the precursor by tuning the aging time as well as heat treatments of the precursor. An aging effect of vanadium precursor directly affects the morphologies, optical switching property and crystallinity of VO{sub 2} films. The optimum condition was achieved at the 7 day aging time with metal insulator transition (MIT) efficiency of 50%.« less

Cardiac Autonomic Regulation and Repolarization During Acute Experimental Hypoglycemia in Type 2 Diabetes

PubMed Central

Chow, Elaine; Bernjak, Alan; Walkinshaw, Emma; Lubina-Solomon, Alexandra; Freeman, Jenny; Macdonald, Ian A.; Sheridan, Paul J.

2017-01-01

Hypoglycemia is associated with increased cardiovascular mortality in trials of intensive therapy in type 2 diabetes mellitus (T2DM). We previously observed an increase in arrhythmias during spontaneous prolonged hypoglycemia in patients with T2DM. We examined changes in cardiac autonomic function and repolarization during sustained experimental hypoglycemia. Twelve adults with T2DM and 11 age- and BMI-matched control participants without diabetes underwent paired hyperinsulinemic clamps separated by 4 weeks. Glucose was maintained at euglycemia (6.0 mmol/L) or hypoglycemia (2.5 mmol/L) for 1 h. Heart rate, blood pressure, and heart rate variability were assessed every 30 min and corrected QT intervals and T-wave morphology every 60 min. Heart rate initially increased in participants with T2DM but then fell toward baseline despite maintained hypoglycemia at 1 h accompanied by reactivation of vagal tone. In control participants, vagal tone remained depressed during sustained hypoglycemia. Participants with T2DM exhibited greater heterogeneity of repolarization during hypoglycemia as demonstrated by T-wave symmetry and principal component analysis ratio compared with control participants. Epinephrine levels during hypoglycemia were similar between groups. Cardiac autonomic regulation during hypoglycemia appears to be time dependent. Individuals with T2DM demonstrate greater repolarization abnormalities for a given hypoglycemic stimulus despite comparable sympathoadrenal responses. These mechanisms could contribute to arrhythmias during clinical hypoglycemic episodes. PMID:28137792

Acute macrovascular dysfunction in patients with type 2 diabetes induced by ingestion of advanced glycated β-lactoglobulins.

PubMed

Stirban, Alin; Kotsi, Paraskevi; Franke, Knut; Strijowski, Ulf; Cai, Weijing; Götting, Christian; Tschoepe, Diethelm

2013-05-01

Recent evidence indicates that heat-enhanced food advanced glycation end products (AGEs) adversely affect vascular function. The aim of this study was to examine the acute effects of an oral load of heat-treated, AGE-modified β-lactoglobulins (AGE-BLG) compared with heat-treated, nonglycated BLG (C-BLG) on vascular function in patients with type 2 diabetes mellitus (T2DM). In a double-blind, controlled, randomized, crossover study, 19 patients with T2DM received, on two different occasions, beverages containing either AGE-BLG or C-BLG. We measured macrovascular [brachial ultrasound of flow-mediated dilatation (FMD)] and microvascular (laser-Doppler measurements of reactive hyperemia in the hand) functions at baseline (T0), 90 (T90), and 180 (T180) min. Following the AGE-BLG, FMD decreased at T90 by 80% from baseline and remained decreased by 42% at T180 (P < 0.05 vs. baseline, P < 0.05 vs. C-BLG at T90). By comparison, following C-BLG, FMD decreased by 27% at T90 and 51% at T180 (P < 0.05 vs. baseline at T180). A significant decrease in nitrite (T180) and nitrate (T90 and T180), as well as a significant increase in N(ε)-carboxymethyllisine, accompanied intake of AGE-BLG. There was no change in microvascular function caused by either beverage. In patients with T2DM, acute oral administration of a single AGE-modified protein class significantly though transiently impaired macrovascular function in concert with decreased nitric oxide bioavailability. These AGE-related changes were independent of heat treatment.

Chotosan (Diaoteng San)-induced improvement of cognitive deficits in senescence-accelerated mouse (SAMP8) involves the amelioration of angiogenic/neurotrophic factors and neuroplasticity systems in the brain

PubMed Central

2011-01-01

Background Chotosan (CTS, Diaoteng San), a Kampo medicine (ie Chinese medicine) formula, is reportedly effective in the treatment of patients with cerebral ischemic insults. This study aims to evaluate the therapeutic potential of CTS in cognitive deficits and investigates the effects and molecular mechanism(s) of CTS on learning and memory deficits and emotional abnormality in an animal aging model, namely 20-week-old senescence-accelerated prone mice (SAMP8), with and without a transient ischemic insult (T2VO). Methods Age-matched senescence-resistant inbred strain mice (SAMR1) were used as control. SAMP8 received T2VO (T2VO-SAMP8) or sham operation (sham-SAMP8) at day 0. These SAMP8 groups were administered CTS (750 mg/kg, p.o.) or water daily for three weeks from day 3. Results Compared with the control group, both sham-SAMP8 and T2VO-SAMP8 groups exhibited cognitive deficits in the object discrimination and water maze tests and emotional abnormality in the elevated plus maze test. T2VO significantly exacerbated spatial cognitive deficits of SAMP8 elucidated by the water maze test. CTS administration ameliorated the cognitive deficits and emotional abnormality of sham- and T2VO-SAMP8 groups. Western blotting and immunohistochemical studies revealed a marked decrease in the levels of phosphorylated forms of neuroplasticity-related proteins, N-methyl-D-aspartate receptor 1 (NMDAR1), Ca2+/calmodulin-dependent protein kinase II (CaMKII), cyclic AMP responsive element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the frontal cortices of sham-SAMP8 and T2VO-SAMP8. Moreover, these animal groups showed significantly reduced levels of vasculogenesis/angiogenesis factors, vascular endothelial growth factor (VEGF), VEGF receptor type 2 (VEGFR2), platelet-derived growth factor-A (PDGF-A) and PDGF receptor α (PDGFRα). CTS treatment reversed the expression levels of these factors down-regulated in the brains of sham- and T2VO-SAMP8. Conclusion Recovery of impaired neuroplasticity system and VEGF/PDGF systems may play a role in the ameliorative effects of CTS on cognitive dysfunction caused by aging and ischemic insult. PMID:21943225

Sarcomere length influences postmortem proteolysis of excised bovine semitendinosus muscle.

PubMed

Weaver, A D; Bowker, B C; Gerrard, D E

2008-08-01

The interaction between sarcomere length and postmortem proteolysis as related to meat tenderness is not clear. The extent of thick and thin filament overlap alters actomyosin binding and may alter substrate availability during aging-induced tenderization. The objective of this study was to determine the influence of sarcomere length on proteolytic degradation in beef. Strips from bovine semitendinosus were either stretched 40% and restrained or allowed to shorten unrestrained in an ice bath. After rigor completion, 0.6-cm cross sections were fabricated and were randomly assigned to 2, 4, 7, or 10 d of aging treatments. Myofibrils were isolated for sarcomere length determination. Samples were collected and frozen for shear force analysis, and muscle proteins were extracted for SDS-PAGE and Western blotting analyses to determine troponin T (TnT) proteolysis. Sarcomere length was greater (P < 0.01) in stretched muscle samples compared with shortened samples (2.57 vs. 1.43 microm, respectively). Correspondingly, shear force values were greater (P < 0.05) in shortened samples than stretched samples. Western blots revealed the presence of 3 major intact TnT bands that diminished with time postmortem and 4 bands (TnT degradation products) that accumulated during postmortem storage. Quantification of intact TnT showed increased (P < 0.05) proteolysis at 4 and 7 d postmortem in samples with long sarcomeres. By 10 d, only traces of the greatest molecular weight intact TnT band were evident in both shortened and stretched samples, suggesting this TnT band may be more susceptible to proteolysis than other intact TnT bands. Degradation products of TnT appeared earlier postmortem in samples with long sarcomeres. The 30-kDa TnT fragment appeared after 7 d of postmortem storage in samples with long sarcomeres but not until 10 d in muscle containing short sarcomeres. Collectively, these data show that postmortem TnT proteolysis is sarcomere length-dependent and suggest that thick and thin filament overlap may influence the postmortem aging process in beef.

Age-dependent loss of the C-terminal amino acid from alpha crystallin

NASA Technical Reports Server (NTRS)

Emmons, T.; Takemoto, L.; Spooner, B. S. (Principal Investigator)

1992-01-01

Antiserum made against the C-terminal region of alpha-A crystallin was used to monitor the purification of a tryptic peptide containing the C-terminus of the molecule from fetal versus adult bovine lenses. Mass spectral analysis of the peptide preparations obtained from these lenses demonstrated the presence of a peptide (T20) containing an intact C-terminus from fetal lenses and the presence of an additional peptide (T20') from older lenses that contained a cleaved C-terminal serine. These results demonstrate an age-dependent processing of alpha-A crystallin in the bovine lens, resulting in removal of the C-terminal amino acid residue.

Longitudinal study of surrogate aging measures during human immunodeficiency virus seroconversion.

PubMed

Leung, Janice M; Fishbane, Nick; Jones, Meaghan; Morin, Alexander; Xu, Stella; Liu, Joseph Cy; MacIsaac, Julie; Milloy, M-J; Hayashi, Kanna; Montaner, Julio; Horvath, Steve; Kobor, Michael; Sin, Don D; Harrigan, P Richard; Man, S F Paul

2017-02-23

Persons living with human immunodeficiency virus (HIV) harbor an increased risk of age-related conditions. We measured changes in telomere length and DNA methylation in the peripheral blood of 31 intravenous drug users, who were followed longitudinally with blood samples pre-HIV (T1), immediately post-HIV (T2; 1.9±1 year from T1), and at a later follow-up time (T3; 2.2±1 year from T2). Absolute telomere length measurements were performed using polymerase chain reaction methods. Methylation profiles were obtained using the Illumina Human Methylation450 platform. Methylation aging was assessed using the Horvath method. Telomere length significantly decreased between T1 and T2 (227±46 at T1 vs. 201±48 kbp/genome at T2, p=0.045), while no differences were observed between T2 and T3 (201±48 at T2 vs. 186±27 kbp/genome at T3, p=0.244). Methylation aging as measured by the age acceleration residual increased over the time course of HIV infection (p=0.035). CpG sites corresponding to PCBP2 and CSRNP1 were differentially methylated between T1 and T2 at a q-value <0.05. Telomere shortening and methylation changes can therefore be observed in the short-term period immediately following HIV seroconversion. Further studies to confirm these results in larger sample sizes and to compare these results to non-HIV and non-injection drug users are warranted.

γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis.

PubMed

Kohlgruber, Ayano C; Gal-Oz, Shani T; LaMarche, Nelson M; Shimazaki, Moto; Duquette, Danielle; Nguyen, Hung N; Mina, Amir I; Paras, Tyler; Tavakkoli, Ali; von Andrian, Ulrich; Banks, Alexander S; Shay, Tal; Brenner, Michael B; Lynch, Lydia

2018-05-01

γδ T cells are situated at barrier sites and guard the body from infection and damage. However, little is known about their roles outside of host defense in nonbarrier tissues. Here, we characterize a highly enriched tissue-resident population of γδ T cells in adipose tissue that regulate age-dependent regulatory T cell (T reg ) expansion and control core body temperature in response to environmental fluctuations. Mechanistically, innate PLZF + γδ T cells produced tumor necrosis factor and interleukin (IL) 17 A and determined PDGFRα + and Pdpn + stromal-cell production of IL-33 in adipose tissue. Mice lacking γδ T cells or IL-17A exhibited decreases in both ST2 + T reg cells and IL-33 abundance in visceral adipose tissue. Remarkably, these mice also lacked the ability to regulate core body temperature at thermoneutrality and after cold challenge. Together, these findings uncover important physiological roles for resident γδ T cells in adipose tissue immune homeostasis and body-temperature control.

Anisotropic H c 2 , thermodynamic and transport measurements, and pressure dependence of T c in K 2 Cr 3 As 3 single crystals

DOE PAGES

Kong, Tai; Bud'ko, Sergey L.; Canfield, Paul C.

2015-01-30

We present a detailed study of single crystalline K 2Cr 3As 3 and analyze its thermodynamic and transport properties, anisotropic H c2(T), and initial pressure dependence of T c. In zero field, the temperature-dependent resistivity is metallic. Deviation from a linear temperature dependence is evident below 100 K and a T 3 dependence is roughly followed from just above T c (~10K) to ~40K. Anisotropic H c2(T) data were measured up to 140 kOe with field applied along and perpendicular to the rodlike crystals. For the applied field perpendicular to the rod, H c2(T) is linear with a slope ~–70more » kOe/K. For field applied along the rod, the slope is about –120 kOe/K below 70 kOe. Above 70 kOe, the magnitude of the slope decreases to ~–70 kOe/K. The electronic specific heat coefficient γ, just above T c, is 73 mJ/mol K 2; the Debye temperature Θ D is 220 K. As a result, the specific heat jump at the superconducting transition ΔC~2.2γT c. Finally, for hydrostatic pressures up to ~7 kbar, T c decreases under pressure linearly at a rate of –0.034K/kbar.« less

Electronic transport properties of intermediately coupled superconductors: PdTe2 and Cu0.04PdTe2

NASA Astrophysics Data System (ADS)

Hooda, M. K.; Yadav, C. S.

2018-01-01

We have investigated the electrical resistivity (1.8-480 K), Seebeck coefficient (2.5-300 K) and thermal conductivity (2.5-300 K) of PdTe2 and 4% Cu intercalated PdTe2 compounds. The electrical resistivity for the compounds shows a Bloch-Gruneisen-type linear temperature (T) dependence for 100 \\text{K}, and Fermi liquid behavior (ρ (T) \\propto T2) for T<50 \\text{K} . Seebeck coefficient data exhibit a strong competition between Normal (N) and Umklapp (U) scattering processes at low T. The low-T, thermal conductivity (κ) of the compounds is strongly dominated by the electronic contribution, and exhibits a rare linear T-dependence below 10 K. However, high-T, κ (T) shows the usual 1/T -dependence, dominated by the U-scattering process. The electron-phonon coupling parameters, estimated from the low-T, specific-heat data and first-principle electronic structure calculations suggest that PdTe2 and Cu0.04PdTe2 are intermediately coupled superconductors.

Long-Term Effects of Radiation Exposure and Metabolic Status on Telomere Length of Peripheral Blood T Cells in Atomic Bomb Survivors.

PubMed

Yoshida, Kengo; Misumi, Munechika; Kubo, Yoshiko; Yamaoka, Mika; Kyoizumi, Seishi; Ohishi, Waka; Hayashi, Tomonori; Kusunoki, Yoichiro

2016-10-01

In a series of studies of atomic bomb survivors, radiation-dose-dependent alterations in peripheral T-cell populations have been reported. For example, reduced size in naïve T-cell pools and impaired proliferation ability of T cells were observed. Because these alterations are also generally observed with human aging, we hypothesized that radiation exposure may accelerate the aging process of the T-cell immune system. To further test this hypothesis, we conducted cross-sectional analyses of telomere length, a hallmark of cellular aging, of naïve and memory CD4 T cells and total CD8 T cells in the peripheral blood of 620 atomic bomb survivors as it relates to age and radiation dose, using fluorescence in situ hybridization with flow cytometry. Since telomere shortening has been recently demonstrated in obesity-related metabolic abnormalities and diseases, the modifying effects of metabolic status were also examined. Our results indicated nonlinear relationships between T-cell telomere length and prior radiation exposure, i.e., longer telomeres with lower dose exposure and a decreasing trend of telomere length with individuals exposed to doses higher than 0.5 Gy. There were associations between shorter T-cell telomeres and higher hemoglobin Alc levels or fatty liver development. In naïve and memory CD4 T cells, radiation dose and high-density lipoprotein (HDL) cholesterol were found to positively interact with telomere length, suggesting that the decreasing trend of telomere length from a higher radiation dose was less conspicuous in individuals with a higher HDL cholesterol. It is therefore likely that radiation exposure perturbs T-cell homeostasis involving telomere length maintenance by multiple biological mechanisms, depending on dose, and that long-term-radiation-induced effects on the maintenance of T-cell telomeres may be modified by the subsequent metabolic conditions of individuals.

Increasing JAK/STAT Signaling Function of Infant CD4+ T Cells during the First Year of Life

PubMed Central

dela Peña-Ponce, Myra Grace; Rodriguez-Nieves, Jennifer; Bernhardt, Janice; Tuck, Ryan; Choudhary, Neelima; Mengual, Michael; Mollan, Katie R.; Hudgens, Michael G.; Peter-Wohl, Sigal; De Paris, Kristina

2017-01-01

Most infant deaths occur in the first year of life. Yet, our knowledge of immune development during this period is scarce and derived from cord blood (CB) only. To more effectively combat pediatric diseases, a deeper understanding of the kinetics and the factors that regulate the maturation of immune functions in early life is needed. Increased disease susceptibility of infants is generally attributed to T helper 2-biased immune responses. The differentiation of CD4+ T cells along a specific T helper cell lineage is dependent on the pathogen type, and on costimulatory and cytokine signals provided by antigen-presenting cells. Cytokines also regulate many other aspects of the host immune response. Therefore, toward the goal of increasing our knowledge of early immune development, we defined the temporal development of the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling function of CD4+ T cells using cross-sectional blood samples from healthy infants ages 0 (birth) to 14 months. We specifically focused on cytokines important in T cell differentiation (IFN-γ, IL-12, and IL-4) or in T cell survival and expansion (IL-2 and IL-7) in infant CD4+ T cells. Independent of the cytokine tested, JAK/STAT signaling in infant compared to adult CD4+ T cells was impaired at birth, but increased during the first year, with the most pronounced changes occurring in the first 6 months. The relative change in JAK/STAT signaling of infant CD4+ T cells with age was distinct for each cytokine tested. Thus, while about 60% of CB CD4+ T cells could efficiently activate STAT6 in response to IL-4, less than 5% of CB CD4+ T cells were able to activate the JAK/STAT pathway in response to IFN-γ, IL-12 or IL-2. By 4–6 months of age, the activation of the cytokine-specific STAT molecules was comparable to adults in response to IL-4 and IFN-γ, while IL-2- and IL-12-induced STAT activation remained below adult levels even at 1 year. These results suggest that common developmental and cytokine-specific factors regulate the maturation of the JAK/STAT signaling function in CD4+ T cells during the first year of life. PMID:28271056

Impact of Muscarinic M3 Receptor Antagonism on the Risk of Type 2 Diabetes in Antidepressant-Treated Patients: A Case-Controlled Study.

PubMed

Tran, Yen-Hao; Schuiling-Veninga, Catharina C M; Bergman, Jorieke E H; Groen, Henk; Wilffert, Bob

2017-06-01

M 3 muscarinic receptor antagonism has been associated with glucose intolerance and disturbance of insulin secretion. Our objective was to examine the risk of type 2 diabetes mellitus (T2DM) in patients using antidepressants with and without M 3 muscarinic receptor antagonism (AD_antaM 3 and AD_nonantaM 3 , respectively). We designed a case-control study using a pharmacy prescription database. We selected a cohort of patients who initiated antidepressant use between the ages of 20 and 40 years and who did not receive any anti-diabetic prescriptions at baseline. Cases were defined as those who developed T2DM [i.e., receiving oral anti-diabetic medication, Anatomical Therapeutic Chemical (ATC) code A10B] during the follow-up period (1994-2014), and ten random controls were picked for each case from the cohort of patients who did not develop T2DM. A total of 530 cases with incident T2DM and 5300 controls were included. Compared with no use of antidepressants during the previous 2 years, recent (within the last 6 months) exposure to AD_antaM 3 was associated with a moderately increased risk of T2DM: adjusted odds ratio 1.55 (95% confidence interval 1.18-2.02). In the stratified analyses, this association was dose dependent (>365 defined daily doses) and significant for patients who were in the younger age group (<45 years at the end of follow-up), were female and had no co-morbidity. On the other hand, recent exposure to AD_nonantaM 3 was not associated with a risk for T2DM in any of our analyses. Our results suggest that exposure to AD_antaM 3 was associated with the development of T2DM among antidepressant users.

"Because if you don't put the top on, it will spill": A longitudinal study of sibling teaching in early childhood.

PubMed

Howe, Nina; Della Porta, Sandra; Recchia, Holly; Ross, Hildy

2016-11-01

Naturalistic dyadic sequences of teaching and learning involving older and younger siblings were investigated in 39 middle-class dyads over a 2-year period in early childhood. Siblings were observed during ongoing interactions in the home setting for 6 90-min sessions at both Time 1 (older sibling M age = 4.4 years; younger sibling M age = 2.4 years) and Time 2 (older sibling M age = 6.3 years; younger sibling M age = 4.4 years). Sequences of sibling-directed teaching (T1 n = 353; T2 n = 1,039) were identified from the observation transcripts and coded for teacher/learner roles, initiation of teaching, teaching strategies, and learner response. Older siblings were more likely to engage in teaching at both time points, but the proportion of younger sibling teaching increased significantly from T1 to T2, partially because older siblings requested teaching more often from their younger siblings at T2. Siblings' use of teaching strategies varied across time points, while both older and younger sibling learners generally accepted or complied with the teaching. A final set of analyses examined birth-order effects while controlling for age by comparing older sibling teachers at age 4 (T1) to younger sibling teachers at age 4 (T2). At T1 first-born older siblings (age 4) engaged in a wider range and more sophisticated teaching strategies than second-born younger siblings (age 4) at T2. Findings highlight the bidirectional nature of teacher-learner interactions and are discussed in light of recent theory and research indicating that the sibling relationship is a rich context for children's learning and development. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Optimal BMI Cut-off Points for Prediction of Incident Diabetes in Chinese population.

PubMed

Ma, Hao; Wu, Xiaoyan; Guo, Xiaoyu; Yang, Jianjun; Ma, Xiaohui; Lv, Mengfan; Li, Ying

2018-05-26

The current BMI classifications have been established based on risk of obesity-related conditions, but not specifically on type 2 diabetes mellitus (T2DM). This study aimed to identify the optimal BMI cutoffs for assessing incident T2DM risk in Chinese population. The longitudinal study cohort consisted of 8,735 non-diabetic participants aged 20-74 years at baseline, with a mean follow-up period of 6.0 years. Body mass index (BMI), 2-h glucose of 75-g oral glucose tolerance test, and glycosylated hemoglobin were measured at baseline and follow-up survey. During the follow-up period, 825 participants were diagnosed with T2DM. In multivariable Cox regression analyses, adjusting for covariates, a strong positive association between BMI and incident T2DM was found among whole population, when stratified by age groups (20-39 years, 40-59 years, 60-74 years), the risk associations between BMI and incident T2DM decreased with increasing age-specific groups, and extinguished in the 60-74 age group (P-value of interaction<0.001). The optimal BMI cut-offs (kg/m 2 ) for predicting T2DM risk for men and women were 25.5 and 24.4 in the 20-39 age group, and 23.5 and 23.0 in the 40-59 age group, respectively. But no predictive performance was observed in the 60-74 age group in both sexes. Our results suggested that the performance of BMI in predicting T2DM risk was the best in younger age and decreased with age. Age- and sex-specific BMI cut-offs should be considered for T2DM risk stratification in Chinese population. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Blood biomarkers in male and female participants after an Ironman-distance triathlon.

PubMed

Danielsson, Tom; Carlsson, Jörg; Schreyer, Hendrik; Ahnesjö, Jonas; Ten Siethoff, Lasse; Ragnarsson, Thony; Tugetam, Åsa; Bergman, Patrick

2017-01-01

While overall physical activity is clearly associated with a better short-term and long-term health, prolonged strenuous physical activity may result in a rise in acute levels of blood-biomarkers used in clinical practice for diagnosis of various conditions or diseases. In this study, we explored the acute effects of a full Ironman-distance triathlon on biomarkers related to heart-, liver-, kidney- and skeletal muscle damage immediately post-race and after one week's rest. We also examined if sex, age, finishing time and body composition influenced the post-race values of the biomarkers. A sample of 30 subjects was recruited (50% women) to the study. The subjects were evaluated for body composition and blood samples were taken at three occasions, before the race (T1), immediately after (T2) and one week after the race (T3). Linear regression models were fitted to analyse the independent contribution of sex and finishing time controlled for weight, body fat percentage and age, on the biomarkers at the termination of the race (T2). Linear mixed models were fitted to examine if the biomarkers differed between the sexes over time (T1-T3). Being male was a significant predictor of higher post-race (T2) levels of myoglobin, CK, and creatinine levels and body weight was negatively associated with myoglobin. In general, the models were unable to explain the variation of the dependent variables. In the linear mixed models, an interaction between time (T1-T3) and sex was seen for myoglobin and creatinine, in which women had a less pronounced response to the race. Overall women appear to tolerate the effects of prolonged strenuous physical activity better than men as illustrated by their lower values of the biomarkers both post-race as well as during recovery.

Dopamine transporter dysfunction in Han Chinese people with chronic methamphetamine dependence after a short-term abstinence.

PubMed

Yuan, Jie; Lv, Rongbin; Robert Brašić, James; Han, Mei; Liu, Xingdang; Wang, Yuankai; Zhang, Guangming; Liu, Congjin; Li, Yu; Deng, Yanping

2014-01-30

Single-photon emission-computed tomography (SPECT) after the administration of (99m)Tc-TRODAT-1 was performed on healthy subjects and subjects with methamphetamine (METH)dependence at time 1 (T1) after 24-48 h of abstinence, time 2 (T2) after 2 weeks of abstinence, and time 3 (T3) after 4 weeks of abstinence. In contrast to values in controls, the values of the striatal DAT specific uptake ratios (SURs) in subjects with METH dependence were significantly lower at T1 (n=25), T2 (n=9), and T3 (n=8); a mild increase in SURs was observed at T2 and T3, but values were still significantly lower than those in controls. In subjects with METH dependence, there was a trend for a negative correlation of striatal DAT SURs and craving for METH at T1. METH craving, anxiety and depression scores significantly decreased from T1 to T2 to T3. We conclude that Han Chinese people with METH dependence experience significant striatal DAT dysfunction, and that these changes may be mildly reversible after 4 weeks of abstinence, but that DAT levels still remain significantly lower than those in healthy subjects. The mild recovery of striatal DAT may parallel improvements in craving, anxiety and depression. © 2013 Published by Elsevier Ireland Ltd.

PROX1 gene CC genotype as a major determinant of early onset of type 2 diabetes in slavic study participants from Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation study

PubMed Central

Hamet, Pavel; Haloui, Mounsif; Harvey, François; Marois-Blanchet, François-Christophe; Sylvestre, Marie-Pierre; Tahir, Muhammad-Ramzan; Simon, Paul H.G.; Kanzki, Beatriz Sonja; Raelson, John; Long, Carole; Chalmers, John; Woodward, Mark; Marre, Michel; Harrap, Stephen; Tremblay, Johanne

2017-01-01

Background: The prevalence of diabetic nephropathy varies according to ethnicity. Environmental as well as genetic factors contribute to the heterogeneity in the presentation of diabetic nephropathy. Our objective was to evaluate this heterogeneity within the Caucasian population. Methods: The geo-ethnic origin of the 3409 genotyped Caucasian type 2 diabetes (T2D) patients of Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation was determined using principal component analysis. Genome-wide association studies analyses of age of onset of T2D were performed for geo-ethnic groups separately and combined. Results: The first principal component separated the Caucasian study participants into Slavic and Celtic ethnic origins. Age of onset of diabetes was significantly lower in Slavic patients (P = 7.3 × 10−20), whereas the prevalence of hypertension (P = 4.9 × 10−31) and albuminuria (5.1 × 10−9) were significantly higher. Age of onset of T2D and albuminuria appear to have an important genetic component as the values of these traits were also different between Slavic and Celtic individuals living in the same countries. Common and geo-ethnic-specific loci were found to be associated to age of onset of diabetes. Among the latter, the PROX1/PROX1-AS1 genes (rs340841) had the highest impact. Single-nucleotide polymorphism rs340841 CC genotype was associated with a 4.4 year earlier onset of T2D in Slavic patients living or not in countries with predominant Slavic populations. Conclusion: These results reveal the presence of distinct genetic architectures between Caucasian ethnic groups that likely have clinical relevance, among them PROX1 gene is a strong candidate of early onset of diabetes with variations depending on ethnicity. PMID:28060188

PROX1 gene CC genotype as a major determinant of early onset of type 2 diabetes in slavic study participants from Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation study.

PubMed

Hamet, Pavel; Haloui, Mounsif; Harvey, François; Marois-Blanchet, François-Christophe; Sylvestre, Marie-Pierre; Tahir, Muhammad-Ramzan; Simon, Paul H G; Kanzki, Beatriz Sonja; Raelson, John; Long, Carole; Chalmers, John; Woodward, Mark; Marre, Michel; Harrap, Stephen; Tremblay, Johanne

2017-05-01

The prevalence of diabetic nephropathy varies according to ethnicity. Environmental as well as genetic factors contribute to the heterogeneity in the presentation of diabetic nephropathy. Our objective was to evaluate this heterogeneity within the Caucasian population. The geo-ethnic origin of the 3409 genotyped Caucasian type 2 diabetes (T2D) patients of Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation was determined using principal component analysis. Genome-wide association studies analyses of age of onset of T2D were performed for geo-ethnic groups separately and combined. The first principal component separated the Caucasian study participants into Slavic and Celtic ethnic origins. Age of onset of diabetes was significantly lower in Slavic patients (P = 7.3 × 10), whereas the prevalence of hypertension (P = 4.9 × 10) and albuminuria (5.1 × 10) were significantly higher. Age of onset of T2D and albuminuria appear to have an important genetic component as the values of these traits were also different between Slavic and Celtic individuals living in the same countries. Common and geo-ethnic-specific loci were found to be associated to age of onset of diabetes. Among the latter, the PROX1/PROX1-AS1 genes (rs340841) had the highest impact. Single-nucleotide polymorphism rs340841 CC genotype was associated with a 4.4 year earlier onset of T2D in Slavic patients living or not in countries with predominant Slavic populations. These results reveal the presence of distinct genetic architectures between Caucasian ethnic groups that likely have clinical relevance, among them PROX1 gene is a strong candidate of early onset of diabetes with variations depending on ethnicity.

Expansions of NK-like αβT cells with chronologic aging: Novel lymphocyte effectors that compensate for functional deficits of conventional NK cells and T cells

PubMed Central

Vallejo, Abbe N.; Mueller, Robert G.; Hamel, David L.; Way, Amanda; Dvergsten, Jeffrey A.; Griffin, Patricia; Newman, Anne B.

2010-01-01

As the repertoire of αβT cell receptors (TCR) contracts with advancing age, there is an associated age-dependent accumulation of oligoclonal T cells expressing of a variety of receptors (NKR), normally expressed on natural killer (NK) cells. Evidences for differential regulation of expression of particular NKRs between T cells and NK cells suggest that NKR expression on T cells is physiologically programmed rather than a random event of the aging process. Experimental studies show NKRs on aged αβT cells may function either as independent receptors, and/or as costimulatory receptors to the TCR. Considering the reported deficits of conventional αβTCR-driven activation and also functional deficits of classical NK cells, NKR+ αβT cells likely represent novel immune effectors that are capable of combining innate and adaptive functions. Inasmuch as immunity is a determinant of individual fitness, the type and density of NKRs could be important contributing factors to the wide heterogeneity of health characteristics of older adults, ranging from institutionalized frail elders who are unable to mount immune responses to functionally independent community-dwelling elders who exhibit protective immunity. Understanding the biology of NKR+ αβT cells could lead to new avenues for age-specific intervention to improve protective immunity. PMID:20932941

Friday on My Mind: The Relation of Partying with Antisocial Behavior of Early Adolescents. The TRAILS Study

ERIC Educational Resources Information Center

Veenstra, Rene; Huitsing, Gijs; Dijkstra, Jan Kornelis; Lindenberg, Siegwart

2010-01-01

The relation between partying and antisocial behavior was investigated using a sample of Dutch early adolescents (T2: N = 1,076; M age = 13.52). Antisocial behavior was divided into rule-breaking and aggressive behavior. Using a goal-framing approach, it was argued that the relation of partying to antisocial behavior depends on the way the need to…

Educational Inequalities in the Transition to Adulthood in Belgium: The Impact of Intergenerational Mobility on Young-Adult Mortality in 2001-2009

PubMed Central

2015-01-01

Several studies have focused on the association between parental and personal socioeconomic position (SEP) and health, with mixed results depending on the specific health outcome, research methodology and population under study. In the last decades, a growing interest is given to the influence of intergenerational mobility on several health outcomes at young ages. This study addresses the following research question: Is educational intergenerational mobility associated with all-cause and cause-specific mortality in young adulthood? To this end, the Belgian 1991 and 2001 censuses are used, providing characteristics of young persons at two time points (T1 = 01/03/91;T2 = 01/10/01) and follow-up information on mortality and emigration between T2 and 31/12/09 (T3). The study population consists of all official inhabitants of Flanders and the Brussels-Capital Region at T2, born between 1972 and 1982 and alive at T2. Parental and personal education are divided into primary (PE), lower secondary (LSE), higher secondary (HSE) and higher education (HE). We analyse mortality between T2 and T3 calculating age-standardised mortality rates (ASMRs) and using Cox regression (hazard ratios = HR). Personal rather than parental education determines the observed mortality rates, with high all-cause mortality rates among those with PE, irrespective of parental education (e.g., among men ASMRPE-PE = 200.0 [95% CI 158.0–241.9]; ASMRHE-PE = 319.7 [183.2–456.3]) and low all-cause mortality among those in higher education, regardless of parental education (ASMRPE-HE = 41.7 [30.8–52.6]; ASMRHE-HE = 38.0 [33.2–42.8]). There is some variation by gender and according to cause of death. This study shows the strong association between personal education and young-adult mortality. PMID:26657691

Ethanol Extract of Cirsium japonicum var. ussuriense Kitamura Exhibits the Activation of Nuclear Factor Erythroid 2-Related Factor 2-dependent Antioxidant Response Element and Protects Human Keratinocyte HaCaT Cells Against Oxidative DNA Damage.

PubMed

Yoo, Ok-Kyung; Choi, Bu Young; Park, Jin-Oh; Lee, Ji-Won; Park, Byoung-Kwon; Joo, Chul Gue; Heo, Hyo-Jung; Keum, Young-Sam

2016-03-01

Keratinocytes are constantly exposed to extracellular insults, such as ultraviolet B, toxic chemicals and mechanical stress, all of which can facilitate the aging of keratinocytes via the generation of intracellular reactive oxygen species (ROS). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that plays a critical role in protecting keratinocytes against oxidants and xenobiotics by binding to the antioxidant response element (ARE), a cis-acting element existing in the promoter of most phase II cytoprotective genes. In the present study, we have attempted to find novel ethanol extract(s) of indigenous plants of Jeju island, Korea that can activate the Nrf2/ARE-dependent gene expression in human keratinocyte HaCaT cells. As a result, we identified that ethanol extract of Cirsium japonicum var. ussuriense Kitamura (ECJUK) elicited strong stimulatory effect on the ARE-dependent gene expression. Supporting this observation, we found that ECJUK induced the expression of Nrf2, hemoxygenase-1, and quinone oxidoreductase-1 and this event was correlated with Akt1 phosphorylation. We also found that ECJUK increased the intracellular reduced glutathione level and suppressed 12-O-tetradecanoylphorbol acetate-induced 8-hydroxyguanosine formation without affecting the overall viability. Collectively, our results provide evidence that ECJUK can protect against oxidative stress-mediated damages through the activation of Nrf2/ARE-dependent phase II cytoprotective gene expression.

The influence of fruit and vegetable intake on the nutritional status and plasma homocysteine levels of institutionalised elderly people.

PubMed

Bermejo, L M; Aparicio, A; Andrés, P; López-Sobaler, A M; Ortega, R M

2007-03-01

To determine the difference in the nutritional status of elderly people depending on their consumption of fruits and vegetables, and to study the possible association between the consumption of these foods and different cardiovascular risk factors, especially total plasma homocysteine (t-Hcys) levels. A cross-sectional study in 152 institutionalised older people from Madrid aged > or = 65 years. Food and nutrient intakes were recorded over 7 days using the 'precise individual weighing' method. The weight, height, and waist and hip circumferences of all subjects were recorded, as were their alpha-erythrocyte glutathione reductase, serum B6, B12 and folate levels, erythrocyte folate levels, t-Hcys levels, serum lipids and blood pressure. The experimental population was then divided into tertiles depending on the serving intake of fruit and vegetables (T1, < 2.29 servings day(-1); T2, 2.29-2.79 servings day(-1); and T3, >2.79 servings day(-1)). Compared with T1 subjects, T3 subjects showed consumptions of cereals, pulses, meat, fish and eggs closer to those recommended (P < 0.05). In addition, the contribution of their diet towards covering the recommended daily intake of vitamin B1, niacin, vitamin B6, folic acid, vitamin C, B12, vitamin A, and P, Mg, Zn and Fe was higher. The intake of fibre increased with consumption of fruit and vegetables (r = 0.6839, P < 0.001). T3 subjects also had better serum and erythrocyte folate levels than T1 and T2 subjects (P < 0.05). A positive correlation was found between the consumption of fruit and vegetables and serum folate (r = 0.2665, P < 0.01) and with erythrocyte folate levels (r = 0.2034, P < 0.05), and a negative correlation with t-Hcys (r = -0.2493, P < 0.01). Greater consumption of fruit and vegetables is associated with better food habits, increased vitamin and mineral intakes and lower t-Hcys levels. Considering that the fruit and vegetable intake in Spanish elderly people is very low, it is recommended that the consumption of fruits and vegetables by elderly people be increased.

MRI assessment of whole-brain structural changes in aging.

PubMed

Guo, Hui; Siu, William; D'Arcy, Ryan Cn; Black, Sandra E; Grajauskas, Lukas A; Singh, Sonia; Zhang, Yunting; Rockwood, Kenneth; Song, Xiaowei

2017-01-01

One of the central features of brain aging is the accumulation of multiple age-related structural changes, which occur heterogeneously in individuals and can have immediate or potential clinical consequences. Each of these deficits can coexist and interact, producing both independent and additive impacts on brain health. Many of the changes can be visualized using MRI. To collectively assess whole-brain structural changes, the MRI-based Brain Atrophy and Lesion Index (BALI) has been developed. In this study, we validate this whole-brain health assessment approach using several clinical MRI examinations. Data came from three independent studies: the Alzheimer's Disease Neuroimaging Initiative Phase II (n=950; women =47.9%; age =72.7±7.4 years); the National Alzheimer's Coordinating Center (n=722; women =55.1%; age =72.7±9.9 years); and the Tianjin Medical University General Hospital Research database on older adults (n=170; women =60.0%; age =62.9±9.3 years). The 3.0-Tesla MRI scans were evaluated using the BALI rating scheme on the basis of T1-weighted (T1WI), T2-weighted (T2WI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), and T2*-weighted gradient-recalled echo (T2*GRE) images. Atrophy and lesion changes were commonly seen in each MRI test. The BALI scores based on different sequences were highly correlated (Spearman r 2 >0.69; P <0.00001). They were associated with age ( r 2 >0.29; P <0.00001) and differed by cognitive status ( χ 2 >26.48, P <0.00001). T2-FLAIR revealed a greater level of periventricular ( χ 2 =29.09) and deep white matter ( χ 2 =26.65, P <0.001) lesions than others, but missed revealing certain dilated perivascular spaces that were seen in T2WI ( P <0.001). Microhemorrhages occurred in 15.3% of the sample examined and were detected using only T2*GRE. The T1WI- and T2WI-based BALI evaluations consistently identified the burden of aging and dementia-related decline of structural brain health. Inclusion of additional MRI tests increased lesion differentiation. Further research is to integrate MRI tests for a clinical tool to aid the diagnosis and intervention of brain aging.

[Age index and an interpretation of survivorship curves (author's transl)].

PubMed

Lohmann, W

1977-01-01

Clinical investigations showed that the age dependences of physiological functions do not show -- as generally assumed -- a linear increase with age, but an exponential one. Considering this result one can easily interpret the survivorship curve of a population (Gompertz plot). The only thing that is required is that the probability of death (death rate) is proportional to a function of ageing given by mu(t) = mu0 exp (alpha t). Considering survivorship curves resulting from annual death statistics and fitting them by suitable parameters, then the resulting alpha-values are in agreement with clinical data.

Effects of Aging on the Evolution of Microstructure and Mechanical Properties of an Al - Li - Cu - Mg Alloy with Ag, Zr, Mn, and Zn Additives

NASA Astrophysics Data System (ADS)

Sun, Zhong-gang; Bao, Peng-li; Ma, Chao; Chen, Jie; Guo, Xuan; Li, Hua-guan; Ling, Juan

2016-03-01

The microstructure and the post-aging hardness of an Al - Li - Cu - Mg alloy is studied by the methods of transmission electron microscopy. Tensile tests are performed. The volume fraction and the size of the particles of the δ', S and T 1 phases are shown to be dependent on the aging temperature and time. The effect of the precipitates of the δ', S and T 1 phases on the hardening of the Al - Li - Cu - Mg alloy during aging is determined.

Removing obstacles for pavement cost reduction by examining early age opening requirements : material properties.

DOT National Transportation Integrated Search

2015-08-01

The risk of cracking in a concrete pavement that is opened to traffic at early ages is related to the maximum tensile stress, , that : develops in the pavement and its relationship to the measured, age dependent, flexural strength of a beam, fr . T...

Effect of clot aging and cholesterol content on ultrasound-assisted thrombolysis.

PubMed

Zhou, Yufeng; Murugappan, Suresh Kanna; Sharma, Vijay Kumar

2014-10-01

Exposure to 2-MHz transcranial diagnostic ultrasound enhances the thrombolytic activity of intravenously administered tissue plasminogen activator (IV-tPA) in acute ischemic stroke (sonothrombolysis). However, rates of arterial recanalization vary widely, depending upon the clot burden, its location, and stroke subtype. We evaluated the influence of age and cholesterol level of the blood clots on sonothrombolysis in an in vitro model. To "age" the clots, serum was replaced by fresh blood periodically. We increased the cholesterol content of the clots by adding cholesterin to the blood. The clots were lysed by tPA and/or transcranial Doppler ultrasound sonication for 1 h. The extent of thrombolysis induced by various treatment protocols (controls, sonication, tPA, and sonothrombolysis) was evaluated with relative changes in the clot weights and in the clot structure by scanning electron microscopy (SEM) at end of the experiment. Sonothrombolysis induced significantly higher weight reduction in fresh clots (37.3 % in 2-h old clots versus 24.8 % in 10-h ones, p < 0.005) as well as the clots with higher cholesterol levels (41.7 versus 30.6 % in normal cholesterol clots, p < 0.005). SEM demonstrated patterns of clot dissolution among various treatment modalities. Sonothrombolysis induced better clot lysis in fresh thrombi with high cholesterol levels.

The Selenocysteine tRNA STAF-Binding Region is Essential for Adequate Selenocysteine tRNA Status, Selenoprotein Expression and Early Age Survival of Mice

USDA-ARS?s Scientific Manuscript database

STAF is a transcription activating factor for a number of RNA Pol III-and RNA Pol II-dependent genes including the selenocysteine (Sec) tRNA gene. Here, the role of STAF in regulating expression of Sec tRNA and selenoproteins was examined in an invivo model. Heterozygous inactivation of the Staf gen...

Metal chaperones prevent zinc-mediated cognitive decline.

PubMed

Adlard, Paul A; Parncutt, Jacqui; Lal, Varsha; James, Simon; Hare, Dominic; Doble, Philip; Finkelstein, David I; Bush, Ashley I

2015-09-01

Zinc transporter-3 (ZnT3) protein is responsible for loading zinc into presynaptic vesicles and consequently controls the availability of zinc at the glutamatergic synapse. ZnT3 has been shown to decline with age and in Alzheimer's disease (AD) and is crucially involved in learning and memory. In this study, we utilised whole animal behavioural analyses in the ZnT3 KO mouse line, together with electrophysiological analysis of long-term potentiation in brain slices from ZnT3 KO mice, to show that metal chaperones (clioquinol, 30 mg/kg/day for 6weeks) can prevent the age-dependent cognitive phenotype that characterises these animals. This likely occurs as a result of a homeostatic restoration of synaptic protein expression, as clioquinol significantly restored levels of various pre- and postsynaptic proteins that are critical for normal cognition, including PSD-95; AMPAR and NMDAR2b. We hypothesised that this clioquinol-mediated restoration of synaptic health resulted from a selective increase in synaptic zinc content within the hippocampus. While we demonstrated a small regional increase in hippocampal zinc content using synchrotron x-ray fluorescence microscopy, further sub-region analyses are required to determine whether this effect is seen in other regions of the hippocampal formation that are more closely linked to the synaptic plasticity effects observed in this study. These data support our recent report on the use of a different metal chaperone (PBT2) to prevent normal age-related cognitive decline and demonstrate that metal chaperones are efficacious in preventing the zinc-mediated cognitive decline that characterises ageing and disease. Copyright © 2014 Elsevier Inc. All rights reserved.

[Loss of total 5-methylcytosine from the genome during cell culture aging coincides with the Hayflick limit].

PubMed

Mazin, A L

1993-01-01

Analyzing the data about the age-related 5-methylcytosine (5mC) loss from DNA of cell cultures, the following conclusions have been made: 1. The rate of 5mC loss from DNA does not depend on the cell donor age; it remains constant during the logarithmic phase of cell growth, and may vary significantly in different cell lines. 2. The rate is inversely proportional to their Hayflick limit and to the species lifespan of cell donors. 3. In immortal cell lines the 5mC content in DNA is stable or increases with aging. 4. Hayflick limit estimations coincide with or are lower than the number of cell population doublings that corresponds to all 5mC loss from cell genome. A simple and fast method has been proposed for Hayflick limit prognostication by analysis of the rate of DNA hypomethylation. It may be used for early diagnosis of precrisis and immortal cell lines. Evidence has been obtained that age-dependent 5mC loss from DNA is the result of accumulating 5mC-->T+C substitutions that occur during DNA methylation in every cell division. The loss of all genomic 5mC residues during the lifespan may correspond to accumulation of about 3 x 10(6) 5mC-->T transitions or, on average, one mutation per gene. This may be one of the main reasons of the "catastrophe of errors" and cessation of cell proliferation. It is calculated that the rate of 5mC-->T transitions in normal cells may be 2.3 x 10(-5) per site in each cell doubling in human, 6 x 10(-5) in hamster, and 4.6 x 10(-4) in mouse. DNA methylation as a generator of mutations may be a "counter" of cell divisions and thus be one of the molecular mechanisms of the Hayflick phenomenon. The conclusion is made that the DNA methylation system may be considered as a genetically programmed mechanism for accumulating mutations during cell aging.

Allergic Diseases and Internalizing Behaviors in Early Childhood

PubMed Central

LeMasters, Grace K.; Levin, Linda; Rothenberg, Marc E.; Assa'ad, Amal H.; Newman, Nicholas; Bernstein, David; Khurana-Hershey, Gurjit; Lockey, James E.; Ryan, Patrick H.

2016-01-01

BACKGROUND AND OBJECTIVES: The relationship between allergic diseases and internalizing disorders has not been well characterized with regard to multiple allergic diseases or longitudinal study. The objective of this study was to examine the association between multiple allergic diseases in early childhood with validated measures of internalizing disorders in the school-age years. METHODS: Children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study underwent skin testing and examinations at ages 1, 2, 3, 4, and 7 years. At age 7, parents completed the Behavior Assessment System for Children, Second Edition (BASC-2), a validated measure of childhood behavior and emotion. The association between allergic diseases at age 4, including allergic rhinitis, allergic persistent wheezing, atopic dermatitis, and allergic sensitization, and BASC-2 internalizing, anxiety, and depression T scores at age 7 was examined by logistic and linear regression, adjusting for covariates. RESULTS: The cohort included 546 children with complete information on allergic disease and BASC-2 outcomes. Allergic rhinitis at age 4 was significantly associated with elevated internalizing (adjusted odds ratio [aOR]: 3.2; 95% confidence interval [CI]: 1.8–5.8), anxiety (aOR: 2.0; 95% CI: 1.2–3.6), and depressive scores (aOR: 3.2; 95% CI: 1.7–6.5) at age 7. Allergic persistent wheezing was significantly associated with elevated internalizing scores (aOR: 2.7; 95% CI: 1.2–6.3). The presence of >1 allergic disease (aOR: 3.6; 95% CI: 1.7–7.6) and allergic rhinitis with comorbid allergic disease(s) (aOR: 4.3; 95% CI: 2.0–9.2) at age 4 had dose-dependent associations with internalizing scores. CONCLUSIONS: Children with allergic rhinitis and allergic persistent wheezing at age 4 are at increased risk of internalizing behaviors at age 7. Furthermore, multiple allergic diseases had a dose-dependent association with elevated internalizing scores. PMID:26715608

Allergic Diseases and Internalizing Behaviors in Early Childhood.

PubMed

Nanda, Maya K; LeMasters, Grace K; Levin, Linda; Rothenberg, Marc E; Assa'ad, Amal H; Newman, Nicholas; Bernstein, David; Khurana-Hershey, Gurjit; Lockey, James E; Ryan, Patrick H

2016-01-01

The relationship between allergic diseases and internalizing disorders has not been well characterized with regard to multiple allergic diseases or longitudinal study. The objective of this study was to examine the association between multiple allergic diseases in early childhood with validated measures of internalizing disorders in the school-age years. Children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study underwent skin testing and examinations at ages 1, 2, 3, 4, and 7 years. At age 7, parents completed the Behavior Assessment System for Children, Second Edition (BASC-2), a validated measure of childhood behavior and emotion. The association between allergic diseases at age 4, including allergic rhinitis, allergic persistent wheezing, atopic dermatitis, and allergic sensitization, and BASC-2 internalizing, anxiety, and depression T scores at age 7 was examined by logistic and linear regression, adjusting for covariates. The cohort included 546 children with complete information on allergic disease and BASC-2 outcomes. Allergic rhinitis at age 4 was significantly associated with elevated internalizing (adjusted odds ratio [aOR]: 3.2; 95% confidence interval [CI]: 1.8-5.8), anxiety (aOR: 2.0; 95% CI: 1.2-3.6), and depressive scores (aOR: 3.2; 95% CI: 1.7-6.5) at age 7. Allergic persistent wheezing was significantly associated with elevated internalizing scores (aOR: 2.7; 95% CI: 1.2-6.3). The presence of >1 allergic disease (aOR: 3.6; 95% CI: 1.7-7.6) and allergic rhinitis with comorbid allergic disease(s) (aOR: 4.3; 95% CI: 2.0-9.2) at age 4 had dose-dependent associations with internalizing scores. Children with allergic rhinitis and allergic persistent wheezing at age 4 are at increased risk of internalizing behaviors at age 7. Furthermore, multiple allergic diseases had a dose-dependent association with elevated internalizing scores. Copyright © 2016 by the American Academy of Pediatrics.

Physical aging effects on the compressive linear viscoelastic creep of IM7/K3B composite

NASA Technical Reports Server (NTRS)

Veazie, David R.; Gates, Thomas S.

1995-01-01

An experimental study was undertaken to establish the viscoelastic behavior of 1M7/K3B composite in compression at elevated temperature. Creep compliance, strain recovery and the effects of physical aging on the time dependent response was measured for uniaxial loading at several isothermal conditions below the glass transition temperature (T(g)). The IM7/K3B composite is a graphite reinforced thermoplastic polyimide with a T(g) of approximately 240 C. In a composite, the two matrix dominated compliance terms associated with time dependent behavior occur in the transverse and shear directions. Linear viscoelasticity was used to characterize the creep/recovery behavior and superposition techniques were used to establish the physical aging related material constants. Creep strain was converted to compliance and measured as a function of test time and aging time. Results included creep compliance master curves, physical aging shift factors and shift rates. The description of the unique experimental techniques required for compressive testing is also given.

Surface Gravities for 228 M, L, and T Dwarfs in the NIRSPEC Brown Dwarf Spectroscopic Survey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, Emily C.; Mace, Gregory N.; McLean, Ian S.

2017-03-20

We combine 131 new medium-resolution ( R ∼ 2000) J -band spectra of M, L, and T dwarfs from the Keck NIRSPEC Brown Dwarf Spectroscopic Survey (BDSS) with 97 previously published BDSS spectra to study surface-gravity-sensitive indices for 228 low-mass stars and brown dwarfs spanning spectral types M5–T9. Specifically, we use an established set of spectral indices to determine surface gravity classifications for all of the M6–L7 objects in our sample by measuring the equivalent widths (EW) of the K i lines at 1.1692, 1.1778, and 1.2529 μ m, and the 1.2 μ m FeH{sub J} absorption index. Our resultsmore » are consistent with previous surface gravity measurements, showing a distinct double peak—at ∼L5 and T5—in K i EW as a function of spectral type. We analyze the K i EWs of 73 objects of known ages and find a linear trend between log(Age) and EW. From this relationship, we assign age ranges to the very low gravity, intermediate gravity, and field gravity designations for spectral types M6–L0. Interestingly, the ages probed by these designations remain broad, change with spectral type, and depend on the gravity-sensitive index used. Gravity designations are useful indicators of the possibility of youth, but current data sets cannot be used to provide a precise age estimate.« less

Prenatal cadmium exposure alters postnatal immune cell development and function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanson, Miranda L.; Holásková, Ida; Elliott, Meenal

2012-06-01

Cadmium (Cd) is generally found in low concentrations in the environment due to its widespread and continual use, however, its concentration in some foods and cigarette smoke is high. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports of immunomodulatory effects of prenatal exposure to Cd. This study was designed to investigate the effects of prenatal exposure to Cd on the immune system of the offspring. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl{sub 2} (10 ppm) and the effects on the immune system of the offspringmore » were assessed at two time points following birth (2 and 7 weeks of age). Thymocyte and splenocyte phenotypes were analyzed by flow cytometry. Prenatal Cd exposure did not affect thymocyte populations at 2 and 7 weeks of age. In the spleen, the only significant effect on phenotype was a decrease in the number of macrophages in male offspring at both time points. Analysis of cytokine production by stimulated splenocytes demonstrated that prenatal Cd exposure decreased IL-2 and IL-4 production by cells from female offspring at 2 weeks of age. At 7 weeks of age, splenocyte IL-2 production was decreased in Cd-exposed males while IFN-γ production was decreased from both male and female Cd-exposed offspring. The ability of the Cd-exposed offspring to respond to immunization with a S. pneumoniae vaccine expressing T-dependent and T-independent streptococcal antigens showed marked increases in the levels of both T-dependent and T-independent serum antibody levels compared to control animals. CD4{sup +}FoxP3{sup +}CD25{sup +} (nTreg) cell percentages were increased in the spleen and thymus in all Cd-exposed offspring except in the female spleen where a decrease was seen. CD8{sup +}CD223{sup +} T cells were markedly decreased in the spleens in all offspring at 7 weeks of age. These findings suggest that even very low levels of Cd exposure during gestation can result in long term detrimental effects on the immune system of the offspring and these effects are to some extent sex-specific. -- Highlights: ► Prenatal exposure to Cd causes no thymocyte phenotype changes in the offspring ► Analysis of the splenocyte phenotype demonstrates a macrophage-specific effect only in male offspring ► The cytokine profiles suggest an effect on peripheral Th1 cells in female and to a lesser degree in male offspring ► There was a marked increase in serum anti-streptococcal antibody levels after immunization in both sexes ► There was a marked decrease in the numbers of splenic CD8{sup +}CD223{sup +} cells in both sexes.« less

Understanding phengite argon closure using single grain fusion age distributions in the Cycladic Blueschist Unit on Syros, Greece

NASA Astrophysics Data System (ADS)

Uunk, Bertram; Brouwer, Fraukje; ter Voorde, Marlies; Wijbrans, Jan

2018-02-01

The preservation of 40Ar/39Ar ages of high pressure (HP) metamorphic white mica reflects an interplay of processes that mobilise 40Ar, either through mica recrystallisation or by diffusive 40Ar loss. The applicability of resulting ages for dating tectonic processes is critically dependent on whether either of these processes can be proven to be efficient and exclusively active in removing 40Ar from mica. If not, preservation of an inherited or mixed age signal in a sample must be considered for interpretation. The Cycladic Blueschist Unit on Syros has become a new focal area in the discussion of the geological significance of argon age results from multi-grain step heating experiments. While some argue that age results can directly be linked to deformation or metamorphic growth events, others interpret age results to reflect the interplay of protracted recrystallisation and partial resetting, preserving a mixed age signal. Here, we demonstrate the potential of a new approach of multiple single grain fusion dating. Using the distribution of ages at the sample, section and regional scale, we show that in Northern Syros mica ages display systematic trends that can be understood as the result of three competing processes: 1) crystallisation along the prograde to peak metamorphic path, 2) a southward trend of increasing 40Ar loss by diffusion and 3) localised and rock type dependent deformation or metamorphic reactions leading to an observed age spread typically limited to ∼10 Myr at the section scale. None of the sections yielded the anomalously old age results that would be diagnostic for significant excess 40Ar. The recorded trends in ages for each of the studied sections reflect a range of P-T conditions and duration of metamorphism. Diffusion modelling shows that in a typical subduction metamorphic loop, subtle variations in P-T-t history can explain that age contrasts occur on a regional scale but are limited on the outcrop scale. Our new approach provides a comprehensive inventory of the range of ages present in different rocks and at different scales, which results in a more refined understanding of argon retention and isotopic closure of phengite and the geological significance of the ages. We verify the added value of our new approach by comparison with multi-grain step heating experiments on selected samples from the same sections.

Defective TFH Cell Function and Increased TFR Cells Contribute to Defective Antibody Production in Aging.

PubMed

Sage, Peter T; Tan, Catherine L; Freeman, Gordon J; Haigis, Marcia; Sharpe, Arlene H

2015-07-14

Defective antibody production in aging is broadly attributed to immunosenescence. However, the precise immunological mechanisms remain unclear. Here, we demonstrate an increase in the ratio of inhibitory T follicular regulatory (TFR) cells to stimulatory T follicular helper (TFH) cells in aged mice. Aged TFH and TFR cells are phenotypically distinct from those in young mice, exhibiting increased programmed cell death protein-1 expression but decreased ICOS expression. Aged TFH cells exhibit defective antigen-specific responses, and programmed cell death protein-ligand 1 blockade can partially rescue TFH cell function. In contrast, young and aged TFR cells have similar suppressive capacity on a per-cell basis in vitro and in vivo. Together, these studies reveal mechanisms contributing to defective humoral immunity in aging: an increase in suppressive TFR cells combined with impaired function of aged TFH cells results in reduced T-cell-dependent antibody responses in aged mice. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Accelerated Post-Weld Natural Ageing in Ultrasonic Welding Aluminium 6111-T4 Automotive Sheet

NASA Astrophysics Data System (ADS)

Chen, Ying-Chun; Prangnell, Phil

In contrast to previously published reports, it is shown that there is an observable HAZ when ultrasonic spot welding (USW) automotive alloys, like AA6111-T4, the severity of which depends on the welding energy. Immediately after welding, softening is seen relative to the T4 condition, but this is rapidly recovered by natural ageing, which masks the presence of a HAZ, and the weld strength eventually exceeds that of the parent material. This behaviour is caused by dissolution of the solute clusters/GPZs in the T4 sheet, due to the high weld temperatures (> 400 °C), combined with accelerated post-weld natural ageing to a more advanced state than in the parent material. Modelling has demonstrated that this accelerated natural ageing behaviour can be attributed to an excess vacancy concentration generated by the USW process.

Increased uncoupling protein-2 mRNA abundance and glucocorticoid action in adipose tissue in the sheep fetus during late gestation is dependent on plasma cortisol and triiodothyronine

PubMed Central

Gnanalingham, MG; Mostyn, A; Forhead, AJ; Fowden, AL; Symonds, ME; Stephenson, T

2005-01-01

The endocrine regulation of uncoupling protein-2 (UCP2), an inner mitochondrial protein, in fetal adipose tissue remains unclear. The present study aimed to determine if fetal plasma cortisol and triiodothyronine (T3) influenced the mRNA abundance of UCP2, glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and 2 (11βHSD2) in fetal adipose tissue in the sheep during late gestation. Perirenal–abdominal adipose tissue was sampled from ovine fetuses to which either cortisol (2–3 mg kg−1 day−1) or saline was infused for 5 days up to 127–130 days gestation, or near term fetuses (i.e. 142–145 days gestation) that were either adrenalectomised (AX) or remained intact. Fetal plasma cortisol and T3 concentrations were higher in the cortisol infused animals and lower in AX fetuses compared with their corresponding control group, and increased with gestational age. UCP2 and GR mRNA abundance were significantly lower in AX fetuses compared with age-matched controls, and increased with gestational age and by cortisol infusion. Glucocorticoid action in fetal adipose tissue was augmented by AX and suppressed by cortisol infusion, the latter also preventing the gestational increase in 11βHSD1 mRNA and decrease in 11βHSD2 mRNA. When all treatment groups were combined, both fetal plasma cortisol and T3 concentrations were positively correlated with UCP2, GR and 11βHSD2 mRNA abundance, but negatively correlated with 11βHSD1 mRNA abundance. In conclusion, plasma cortisol and T3 are both required for the late gestation rise in UCP2 mRNA and differentially regulate glucocorticoid action in fetal adipose tissue in the sheep during late gestation. PMID:15961419

A Link between Adolescent Nicotine Metabolism and Smoking Topography

PubMed Central

Moolchan, Eric T.; Parzynski, Craig S.; Jaszyna-Gasior, Maria; Collins, Charles C.; Leff, Michelle K.; Zimmerman, Debra L.

2009-01-01

Adult slow nicotine metabolizers have lower smoke exposure, carbon monoxide levels, and plasma nicotine levels than normal and fast metabolizers. Emerging evidence suggests nicotine metabolism influences smoking topography. This study investigated the association of nicotine metabolism (the ratio of plasma 3-hydroxycotinine to cotinine; 3OHCOT/COT) with smoking topography in adolescent smokers (N=85, 65% female, 68% European American, mean age 15.3 ± 1.2, mean cigarettes per day (CPD) 18.5 ± 8.5, mean Fagerström Test for Nicotine Dependence (FTND) 7.0 ± 1.2) presenting for a nicotine replacement therapy trial. Measures obtained included puff volume, inter-puff interval, number of puffs, puff duration, and puff velocity. Linear regression analysis controlling for hormonal contraception use showed that 3OHCOT/COT ratios predicted mean puff volume in the overall sample (t = 2.126, p = .037, adjusted R2 = .067). After gender stratification, faster metabolism predicted higher mean puff volume (t = 2.81, p = .009, adjusted R2 = .192) but fewer puffs (t = −3.160, p=0.004, adjusted R2 = .237) and lower mean puff duration (t = −2.06, p = .048, adjusted R2 = .101) among boys only, suggesting that as nicotine metabolism increases, puff volume increases but puffing frequency decreases. No significant relationships were found between nicotine metabolism and total puff volume, mean puff duration, inter-puff interval, or puff velocity. If confirmed in a broader sample of adolescent smokers, these findings suggest that, as among dependent adult smokers, rate of metabolism among adolescent boys is linked to select parameters of puffing behavior that may impact cessation ability. PMID:19423535

Effect of parental history of diabetes on markers of inflammation, insulin resistance and atherosclerosis in first degree relatives of patients with type 2 diabetes mellitus.

PubMed

Dash, Deepak Kumar; Choudhury, Arun Kumar; Singh, Mamta; Mangaraj, Swayamsidha; Mohanty, Binoy Kumar; Baliarsinha, Anoj Kumar

2018-05-01

To study the effect of parental history of diabetes on markers of inflammation, insulin resistance, adiposity indices and carotid intima media thickness (cIMT) in first degree relatives of patients with type 2 diabetes mellitus (T2DM). Normal glucose tolerant (NGT) first degree relatives of T2DM patients of age group 20-40 years designated as FH positive were enrolled in the cross sectional study. Depending on the parental history of diabetes they were divided into three groups: family history positive in father (FH father ), family history positive in mother (FH mother ) and family history positive in both (FH both ). Age, sex and BMI matched controls without any history of diabetes in their parents designated as FH negative were taken for comparison. All subjects underwent detailed clinical evaluation and biochemical investigations. cIMT and adiposity indices like visceral adipose tissue thickness (VAT) and subcutaneous adipose tissue thickness (SAT) were assessed using ultrasonography. No difference existed with regards to BMI, hsCRP, degree of insulin resistance, adiposity markers and cIMT between FH mother and FH father group. Subjects in FH both group had significantly higher degree of insulin resistance, subclinical inflammation, increased atherosclerosis and adiposity indices in contrast to those who have a single parent T2DM family history. hsCRP and cIMT are significantly higher in the first degree relatives of type2 diabetes mellitus patients than controls. Individuals with history of T2DM in both parents have significantly worse glycemic status, increased cIMT and adverse cardiovascular risk profile than those with T2DM history in only single parent. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Nasal Carriage of Staphylococcus aureus among Children in the Ashanti Region of Ghana.

PubMed

Eibach, Daniel; Nagel, Michael; Hogan, Benedikt; Azuure, Clinton; Krumkamp, Ralf; Dekker, Denise; Gajdiss, Mike; Brunke, Melanie; Sarpong, Nimako; Owusu-Dabo, Ellis; May, Jürgen

2017-01-01

Nasal carriage with Staphylococcus aureus is a common risk factor for invasive infections, indicating the necessity to monitor prevalent strains, particularly in the vulnerable paediatric population. This surveillance study aims to identify carriage rates, subtypes, antimicrobial susceptibilities and virulence markers of nasal S. aureus isolates collected from children living in the Ashanti region of Ghana. Nasal swabs were obtained from children < 15 years of age on admission to the Agogo Presbyterian Hospital between April 2014 and January 2015. S. aureus isolates were characterized by their antimicrobial susceptibility, the presence of genes encoding for Panton-Valentine leukocidin (PVL) and toxic shock syndrome toxin-1 (TSST-1) and further differentiated by spa-typing and multi-locus-sequence-typing. Out of 544 children 120 (22.1%) were colonized with S. aureus, with highest carriage rates during the rainy seasons (27.2%; p = 0.007), in females aged 6-8 years (43.7%) and males aged 8-10 years (35.2%). The 123 isolates belonged to 35 different spa-types and 19 sequence types (ST) with the three most prevalent spa-types being t355 (n = 25), t84 (n = 18), t939 (n = 13), corresponding to ST152, ST15 and ST45. Two (2%) isolates were methicillin-resistant S. aureus (MRSA), classified as t1096 (ST152) and t4454 (ST45), and 16 (13%) were resistant to three or more different antimicrobial classes. PVL and TSST-1 were detected in 71 (58%) and 17 (14%) isolates respectively. S. aureus carriage among Ghanaian children seems to depend on age, sex and seasonality. While MRSA rates are low, the high prevalence of PVL is of serious concern as these strains might serve not only as a source for severe invasive infections but may also transfer genes, leading to highly virulent MRSA clones.

The relationship between body composition and femoral neck osteoporosis or osteopenia in adults with previous poliomyelitis.

PubMed

Chang, Kwang-Hwa; Tseng, Sung-Hui; Lin, Yu-Ching; Lai, Chien-Hung; Hsiao, Wen-Tien; Chen, Shih-Ching

2015-04-01

Articles in the literature describing the association between body composition and osteoporosis in subjects with poliomyelitis are scarce. To assess the relationship between body composition and femoral neck osteoporosis or osteopenia in adults with previous polio. After excluding postmenopausal women, 44 polio (mean age ± standard deviation, 46.1 ± 3.3 years) and 44 able-bodied control volunteers (47.0 ± 4.0 years) participated in the study. Each participant's femoral neck bone mineral density (FNBMD) and whole body composition were measured using dual-energy X-ray absorptiometry. With local reference BMD values of normal young adults installed in the instrument, we obtained T-score values that depended on each FNBMD value. A T-score value of ≤-1.0 indicated decreased T-score, including osteoporosis (T-score ≤ -2.5) and osteopenia (-1.0 to -2.5). This study conducted logistic regression analyses to find factors associated with osteoporosis and osteopenia. Based on the FNBMD T-score values, 60.0% of middle-aged men with polio had osteoporosis. In adjusted logistic regression analyses, total lean tissue mass (Adjusted odds ratio [95% confidence interval], 0.74 [0.56-0.99], P < 0.05) and male gender (947.16 [6.02-148,926.16], P < 0.01) were important factors associated with decreased T-score in polio group. Osteoporosis or osteopenia is a common medical problem for middle-aged men with polio. Reduced total lean tissue mass seems to be one of the important factors associated with osteoporosis or osteopenia among subjects with polio. Further research for a clinical tool to assess lean tissue mass for subjects with polio is needed. Copyright © 2015 Elsevier Inc. All rights reserved.

Relationship between aging and T1 relaxation time in deep gray matter: A voxel-based analysis.

PubMed

Okubo, Gosuke; Okada, Tomohisa; Yamamoto, Akira; Fushimi, Yasutaka; Okada, Tsutomu; Murata, Katsutoshi; Togashi, Kaori

2017-09-01

To investigate age-related changes in T 1 relaxation time in deep gray matter structures in healthy volunteers using magnetization-prepared 2 rapid acquisition gradient echoes (MP2RAGE). In all, 70 healthy volunteers (aged 20-76, mean age 42.6 years) were scanned at 3T magnetic resonance imaging (MRI). A MP2RAGE sequence was employed to quantify T 1 relaxation times. After the spatial normalization of T 1 maps with the diffeomorphic anatomical registration using the exponentiated Lie algebra algorithm, voxel-based regression analysis was conducted. In addition, linear and quadratic regression analyses of regions of interest (ROIs) were also performed. With aging, voxel-based analysis (VBA) revealed significant T 1 value decreases in the ventral-inferior putamen, nucleus accumbens, and amygdala, whereas T 1 values significantly increased in the thalamus and white matter as well (P < 0.05 at cluster level, false discovery rate). ROI analysis revealed that T 1 values in the nucleus accumbens linearly decreased with aging (P = 0.0016), supporting the VBA result. T 1 values in the thalamus (P < 0.0001), substantia nigra (P = 0.0003), and globus pallidus (P < 0.0001) had a best fit to quadratic curves, with the minimum T 1 values observed between 30 and 50 years of age. Age-related changes in T 1 relaxation time vary by location in deep gray matter. 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:724-731. © 2017 International Society for Magnetic Resonance in Medicine.

Age-Dependent Changes in Resting Energy Expenditure (REE): Insights from Detailed Body Composition Analysis in Normal and Overweight Healthy Caucasians.

PubMed

Geisler, Corinna; Braun, Wiebke; Pourhassan, Maryam; Schweitzer, Lisa; Glüer, Claus-Christian; Bosy-Westphal, Anja; Müller, Manfred J

2016-06-01

Age-related changes in organ and tissue masses may add to changes in the relationship between resting energy expenditure (REE) and fat free mass (FFM) in normal and overweight healthy Caucasians. Secondary analysis using cross-sectional data of 714 healthy normal and overweight Caucasian subjects (age 18-83 years) with comprehensive information on FFM, organ and tissue masses (as assessed by magnetic resonance imaging (MRI)), body density (as assessed by Air Displacement Plethysmography (ADP)) and hydration (as assessed by deuterium dilution (D₂O)) and REE (as assessed by indirect calorimetry). High metabolic rate organs (HMR) summarized brain, heart, liver and kidney masses. Ratios of HMR organs and muscle mass (MM) in relation to FFM were considered. REE was calculated (REEc) using organ and tissue masses times their specific metabolic rates. REE, FFM, specific metabolic rates, the REE-FFM relationship, HOMA, CRP, and thyroid hormone levels change with age. The age-related decrease in FFM explained 59.7% of decreases in REE. Mean residuals of the REE-FFM association were positive in young adults but became negative in older subjects. When compared to young adults, proportions of MM to FFM decreased with age, whereas contributions of liver and heart did not differ between age groups. HOMA, TSH and inflammation (plasma CRP-levels) explained 4.2%, 2.0% and 1.4% of the variance in the REE-FFM residuals, but age and plasma T3-levels had no effects. HMR to FFM and MM to FFM ratios together added 11.8% on to the variance of REE-FFM residuals. Differences between REE and REEc increased with age, suggesting age-related changes in specific metabolic rates of organs and tissues. This bias was partly explained by plasmaT3-levels. Age-related changes in REE are explained by (i) decreases in fat free mass; (ii) a decrease in the contributions of organ and muscle masses to FFM; and (iii) decreases in specific organ and tissue metabolic rates. Age-dependent changes in the REE-FFMassociation are explained by composition of FFM, inflammation and thyroid hormones.

TAS2R bitter taste receptors regulate thyroid function

PubMed Central

Clark, Adam A.; Dotson, Cedrick D.; Elson, Amanda E. T.; Voigt, Anja; Boehm, Ulrich; Meyerhof, Wolfgang; Steinle, Nanette I.; Munger, Steven D.

2015-01-01

Dysregulation of thyroid hormones triiodothyronine and thyroxine (T3/T4) can impact metabolism, body composition, and development. Thus, it is critical to identify novel mechanisms that impact T3/T4 production. We found that type 2 taste receptors (TAS2Rs), which are activated by bitter-tasting compounds such as those found in many foods and pharmaceuticals, negatively regulate thyroid-stimulating hormone (TSH)-dependent Ca2+ increases and TSH-dependent iodide efflux in thyrocytes. Immunohistochemical Tas2r-dependent reporter expression and real-time PCR analyses reveal that human and mouse thyrocytes and the Nthy-Ori 3-1 human thyrocyte line express several TAS2Rs. Five different agonists for thyrocyte-expressed TAS2Rs reduced TSH-dependent Ca2+ release in Nthy-Ori 3-1 cells, but not basal Ca2+ levels, in a dose-dependent manner. Ca2+ responses were unaffected by 6-n-propylthiouracil, consistent with the expression of an unresponsive variant of its cognate receptor, TAS2R38, in these cells. TAS2R agonists also inhibited basal and TSH-dependent iodide efflux. Furthermore, a common TAS2R42 polymorphism is associated with increased serum T4 levels in a human cohort. Our findings indicate that TAS2Rs couple the detection of bitter-tasting compounds to changes in thyrocyte function and T3/T4 production. Thus, TAS2Rs may mediate a protective response to overingestion of toxic materials and could serve as new druggable targets for therapeutic treatment of hypo- or hyperthyroidism.—Clark, A. A., Dotson, C. D., Elson, A. E. T., Voigt, A., Boehm, U., Meyerhof, W., Steinle, N. I., Munger, S. D. TAS2R bitter taste receptors regulate thyroid function. PMID:25342133

Innate inflammation in Type 1 diabetes

PubMed Central

Cabrera, Susanne M.; Henschel, Angela M.; Hessner, Martin J.

2015-01-01

Type 1 diabetes mellitus (T1D) is an autoimmune disease often diagnosed in childhood that results in pancreatic β-cell destruction and life-long insulin dependence. T1D susceptibility involves a complex interplay of genetic and environmental factors and has historically been attributed to adaptive immunity, though there is now increasing evidence for a role of innate inflammation. Here, we review studies that define a heightened age-dependent innate inflammatory state in T1D families that is paralleled with high fidelity by the T1D-susceptible BioBreeding rat. Innate inflammation may be driven by changes in interactions between the host and environment, such as through an altered microbiome, intestinal hyper-permeability, or viral exposures. Special focus is placed on the temporal measurement of plasma induced transcriptional signatures of recent onset T1D patients and their siblings as well as in the Biobreeding rat as it defines the natural history of innate inflammation. These sensitive and comprehensive analyses have also revealed that those who successfully managed T1D risk develop an age-dependent immunoregulatory state, providing a possible mechanism for the juvenile nature of T1D. Therapeutic targeting of innate inflammation has been proven effective in preventing and delaying T1D in rat models. Clinical trials of agents that suppress innate inflammation have had more modest success, but efficacy is improved by the addition of combinatorial approaches that target other aspects of T1D pathogenesis. An understanding of innate inflammation and mechanisms by which this susceptibility is both potentiated and mitigated offers important insight into T1D progression and avenues for therapeutic intervention. PMID:25980926

Buffer or amplifier? Longitudinal effects of social support for functional autonomy/dependence on older adults' chronic pain experiences.

PubMed

Matos, Marta; Bernardes, Sónia F; Goubert, Liesbet; Beyers, Wim

2017-12-01

This longitudinal study aimed to investigate (a) the moderating role of formal social support for functional autonomy versus dependence on the relationship between pain intensity and pain-related disability among older adults with chronic pain and (b) the mediating role of pain-related self-efficacy and pain-related fear in this moderation. One hundred and seventy older adults (Mage = 78.0; SD = 8.7) with chronic musculoskeletal pain participated in a 3-month prospective study, with 3 measurement moments. Participants filled out the Formal Social Support for Autonomy and Dependence in Pain Inventory, the Portuguese versions of the Brief Pain Inventory, the Pain Self-Efficacy Questionnaire, and the Tampa Scale of Kinesiophobia. Using structural equation modeling, it was found that perceived promotion of autonomy, at Time 1, moderated the relationship between pain intensity (T1) and pain-related disability (T2); this moderation was fully mediated by pain-related self-efficacy (T2). Perceived promotion of dependence was not a significant moderator. These findings highlight the importance of social support for functional autonomy in buffering the impact of pain intensity on older adults' pain-related disability. Also, they clarify the role of pain-related self-efficacy in this effect. Implications for the development of intervention programs, with formal caregivers, to reduce the impact of chronic pain on older adults' healthy ageing process, are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The in vitro MIMIC® platform reflects age-associated changes in immunological responses after influenza vaccination.

PubMed

Dauner, Allison; Agrawal, Pankaj; Salvatico, Jose; Tapia, Tenekua; Dhir, Vipra; Shaik, S Farzana; Drake, Donald R; Byers, Anthony M

2017-10-04

Increasing research and development costs coupled with growing concerns over healthcare expenditures necessitate the generation of pre-clinical testing models better able to predict the efficacy of vaccines, drugs and biologics. An ideal system for evaluating vaccine immunogenicity will not only be reliable but also physiologically relevant, able to be influenced by immunomodulatory characteristics such as age or previous exposure to pathogens. We have previously described a fully autologous human cell-based MIMIC® (Modular IMmune In vitro Construct) platform which enables the evaluation of innate and adaptive immunity in vitro, including naïve and recall responses. Here, we establish the ability of this module to display reduced antibody production and T cell activation upon in vitro influenza vaccination of cells from elderly adults. In the MIMIC® system, we observe a 2.7-4.2-fold reduction in strain-specific IgG production to seasonal trivalent influenza vaccine (TIV) in the elderly when compared to adults, as well as an age-dependent decline in the generation of functional antibodies. A parallel decline in IgG production with increasing age was detected via short-term ex vivo stimulation of B cells after in vivo TIV vaccination in the same cohort. Using MIMIC®, we also detect a reduction in the number but not proportion of TIV-specific multifunctional CD154 + IFNγ + IL-2 + TNFα + CD4 + T cells in elderly adults. Inefficient induction of multifunctional helper T cells with TIV stimulation in MIMIC® despite a normalized number of initial CD4 + T cells suggests a possible mechanism for an impaired anti-TIV IgG response in elderly adults. The ability of the MIMIC® system to recapitulate differential age-associated responses in vitro provides a dynamic platform for the testing of vaccine candidates and vaccine enhancement strategies in a fully human model including the ability to interrogate specific populations, such as elderly adults. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vδ2+ and α/ß T cells show divergent trajectories during human aging.

PubMed

Tan, Crystal Tze Ying; Wistuba-Hamprecht, Kilian; Xu, Weili; Nyunt, Ma Schwe Zin; Vasudev, Anusha; Lee, Bernett Teck Kwong; Pawelec, Graham; Puan, Kia Joo; Rotzschke, Olaf; Ng, Tze Pin; Larbi, Anis

2016-07-19

Chronological aging and a variety of stressors are driving forces towards immunosenescence. While much attention was paid to the main T cell component, α/β T cells, few studies concentrate on the impact of age on γ/δ T cells' characteristics. The latter are important players of adaptive immunity but also have features associated with innate immunity. Vδ2+ are the main component of γ/δ while Vδ1+ T cells expand upon Cytomegalovirus (CMV) infection and with age. The Vδ2+ T cells are not influenced by persistent infections but do contribute to immunosurveillance against bacterial pathogens. Here, we focus on Vδ2+ T cells and report that their composition and functionality is not altered in older adults. We have performed a side-by-side comparison of α/β and Vδ2 cells by using two robust markers of T cell replicative history and cell differentiation (CD28 and CD27), and cytokine secretion (IFN-γ and TNF-α). Significant differences in Vδ2 versus α/β homeostasis, as well as phenotypic and functional changes emerged. However, the data strongly suggest a sustained functionality of the Vδ2 population with age, independently of the challenge. This suggests differential trajectories towards immunosenescence in α/β and Vδ2+ T cells, most likely explained by their intrinsic functions.

Factors affecting reconstitution of the T cell compartment in allogeneic haematopoietic cell transplant recipients.

PubMed

Fallen, P R; McGreavey, L; Madrigal, J A; Potter, M; Ethell, M; Prentice, H G; Guimarães, A; Travers, P J

2003-11-01

The factors affecting T cell reconstitution post haematopoietic cell transplantation (HCT) are not well characterised. We carried out a longitudinal analysis of T cell reconstitution in 32 HCT recipients during the first 12 months post transplant. We analysed reconstitution of naïve, memory and effector T cells, their diversity and monitored thymic output using TCR rearrangement excision circles (TRECs). Thymic-independent pathways were responsible for the rapid reconstitution of memory and effector T cells less than 6 months post HCT. Thymic-dependent pathways were activated between 6 and 12 months in the majority of patients with naïve T cell numbers increasing in parallel with TREC levels. Increasing patient age, chronic GVHD and T cell depletion (with or without pretransplant Campath-1H) predicted low TREC levels and slow naïve T cell recovery. Furthermore, increasing patient age also predicted high memory and effector T cell numbers. The effects of post HCT immunosuppression, total body irradiation, donor leucocyte infusions, T cell dose and post HCT infections on T cell recovery were also analysed. However, no effects of these single variables across a variety of different age, GVHD and T cell depletion groups were apparent. This study suggests that future analysis of the factors affecting T cell reconstitution and studies aimed at reactivating the thymus through therapeutic intervention should be analysed in age-, GVHD- and TCD-matched patient groups.

Plasma Protein Oxidation and Its Correlation with Antioxidant Potential During Human Aging

PubMed Central

Pandey, Kanti Bhooshan; Mehdi, Mohd Murtaza; Maurya, Pawan Kumar; Rizvi, Syed Ibrahim

2010-01-01

Previous studies have indicated that the main molecular characteristic of aging is the progressive accumulation of oxidative damages in cellular macromolecules. Proteins are one of the main molecular targets of age-related oxidative stress, which have been observed during aging process in cellular systems. Reactive oxygen species (ROS) can lead to oxidation of amino acid side chains, formation of protein-protein cross-linkages, and oxidation of the peptide backbones. In the present study, we report the age-dependent oxidative alterations in biomarkers of plasma protein oxidation: protein carbonyls (PCO), advanced oxidation protein products (AOPPs) and plasma total thiol groups (T-SH) in the Indian population and also correlate these parameters with total plasma antioxidant potential. We show an age dependent decrease in T-SH levels and increase in PCO and AOPPs level. The alterations in the levels of these parameters correlated significantly with the total antioxidant capacity of the plasma. The levels of oxidized proteins in plasma provide an excellent biomarker of oxidative stress due to the relative long half-life of such oxidized proteins. PMID:20826915

78 FR 5195 - Filing of Plats of Survey: California

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-24

... sections accepted October 18, 2012. T. 18 N., R. 10 W., dependent resurvey and subdivision accepted... Meridian, California T. 11 N., R. 3 E., corrective dependent resurvey, resurvey and subdivision accepted November 27, 2012. T. 2 N., R. 2 and 3 W., dependent resurvey and metes-and-bounds survey accepted November...

Gender Differences in Physical Activity Levels of Older People With Type 2 Diabetes Mellitus.

PubMed

Kelly, Joan; Edney, Katrina; Moran, Chris; Srikanth, Velandai; Callisaya, Michele

2016-04-01

Physical activity (PA) is important in managing Type 2 Diabetes Mellitus (T2DM). This study aimed to determine 1) the number of daily steps taken by older people with T2DM, 2) if T2DM is associated with taking fewer steps per day and less likelihood of meeting PA guidelines, and 3) whether these associations are modified by age or gender. PA was obtained by pedometer from 2 cohorts of older adults with and without T2DM. Multivariable regression was used to determine associations between T2DM, mean steps per day and meeting a guideline equivalent (7 100 steps per day). There were 293 participants with T2DM (mean age 67.6 ± 6.8 years) and 336 without T2DM (mean age 72.1 ± 7.1 years). In women, T2DM was associated with fewer mean steps per day (β = -1306.4; 95% CI -2052.5, -560.3; P = .001) and not meeting the PA guidelines (OR 0.51; 95% CI 0.28, 0.92; P = .03). Associations were not significant in men (P > .05). Only 29.7% of those with T2DM and 33.3% of those without T2DM met PA guidelines. Greater focus is needed on how to maintain and increase PA in older age with particular focus on women with T2DM.

Absolute parameters of young stars: QZ Carinae

NASA Astrophysics Data System (ADS)

Walker, W. S. G.; Blackford, M.; Butland, R.; Budding, E.

2017-09-01

New high-resolution spectroscopy and BVR photometry together with literature data on the complex massive quaternary star QZ Car are collected and analysed. Absolute parameters are found as follows. System A: M1 = 43 (±3), M2 = 19 (+3 -7), R1 = 28 (±2), R2 = 6 (±2), (⊙); T1 ˜ 28 000, T2 ˜ 33 000 K; System B: M1 = 30 (±3), M2 = 20 (±3), R1 = 10 (±0.5), R2 = 20 (±1), (⊙); T1 ˜ 36 000, T2 ˜ 30 000 K (model dependent temperatures). The wide system AB: Period = 49.5 (±1) yr, Epochs, conjunction = 1984.8 (±1), periastron = 2005.3 (±3) yr, mean separation = 65 (±3), (au); orbital inclination = 85 (+5 -15) deg, photometric distance ˜2700 (±300) pc, age = 4 (±1) Myr. Other new contributions concern: (a) analysis of the timing of minima differences (O - C)s for the eclipsing binary (System B); (b) the width of the eclipses, pointing to relatively large effects of radiation pressure; (c) inferences from the rotational widths of lines for both Systems A and B; and (d) implications for theoretical models of early-type stars. While feeling greater confidence on the quaternary's general parametrization, observational complications arising from strong wind interactions or other, unclear, causes still inhibit precision and call for continued multiwavelength observations. Our high-inclination value for the AB system helps to explain failures to resolve the wide binary in the previous years. The derived young age independently confirms membership of QZ Car to the open cluster Collinder 228.

Rate of occurrence, gross appearance, and age relation of hyperostosis frontalis interna in females: a prospective autopsy study.

PubMed

Nikolić, Slobodan; Djonić, Danijela; Zivković, Vladimir; Babić, Dragan; Juković, Fehim; Djurić, Marija

2010-09-01

The aim of our study was to determine rate of occurrence and appearance of hyperostosis frontalis interna (HFI) in females and correlation of this phenomenon with ageing. The sample included 248 deceased females: 45 of them with different types of HFI, and 203 without HFI, average age 68.3 +/- 15.4 years (range, 19-93), and 58.2 +/- 20.2 years (range, 10-101), respectively. According to our results, the rate of HFI was 18.14%. The older the woman was, the higher the possibility of HFI occurring (Pearson correlation 0.211, N=248, P=0.001), but the type of HFI did not correlate with age (Pearson correlation 0.229, N=45, P=0.131). Frontal and temporal bone were significantly thicker in women with than in women without HFI (t= -10.490, DF=246, P=0.000, and t= -5.658, DF=246, P=0.000, respectively). These bones became thicker with ageing (Pearson correlation 0.178, N=248, P=0.005, and 0.303, N=248, P=0.000, respectively). The best predictors of HFI occurrence were respectively, frontal bone thickness, temporal bone thickness, and age(Wald. coeff.=35.487, P=0.000; Wald. coeff.=3.288, P=0.070, and Wald.coeff. =2.727, P =0.099). Diagnosis of HFI depends not only on frontal bone thickness, but also on waviness of internal plate of the frontal bone, as well as-the involvement of the inner bone surface.

Oxygen consumption of the chicken embryo: interaction between temperature and oxygenation.

PubMed

Mortola, Jacopo P; Labbè, Katherine

2005-03-01

We measured the effects of hypoxia and changes in ambient temperature (T) on the oxygen consumption (VO2) of chicken embryos at embryonic days 11, 16 and 20 (E11, E16 and E20, respectively), and post-hatching day 1 (H1). Between 30 and 39 degrees C, at E11 and E16, VO2 changed linearly with T, as in ectothermic animals, with a Q10 of about 2.1. At E20, VO2 did not significantly change with T, indicating the onset of endothermy. At H1, a drop in T increased VO2, a clear thermogenic response. Hypoxia (11% O2 for 30 min) decreased VO2, by an amount that varied with T and age. At H1, hypoxia lowered VO2 especially at low T. At E20, hypoxic hypometabolism was similar at all T. At E11 and E16, hypoxia lowered VO2 only at the higher T. In fact, at E11, with T=39 degrees C even a modest hypoxia (15-18% O2) decreased VO2. Upon return to normoxia after 40 min of 11% O2, VO2 did not rise above the pre-hypoxic level, indicating that the hypometabolism during hypoxia did not generate an O2 debt. At E11, during modest hypoxia (16% O2) at 36 degrees C, the drop in VO2 was lifted by raising the T to 39 degrees C, suggesting that the hypoxic hypometabolism at 36 degrees C was not due to O2-supply limitation. In conclusion, the hypometabolic effects of hypoxia on the chicken embryo's VO2 depend on the development of the thermogenic ability, occurring predominantly at high T during the early (ectothermic phase) and at low T during the late (endothermic) phase. At E11, both low T and low oxygen force VO2 to drop. However, at a near-normal T, modest hypoxia promotes a hypometabolic response with the characteristics of regulated O2 conformism.

Factors influencing the dosimetry for high-intensity focused ultrasound ablation of uterine fibroids: a retrospective study.

PubMed

Peng, Song; Zhang, Lian; Hu, Liang; Chen, Jinyun; Ju, Jin; Wang, Xi; Zhang, Rong; Wang, Zhibiao; Chen, Wenzhi

2015-04-01

The aim of this article is to analyze factors affecting sonication dose and build a dosimetry model of high-intensity focused ultrasound (HIFU) ablation for uterine fibroids. Four hundred and three patients with symptomatic uterine fibroids who underwent HIFU were retrospectively analyzed. The energy efficiency factor (EEF) was set as dependent variable, and the factors possibly affecting sonication dose included age, body mass index, size of uterine fibroid, abdominal wall thickness, the distance from uterine fibroid dorsal side to sacrum, the distance from uterine fibroid ventral side to skin, location of uterus, location of uterine fibroids, type of uterine fibroids, abdominal wall scar, signal intensity on T2-weighted imaging (T2WI), and enhancement type on T1-weighted imaging (T1WI) were set as predictors to build a multiple regression model. The size of uterine fibroid, distance from fibroid ventral side to skin, location of uterus, location of uterine fibroids, type of uterine fibroids, signal intensity on T2WI, and enhancement type on T1WI had a linear correlation with EEF. The distance from fibroid ventral side to skin, enhancement type on T1WI, size of uterine fibroid, and signal intensity on T2WI were eventually incorporated into the dosimetry model. The distance from fibroid ventral side to skin, enhancement type on T1WI, size of uterine fibroid, and signal intensity on T2WI can be used as dosimetric predictors for HIFU for uterine fibroids.

Bone microarchitecture, biomechanical properties, and advanced glycation end-products in the proximal femur of adults with type 2 diabetes.

PubMed

Karim, Lamya; Moulton, Julia; Van Vliet, Miranda; Velie, Kelsey; Robbins, Ann; Malekipour, Fatemeh; Abdeen, Ayesha; Ayres, Douglas; Bouxsein, Mary L

2018-05-29

Skeletal fragility is a major complication of type 2 diabetes mellitus (T2D), but there is a poor understanding of mechanisms underlying T2D skeletal fragility. The increased fracture risk has been suggested to result from deteriorated bone microarchitecture or poor bone quality due to accumulation of advanced glycation end-products (AGEs). We conducted a clinical study to determine whether: 1) bone microarchitecture, AGEs, and bone biomechanical properties are altered in T2D bone, 2) bone AGEs are related to bone biomechanical properties, and 3) serum AGE levels reflect those in bone. To do so, we collected serum and proximal femur specimens from T2D (n = 20) and non-diabetic (n = 33) subjects undergoing total hip replacement surgery. A section from the femoral neck was imaged by microcomputed tomography (microCT), tested by cyclic reference point indentation, and quantified for AGE content. A trabecular core taken from the femoral head was imaged by microCT and subjected to uniaxial unconfined compression tests. T2D subjects had greater HbA 1 c (+23%, p ≤ 0.0001), but no difference in cortical tissue mineral density, cortical porosity, or trabecular microarchitecture compared to non-diabetics. Cyclic reference point indentation revealed that creep indentation distance (+18%, p ≤ 0.05) and indentation distance increase (+20%, p ≤ 0.05) were greater in cortical bone from T2D than in non-diabetics, but no other indentation variables differed. Trabecular bone mechanical properties were similar in both groups, except for yield stress, which tended to be lower in T2D than in non-diabetics. Neither serum pentosidine nor serum total AGEs were different between groups. Cortical, but not trabecular, bone AGEs tended to be higher in T2D subjects (21%, p = 0.09). Serum AGEs and pentosidine were positively correlated with cortical and trabecular bone AGEs. Our study presents new data on biomechanical properties and AGEs in adults with T2D, which are needed to better understand mechanisms contributing to diabetic skeletal fragility. Copyright © 2017. Published by Elsevier Inc.

Local strain-induced band gap fluctuations and exciton localization in aged WS2 monolayers

NASA Astrophysics Data System (ADS)

Krustok, J.; Kaupmees, R.; Jaaniso, R.; Kiisk, V.; Sildos, I.; Li, B.; Gong, Y.

2017-06-01

Optical properties of aged WS2 monolayers grown by CVD method on Si/SiO2 substrates are studied using temperature dependent photoluminescence and reflectance contrast spectroscopy. Aged WS2 monolayers have a typical surface roughness about 0.5 nm and, in addition, a high density of nanoparticles (nanocaps) with the base diameter about 30 nm and average height of 7 nm. The A-exciton of aged monolayer has a peak position at 1.951 eV while in as-grown monolayer the peak is at about 24 meV higher energy at room temperature. This red-shift is explained using local tensile strain concept, where strain value of 2.1% was calculated for these nanocap regions. Strained nanocaps have lower band gap energy and excitons will funnel into these regions. At T=10K a double exciton and trion peaks were revealed. The separation between double peaks is about 20 meV and the origin of higher energy peaks is related to the optical band gap energy fluctuations caused by random distribution of local tensile strain due to increased surface roughness. In addition, a wide defect related exciton band XD was found at about 1.93 eV in all aged monolayers. It is shown that the theory of localized excitons describes well the temperature dependence of peak position and halfwidth of the A-exciton band. The possible origin of nanocaps is also discussed.

On the nature of magnetic state in the spinel Co₂SnO₄.

PubMed

Thota, S; Narang, V; Nayak, S; Sambasivam, S; Choi, B C; Sarkar, T; Andersson, M S; Mathieu, R; Seehra, M S

2015-04-29

In the spinel Co2SnO4, coexistence of ferrimagnetic ordering below T(N) ≃ 41 K followed by a spin glass state below T(SG) ≃ 39 K was proposed recently based on the temperature dependence of magnetization M(T) data. Here new measurements of the temperature dependence of the specific heat C(P)(T), ac-susceptibilities χ'(T) and χ″(T) measured at frequencies between 0.51 and 1.2 kHz, and the hysteresis loop parameters (coercivity H(C)(T) and remanence M(R)(T)) in two differently prepared samples of Co2SnO4 are reported. The presence of the Co(2+) and Sn(4+) states is confirmed by x-ray photoelectron spectroscopy (XPS) yielding the structure: Co2SnO4 = [Co(2+)][Co(2+)Sn(4+)]O4. The data of C(P) versus T shows only an inflection near 39 K characteristic of spin-glass ordering. The analysis of the frequency dependence of ac-magnetic susceptibility data near 39 K using the Vogel-Fulcher law and the power-law of the critical slowing-down suggests the presence of spin clusters in the system which is close to a spin-glass state. With a decrease in temperature below 39 K, the temperature dependence of the coercivity H(C) and remanence M(R) for the zero-field cooled samples show both H(C) and M(R) reaching their peak magnitudes near 25 K, then decreasing with decreasing T and becoming negligible below 15 K. The plot of C(P)/T versus T also yields a weak inflection near 15 K. This temperature dependence of H(C) and remanence M(R) is likely associated with the different magnitudes of the magnetic moments of Co(2+) ions on the 'A' and 'B' sites and their different temperature dependence.

AURORA: bariatric surgery registration in women of reproductive age - a multicenter prospective cohort study.

PubMed

Jans, Goele; Matthys, Christophe; Bel, Sarah; Ameye, Lieveke; Lannoo, Matthias; Van der Schueren, Bart; Dillemans, Bruno; Lemmens, Luc; Saey, Jean-Pierre; van Nieuwenhove, Yves; Grandjean, Pascale; De Becker, Ben; Logghe, Hilde; Coppens, Marc; Roelens, Kristien; Loccufier, Anne; Verhaeghe, Johan; Devlieger, Roland

2016-07-29

The expansion of the obesity epidemic is accompanied with an increase in bariatric procedures, in particular in women of reproductive age. The weight loss induced by the surgery is believed to reverse the negative impact of overweight and obesity on female reproduction, however, research is limited to in particular retrospective cohort studies and a growing number of small case-series and case-(control) studies. AURORA is a multicenter prospective cohort study. The main objective is to collect long-term data on reproductive outcomes before and after bariatric surgery and in a subsequent pregnancy. Women aged 18-45 years are invited to participate at 4 possible inclusion moments: 1) before surgery, 2) after surgery, 3) before 15 weeks of pregnancy and 4) in the immediate postpartum period (day 3-4). Depending on the time of inclusion, data are collected before surgery (T1), 3 weeks and 3, 6, 12 or x months after surgery (T2-T5) and during the first, second and third trimester of pregnancy (T6-T8), at delivery (T9) and 6 weeks and 6 months after delivery (T10-T11). Online questionnaires are send on the different measuring moments. Data are collected on contraception, menstrual cycle, sexuality, intention of becoming pregnant, diet, physical activity, lifestyle, psycho-social characteristics and dietary supplement intake. Fasting blood samples determine levels of vitamin A, D, E, K, B-1, B-12 and folate, albumin, total protein, coagulation parameters, magnesium, calcium, zinc and glucose. Participants are weighted every measuring moment. Fetal ultrasounds and pregnancy course and complications are reported every trimester of pregnancy. Breastfeeding is recorded and breast milk composition in the postpartum period is studied. AURORA is a multicenter prospective cohort study extensively monitoring women before undergoing bariatric surgery until a subsequent pregnancy and postpartum period. Retrospectively registered (July 2015 - NCT02515214 ).

Factors affecting return to oral intake in inpatient rehabilitation after acquired brain injury.

PubMed

Kjaersgaard, Annette; Nielsen, Lars Hedemann; Sjölund, Bengt H

2015-01-01

To extend previous observations by investigating if differences exist in time to initiation or to recovery of total oral intake in patients with acquired brain injury assessed by either Facial-Oral Tract Therapy (F.O.T.T.) or Fibreoptic Endoscopic Evaluation of Swallowing (FEES) and to investigate whether other factors influence these outcomes. Randomized controlled trial. One hundred and nineteen patients with dysphagia in inpatient neurorehabilitation were randomized. The main outcome was time to maximum on the Functional Oral Intake Scale. There was no difference in time to initiation or recovery of total oral intake using F.O.T.T. or FEES. Oral intake was initiated for 42% on admission and 92% at discharge; 2.5% of the patients were on total oral intake within 24 hours of admission and 37% at discharge. The likelihood of recovery to total oral intake before discharge was found to depend on age, Functional Independence Measure score, length of stay and number of dysphagia interventions. There was no significant difference in time to initiation and recovery of total oral intake before discharge, whether assessed by F.O.T.T. or FEES, indicating that an instrumental assessment is unnecessary for standard evaluation. Age, functional independence and length of stay had a significant influence.

Fracture risk in patients with type 2 diabetes mellitus and possible risk factors: a systematic review and meta-analysis

PubMed Central

Moayeri, Ardeshir; Mohamadpour, Mahmoud; Mousavi, Seyedeh Fatemeh; Shirzadpour, Ehsan; Mohamadpour, Safoura; Amraei, Mansour

2017-01-01

Aim Patients with type 2 diabetes mellitus (T2DM) have an increased risk of bone fractures. A variable increase in fracture risk has been reported depending on skeletal site, diabetes duration, study design, insulin use, and so on. The present meta-analysis aimed to investigate the association between T2DM with fracture risk and possible risk factors. Methods Different databases including PubMed, Institute for Scientific Information, and Scopus were searched up to May 2016. All epidemiologic studies on the association between T2DM and fracture risk were included. The relevant data obtained from these papers were analyzed by a random effects model and publication bias was assessed by funnel plot. All analyses were done by R software (version 3.2.1) and STATA (version 11.1). Results Thirty eligible studies were selected for the meta-analysis. We found a statistically significant positive association between T2DM and hip, vertebral, or foot fractures and no association between T2DM and wrist, proximal humerus, or ankle fractures. Overall, T2DM was associated with an increased risk of any fracture (summary relative risk =1.05, 95% confidence interval: 1.04, 1.06) and increased with age, duration of diabetes, and insulin therapy. Conclusion Our findings strongly support an association between T2DM and increased risk of overall fracture. These findings emphasize the need for fracture prevention strategies in patients with diabetes. PMID:28442913

Association of RAGE gene polymorphism with circulating AGEs level and paraoxonase activity in relation to macro-vascular complications in Indian type 2 diabetes mellitus patients.

PubMed

Bansal, Savita; Chawla, Diwesh; Banerjee, Basu Dev; Madhu, Sri Venkata; Tripathi, Ashok Kumar

2013-09-10

Sustained interaction of advanced glycation end products (AGEs) with their receptor RAGE and subsequent signaling plays an important role in the development of diabetic complications. Genetic variation of RAGE gene may be associated with the development of vascular complications in type 2 diabetes mellitus (T2DM). The present study aimed to explore the possible association of RAGE gene polymorphisms namely -374T/A, -429T/C and G82S with serum level of AGEs, paraoxonase (PON1) activity and macro-vascular complications (MVC) in Indian type 2 diabetes mellitus patients (T2DM). A total of 265 diabetic patients, including DM without any complications (n=135), DM-MVC (n=130) and 171 healthy individuals were enrolled. Genotyping of RAGE variants were assessed by polymerase chain reaction-restriction fragment length polymorphism. Serum AGEs were estimated by ELISA and fluorometrically. and PON1 activity was assessed spectrophotometrically. Of the three examined SNPs, association of -429T/C polymorphism with MVC in T2DM was observed (OR=3.001, p=0.001) in the dominant model. Allele 'A' of -374T/A polymorphism seems to confer better cardiac outcome in T2DM. Patients carrying C allele (-429T/C) and S allele (G82S) had significantly higher AGEs levels. -429T/C polymorphism was also found to be associated with low PON1 activity. Interaction analysis revealed that the risk of development of MVC was higher in T2DM patients carrying both a CC genotype of -429T/C polymorphism and a higher level of AGEs (OR=1.343, p=0.040). RAGE gene polymorphism has a significant effect on AGEs level and PON1 activity in diabetic subjects compared to healthy individuals. Diabetic patients with a CC genotype of -429T/C are prone to develop MVC, more so if AGEs levels are high and PON1 activity is low. Copyright © 2013 Elsevier B.V. All rights reserved.

Telomere Length Attrition, a Marker of Biological Senescence, Is Inversely Correlated with Triglycerides and Cholesterol in South Asian Males with Type 2 Diabetes Mellitus

PubMed Central

Harte, Alison L.; da Silva, Nancy F.; Miller, Michelle A.; Cappuccio, Francesco P.; Kelly, Ann; O'Hare, Joseph P.; Barnett, Anthony H.; Al-Daghri, Nasser M.; Al-Attas, Omar; Alokail, Majed; Sabico, Shaun; Tripathi, Gyanendra; Bellary, Srikanth; Kumar, Sudhesh; McTernan, Philip G.

2012-01-01

South Asians have a higher risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) than white Caucasians, for a given BMI. Premature biological ageing, assessed by reduction in telomere length (TL), may be mediated by factors resulting from altered metabolic profiles associated with obesity. We hypothesise that ethnicity and metabolic status represent detrimental factors contributing to premature biological ageing. Therefore we assessed TL in two South Asian, age and BMI-matched cohorts [T2DM (n = 142) versus non-T2DM (n = 76)] to determine the effects of BMI, gender, lipid and CVD profile on biological ageing. Genomic DNA was obtained from the UKADS cohort; biochemical and anthropometric data was collected and TL was measured by quantitative real-time PCR. Our findings indicated a gender-specific effect with reduced TL in T2DM men compared with non-T2DM men (P = 0.006). Additionally, in T2DM men, TL was inversely correlated with triglycerides and total cholesterol (r = −0.419, P < 0.01; r = −0.443, P < 0.01). In summary, TL was reduced amongst South Asian T2DM men and correlated with triglycerides and total cholesterol. This study highlights enhanced biological ageing among South Asian, T2DM men, which appears to be tracked by changes in lipids and BMI, suggesting that raised lipids and BMI may directly contribute to premature ageing. PMID:22474429

Can data extraction from general practitioners' electronic records be used to predict clinical outcomes for patients with type 2 diabetes?

PubMed

Staff, Michael

2012-01-01

The review of clinical data extraction from electronic records is increasingly being used as a tool to assist general practitioners (GPs) manage their patients in Australia. Type 2 diabetes (T2DM) is a chronic condition cared for primarily in the general practice setting that lends itself to the application of tools in this area. To assess the feasibility of extracting data from a general practice medical record software package to predict clinically significant outcomes for patients with T2DM. A pilot study was conducted involving two large practices where routinely collected clinical data were extracted and inputted into the United Kingdom Prospective Diabetes Study Outcomes Model to predict life expectancy. An initial assessment of the completeness of data available was performed and then for those patients aged between 45 and 64 years with adequate data life expectancies estimated. A total of 1019 patients were identified as current patients with T2DM. There were sufficient data available on 40% of patients from one practice and 49% from the other to provide inputs into the UKPDS Outcomes Model. Predicted life expectancy was similar across the practices with women having longer life expectancies than men. Improved compliance with current management guidelines for glycaemic, lipid and blood pressure control was demonstrated to increase life expectancy between 1.0 and 2.4 years dependent on gender and age group. This pilot demonstrated that clinical data extraction from electronic records is feasible although there are several limitations chiefly caused by the incompleteness of data for patients with T2DM.

Functional cartilage MRI T2 mapping: evaluating the effect of age and training on knee cartilage response to running.

PubMed

Mosher, T J; Liu, Y; Torok, C M

2010-03-01

To characterize effects of age and physical activity level on cartilage thickness and T2 response immediately after running. Institutional review board approval was obtained and all subjects provided informed consent prior to study participation. Cartilage thickness and magnetic resonance imaging (MRI) T2 values of 22 marathon runners and 15 sedentary controls were compared before and after 30 min of running. Runner and control groups were stratified by ageor=46 years. Multi-echo [(Time to Repetition (TR)/Time to Echo (TE) 1500 ms/9-109 ms)] MR images obtained using a 3.0 T scanner were used to calculate thickness and T2 values from the central femoral and tibial cartilage. Baseline cartilage T2 values, and change in cartilage thickness and T2 values after running were compared between the four groups using one-way analysis of variance (ANOVA). After running MRI T2 values decreased in superficial femoral (2 ms-4 ms) and tibial (1 ms-3 ms) cartilage along with a decrease in cartilage thickness: (femoral: 4%-8%, tibial: 0%-12%). Smaller decrease in cartilage T2 values were observed in the middle zone of cartilage, and no change was observed in the deepest layer. There was no difference cartilage deformation or T2 response to running as a function of age or level of physical activity. Running results in a measurable decrease in cartilage thickness and MRI T2 values of superficial cartilage consistent with greater compressibility of the superficial cartilage layer. Age and level of physical activity did not alter the T2 response to running. Copyright 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Evaluation of the relationship between T1ρ and T2 values and patella cartilage degeneration in patients of the same age group.

PubMed

Nishioka, Hiroaki; Hirose, Jun; Okamoto, Nobukazu; Okada, Tatsuya; Oka, Kiyoshi; Taniwaki, Takuya; Nakamura, Eiichi; Yamashita, Yasuyuki; Mizuta, Hiroshi

2015-03-01

The aim of this study was to investigate the association between the T1ρ and T2 values and the progression of cartilage degeneration in patients of the same age group. Sagittal T1ρ and T2 mapping and three-dimensional (3D) gradient-echo images were obtained from 78 subjects with medial knee osteoarthritis (OA). The degree of patella cartilage degeneration was classified into four groups using MRI-based grading: apparently normal cartilage, mild OA, moderate OA, and severe OA group. We measured the T1ρ and T2 values (ms) in the regions of interest set on the full-thickness patella cartilage. Then, we analyzed the relationship between the T1ρ and T2 values and the degree of patella cartilage degeneration. There were no significant differences in age among the four groups. Both the T1ρ and T2 values showed a positive correlation with the degree of OA progression (ρ=0.737 and ρ=0.632, respectively). By comparison between the apparently normal cartilage and the mild OA groups, there were significant differences in the T1ρ mapping, but not in the T2 mapping. Our study confirmed that T1ρ and T2 mapping can quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Pharmacokinetics of ranitidine in preterm and term neonates with gastroesophageal reflux.

PubMed

Asseff, Ismael Lares; Gaucin, Graciela Benitez; Olguín, Hugo Juárez; Nájera, Jose Antonio Godinez; López, Alejandra Toledo; Guillé, Gabriela Pérez; Torres, Fausto Zamura

2016-07-13

The aim of this study was to determine the effect of gestational age on pharmacokinetics of ranitidine in newborns with gastroesophageal reflux. A prospective, descriptive and pharmacokinetic study was carried out in 30 pre-term and 20 full-term babies. 3 mg/kg of ranitidine was administered intravenously to all the babies and at 0.25, 0.5, 1, 2, 4, and 8 h following the administration, samples of blood were drawn to assess ranitidine levels using high performance liquid chromatographic technique. Pharmacokinetics of ranitidine had a bi-exponential behavior with a half-life elimination of (t1/2el) 2.79 h, area under curve (AUC) of 1688 ng/mL, volume of distribution (Vd) of 1.44 L/kg, and clearance (Cl) of 5.9 L/kg/h. The median plasmatic concentration in pre-terms was 1113 ng/mL and 280 ng/mL in full-terms. Vd, t1/2 and Cl presented high values in preterm although the correlation of Cl with glomerular filtration in term newborns was better. Plasma levels of ranitidine depend on the gestational age of the newborns. However, the possible relationship between after-birth age and pharmacokinetics of the neonates as their internal organs get matured without minding their gestational background.

Hyperglycemia and advanced glycation end products (AGEs) suppress the differentiation of 3T3-L1 preadipocytes.

PubMed

Chang, Chia-Chu; Chen, Chen-Yu; Chang, Geen-Dong; Chen, Ting-Huan; Chen, Woan-Ling; Wen, Hui-Chin; Huang, Chih-Yang; Chang, Chung-Ho

2017-08-15

Aging is characterized by mild hyperglycemia and accumulation of advanced glycation end products (AGEs). Effects of chronic exposure to hyperglycemia or AGEs on the adipogenic differentiation of 3T3-L1 preadipocytes remain unclear. We examined the chronic effect of AGEs and high glucose on the differentiation of 3T3-L1 cells by culturing 3T3-L1 cells in the presence of AGEs or 25 mM glucose for 1 month. Chronic incubation of 3T3-L1 cells with AGEs or high glucose blocked their differentiation into mature adipocytes as evidenced by reduced levels of adipocyte markers such as accumulated oil droplets, GPDH, aP2, adiponectin and of adipogenesis regulators PPARγ and C/EBPα. Levels or activities of Src, PDK1, Akt, and NF-κB were higher in AGEs- and high glucose-treated cells than those in 3T3-L1 cells. Levels of Bcl-2 were elevated in AGEs- and high glucose-treated cells, and were attenuated by inhibitors of PI3-kinase, Akt and NF-κB. Moreover, adipogenesis was attenuated in 3T3-L1 cells stably expressing Bcl-2 or YAP. These results suggest that chronic AGEs and high glucose treatments up-regulate Bcl-2 and YAP via the Akt-NF-κB pathway and impair adipogenesis.

Hyperglycemia and advanced glycation end products (AGEs) suppress the differentiation of 3T3-L1 preadipocytes

PubMed Central

Chang, Geen-Dong; Chen, Ting-Huan; Chen, Woan-Ling; Wen, Hui-Chin; Huang, Chih-Yang; Chang, Chung-Ho

2017-01-01

Aging is characterized by mild hyperglycemia and accumulation of advanced glycation end products (AGEs). Effects of chronic exposure to hyperglycemia or AGEs on the adipogenic differentiation of 3T3-L1 preadipocytes remain unclear. We examined the chronic effect of AGEs and high glucose on the differentiation of 3T3-L1 cells by culturing 3T3-L1 cells in the presence of AGEs or 25 mM glucose for 1 month. Chronic incubation of 3T3-L1 cells with AGEs or high glucose blocked their differentiation into mature adipocytes as evidenced by reduced levels of adipocyte markers such as accumulated oil droplets, GPDH, aP2, adiponectin and of adipogenesis regulators PPARγ and C/EBPα. Levels or activities of Src, PDK1, Akt, and NF-κB were higher in AGEs- and high glucose-treated cells than those in 3T3-L1 cells. Levels of Bcl-2 were elevated in AGEs- and high glucose-treated cells, and were attenuated by inhibitors of PI3-kinase, Akt and NF-κB. Moreover, adipogenesis was attenuated in 3T3-L1 cells stably expressing Bcl-2 or YAP. These results suggest that chronic AGEs and high glucose treatments up-regulate Bcl-2 and YAP via the Akt-NF-κB pathway and impair adipogenesis. PMID:28903400

Persistent viral infections and immune aging.

PubMed

Brunner, Stefan; Herndler-Brandstetter, Dietmar; Weinberger, Birgit; Grubeck-Loebenstein, Beatrix

2011-07-01

Immunosenescence comprises a set of dynamic changes occurring to both, the innate as well as the adaptive immune system that accompany human aging and result in complex manifestations of still poorly defined deficiencies in the elderly population. One of the most prominent alterations during aging is the continuous involution of the thymus gland which is almost complete by the age of 50. Consequently, the output of naïve T cells is greatly diminished in elderly individuals which puts pressure on homeostatic forces to maintain a steady T cell pool for most of adulthood. In a great proportion of the human population, this fragile balance is challenged by persistent viral infections, especially Cytomegalovirus (CMV), that oblige certain T cell clones to monoclonally expand repeatedly over a lifetime which then occupy space within the T cell pool. Eventually, these inflated memory T cell clones become exhausted and their extensive accumulation accelerates the age-dependent decline of the diversity of the T cell pool. As a consequence, infectious diseases are more frequent and severe in elderly persons and immunological protection following vaccination is reduced. This review therefore aims to shed light on how various types of persistent viral infections, especially CMV, influence the aging of the immune system and highlight potential measures to prevent the age-related decline in immune function. Copyright © 2010 Elsevier B.V. All rights reserved.

Longitudinal change of selected human milk oligosaccharides and association to infants' growth, an observatory, single center, longitudinal cohort study.

PubMed

Sprenger, Norbert; Lee, Le Ye; De Castro, Carlos Antonio; Steenhout, Philippe; Thakkar, Sagar K

2017-01-01

Human milk is the recommended and sole nutrient source for newborns. One of the largest components of human milk is oligosaccharides (HMOs) with major constituents determined by the mother genotype for the fucosyltransferase 2 (FUT2, secretor) gene. HMO variation has been related with infant microbiota establishment, diarrhea incidence, morbidity and mortality, IgE associated eczema and body composition. We investigated the (i) dependence of several major representative HMOs on the FUT2 status assessed through breast milk 2'Fucosyllactose (2'FL) and (ii) the relation of the 2'FL status with infant growth up to 4 months of life. From an open observatory, single center, longitudinal cohort study with quantitative human milk collection at 30, 60, and 120 days postpartum from 50 mothers, who gave birth to 25 female and 25 male singleton infants, we collected a representative sample of human milk. We quantified the following 5 representative HMOs: 2'FL, Lacto-N-tetraose (LNT), Lacto-N-neotetraose (LNnT), 3'Sialyllactose (3'SL) and 6'Sialyllactose (6'SL). We grouped the milk samples and corresponding infants according to the measured milk 2'FL concentrations at 30 days of lactation, which clustered around low concentrations (95% CI of mean 12-42 mg/L) and high concentrations (95% CI of mean 1880-2460 mg/L) with the former likely representing Secretor negative mothers. Infant anthropometric measures were recorded at birth, 1, 2 and 4 months of age. Relations among the quantified HMOs and the relation of the high and low 2'FL HMOs groups with infant growth parameters were investigated via linear mixed models. The milk samples with low 2'FL concentration had higher LNT and lower LNnT concentrations compared to the samples with high 2'FL. The milk 3'- and 6'SL concentrations were independent of 2'FL. Over lactation time we observed a drop in the concentration of 2'FL, LNT, LNnT and 6'SL, especially from 1 to 2 months, while 3'SL remained at relatively constant concentration from 1 month onwards. Up to 4 months of age, we did not observe significant differences in body weight, body length, body mass index and head circumference of the infants who consumed breast milk with low or high FUT2 associated HMO concentrations and composition. Our findings on HMO concentrations over time of lactation and clusters based on 2'FL concentrations confirm previous observations and suggest that LNnT and LNT are 'co-regulated' with the FUT2 dependent 2'FL concentration, with LNnT showing a positive and LNT a negative relation. Further, our findings also suggest that the relatively substantial variation in HMOs between the high and low 2'FL clusters do not impact infant growth of either sex up to 4 months of age. The study was registered in www.ClinicalTrial.gov (NCT01805011).

The PreS2 activator MHBs(t) of hepatitis B virus activates c-raf-1/Erk2 signaling in transgenic mice.

PubMed

Hildt, Eberhard; Munz, Barbara; Saher, Gesine; Reifenberg, Kurt; Hofschneider, Peter Hans

2002-02-15

The large hepatitis B virus (HBV) surface protein (LHBs) and C-terminally truncated middle size surface proteins (MHBs(t)) form the family of the PreS2 activator proteins of HBV. Their transcriptional activator function is based on the cytoplasmic orientation of the PreS2 domain. MHBs(t) activators are paradigmatic for this class of activators. Here we report that MHBs(t) is protein kinase C (PKC)-dependently phosphorylated at Ser28. The integrity of the phosphorylation site is essential for the activator function. MHBs(t) triggers PKC-dependent activation of c-Raf-1/Erk2 signaling that is a prerequisite for MHBs(t)-dependent activation of AP-1 and NF-kappaB. To analyze the pathophysiological relevance of these data in vivo, transgenic mice were established that produce the PreS2 activator MHBs(t) specifically in the liver. In these mice, a permanent PreS2-dependent specific activation of c-Raf-1/Erk2 signaling was observed, resulting in an increased hepatocyte proliferation rate. In transgenics older than 15 months, an increased incidence of liver tumors occurs. These data suggest that PreS2 activators LHBs and MHBs(t) exert a tumor promoter-like function by activation of key enzymes of proliferation control.

Two separate defects affecting true naive or virtual memory T cell precursors combine to reduce naive T cell responses with aging.

PubMed

Renkema, Kristin R; Li, Gang; Wu, Angela; Smithey, Megan J; Nikolich-Žugich, Janko

2014-01-01

Naive T cell responses are eroded with aging. We and others have recently shown that unimmunized old mice lose ≥ 70% of Ag-specific CD8 T cell precursors and that many of the remaining precursors acquire a virtual (central) memory (VM; CD44(hi)CD62L(hi)) phenotype. In this study, we demonstrate that unimmunized TCR transgenic (TCRTg) mice also undergo massive VM conversion with age, exhibiting rapid effector function upon both TCR and cytokine triggering. Age-related VM conversion in TCRTg mice directly depended on replacement of the original TCRTg specificity by endogenous TCRα rearrangements, indicating that TCR signals must be critical in VM conversion. Importantly, we found that VM conversion had adverse functional effects in both old wild-type and old TCRTg mice; that is, old VM, but not old true naive, T cells exhibited blunted TCR-mediated, but not IL-15-mediated, proliferation. This selective proliferative senescence correlated with increased apoptosis in old VM cells in response to peptide, but decreased apoptosis in response to homeostatic cytokines IL-7 and IL-15. Our results identify TCR as the key factor in differential maintenance and function of Ag-specific precursors in unimmunized mice with aging, and they demonstrate that two separate age-related defects--drastic reduction in true naive T cell precursors and impaired proliferative capacity of their VM cousins--combine to reduce naive T cell responses with aging.

Pre-teen insulin resistance predicts weight gain, impaired fasting glucose, and type 2 diabetes at age 18-19 y: a 10-y prospective study of black and white girls.

PubMed

Morrison, John A; Glueck, Charles J; Horn, Paul S; Schreiber, George B; Wang, Ping

2008-09-01

Identifying early pre-teen predictors of adolescent weight gain and the development of impaired fasting glucose (IFG) and type 2 diabetes (T2DM) at age 18-19 y could provide avenues for prevention. We evaluated possible pre-teen predictors for development of IFG, T2DM, and changes in body mass index at age 18-19 y in black and white girls. In a prospective cohort study, body habitus and fasting insulin and glucose were measured at ages 9-10 and 18-19 y, and multiple 3-d diet records were collected. Factors predicting 10-y change in body mass index and development of IFG and T2DM together were assessed. In multivariate analyses, 10-y change in homeostatic model assessment of insulin resistance (HOMA-IR) and the age 9-10 y HOMA-IR x percentage of calories from fat interaction were positive predictors of 10-y changes in body mass index. At age 18-19 y, there were 5 incident cases of T2DM, 37 cases of IFG, and 597 noncases. Age 9-10 y IFG and HOMA-IR (or insulin), 10-y change in HOMA-IR (or insulin), and the age 9-10 y insulin x total caloric intake interaction predicted IFG and T2DM at age 18-19 y. Pre-teen IFG, insulin resistance (and insulin), and rapidly increasing insulin resistance during adolescence identifies girls who are at greater risk of future IFG and T2DM. In addition, insulin resistance, interacting with high-fat diets, identifies girls who are at risk of greater weight gain. These findings could open avenues to primary prevention of obesity, IFG, and T2DM in children.

Hypertrophic cardiomyopathy mutation in cardiac troponin T (R95H) attenuates length-dependent activation in guinea pig cardiac muscle fibers.

PubMed

Mickelson, Alexis V; Chandra, Murali

2017-12-01

The central region of cardiac troponin T (TnT) is important for modulating the dynamics of muscle length-mediated cross-bridge recruitment. Therefore, hypertrophic cardiomyopathy mutations in the central region may affect cross-bridge recruitment dynamics to alter myofilament Ca 2+ sensitivity and length-dependent activation of cardiac myofilaments. Given the importance of the central region of TnT for cardiac contractile dynamics, we studied if hypertrophic cardiomyopathy-linked mutation (TnT R94H )-induced effects on contractile function would be differently modulated by sarcomere length (SL). Recombinant wild-type TnT (TnT WT ) and the guinea pig analog of the human R94H mutation (TnT R95H ) were reconstituted into detergent-skinned cardiac muscle fibers from guinea pigs. Steady-state and dynamic contractile measurements were made at short and long SLs (1.9 and 2.3 µm, respectively). Our results demonstrated that TnT R95H increased pCa 50 (-log of free Ca 2+ concentration) to a greater extent at short SL; TnT R95H increased pCa 50 by 0.11 pCa units at short SL and 0.07 pCa units at long SL. The increase in pCa 50 associated with an increase in SL from 1.9 to 2.3 µm (ΔpCa 50 ) was attenuated nearly twofold in TnT R95H fibers; ΔpCa 50 was 0.09 pCa units for TnT WT fibers but only 0.05 pCa units for TnT R95H fibers. The SL dependency of rate constants of cross-bridge distortion dynamics and tension redevelopment was also blunted by TnT R95H Collectively, our observations on the SL dependency of pCa 50 and rate constants of cross-bridge distortion dynamics and tension redevelopment suggest that mechanisms underlying the length-dependent activation cardiac myofilaments are attenuated by TnT R95H NEW & NOTEWORTHY Mutant cardiac troponin T (TnT R95H ) differently affects myofilament Ca 2+ sensitivity at short and long sarcomere length, indicating that mechanisms underlying length-dependent activation are altered by TnT R95H TnT R95H enhances myofilament Ca 2+ sensitivity to a greater extent at short sarcomere length, thus attenuating the length-dependent increase in myofilament Ca 2+ sensitivity. Copyright © 2017 the American Physiological Society.

Fluorophores advanced glycation end products (AGEs)-to-NADH ratio is predictor for diabetic chronic kidney and cardiovascular disease.

PubMed

Ciobanu, Dana M; Olar, Loredana E; Stefan, Razvan; Veresiu, Ioan A; Bala, Cornelia G; Mircea, Petru A; Roman, Gabriela

2015-01-01

An imbalance in advanced glycation end products (AGEs) and NADH formation has been associated with diabetic chronic kidney disease (CKD) and cardiovascular disease (CVD). No data have been reported on simultaneous measurement of AGEs and NADH in type 2 diabetes (T2DM) patients. We aimed to compare AGEs, NADH and the AGEs-to-NADH ratio in T2DM and controls, and to assess its relationship with diabetic CKD and CVD. In this cross-sectional study, we measured serum AGEs (370/435nm) and NADH (370/460nm) in T2DM patients (n=63) and controls (n=25) using fluorescence spectroscopy. The AGEs-to-NADH ratio was analyzed according to diabetic CKD and CVD. We found significantly higher AGEs-to-NADH ratio in T2DM compared to controls. The AGEs-to-NADH ratio was significantly associated with triglycerides, blood glucose, HDL-cholesterol, estimated glomerular filtration rate. The AGEs-to-NADH ratio was a significant predictor for the presence of diabetic CKD and CVD when using ROC curves. Multivariate analysis showed that triglycerides and the presence of T2DM were predictors for the AGEs-to-NADH ratio. These findings suggest that the fluorophores AGEs-to-NADH ratio could be a new biomarker for the presence of diabetic CKD and CVD. Copyright © 2015 Elsevier Inc. All rights reserved.

Detailing magnetic field strength dependence and segmental artifact distribution of myocardial effective transverse relaxation rate at 1.5, 3.0, and 7.0 T.

PubMed

Meloni, Antonella; Hezel, Fabian; Positano, Vincenzo; Keilberg, Petra; Pepe, Alessia; Lombardi, Massimo; Niendorf, Thoralf

2014-06-01

Realizing the challenges and opportunities of effective transverse relaxation rate (R2 *) mapping at high and ultrahigh fields, this work examines magnetic field strength (B0 ) dependence and segmental artifact distribution of myocardial R2 * at 1.5, 3.0, and 7.0 T. Healthy subjects were considered. Three short-axis views of the left ventricle were examined. R2 * was calculated for 16 standard myocardial segments. Global and mid-septum R2 * were determined. For each segment, an artifactual factor was estimated as the deviation of segmental from global R2 * value. The global artifactual factor was significantly enlarged at 7.0 T versus 1.5 T (P = 0.010) but not versus 3.0 T. At 7.0 T, the most severe susceptibility artifacts were detected in the inferior lateral wall. The mid-septum showed minor artifactual factors at 7.0 T, similar to those at 1.5 and 3.0 T. Mean R2 * increased linearly with the field strength, with larger changes for global heart R2 * values. At 7.0 T, segmental heart R2 * analysis is challenging due to macroscopic susceptibility artifacts induced by the heart-lung interface and the posterior vein. Myocardial R2 * depends linearly on the magnetic field strength. The increased R2 * sensitivity at 7.0 T might offer means for susceptibility-weighted and oxygenation level-dependent MR imaging of the myocardium. Copyright © 2013 Wiley Periodicals, Inc.

Associations Among Parental Education, Home Environment Quality, Effortful Control, and Preacademic Knowledge

PubMed Central

Merz, Emily C.; Landry, Susan H.; Williams, Jeffrey M.; Barnes, Marcia A.; Eisenberg, Nancy; Spinrad, Tracy L.; Valiente, Carlos; Assel, Michael; Taylor, Heather B.; Lonigan, Christopher J.; Phillips, Beth M.; Clancy-Menchetti, Jeanine

2014-01-01

This study used a longitudinal design to examine whether effortful control mediated the associations of parental education and home environment quality with preacademic knowledge in toddlers and young preschoolers. The sample consisted of 226 children (2 to 4 years of age at T1) from socioeconomically disadvantaged backgrounds. Parents provided data on parent education and home environment quality. Children completed effortful control, early literacy, and early math assessments. T2 effortful control partially mediated the associations of T1 parental education and T1 home environment quality with T3 emergent literacy after accounting for child age, gender, race/ethnicity, T1 effortful control, and T2 early literacy. T2 effortful control partially mediated the association between T1 parental education and T3 emergent math after accounting for child age, gender, race/ethnicity, T1 effortful control, and T2 early math. Prior to entry into preschool, parental education and home environment quality may shape effortful control which in turn influences preacademic knowledge. PMID:25110382

2MASS J13243553+6358281 Is an Early T-type Planetary-mass Object in the AB Doradus Moving Group

NASA Astrophysics Data System (ADS)

Gagné, Jonathan; Allers, Katelyn N.; Theissen, Christopher A.; Faherty, Jacqueline K.; Bardalez Gagliuffi, Daniella; Artigau, Étienne

2018-02-01

We present new radial velocity and trigonometric distance measurements indicating that the unusually red and photometrically variable T2 dwarf 2MASS J13243553+6358281 is a member of the young (∼150 Myr) AB Doradus moving group (ABDMG) based on its space velocity. We estimate its model-dependent mass in the range 11–12 M Jup at the age of the ABDMG, and its trigonometric distance of 12.7 ± 1.5 pc makes it one of the nearest known isolated planetary-mass objects. The unusually red continuum of 2MASS J13243553+6358281 in the near-infrared was previously suspected to be caused by an unresolved L + T brown dwarf binary, although it was never observed with high spatial resolution imaging. This new evidence of youth suggests that a low surface gravity may be sufficient to explain this peculiar feature. Using the new parallax we find that its absolute J-band magnitude is ∼0.4 mag fainter than equivalent-type field brown dwarfs, suggesting that the binary hypothesis is unlikely. The fundamental properties of 2MASS J13243553+6358281 follow the spectral type sequence of other known high-likelihood members of the ABDMG. The effective temperature of 2MASS J13243553+6358281 provides the first precise constraint on the L/T transition at a known young age and indicates that it happens at a temperature of ∼1150 K at ∼150 Myr, compared to ∼1250 K for field brown dwarfs.

Mechanical property quantification of endothelial cells using scanning acoustic microscopy

NASA Astrophysics Data System (ADS)

Shelke, A.; Brand, S.; Kundu, T.; Bereiter-Hahn, J.; Blase, C.

2012-04-01

The mechanical properties of cells reflect dynamic changes of cellular organization which occur during physiologic activities like cell movement, cell volume regulation or cell division. Thus the study of cell mechanical properties can yield important information for understanding these physiologic activities. Endothelial cells form the thin inner lining of blood vessels in the cardiovascular system and are thus exposed to shear stress as well as tensile stress caused by the pulsatile blood flow. Endothelial dysfunction might occur due to reduced resistance to mechanical stress and is an initial step in the development of cardiovascular disease like, e.g., atherosclerosis. Therefore we investigated the mechanical properties of primary human endothelial cells (HUVEC) of different age using scanning acoustic microscopy at 1.2 GHz. The HUVECs are classified as young (tD < 90 h) and old (tD > 90 h) cells depending upon the generation time for the population doubling of the culture (tD). Longitudinal sound velocity and geometrical properties of cells (thickness) were determined using the material signature curve V(z) method for variable culture condition along spatial coordinates. The plane wave technique with normal incidence is assumed to solve two-dimensional wave equation. The size of the cells is modeled using multilayered (solid-fluid) system. The propagation of transversal wave and surface acoustic wave are neglected in soft matter analysis. The biomechanical properties of HUVEC cells are quantified in an age dependent manner.

The impact of self-reported life stress on current impulsivity in cocaine dependent adults

PubMed Central

Ross, Elizabeth L.; Yoon, Jin H.; Mahoney, James J.; Omar, Yasmine; Newton, Thomas F.; De La Garza, Richard

2014-01-01

Current cocaine treatments may be enhanced with a better understanding of the underlying mechanisms that contribute to the onset and maintenance of the disease, such as life stress and impulsivity. Life stress and impulsivity have previously been studied independently as contributors to drug use, and the current study expands upon past research by examining how these factors interact with one another. The aim of the current study was to evaluate the role of life stress in predicting impulsivity in a non-treatment seeking cocaine-dependent sample (N = 112). Analyses revealed that trait impulsivity (as measured by the Barratt Impulsiveness Scale) was associated with education (r = −3.09, p < 0.01), as those who had higher educational attainment also reported lower rates of trait impulsivity. In addition, those over the age of 30 demonstrated lower impulsivity in decision-making (as measured by delay discounting) than those under 30 (t = 2.21, p = 0.03). Overall exposure to life stress was not significantly correlated to either aspect of impulsivity. However several specific life stressors were significantly related to greater impulsivity including having been put up for adoption or in foster care (t = −2.96, p < 0.01), and having a child taken away against their will (t = −2.68, p = 0.01). These findings suggest that age and education relate to impulsivity; and that while an overall compilation of life stress scores was not related to impulsivity, specific types of stress related to either being taken away from a parent or having a child taken away were. Future studies should assess these constructs longitudinally to restrict response bias. PMID:23796525

Dopaminergic function in cannabis users and its relationship to cannabis-induced psychotic symptoms.

PubMed

Bloomfield, Michael A P; Morgan, Celia J A; Egerton, Alice; Kapur, Shitij; Curran, H Valerie; Howes, Oliver D

2014-03-15

Cannabis is the most widely used illicit drug globally, and users are at increased risk of mental illnesses including psychotic disorders such as schizophrenia. Substance dependence and schizophrenia are both associated with dopaminergic dysfunction. It has been proposed, although never directly tested, that the link between cannabis use and schizophrenia is mediated by altered dopaminergic function. We compared dopamine synthesis capacity in 19 regular cannabis users who experienced psychotic-like symptoms when they consumed cannabis with 19 nonuser sex- and age-matched control subjects. Dopamine synthesis capacity (indexed as the influx rate constant [Formula: see text] ) was measured with positron emission tomography and 3,4-dihydroxy-6-[(18)F]-fluoro-l-phenylalanine ([(18)F]-DOPA). Cannabis users had reduced dopamine synthesis capacity in the striatum (effect size: .85; t36 = 2.54, p = .016) and its associative (effect size: .85; t36 = 2.54, p = .015) and limbic subdivisions (effect size: .74; t36 = 2.23, p = .032) compared with control subjects. The group difference in dopamine synthesis capacity in cannabis users compared with control subjects was driven by those users meeting cannabis abuse or dependence criteria. Dopamine synthesis capacity was negatively associated with higher levels of cannabis use (r = -.77, p < .001) and positively associated with age of onset of cannabis use (r = .51, p = .027) but was not associated with cannabis-induced psychotic-like symptoms (r = .32, p = .19). These findings indicate that chronic cannabis use is associated with reduced dopamine synthesis capacity and question the hypothesis that cannabis increases the risk of psychotic disorders by inducing the same dopaminergic alterations seen in schizophrenia. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Local NMR relaxation rates T1-1 and T2-1 depending on the d -vector symmetry in the vortex state of chiral and helical p -wave superconductors

NASA Astrophysics Data System (ADS)

Tanaka, Kenta K.; Ichioka, Masanori; Onari, Seiichiro

2018-04-01

Local NMR relaxation rates in the vortex state of chiral and helical p -wave superconductors are investigated by the quasiclassical Eilenberger theory. We calculate the spatial and resonance frequency dependences of the local NMR spin-lattice relaxation rate T1-1 and spin-spin relaxation rate T2-1. Depending on the relation between the NMR relaxation direction and the d -vector symmetry, the local T1-1 and T2-1 in the vortex core region show different behaviors. When the NMR relaxation direction is parallel to the d -vector component, the local NMR relaxation rate is anomalously suppressed by the negative coherence effect due to the spin dependence of the odd-frequency s -wave spin-triplet Cooper pairs. The difference between the local T1-1 and T2-1 in the site-selective NMR measurement is expected to be a method to examine the d -vector symmetry of candidate materials for spin-triplet superconductors.

Effects of 6 months of resveratrol versus placebo on pentraxin 3 in patients with type 2 diabetes mellitus: a double-blind randomized controlled trial.

PubMed

Bo, S; Ponzo, V; Evangelista, A; Ciccone, G; Goitre, I; Saba, F; Procopio, M; Cassader, M; Gambino, R

2017-05-01

The anti-inflammatory effects of the polyphenol resveratrol in patients with type 2 diabetes mellitus (T2DM) are controversial. Its role on pentraxin 3 (PTX3) concentrations, a human acute phase protein, has never been evaluated. Our aim was to determine whether a two-dosage resveratrol supplementation (500 and 40 mg/day) has an impact on PTX3 values in T2DM patients from a double-blind randomized placebo-controlled trial. Variations in total antioxidant status (TAS) were evaluated too. A total of 192 T2DM patients were randomized to receive resveratrol 500 mg/day (Resv 500 arm), resveratrol 40 mg/day (Resv 40 arm) or placebo for 6 months. At baseline and at the trial end, PTX3 and TAS values were determined. A dose-dependent increase in PTX3 concentrations of 4.7% (Resv 40 arm) and 26.3% (Resv 500 arm), and 8.0% reduction after placebo were found. Adjusted mean differences of change versus placebo were 0.16 (95% CI 0.01-0.32) and 0.25 (0.09-0.42) in the Resv 40 and Resv 500 arms, respectively. At subgroup analyses, lower diabetes duration, aspirin, alcohol use, younger age, female gender, smoking (Resv 500 arm) and female gender and aspirin use (Resv 40 arm) were associated with higher PTX3 increments. A dose-dependent increment in TAS values in the resveratrol arms (1.4 and 6.4% for Resv 40 and Resv 500, respectively), and a reduction in placebo arm (-8.9%) were observed. Adjusted mean differences of change were 28.5 (95% CI 10.1-46.8) and 44.8 (25.4-64.1) in the Resv 40 and Resv 500 arms, respectively. Resveratrol supplementation increased PTX3 and TAS levels in a dose-dependent manner in T2DM patients. At present, potential clinical implications of these results remain unclear. CLINICALTRIALS. NCT02244879.

Normative values for volume and fat content of the hip abductor muscles and their dependence on side, age and gender in a healthy population.

PubMed

Marcon, Magda; Berger, Nicole; Manoliu, Andrei; Fischer, Michael A; Nanz, Daniel; Andreisek, Gustav; Ulbrich, Erika J

2016-04-01

To determine normative values for volume and fat content of the gluteus medius (GMed) and minimus (GMin) muscle in healthy volunteers and to evaluate their dependence on age, gender and leg dominance. The IRB approval was obtained for this study. 80 healthy volunteers (females, 40; males, 40; age range 20-62 years), divided into four age groups, were included. Fat- and water-signal-separated MR images of the pelvis were acquired on a 3.0 T MR with a 3-point mDIXON sequence. Normalized volume and fat-signal fraction (FSF) of the GMed (ViGMed, FSFGMed) and GMin (ViGMin, FSFGMin) muscles were determined. The overall mean volumes (normalized) and FSF ± SD: ViGMed 105.13 ± 16.30 cm(3); ViGMin 30.24 ± 5.15 cm(3); FSFGMed 8.13 ± 1.70 % and FSFGMin 9.89 ± 2.72 %. Comparing different age subgroups within each gender no significant differences were found concerning the volumes and FSFs (except FSFGMin in male subgroup aged 20-29 versus 50-62 years, P = 0.014). Comparing FSFs differences between the two genders, only in 20-29 years subgroup, FSFGMed (P =0.003) and FSFGMin (P =0.002) were greater in female. Volume differences between the two legs were not significant (P > 0.077); FSFGMed and FSFGMin (P =0.005 for both) were significantly lower in the dominant leg in female but not in male group (P = 0.454 for FSFGMed and P = 0.643 for FSFMin). No age dependency was evident for volume normative data for GMed and GMin and normative data for FSF values showed no age- or gender dependency.

Impact of mandibular implant prostheses on the oral health-related quality of life in partially and completely edentulous patients.

PubMed

Yunus, Norsiah; Masood, Mohd; Saub, Roslan; Al-Hashedi, Ashwaq Ali; Taiyeb Ali, Tara Bai; Thomason, John Mark

2016-07-01

To assess the oral health-related quality of life (OHRQoL) of patients provided with mandibular implant fixed partial prostheses (IFPP) for rehabilitation of two adjacent missing posterior teeth and complete denture patients provided with mandibular implant-supported overdenture (ISOD). The response to change in OHRQoL with implant prostheses was additionally compared. In this prospective study, 20 IFPP (mean age 47.0; SD 12.9 years) and 28 ISOD (mean age 61.5; SD 9.1 years) patients received 2 mandibular implants. Metal ceramic nonsplinted fixed prostheses were provided in IFPP group, while in ISOD group, the mandibular overdentures were retained by nonsplinted attachments. Patients rated their oral health-related quality of life using OHIP-14 Malaysian version at baseline (T0), 2-3 months (T1) and 1 year (T2) postimplant treatment. Mean OHIP-14 for total and domain scores between groups and intervals was analysed using repeated-measures ANOVA and t-test. Mann-Whitney and Wilcoxon signed-rank tests were used for the comparison of mean score change and effect size, while the association between pre- and post-treatment scores was determined using multivariate linear regression modelling. The total OHIP and domain scores before implant treatment were significantly higher (lower OHRQoL) in IFPP than in ISOD groups, except for physical pain where this domain showed similar impact in both groups. Postimplant scores between groups at T1 and T2 showed no significant difference. The mean score changes at T0-T1 and T0-T2 for total OHIP-14 and domains were significantly greater in IFPP except in the domains of physical pain and disability which showed no difference. Large effect size (ES) was observed for total OHIP-14 in IFPP while moderate in ISOD. Improved OHRQoL was dependent on the treatment group and pretreatment score. Improvement in OHRQoL occurred following both mandibular implant-supported overdentures and implant fixed partial prostheses. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Diabetes confers in vitro calcific potential on serum which associates with in vivo vascular calcification.

PubMed

Patidar, Ashish; Singh, Dhruv K; Thakur, Shori; Winocour, Peter; Farrington, Ken; Baydoun, Anwar R

2017-05-01

Although vascular calcification (VC) is prevalent in Type 2 diabetes mellitus (T2DM), underlying mechanisms remain unclear. Neither is it known whether T2DM confers calcific potential (CP) on serum, enabling it to induce VC outside the disease milieu. We, therefore, investigated the CP of serum from controls and subjects with T2DM with and without in vivo VC . Samples from 20 healthy controls and 44 age- and sex-matched patients with T2DM with modification of diet in renal disease estimated glomerular filtration rate (MDRD-4 eGFR) > 60 ml·min -1 were analysed for CP using rat aortic smooth muscle cells in vitro CT scans of femoral arteries identified individuals with in vivo calcification. Serum from subjects with T2DM revealed significantly greater CP than controls. This was further enhanced in the presence of in vivo VC. Addition of β-glycerophosphate (β-GP) plus CaCl 2 increased the CP of T2DM serum but not of controls. Along with age, CP was an independent predictor of the presence of VC. In receiver operator curve (ROC) analysis, CP was a significant predictor of femoral arterial VC (C-statistic 0.70: P =0.009). The distribution of CP was bimodal around a cutoff of 100 nmoles of Ca 2+ protein mg -1 , with a higher proportion of Type 2 diabetes subjects with in vivo calcification (T2DM+) sera above the cutoff value. This group also showed elevated levels of osteoprotegerin (OPG) and matrix Gla protein (MGP). Diabetes confers CP on the serum which is enhanced by the presence of in vivo VC. The CP acquired may be dependent on levels of OPG and MGP. These findings may be clinically relevant for early identification of individuals at risk of VC and for informing therapeutic strategies. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Reconstruction of ionic currents in a molluscan photoreceptor.

PubMed Central

Sakakibara, M.; Ikeno, H.; Usui, S.; Collin, C.; Alkon, D. L.

1993-01-01

Two-microelectrode voltage-clamp measurements were made to determine the kinetics and voltage dependence of ionic currents across the soma membrane of the Hermissenda type B photoreceptor. The voltage-dependent outward potassium currents, IA and ICa(2+)-K+, the inward voltage-dependent calcium current, ICa2+ and the light-induced current, IIgt, were then described with Hodgkin-Huxley-type equations. The fast-activating and inactivating potassium current, IA, was described by the equation; IA(t) = gA(max)(ma infinity[1-exp(-t/tau ma)])3 x (ha infinity [1-exp(-t/tau ha)] + exp(-t/tau ha)) (Vm-EK), where the parameters ma infinity, ha infinity, tau ma, and tau ha are functions of membrane potential, Vm, and ma infinity and ha infinity are steady-state activation and inactivation parameters. Similarly, the calcium-dependent outward potassium current, ICa(2+)-K+, was described by the equation, ICa(2+)-K+ (t) = gc(max)(mc infinity(VC)(1-exp[-t/tau mc (VC)]))pc (hc infinity(VC) [1-exp(-t/tau hc)] + exp(-t/tau hc(VC)])pc(VC-EK). In high external potassium, ICa(2+)-K+ could be measured in approximate isolation from other currents as a voltage-dependent inward tail current following a depolarizing command pulse from a holding potential of -60 mV. A voltage-dependent inward calcium current across the type B soma membrane, ICa2+, activated rapidly, showed little inactivation, and was described by the equation: ICa2+ = gCa(max) [1 + exp](-Vm-5)/7]-1 (Vm-ECa), where gCa(max) was 0.5 microS. The light-induced current with both fast and slow phases was described by: IIgt(t) = IIgt1 + IIgt2 + IIgt3, IIgti = gIgti [1-exp(- ton/tau mi)] exp(-ton/tau hi)(Vm-EIgti) (i = 1, 2). For i = 3, /Igt(t) = gigt3m33h3(Vm - Eigt3)exp(-ton/Ton) x exp(-tfoff/t Off). Based on these reconstructions of ionic currents, learning-induced enhancement of the long lasting depolarization (LLD) of the photoreceptor'slight response was shown to arise from progressive inactivation of /A, lca2+ -K+, and lCa2+. PMID:8369456

The impact of acute high-intensity interval exercise on biomarkers of cardiovascular health in type 2 diabetes.

PubMed

Francois, Monique E; Little, Jonathan P

2017-08-01

High-intensity interval training (HIIT) interventions improve cardiovascular health, yet the acute effects on circulating and functional biomarkers of cardiovascular function are unclear in individuals with type 2 diabetes (T2D). To explore this, we conducted two investigations to examine the acute response to HIIT in individuals with T2D. Study 1 measured blood pressure, endothelial-dependent dilation, circulating measures of endothelial activation, and troponin T, 30 min and 2 h after HIIT (7 × 1-min intervals) in T2D (n = 8) and age-matched normoglycemic controls (CTL; n = 8). Study 2 assessed circulating measures of endothelial activation and troponin T, 30 min, and 24 h after HIIT (10 × 1-min intervals) in ten previously trained T2D men. In study 1, markers of endothelial function and activation within the first 2 h after HIIT did not differ from baseline between T2D and CTL participants, except at 30 min after HIIT for glucose, which was reduced more in T2D than CTL (by -0.8 ± 1.2 mmol/L, p = 0.04), and VCAM-1, which was reduced more 30 min after HIIT in CTL compared to T2D (by -187 ± 221 ng/mL, p = 0.05). Study 2 saw no significant difference in any circulating markers of endothelial activation and troponin T, 30 min, and 24 h after HIIT in trained T2D males. Exploratory findings from these two studies suggest that acute HIIT does not substantially alter circulating and functional markers of cardio(vascular) health in individuals with T2D who are unaccustomed (study 1) and accustomed to HIIT (study 2).

T2 relaxation times of the glenohumeral joint at 3.0 T MRI in patients with and without primary and secondary osteoarthritis.

PubMed

Lee, So-Yeon; Park, Hee-Jin; Kwon, Heon-Ju; Kim, Mi Sung; Choi, Seon Hyeong; Choi, Yoon Jung; Kim, Eugene

2015-11-01

Quantitative magnetic resonance imaging (MRI) of cartilage has recently been applied to patients with osteoarthritis (OA). T2 mapping is a sensitive method of detecting changes in the chemical composition and structure of cartilage. To establish baseline T2 values of glenohumeral joint cartilage at 3.0 T and compare T2 values among subjects with and without OA. The study involved 30 patients (18 women, 12 men; median age, 67 years; age range, 51-78 years) with primary (n = 7) and secondary OA (n = 23) in the glenohumeral joint and 34 subjects without OA (19 women, 15 men; median age, 49 years; age range, 23-63 years). All subjects were evaluated by radiography and 3.0 T MRI including a multi-echo T2-weighted spin echo pulse sequence. The T2 value of the cartilage was measured by manually drawing the region of interest on the T2 map. Per-zone comparison of T2 values was performed using Mann-Whitney U test. Median T2 values differed significantly between subjects without OA (36.00 ms [interquartile range, 33.89-37.31 ms]) and those with primary (37.52 ms [36.84-39.11], P = 0.028), but not secondary (36.87 ms [34.70-41.10], P = 0.160) OA. Glenohumeral cartilage T2 values were higher in different zones between patients with primary and secondary OA than in subjects without OA. These T2 values can be used for comparison to assess cartilage degeneration in patients with shoulder OA. Significant differences in T2 were observed among subjects without OA and those with primary and secondary OA. © The Foundation Acta Radiologica 2014.

Evaluation of [¹⁸F]PFH PET renography to predict future disease progression in a rat model of autosomal dominant polycystic kidney disease.

PubMed

Pathuri, Gopal; Hedrick, Andria F; Awasthi, Vibhudutta; Cowley, Benjamin D; Gali, Hariprasad

2016-01-01

Prognostic markers for progression of polycystic kidney disease (PKD) are limited. We evaluated the potential of early para-[(18)F]fluorohippurate ([(18)F]PFH) positron emission tomography (PET) renography to predict future progression of PKD in Han:SPRD rats with slowly progressive autosomal dominant PKD. Male and female heterozygous (Cy/+) and normal littermate (+/+) Han:SPRD rats underwent [(18)F]PFH PET renography and blood sampling to measure serum creatinine (S-Cr) and serum urea nitrogen (SUN) concentrations at 6 and 26 wk of age. T2 and T20 values, which represent the percent of the injected dose of [(18)F]PFH in kidneys at 2 and 20 min after injection, were determined from imaging data. T20/T2 ratio was assessed as a prognostic marker. Rats were euthanized after renography at 26 wk of age, and kidney weight/body weight ratios (KW/BW%) were determined as a measure of PKD progression. Male and female Cy/+ rats are known to manifest PKD of different severity, male Cy/+ rats display much more severe PKD than female rats. S-Cr and SUN concentrations did not differ between +/+ and Cy/+ rats and between female and male Cy/+ rats at 6 wk of age, but they were higher at 26 wk of age and male rats displayed higher values than female rats, which indicates inability of S-Cr and SUN to measure disease severity at an early stage. T20/T2 ratios were higher for Cy/+ than +/+ rats at 6 wk of age. Importantly, male Cy/+ rats displayed higher T20/T2 ratios than female Cy/+ rats. T20/T2 ratios obtained at 6 wk of age correlated well with S-Cr, SUN, and KW/BW% values obtained at 26 wk of age. This study indicates that T20/T2 ratio derived from [(18)F]PFH PET renography at an early age could be useful as a novel prognostic marker to predict future disease severity in a rat model of ADPKD. Copyright © 2015 Elsevier Inc. All rights reserved.

Variability of the hemodynamic response as a function of age and frequency of epileptic discharge in children with epilepsy.

PubMed

Jacobs, Julia; Hawco, Colin; Kobayashi, Eliane; Boor, Rainer; LeVan, Pierre; Stephani, Ulrich; Siniatchkin, Michael; Gotman, Jean

2008-04-01

EEG-fMRI is a non-invasive tool to investigate epileptogenic networks in patients with epilepsy. Different patterns of BOLD responses have been observed in children as compared to adults. A high intra- and intersubject variability of the hemodynamic response function (HRF) to epileptic discharges has been observed in adults. The actual HRF to epileptic discharges in children and its dependence on age are unknown. We analyzed 64 EEG-fMRI event types in 37 children (3 months to 18 years), 92% showing a significant BOLD response. HRFs were calculated for each BOLD cluster using a Fourier basis set. After excluding HRFs with a low signal-to-noise ratio, 126 positive and 98 negative HRFs were analyzed. We evaluated age-dependent changes as well as the effect of increasing numbers of spikes. Peak time, amplitude and signal-to-noise ratio of the HRF and the t-statistic score of the cluster were used as dependent variables. We observed significantly longer peak times of the HRF in the youngest children (0 to 2 years), suggesting that the use of multiple HRFs might be important in this group. A different coupling between neuronal activity and metabolism or blood flow in young children may cause this phenomenon. Even if the t-value increased with frequent spikes, the amplitude of the HRF decreased significantly with spike frequency. This reflects a violation of the assumptions of the General Linear Model and therefore the use of alternative analysis techniques may be more appropriate with high spiking rates, a common situation in children.

Variability of the hemodynamic response as a function of age and frequency of epileptic discharge in children with epilepsy

PubMed Central

Jacobs, Julia; Hawco, Colin; Kobayashi, Eliane; Boor, Rainer; LeVan, Pierre; Stephani, Ulrich; Siniatchkin, Michael; Gotman, Jean

2013-01-01

EEG-fMRI is a non-invasive tool to investigate epileptogenic networks in patients with epilepsy. Different patterns of BOLD responses have been observed in children as compared to adults. A high intra- and intersubject variability of the hemodynamic response function (HRF) to epileptic discharges has been observed in adults. The actual HRF to epileptic discharges in children and its dependence on age are unknown. We analyzed 64 EEG-fMRI event types in 37 children (3 months to 18 years), 92% showing a significant BOLD response. HRFs were calculated for each BOLD cluster using a Fourier basis set. After excluding HRFs with a low signal-to-noise ratio, 126 positive and 98 negative HRFs were analyzed. We evaluated age-dependent changes as well as the effect of increasing numbers of spikes. Peak time, amplitude and signal-to-noise ratio of the HRF and the t-statistic score of the cluster were used as dependent variables. We observed significantly longer peak times of the HRF in the youngest children (0 to 2 years), suggesting that the use of multiple HRFs might be important in this group. A different coupling between neuronal activity and metabolism or blood flow in young children may cause this phenomenon. Even if the t-value increased with frequent spikes, the amplitude of the HRF decreased significantly with spike frequency. This reflects a violation of the assumptions of the General Linear Model and therefore the use of alternative analysis techniques may be more appropriate with high spiking rates, a common situation in children. PMID:18221891

Effects of methyltestosterone on immunity against Salmonella Pullorum in dwarf chicks.

PubMed

Li, H; Zhang, Y; Zuo, S F; Lian, Z X; Li, N

2009-12-01

This study was conducted to determine effects of methyltestosterone on innate immunity and adaptive immunity against Salmonella Pullorum in dwarf chicks. In vivo experiment, comparisons of pathological sections, viable counts of bacteria, specific antibody levels, and subsets of T lymphocytes were set forth between chicks with or without 10(-7) M methyltestosterone treatment (2 d of age through 21 d of age) and challenged with 5 x 10(8) virulent Salmonella Pullorum (7 d of age), and in vitro experiment, phagocytic and killing abilities, reactive oxygen intermediate production, and reactive nitrogen intermediate production of monocytes-macrophages treated with high (10(-8) M/10(6) cell) or physiological (10(-14) M/10(6) cell) concentration of methyltestosterone were examined after Salmonella Pullorum infection. The results showed that (1) in vivo, administration of methyltestosterone enhanced susceptibility to Salmonella Pullorum infection and depressed cellular immunity against Salmonella Pullorum, whereas it had no effect on humoral immunity in dwarf chicks; (2) in vitro, at high concentration, methyltestosterone reduced (P < 0.05) monocytes-macrophages mediated reactive oxygen intermediate-dependent killing of Salmonella Pullorum, whereas low concentration of methyltestosterone enhanced (P < 0.05) reactive oxygen intermediate-dependent killing of Salmonella Pullorum in male dwarf chicks but not in females; and (3) although challenged with Salmonella Pullorum, phagocytic ability and monocytes-macrophages mediated reactive nitrogen intermediate-dependent killing were not affected by methyltestosterone in vitro. The results indicated that methyltestosterone affected the immune response to Salmonella Pullorum in dwarf chicks by changing monocytes-macrophages mediated reactive oxygen intermediate-dependent killing and cellular immunity, and the effects were dose-dependent; furthermore, the former 2 pathways played important roles in preventing Salmonella Pullorum infection in dwarf chicks, although the mechanism needs further study.

The Hayflick Limit and Age-Related Adaptive Immune Deficiency.

PubMed

Gill, Zoe; Nieuwoudt, Martin; Ndifon, Wilfred

2018-01-01

The adaptive immune system (AIS) acquires significant deficiency during chronological ageing, making older individuals more susceptible to infections and less responsive to vaccines compared to younger individuals. At the cellular level, one of the most striking features of this ageing-related immune deficiency is the dramatic loss of T-cell diversity that occurs in elderly humans. After the age of 70 years, there is a sharp decline in the diversity of naïve T cells, including a >10-fold decrease in the CD4+ compartment and a >100-fold decrease in the CD8+ compartment. Such changes are detrimental because the AIS relies on a diverse naïve T-cell pool to respond to novel pathogens. Recent work suggests that this collapse of naïve T-cell diversity results from T cells reaching the Hayflick limit and being eliminated through both antigen-dependent and -independent pathways. The progressive attrition of telomeres is the molecular mechanism that underlies this Hayflick limit. Therefore, we propose that by measuring the telomere lengths of T cells with high resolution, it is possible to develop a unique biomarker of immune deficiency, potentially much better correlated with individual susceptibility to diseases compared to chronological age alone. © 2017 S. Karger AG, Basel.

Forming characteristics of artificial aging Al-Mg-Si-Cu sheet alloys

NASA Astrophysics Data System (ADS)

Klos, Artur; Kellner, Sven; Wortberg, Daniel; Walter, Philipp; Bassi, Corrado; Merklein, Marion

2017-10-01

AA6111 is a commonly used aluminum alloy for body-in-white (BIW) components with good bake-hardening response, high strength and excellent formability. For industrial applications various process strategies are considered to reach strength of about 250 MPa in the final body part with that type of alloy. The purpose of this paper is to discuss recent process strategies of high-strength AA6111 sheets to evaluate the forming characteristics, precipitation kinetics dissolution and mechanical properties in the final condition. The forming behavior is investigated by four potential process chains after single-stage or multi-stage heat treatment including T4 (pre-aged at > 80 °C after quenching), T61 (T4 + artificial aged at 120-150 °C for 10-18 h), T6 (T4 + artificial aged at 180-220°C up to 12 h) and PFHT (T4 + post form heat treatment at 205°C for 30 min). The experimental input for characterization of the formability consists of tensile tests, bending tests and drawing tests. Differential Scanning Calorimetry (DSC) is used, to correlate the forming behavior with the precipitation distribution in the advanced stages of aging. The study shows that the forming behavior is strongly dependent on the condition the alloy.

Differences in clinical and biological characteristics and prevalence of chronic complications related to aging in patients with type 2 diabetes.

PubMed

Basanta-Alario, María Luisa; Ferri, Jordi; Civera, Miguel; Martínez-Hervás, Sergio; Ascaso, Juan Francisco; Real, José Tomás

2016-02-01

Type 2 diabetes mellitus (T2DM) is a chronic, highly prevalent disease that increases with age. Because of this, and due to its chronic complications, T2DM causes high human, social, and financial costs. In addition, the elderly population with T2DM has a marked clinical heterogeneity. Therefore, our main objective was to analyze the relationship of age with the clinical and biological manifestations of the disease and the prevalence of chronic complications in patients with T2DM. A cross-sectional study of a large population with T2DM (n=405) randomly selected from a Diabetes Unit and 2 health care centers (60%). The clinical, anthropometric, and biochemical variables of the subjects were collected using standard methods to assess the effect of age on the clinical and biochemical phenotype of patients with T2DM. We have noted that patients with T2DM > 70 years old have a clinical and biochemical phenotype different from younger subjects (<60 years) including longer times since diabetes onset, higher diastolic blood pressure levels, and lower body mass index (BMI) values. As regards to biological variables, these patients have lower triglyceride levels, impaired kidney function, and lower HbA1c values. Prevalence of metabolic syndrome is lower in patients with T2DM > 70 years of age. Age was inversely related to parameters associated to metabolic syndrome (BMI, waist circumference, blood pressure, and triglyceride levels). We have defined the clinical and biochemical profile of patients with T2DM > 70 years attending health care centers. In addition, the prevalence of stroke, kidney disease, and distal symmetrical polyneuropathy is higher in patients with T2DM >70 years as compared to younger patients (<60 years). Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Studies on B-cell memory. III. T-dependent aspect of B memory generation in mice immunized with T-independent type-2(TI-2) antigen.

PubMed

Hosokawa, T; Tanaka, Y; Aoike, A; Kawai, K; Muramatsu, S

1984-09-01

The time course of B-cell memory development to a dinitrophenyl (DNP) T-independent type-2 (TI-2) antigen was investigated by adoptive cell transfer. Strong IgM and IgG memory developed in BALB/c mice after immunization with DNP-dextran, to be recalled by challenge with either T-dependent (TD) antigen or TI-2 antigen. However, only weak IgM memory and very feeble IgG memory were detected in athymic nude mice receiving the same immunization as euthymic mice. Once memory was established under probable T cell influence, its recall by TI-2 antigen challenge seemed independent of T cell help and did not require sharing of carriers between priming and challenge antigens. The following may be concluded. (i) Long-term IgM and IgG memory is induced by TI-2 antigen priming in the presence of functional T cells. (ii) The class switch from IgM to IgG in the memory B cell pool is driven effectively by TI-2 antigen and is probably T cell-dependent.

Ca2+/calmodulin-dependent transcriptional pathways: potential mediators of skeletal muscle growth and development.

PubMed

Al-Shanti, Nasser; Stewart, Claire E

2009-11-01

The loss of muscle mass with age and disuse has a significant impact on the physiological and social well-being of the aged; this is an increasingly important problem as the population becomes skewed towards older age. Exercise has psychological benefits but it also impacts on muscle protein synthesis and degradation, increasing muscle tissue volume in both young and older individuals. Skeletal muscle hypertrophy involves an increase in muscle mass and cross-sectional area and associated increased myofibrillar protein content. Attempts to understand the molecular mechanisms that underlie muscle growth, development and maintenance, have focused on characterising the molecular pathways that initiate, maintain and regenerate skeletal muscle. Such understanding may aid in improving targeted interventional therapies for age-related muscle loss and muscle wasting associated with diseases. Two major routes through which skeletal muscle development and growth are regulated are insulin-like growth factor I (IGF-I) and Ca(2+)/calmodulin-dependent transcriptional pathways. Many reviews have focused on understanding the signalling pathways of IGF-I and its receptor, which govern skeletal muscle hypertrophy. However, alternative molecular signalling pathways such as the Ca(2+)/calmodulin-dependent transcriptional pathways should also be considered as potential mediators of muscle growth. These latter pathways have received relatively little attention and the purpose herein is to highlight the progress being made in the understanding of these pathways and associated molecules: calmodulin, calmodulin kinases (CaMKs), calcineurin and nuclear factor of activated T-cell (NFAT), which are involved in skeletal muscle regulation. We describe: (1) how conformational changes in the Ca(2+) sensor calmodulin result in the exposure of binding pockets for the target proteins (CaMKs and calcineurin). (2) How Calmodulin consequently activates either the Ca(2+)/calmodulin-dependent kinases pathways (via CaMKs) or calmodulin-dependent serine/threonine phosphatases (via calcineurin). (3) How calmodulin kinases alter transcription in the nucleus through the phosphorylation, deactivation and translocation of histone deacetylase 4 (HDAC4) from the nucleus to the cytoplasm. (4) How calcineurin transmits signals to the nucleus through the dephosphorylation and translocation of NFAT from the cytoplasm to the nucleus.

The effect of hyperglycaemia on osseointegration: a review of animal models of diabetes mellitus and titanium implant placement.

PubMed

King, Shalinie; Klineberg, Iven; Levinger, Itamar; Brennan-Speranza, Tara C

2016-12-01

Patients with type 2 diabetes mellitus have a higher risk of dental and/or orthopaedic implant failure. However, the mechanism behind this phenomenon is unclear, and animal studies may prove useful in shedding light on the processes involved. This review considers the available literature on rat models of diabetes and titanium implantation. The process of osseointegration whereby direct contact is achieved between bone and an implant surface depends on healthy bone metabolism. Collective evidence suggests that hyperglycaemia adversely affects bone turnover and the quality of the organic matrix resulting in an overall deterioration in the quality, resilience and structure of the bone tissue. This in turn results in compromised osseointegration in patients receiving dental and orthopaedic implants. The incidence of diabetes mellitus (DM), which is a chronic metabolic disorder resulting in hyperglycaemia, is rising. Of particular significance is the rising incidence of adult onset type 2 diabetes mellitus (T2DM) in an ageing population. Understanding the effects of hyperglycaemia on osseointegration will enable clinicians to manage health outcomes for patients receiving implants. Much of our understanding of how hyperglycaemia affects osseointegration comes from animal studies. In this review, we critically analyse the current animal studies. Our review has found that most studies used a type 1 diabetes mellitus (T1DM) rodent model and looked at a young male population of rodents. The pathophysiology of T1DM is however very different to that of T2DM and is not representative of T2DM, the incidence of which is rising in the ageing adult population. Genetically modified rats have been used to model T2DM, but none of these studies have included female rats and the metabolic changes in bone for some of these models used are not adequately characterized. Therefore, the review suggests that the study population needs to be broadened to include both T1DM and T2DM models, older rats as well as young rats, and importantly animals from both sexes to reflect more accurately clinical practice.

Chromosome 7p linkage and association study for diabetes related traits and type 2 diabetes in an African-American population enriched for nephropathy.

PubMed

Leak, Tennille S; Langefeld, Carl D; Keene, Keith L; Gallagher, Carla J; Lu, Lingyi; Mychaleckyj, Josyf C; Rich, Stephen S; Freedman, Barry I; Bowden, Donald W; Sale, Michèle M

2010-02-08

Previously we performed a linkage scan of 638 African American affected sibling pairs (ASP) with type 2 diabetes (T2D) enriched for end-stage renal disease (ESRD). Ordered subset linkage analysis (OSA) revealed a linkage peak on chromosome 7p in the subset of families with earlier age of T2D diagnosis. We fine mapped this region by genotyping 11 additional polymorphic markers in the same ASP and investigated a total of 68 single nucleotide polymorphisms (SNPs) in functional candidate genes (GCK1, IL6, IGFBP1 and IGFBP3) for association with age of T2D diagnosis, age of ESRD diagnosis, duration of T2D to onset of ESRD, body mass index (BMI) in African American cases and T2D-ESRD in an African American case-control cohort. OSA of fine mapping markers supported linkage at 28 cM on 7p (near D7S3051) in early-onset T2D families (max. LOD = 3.61, P = 0.002). SNPs in candidate genes and 70 ancestry-informative markers (AIMs) were evaluated in 577 African American T2D-ESRD cases and 596 African American controls. The most significant association was observed between ESRD age of diagnosis and SNP rs730497, located in intron 1 of the GCK1 gene (recessive T2D age-adjusted P = 0.0006). Nominal associations were observed with GCK1 SNPs and T2D age of diagnosis (BMI-adjusted P = 0.014 to 0.032). Also, one IGFBP1 and four IGFBP3 SNPs showed nominal genotypic association with T2D-ESRD (P = 0.002-0.049). After correcting for multiple tests, only rs730497 remanined significant. Variant rs730947 in the GCK1 gene appears to play a role in early ESRD onset in African Americans.

Early risk factors for being a bully, victim, or bully/victim in late elementary and early secondary education. The longitudinal TRAILS study

PubMed Central

2011-01-01

Background Data regarding the impact of early risk factors on later involvement in bullying are scarce. We investigated the impact of preschool behaviors, family characteristics (socio-economic status, family breakup) and parental mental health on bullying and victimization at age 11 (T1) and age 13.5 (T2). Methods longitudinal data from a subsample of the TRacking Adolescents' Individual Lives Survey (TRAILS) (T1: N = 982; T2: N = 977). TRAILS is a prospective study of adolescent mental health in a mixed urban and rural region of the Netherlands. At T1 parents reported on family characteristics, parental mental health and retrospectively on children's preschool behavior at age 4-5. Schoolmates reported involvement of adolescents in bullying or victimization at T1 and T2. Results Children with preschool anxiety were less likely to be bully/victim at T1. Children with preschool aggressiveness were more likely to be bully (T1), bully/victim (T1 and T2) and victim (T2) and children with good preschool motor functioning were more likely to be bully (T1) and less likely to be victim (T1 and T2). Children from low socioeconomic status families were more likely be to be bully, victim, or bully/victim and less likely to be uninvolved both at T1 and T2. Finally, children from intact two parent families were more likely to be uninvolved at T2. Conclusion Preschool behavioral, emotional and motor problems, socioeconomic status, and family breakup are related to involvement in bullying at a later age. Prevention of bullying and its consequences can be enhanced by focusing on risk groups in early life. PMID:21645403

The basis of distinctive IL-2- and IL-15-dependent signaling: weak CD122-dependent signaling favors CD8+ T central-memory cell survival but not T effector-memory cell development.

PubMed

Castro, Iris; Yu, Aixin; Dee, Michael J; Malek, Thomas R

2011-11-15

Recent work suggests that IL-2 and IL-15 induce distinctive levels of signaling through common receptor subunits and that such varied signaling directs the fate of Ag-activated CD8(+) T cells. In this study, we directly examined proximal signaling by IL-2 and IL-15 and CD8(+) T cell primary and memory responses as a consequence of varied CD122-dependent signaling. Initially, IL-2 and IL-15 induced similar p-STAT5 and p-S6 activation, but these activities were only sustained by IL-2. Transient IL-15-dependent signaling is due to limited expression of IL-15Rα. To investigate the outcome of varied CD122 signaling for CD8(+) T cell responses in vivo, OT-I T cells were used from mouse models where CD122 signals were attenuated by mutations within the cytoplasmic tail of CD122 or intrinsic survival function was provided in the absence of CD122 expression by transgenic Bcl-2. In the absence of CD122 signaling, generally normal primary response occurred, but the primed CD8(+) T cells were not maintained. In marked contrast, weak CD122 signaling supported development and survival of T central-memory (T(CM)) but not T effector-memory (T(EM)) cells. Transgenic expression of Bcl-2 in CD122(-/-) CD8(+) T cells also supported the survival and persistence of T(CM) cells but did not rescue T(EM) development. These data indicate that weak CD122 signals readily support T(CM) development largely through providing survival signals. However, stronger signals, independent of Bcl-2, are required for T(EM) development. Our findings are consistent with a model whereby low, intermediate, and high CD122 signaling support T(CM) memory survival, T(EM) programming, and terminal T effector cell differentiation, respectively.

The FTD-like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism.

PubMed

Kleinberger, Gernot; Brendel, Matthias; Mracsko, Eva; Wefers, Benedikt; Groeneweg, Linda; Xiang, Xianyuan; Focke, Carola; Deußing, Maximilian; Suárez-Calvet, Marc; Mazaheri, Fargol; Parhizkar, Samira; Pettkus, Nadine; Wurst, Wolfgang; Feederle, Regina; Bartenstein, Peter; Mueggler, Thomas; Arzberger, Thomas; Knuesel, Irene; Rominger, Axel; Haass, Christian

2017-07-03

Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk for several neurodegenerative diseases including Alzheimer's disease and frontotemporal dementia (FTD). Homozygous TREM2 missense mutations, such as p.T66M, lead to the FTD-like syndrome, but how they cause pathology is unknown. Using CRISPR/Cas9 genome editing, we generated a knock-in mouse model for the disease-associated Trem2 p.T66M mutation. Consistent with a loss-of-function mutation, we observe an intracellular accumulation of immature mutant Trem2 and reduced generation of soluble Trem2 similar to patients with the homozygous p.T66M mutation. Trem2 p.T66M knock-in mice show delayed resolution of inflammation upon in vivo lipopolysaccharide stimulation and cultured macrophages display significantly reduced phagocytic activity. Immunohistochemistry together with in vivo TSPO small animal positron emission tomography (μPET) demonstrates an age-dependent reduction in microglial activity. Surprisingly, perfusion magnetic resonance imaging and FDG-μPET imaging reveal a significant reduction in cerebral blood flow and brain glucose metabolism. Thus, we demonstrate that a TREM2 loss-of-function mutation causes brain-wide metabolic alterations pointing toward a possible function of microglia in regulating brain glucose metabolism. © 2017 The Authors.

Evaluating the sensitivity of EQ-5D in a sample of patients with type 2 diabetes mellitus in two tertiary health care facilities in Nigeria.

PubMed

Ekwunife, Obinna Ikechukwu; Ezenduka, Charles C; Uzoma, Bede Emeka

2016-01-12

The EQ-5D instrument is arguably the most well-known and commonly used generic measure of health status internationally. Although the instrument has been employed in outcomes studies of diabetes mellitus in many countries, it has not yet been used in Nigeria. This study was carried out to assess the sensitivity of the EQ-5D instrument in a sample of Nigerian patients with type 2 diabetes mellitus (T2DM). A cross-sectional study was conducted using the EQ-5D instrument to assess the self-reported quality of life of patients with T2DM attending two tertiary healthcare facilities in south eastern Nigeria consenting patients completed the questionnaire while waiting to see a doctor. A priori hypotheses were examined using multiple regression analysis to model the relationship between the dependent variables (EQ VAS and EQ-5D Index) and hypothesized independent variables. A total of 226 patients with T2DM participated in the study. The average age of participants was 57 years (standard deviation 10 years) and 61.1% were male. The EQ VAS score and EQ-5D index averaged 66.19 (standard deviation 15.42) and 0.78 (standard deviation 0.21) respectively. Number of diabetic complications, number of co-morbidities, patient's age and being educated predicted EQ VAS score by -6.76, -6.15, -0.22, and 4.51 respectively. Also, number of diabetic complications, number of co-morbidities, patient's age and being educated predicted EQ-5D index by -0.12, -0.07, -0.003, and 0.06 respectively.. Our findings indicate that the EQ-5D could adequately capture the burden of type 2 diabetes and related complications among Nigerian patients.

Blood biomarkers in male and female participants after an Ironman-distance triathlon

PubMed Central

Danielsson, Tom; Carlsson, Jörg; Schreyer, Hendrik; Ahnesjö, Jonas; Ten Siethoff, Lasse; Ragnarsson, Thony; Tugetam, Åsa

2017-01-01

Background While overall physical activity is clearly associated with a better short-term and long-term health, prolonged strenuous physical activity may result in a rise in acute levels of blood-biomarkers used in clinical practice for diagnosis of various conditions or diseases. In this study, we explored the acute effects of a full Ironman-distance triathlon on biomarkers related to heart-, liver-, kidney- and skeletal muscle damage immediately post-race and after one week’s rest. We also examined if sex, age, finishing time and body composition influenced the post-race values of the biomarkers. Methods A sample of 30 subjects was recruited (50% women) to the study. The subjects were evaluated for body composition and blood samples were taken at three occasions, before the race (T1), immediately after (T2) and one week after the race (T3). Linear regression models were fitted to analyse the independent contribution of sex and finishing time controlled for weight, body fat percentage and age, on the biomarkers at the termination of the race (T2). Linear mixed models were fitted to examine if the biomarkers differed between the sexes over time (T1-T3). Results Being male was a significant predictor of higher post-race (T2) levels of myoglobin, CK, and creatinine levels and body weight was negatively associated with myoglobin. In general, the models were unable to explain the variation of the dependent variables. In the linear mixed models, an interaction between time (T1-T3) and sex was seen for myoglobin and creatinine, in which women had a less pronounced response to the race. Conclusion Overall women appear to tolerate the effects of prolonged strenuous physical activity better than men as illustrated by their lower values of the biomarkers both post-race as well as during recovery. PMID:28609447

Immunomodulating activity of Pidotimod in children with Down syndrome.

PubMed

Zuccotti, G V; Mameli, C; Trabattoni, D; Beretta, S; Biasin, M; Guazzarotti, L; Clerici, M

2013-01-01

Acute respiratory tract infections (ARTIs) are the most frequent illnesses in pediatric age, frequently experienced in children with Down Syndrome (DS) due to the associated immune defects of both specific and non-specific immunity. Pidotimod, a synthetic immunostimulant, was shown to reduce the rates of ARTIs in children with DS, however the mechanisms associated with this effect is currently unknown. We analyzed immune parameters in DS children who received the seasonal 2011–2012 virosomal-adjuvanted influenza vaccine. Eighteen children aged 3-10 years (mean age 7.1+/-2.6 years) were randomly assigned (1:1 ratio) to receive Pidotimod 400 mg, administered orally once a day for 90 days or placebo. At the recruitment (T0) all children received a single dose of virosomal-adjuvanted influenza vaccine (Flu). Blood samples were collected at T0 and 3 months after the recruitment (T3) in order to evaluate innate and adaptative immune responses pathway. Flu-specific IgG1 and IgG3 levels in plasma samples were determined at pre-vaccination (T0), and 1 (T1) and 3 months (T3) post-vaccination. The use of Pidotimod was associated with the upregulation of a number of genes involved in the activation of innate immune responses and in antimicrobial activity. Interestingly the ratio of Flu-specific IgG1/IgG3 was skewed in pidotimod-treated individuals, suggesting a preferential activation of complement-dependent effector mechanisms. Although preliminary these data suggest that Pidotimod can potentiate the beneficial effect of immunization, possibly resulting in a stronger activity of both innate and adaptive immune responses.

Attitudes of German undergraduate dental students towards the aged.

PubMed

Nitschke, Ina; Clarenbach-Tran, Thanh-Ha; Schlegel, Daphne; Reiber, Thomas; Sobotta, Bernhard A J

2015-03-01

To describe attitudes towards the aged and changes in attitudes of dental students during their participation in an undergraduate gerodontology programme. Attitudes of dentists have been shown to influence their willingness to provide dental services to the aged. A questionnaire was administered to 160 (50 men) dental students at Leipzig University aged 19.2-30.5 (mean, 21.7; SD, 2.3) years before entering (T1) and when completing (T2) a gerodontology course. A definition of being young and old and of hopes and fears associated with age was requested. The semantic ageing differential (SAD) was used to measure the students' attitudes towards the aged in three categories. Statistical analysis comprised mean age definitions by gender and mean scores of the SAD at T1 and T2. Old age was defined as beginning between 56 and 64 years. Female students at T1 regarded a woman as young up to 35.8 years, for male students a woman was young only up to 33.5 years. Male students consider men as old from 60.1 years and women 4.4 years earlier from 55.7 years. Old age fears related mainly to impairment of health and loss of relatives. Hopes for relaxation, rest and serenity were paramount. The SAD results were near neutral in all three dimensions. Minor changes between T1 and T2 occurred. Students' attitudes were well balanced. Specific barriers to the provision of dental care to the aged emanating from dental students' negative attitudes or fears were not identified. Changes in attitudes occurring during the course appeared small. © 2013 The Gerodontology Society and John Wiley & Sons A/S.

Temperature dependence of the structural relaxation time in equilibrium below the nominal T(g): results from freestanding polymer films.

PubMed

Ngai, K L; Capaccioli, Simone; Paluch, Marian; Prevosto, Daniele

2014-05-22

When the thickness is reduced to nanometer scale, freestanding high molecular weight polymer thin films undergo large reduction of degree of cooperativity and coupling parameter n in the Coupling Model (CM). The finite-size effect together with the surfaces with high mobility make the α-relaxation time of the polymer in nanoconfinement, τ(α)(nano)(T), much shorter than τ(α)(bulk)(T) in the bulk. The consequence is avoidance of vitrification at and below the bulk glass transition temperature, T(g)(bulk), on cooling, and the freestanding polymer thin film remains at thermodynamic equilibrium at temperatures below T(g)(bulk). Molecular dynamics simulations have shown that the specific volume of the freestanding film is the same as the bulk glass-former at equilibrium at the same temperatures. Extreme nanoconfinement renders total or almost total removal of cooperativity of the α-relaxation, and τ(α)(nano)(T) becomes the same or almost the same as the JG β-relaxation time τ(β)(bulk)(T) of the bulk glass-former at equilibrium and at temperatures below T(g)(bulk). Taking advantage of being able to obtain τ(β)(bulk)(T) at equilibrium density below T(g)(bulk) by extreme nanoconfinement of the freestanding films, and using the CM relation between τ(α)(bulk)(T) and τ(β)(bulk)(T), we conclude that the Vogel-Fulcher-Tammann-Hesse (VFTH) dependence of τ(α)(bulk)(T) cannot hold for glass-formers in equilibrium at temperatures significantly below T(g)(bulk). In addition, τ(α)(bulk)(T) does not diverge at the Vogel temperature, T₀, as suggested by the VFTH-dependence and predicted by some theories of glass transition. Instead, τ(α)(bulk)(T) of the glass-former at equilibrium has a much weaker temperature dependence than the VFTH-dependence at temperature below T(g)(bulk) and even below T₀. This conclusion from our analysis is consistent with the temperature dependence of τ(α)(bulk)(T) found experimentally in polymers aged long enough time to attain the equilibrium state at various temperatures below T(g)(bulk).

T-kininogen can either induce or inhibit proliferation in Balb/c 3T3 fibroblasts, depending on the route of administration.

PubMed

Aravena, M; Pérez, C; Pérez, V; Acuña-Castillo, C; Gómez, C; Leiva-Salcedo, E; Nishimura, S; Sabaj, V; Walter, R; Sierra, F

2005-03-01

T-kininogen (T-KG) is a precursor of T-kinin, the most abundant kinin in rat serum, and also acts as a strong and specific cysteine proteinase inhibitor. Its expression is strongly induced during aging in rats, and expression of T-KG in Balb/c 3T3 fibroblasts results in inhibition of cell proliferation. However, T-KG is a serum protein produced primarily in the liver, and thus, most cells are only exposed to the protein from the outside. To test the effect of T-KG on fibroblasts exposed to exogenous T-KG, we purified the protein from the serum of K-kininogen-deficient Katholiek rats. In contrast to the results obtained by transfection, exposure of Balb/c 3T3 fibroblasts to exogenously added T-KG leads to a dose-dependent increase in [3H]-thymidine incorporation. This response does not require kinin receptors, but it is clearly mediated by activation of the ERK pathway. As a control, we repeated the transfection experiments, using a different promoter. The results are consistent with our published data showing that, under these circumstances, T-KG inhibits cell proliferation. We conclude that T-KG exerts opposite effects on fibroblast proliferation, depending exclusively on the way that it is administered to the cells (transfection versus exogenous addition).

Magnetic susceptibility induced echo time shifts: Is there a bias in age-related fMRI studies?

PubMed Central

Ngo, Giang-Chau; Wong, Chelsea N.; Guo, Steve; Paine, Thomas; Kramer, Arthur F.; Sutton, Bradley P.

2016-01-01

Purpose To evaluate the potential for bias in functional MRI (fMRI) aging studies resulting from age-related differences in magnetic field distributions which can impact echo time and functional contrast. Materials and Methods Magnetic field maps were taken on 31 younger adults (age: 22 ± 2.9 years) and 46 older adults (age: 66 ± 4.5 years) on a 3 T scanner. Using the spatial gradients of the magnetic field map for each participant, an echo planar imaging (EPI) trajectory was simulated. The effective echo time, time at which the k-space trajectory is the closest to the center of k-space, was calculated. This was used to examine both within-subject and across-age-group differences in the effective echo time maps. The Blood Oxygenation Level Dependent (BOLD) percent signal change resulting from those echo time shifts was also calculated to determine their impact on fMRI aging studies. Result For a single subject, the effective echo time varied as much as ± 5 ms across the brain. An unpaired t-test between the effective echo time across age group resulted in significant differences in several regions of the brain (p<0.01). The difference in echo time was only approximately 1 ms, however which is not expected to have an important impact on BOLD fMRI percent signal change (< 4%). Conclusion Susceptibility-induced magnetic field gradients induce local echo time shifts in gradient echo fMRI images, which can cause variable BOLD sensitivity across the brain. However, the age-related differences in BOLD signal are expected to be small for an fMRI study at 3 T. PMID:27299727

Age-related T2 changes in hindlimb muscles of mdx mice.

PubMed

Vohra, Ravneet S; Mathur, Sunita; Bryant, Nathan D; Forbes, Sean C; Vandenborne, Krista; Walter, Glenn A

2016-01-01

Magnetic resonance imaging (MRI) was used to monitor changes in the transverse relaxation time constant (T2) in lower hindlimb muscles of mdx mice at different ages. Young (5 weeks), adult (44 weeks), and old mdx (96 weeks), and age-matched control mice were studied. Young mdx mice were imaged longitudinally, whereas adult and old mdx mice were imaged at a single time-point. Mean muscle T2 and percent of pixels with elevated T2 were significantly different between mdx and control mice at all ages. In young mdx mice, mean muscle T2 peaked at 7-8 weeks and declined at 9-11 weeks. In old mdx mice, mean muscle T2 was decreased compared with young and adult mice, which could be attributed to fibrosis. MRI captured longitudinal changes in skeletal muscle integrity of mdx mice. This information will be valuable for pre-clinical testing of potential therapeutic interventions for muscular dystrophy. © 2015 Wiley Periodicals, Inc.

London penetration depth measurements in Ba (Fe 1-xT x) 2As 2(T=Co,Ni,Ru,Rh,Pd,Pt,Co+Cu) superconductors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gordon, Ryan T.

2011-01-01

The London penetration depth has been measured in various doping levels of single crystals of Ba(Fe 1-xT x) 2As 2 (T=Co,Ni,Ru,Rh,Pd,Pt,Co+Cu) superconductors by utilizing a tunnel diode resonator (TDR) apparatus. All in-plane penetration depth measurements exhibit a power law temperature dependence of the form Δλ ab(T) = CT n, indicating the existence of low-temperature, normal state quasiparticles all the way down to the lowest measured temperature, which was typically 500 mK. Several different doping concentrations from the Ba(Fe 1-xT x) 2As 2 (T=Co,Ni) systems have been measured and the doping dependence of the power law exponent, n, is compared tomore » results from measurements of thermal conductivity and specific heat. In addition, a novel method has been developed to allow for the measurement of the zero temperature value of the in-plane penetration depth, λ ab(0), by using TDR frequency shifts. By using this technique, the doping dependence of λ ab(0) has been measured in the Ba(Fe 1-xCo x) 2As 2 series, which has allowed also for the construction of the doping-dependent superfluid phase stiffness, ρ s(T) = [λ(0)/λ(T)] 2. By studying the effects of disorder on these superconductors using heavy ion irradiation, it has been determined that the observed power law temperature dependence likely arises from pair-breaking impurity scattering contributions, which is consistent with the proposed s±-wave symmetry of the superconducting gap in the dirty scattering limit. This hypothesis is supported by the measurement of an exponential temperature dependence of the penetration depth in the intrinsically clean LiFeAs, indicative of a nodeless superconducting gap.« less

A new insight into mechanisms of age-related changes in heart rate.

PubMed

Zefirov, T L; Svyatova, N V; Ziyatdinova, N I

2001-06-01

Changes in cardiac rhythm induced by blockade of hyperpolarization currents with ZD 7288 depend on animal's age. The increase in cardiointerval duration is related to prolongation of T-P segment on ECG. It is hypothesized that the age-related changes in activity of hyperpolarization channels are determined by a modulating effect of the autonomic nervous system.

Trichomonas vaginalis infection in Nigerian pregnant women and risk factors associated with sexually transmitted infections.

PubMed

Oyeyemi, Oyetunde T; Fadipe, Olamide; Oyeyemi, Ifeoluwa T

2016-11-01

Trichomoniasis poses a public health threat to pregnant women and neonatal health. This study evaluated Trichomonas vaginalis and other common sexually transmitted infections (STIs) status in pregnant women, and risk factors associated with them. The study was cross-sectional and descriptive and a total of 198 pregnant women were recruited for T. vaginalis screening by microscopic examination. Questionnaires were also administered to 108 pregnant women to access information related to socio-demography and other factors associated with STI transmission. The overall prevalence of T. vaginalis was 18.7%. While prevalence of T. vaginalis was neither age nor parity dependent (p > 0.05), women in their first trimester showed significantly higher prevalence of trichomoniasis compared to women in their second and third trimesters (p < 0.05). The frequency of STIs was lowest (18.2%) and highest (71.4%) in age groups ≥ 39 and 15-20 years, respectively. Low levels of education, multiple sexual partners, lack of knowledge on partners' STI history, and having sex under the influence of alcohol or drugs were risk factors of for STIs (p < 0.05). We found a high prevalence of T. vaginalis in pregnant women, with those at an early gestational age at greater risk. The improved education of women on safe sex and the need to know partners' STI status are advocated. © The Author(s) 2015.

A New Strategy for Fast MRI-Based Quantification of the Myelin Water Fraction: Application to Brain Imaging in Infants

PubMed Central

Kulikova, Sofya; Hertz-Pannier, Lucie; Dehaene-Lambertz, Ghislaine

2016-01-01

The volume fraction of water related to myelin (fmy) is a promising MRI index for in vivo assessment of brain myelination, that can be derived from multi-component analysis of T1 and T2 relaxometry signals. However, existing quantification methods require rather long acquisition and/or post-processing times, making implementation difficult both in research studies on healthy unsedated children and in clinical examinations. The goal of this work was to propose a novel strategy for fmy quantification within acceptable acquisition and post-processing times. Our approach is based on a 3-compartment model (myelin-related water, intra/extra-cellular water and unrestricted water), and uses calibrated values of inherent relaxation times (T1c and T2c) for each compartment c. Calibration was first performed on adult relaxometry datasets (N = 3) acquired with large numbers of inversion times (TI) and echo times (TE), using an original combination of a region contraction approach and a non-negative least-square (NNLS) algorithm. This strategy was compared with voxel-wise fitting, and showed robust estimation of T1c and T2c. The accuracy of fmy calculations depending on multiple factors was investigated using simulated data. In the testing stage, our strategy enabled fast fmy mapping, based on relaxometry datasets acquired with reduced TI and TE numbers (acquisition <6 min), and analyzed with NNLS algorithm (post-processing <5min). In adults (N = 13, mean age 22.4±1.6 years), fmy maps showed variability across white matter regions, in agreement with previous studies. In healthy infants (N = 18, aged 3 to 34 weeks), asynchronous changes in fmy values were demonstrated across bundles, confirming the well-known progression of myelination. PMID:27736872

Armc5 deletion causes developmental defects and compromises T-cell immune responses

PubMed Central

Hu, Yan; Lao, Linjiang; Mao, Jianning; Jin, Wei; Luo, Hongyu; Charpentier, Tania; Qi, Shijie; Peng, Junzheng; Hu, Bing; Marcinkiewicz, Mieczyslaw Martin; Lamarre, Alain; Wu, Jiangping

2017-01-01

Armadillo repeat containing 5 (ARMC5) is a cytosolic protein with no enzymatic activities. Little is known about its function and mechanisms of action, except that gene mutations are associated with risks of primary macronodular adrenal gland hyperplasia. Here we map Armc5 expression by in situ hybridization, and generate Armc5 knockout mice, which are small in body size. Armc5 knockout mice have compromised T-cell proliferation and differentiation into Th1 and Th17 cells, increased T-cell apoptosis, reduced severity of experimental autoimmune encephalitis, and defective immune responses to lymphocytic choriomeningitis virus infection. These mice also develop adrenal gland hyperplasia in old age. Yeast 2-hybrid assays identify 16 ARMC5-binding partners. Together these data indicate that ARMC5 is crucial in fetal development, T-cell function and adrenal gland growth homeostasis, and that the functions of ARMC5 probably depend on interaction with multiple signalling pathways. PMID:28169274

Decrease of Perivascular Adipose Tissue Browning Is Associated With Vascular Dysfunction in Spontaneous Hypertensive Rats During Aging.

PubMed

Kong, Ling-Ran; Zhou, Yan-Ping; Chen, Dong-Rui; Ruan, Cheng-Chao; Gao, Ping-Jin

2018-01-01

Functional perivascular adipose tissue (PVAT) is necessary to maintain vascular physiology through both mechanical support and endocrine or paracrine ways. PVAT shows a brown adipose tissue (BAT)-like feature and the browning level of PVAT is dependent on the anatomic location and species. However, it is not clear whether PVAT browning is involved in the vascular tone regulation in spontaneously hypertensive rats (SHRs). In the present study, we aimed to illustrate the effect of aging on PVAT browning and subsequent vasomotor reaction in SHRs. Herein we utilized histological staining and western blot to detect the characteristics of thoracic PVAT (tPVAT) in 8-week-old and 16-week-old SHR and Wistar-Kyoto (WKY) rats. We also detected vascular reactivity analysis to determine the effect of tPVAT on vasomotor reaction during aging. The results showed that tPVAT had a similar phenotype to BAT, including smaller adipocyte size and positive uncoupling protein-1 (UCP1) staining. Interestingly, the tPVAT of 8-week-old SHR showed increased BAT phenotypic marker expression compared to WKY, whereas the browning level of tPVAT had a more dramatic decrease from 8 to 16 weeks of age in SHR than age-matched WKY rats. The vasodilation effect of tPVAT on aortas had no significant difference in 8-week-old WKY and SHR, whereas this effect is obviously decreased in 16-week-old SHR compared to WKY. In contrast, tPVAT showed a similar vasoconstriction effect in 8- or 16-week-old WKY and SHR rats. Moreover, we identified an important vasodilator adenosine, which regulates adipocyte browning and may be a potential PVAT-derived relaxing factor. Adenosine is dramatically decreased from 8 to 16 weeks of age in the tPVAT of SHR. In summary, aging is associated with a decrease of tPVAT browning and adenosine production in SHR rats. These may result in attenuated vasodilation effect of the tPVAT in SHR during aging.

Relationship between cyberbullying and health-related quality of life in a sample of children and adolescents.

PubMed

González-Cabrera, J; León-Mejía, A; Beranuy, M; Gutiérrez-Ortega, M; Alvarez-Bardón, A; Machimbarrena, J M

2018-06-07

Health-related quality of life (HRQoL) is a well-known construct that refers to a state of complete physical, mental, and social well-being. Its relationship with multiple forms of violence, including bullying, has been widely explored, but this is not the case for cyberbullying. The main objective is to analyze how HRQoL varies depending on the role played in cyberbullying, its temporal stability, and gender and age differences. An analytical and longitudinal study was conducted at two temporal moments. At Time 1 (December 2015), 920 Spanish students aged between 11 and 18 years participated (M age  = 13.36, SD = 1.83: 48.9% boys and 51.1% girls). At Time 2 (April 2016), there were 313 participants (M age 12.81 years, SD = 1.59: 53.4% boys and 46.6% girls). We used the Cyberbullying Test (technological scale) and the Spanish version of the KIDSCREEN-52. Cybervictims and cyberbully-victims present worse scores in all dimensions of the KIDSCREEN-52 (p < .001), compared to cyberbystanders or uninvolved individuals. There are gender differences only in cyberaggression and cyberbystanding. There are significant inverse correlations between all the dimensions of the KIDSCREEN-52 and cybervictimization, with Bullying (r = - .603, p < .001), Mood (r = - .329, p < .001), and School environment (r = - .327, p < .001) being particularly relevant. There were statistically significant differences between T1 and T2 for cyberbystanding (lower scores at T2). Cybervictims and cyberbully-victims have worse quality of life in all the dimensions than uninvolved individuals, especially in Psychological well-being, School environment, and Bullying.

Reproductive performance and oviductal expression of avidin and avidin-related protein-2 in young and old broiler breeder hens orally exposed to supplementary biotin.

PubMed

Daryabari, H; Akhlaghi, A; Zamiri, M J; Mianji, G Rahimi; Pirsaraei, Z Ansari; Deldar, H; Eghbalian, A N

2014-09-01

Published data on the probable involvement of avidin and avidin-related protein-2 (AVR2) in sustaining sperm viability in sperm storage tubules in 38-wk-old turkeys, and the high affinity of avidin or its analogs to biotin suggest that supplementary biotin may increase oviductal avidin and AVR2 expression, thereby attenuating the adverse effect of aging on hen reproductive performance. Broiler breeder hens (n = 120) were randomly assigned to receive 0 (T0), 0.30 (T1), or 0.45 (T2) mg of biotin/L of drinking water from 30 to 33 (young) and 53 to 56 (old) wk of age, and artificially inseminated to determine their reproductive performance. At the end of each period of biotin administration, 8 hens from each treatment group were killed for RNA extraction from the uterovaginal junction. Egg production was lower in the old hens (44%) compared with the young ones (82%), and biotin supplementation increased egg production only in the latter. Administering supplementary biotin to young hens increased their oviductal expression of AVR2, which was much higher in the old hens (1.0 and 4.6 for young and old groups, respectively). Fertility rate was not different between young and old hens, and was increased (4.4%) at the higher level of biotin supplementation. Hatchability and hatchling quality were not affected by biotin supplementation. Embryonic mortality between 17 to 21 d of incubation was higher in young (5.2%) compared with old (1.4%) birds. Egg fertility rate showed a moderate correlation (P < 0.05) with avidin (r = 0.59) and AVR2 (r = 0.55) expression in the young-age group, and very low correlations in old-age group (0.04 and 0.17). Regardless of the hen's age, the correlation coefficient of hatchability with avidin or AVR2 expression was very low (-0.16 and 0.18). Overall, the effect of biotin supplementation on AVR2 expression, and the relationship between biotin administration and oviductal expression of avidin and AVR2 was dependent on the hen's age, being higher in the young hens. © 2014 Poultry Science Association Inc.

Nicergoline inhibits T-type Ca2+ channels in rat isolated hippocampal CA1 pyramidal neurones.

PubMed Central

Takahashi, K.; Akaike, N.

1990-01-01

1. The effects of nicergoline on the T- and L-type Ca2+ currents in pyramidal cells freshly isolated from rat hippocampal CA1 region were investigated by use of a 'concentration-clamp' technique. The technique combines a suction-pipette technique, which allows intracellular perfusion under a single-electrode voltage-clamp, and rapid exchange of extracellular solution within 2 ms. 2. T-type Ca2+ currents were evoked by step depolarizations from a holding potential of -100 mV to potentials more positive than -70 to -60 mV, and reached a peak at about -30 mV in the current-voltage relationship. Activation and inactivation of T-type Ca2+ currents were highly potential-dependent. 3. Nicergoline and other Ca2+ antagonists dose-dependently blocked the T-type Ca2+ channel with an order of potency nicardipine greater than nicergoline greater than diltiazem. 4. The L-type Ca2+ channel was also blocked in the order nicardipine greater than nicergoline greater than diltiazem, although the T-type Ca2+ channel was more sensitive to nicergoline. 5. The inhibitory effects of nicergoline and nicardipine on the T-type Ca2+ current were voltage-, time-, and use-dependent, and the inhibition increased with a decrease in the external Ca2+ concentration. Diltiazem showed only a use-dependent block. PMID:2169937

Nicergoline inhibits T-type Ca2+ channels in rat isolated hippocampal CA1 pyramidal neurones.

PubMed

Takahashi, K; Akaike, N

1990-08-01

1. The effects of nicergoline on the T- and L-type Ca2+ currents in pyramidal cells freshly isolated from rat hippocampal CA1 region were investigated by use of a 'concentration-clamp' technique. The technique combines a suction-pipette technique, which allows intracellular perfusion under a single-electrode voltage-clamp, and rapid exchange of extracellular solution within 2 ms. 2. T-type Ca2+ currents were evoked by step depolarizations from a holding potential of -100 mV to potentials more positive than -70 to -60 mV, and reached a peak at about -30 mV in the current-voltage relationship. Activation and inactivation of T-type Ca2+ currents were highly potential-dependent. 3. Nicergoline and other Ca2+ antagonists dose-dependently blocked the T-type Ca2+ channel with an order of potency nicardipine greater than nicergoline greater than diltiazem. 4. The L-type Ca2+ channel was also blocked in the order nicardipine greater than nicergoline greater than diltiazem, although the T-type Ca2+ channel was more sensitive to nicergoline. 5. The inhibitory effects of nicergoline and nicardipine on the T-type Ca2+ current were voltage-, time-, and use-dependent, and the inhibition increased with a decrease in the external Ca2+ concentration. Diltiazem showed only a use-dependent block.

Suppression of antioxidant Nrf-2 and downstream pathway in H9c2 cells by advanced glycation end products (AGEs) via ERK phosphorylation.

PubMed

Ko, Shun-Yao; Chang, Shu-Shing; Lin, I-Hsuan; Chen, Hong-I

2015-11-01

Diabetic cardiomyopathy is related to oxidative stress and correlated with the presence of advanced glycation end products (AGEs). In a clinical setting, AGEs can be detected in patients presenting diabetic cardiomyopathy; however, the underlying mechanism has yet to be elucidated. In our previous study, AGEs increase cell hypertrophy via ERK phosphorylation in a process closely related to ROS production. Thus, we propose that AGEs regulate the antioxidant gene nuclear factor-erythroid 2-related factor (Nrf-2). In H9c2 cells treated with AGEs, the expression of Nrf-2 was reduced; however, ERK phosphorylation was shown to increase. Treatment with H2O2 was also shown to increase Nrf-2 and ERK phosphorylation. In cells pretreatment with ROS scavenger NAC, the effects of H2O2 were reduced; however, the effects of the AGEs remained largely unchanged. Conversely, when cells were pretreated with PD98059 (ERK inhibitor), the expression of Nrf-2 was recovered following treatment with AGEs. Our results suggest that AGEs inhibit Nrf-2 via the ERK pathway; however, this influence is partly associated with ROS. Our finding further indicated that AGEs possess both ROS-dependent and ROS-independent pathways, resulting in a reduction in Nrf-2. This report reveals an important mechanism underlying the regulation of diabetic cardiomyopathy progression by AGEs. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Age-dependent effects of brain stimulation on network centrality.

PubMed

Antonenko, Daria; Nierhaus, Till; Meinzer, Marcus; Prehn, Kristin; Thielscher, Axel; Ittermann, Bernd; Flöel, Agnes

2018-04-18

Functional magnetic resonance imaging (fMRI) studies have suggested that advanced age may mediate the effects of transcranial direct current stimulation (tDCS) on brain function. However, studies directly comparing neural tDCS effects between young and older adults are scarce and limited to task-related imaging paradigms. Resting-state (rs-) fMRI, that is independent of age-related differences in performance, is well suited to investigate age-associated differential neural tDCS effects. Three "online" tDCS conditions (anodal, cathodal, sham) were compared in a cross-over, within-subject design, in 30 young and 30 older adults. Active stimulation targeted the left sensorimotor network (active electrode over left sensorimotor cortex with right supraorbital reference electrode). A graph-based rs-fMRI data analysis approach (eigenvector centrality mapping) and complementary seed-based analyses characterized neural tDCS effects. An interaction between anodal tDCS and age group was observed. Specifically, centrality in bilateral paracentral and posterior regions (precuneus, superior parietal cortex) was increased in young, but decreased in older adults. Seed-based analyses revealed that these opposing patterns of tDCS-induced centrality modulation originated from differential effects of tDCS on functional coupling of the stimulated left paracentral lobule. Cathodal tDCS did not show significant effects. Our study provides first evidence for differential tDCS effects on neural network organization in young and older adults. Anodal stimulation mainly affected coupling of sensorimotor with ventromedial prefrontal areas in young and decoupling with posteromedial areas in older adults. Copyright © 2018 Elsevier Inc. All rights reserved.

A Reference Database of Cartilage 3 Tesla MRI T2 Values in Knees without Diagnostic Evidence of Cartilage Degeneration: Data from the Osteoarthritis Initiative

PubMed Central

Joseph, Gabby B.; McCulloch, Charles E.; Nevitt, Michael C.; Heilmeier, Ursula; Nardo, Lorenzo; Lynch, John A.; Liu, Felix; Baum, Thomas; Link, Thomas M.

2015-01-01

Objective The purpose of this study was 1) to establish a gender- and BMI-specific reference database of cartilage T2 values, and 2) to assess the associations between cartilage T2 values and gender, age, and BMI in knees without radiographic osteoarthritis or MRI-based (WORMS 0/1) evidence of cartilage degeneration. Design 481 subjects between the ages of 45-65 years with Kellgren-Lawrence Scores 0/1 in the study knee were selected from the Osteoarthritis Initiative database. Baseline morphologic cartilage 3T MRI readings (WORMS scoring) and T2 measurements (resolution=0.313mmx0.446mm) were performed in the medial femur, lateral femur, medial tibia, lateral tibia, and patella compartments. In order to create a reference database, a logarithmic transformation was applied to the data to obtain the 5th-95th percentile values for T2. Results Significant differences in mean cartilage T2 values were observed between joint compartments. Although females had slightly higher T2 values than males in a majority of compartments, the differences were only significant in the medial femur (p<0.0001). A weak positive association was seen between age and T2 in all compartments, and was most pronounced in the patella (3.27% increase in median T2/10 years, p=0.009). Significant associations between BMI and T2 were observed, and were most pronounced in the lateral tibia (5.33% increase in median T2/5 kg/m2 increase in BMI, p<0.0001), and medial tibia (4.81% increase in median T2 /5 kg/m2 increase in BMI, p<0.0001). Conclusions This study established the first reference database of T2 values in a large sample of morphologically normal cartilage plates in knees without radiographic knee osteoarthritis. While cartilage T2 values were weakly associated with age and gender, they had the highest correlations with BMI. PMID:25680652

Temperature-Dependent Ellipsometry Measurements of Partial Coulomb Energy in Superconducting Cuprates

DOE PAGES

Levallois, J.; Tran, M. K.; Pouliot, D.; ...

2016-08-24

Here we performed an experimental study of the temperature and doping dependence of the energy-loss function of the bilayer and trilayer bismuth cuprates family. The primary aim is to obtain information on the energy stored in the Coulomb interaction between the conduction electrons, on the temperature dependence thereof, and on the change of Coulomb interaction when Cooper pairs are formed. We performed temperature-dependent ellipsometry measurements on several Bi 2Sr 2CaCu 2O 8₋x single crystals: underdoped with T c=60, 70, and 83 K; optimally doped with T c=91 K; overdoped with T c=84, 81, 70, and 58 K; as well asmore » optimally doped Bi 2Sr 2Ca 2Cu 3O 10+x with T c=110 K. Our first observation is that, as the temperature drops through T c, the loss function in the range up to 2 eV displays a change of temperature dependence as compared to the temperature dependence in the normal state. This effect at—or close to—T c depends strongly on doping, with a sign change for weak overdoping. The size of the observed change in Coulomb energy, using an extrapolation with reasonable assumptions about its q dependence, is about the same size as the condensation energy that has been measured in these compounds. Our results therefore lend support to the notion that the Coulomb energy is an important factor for stabilizing the superconducting phase. Lastly, because of the restriction to small momentum, our observations do not exclude a possible significant contribution to the condensation energy of the Coulomb energy associated with the region of q around (π,π).« less

Gender disparities in the associations of behavioral factors, serious psychological distress and chronic diseases with type 2 diabetes screening among US adults.

PubMed

Xie, Xin; Wang, Nianyang; Liu, Ying

2018-01-01

The increasing prevalence of undiagnosed and diagnosed type 2 diabetes (T2D) posed a major challenge for public health and thus screening for T2D becomes essentially important. The social-demographical factors associated with the use of T2D screening have been widely studied, however, little is known about the impact of behavioral factors, mental health and chronic diseases on prevalence of screening, especially by gender and age groups. We investigated the impact of behavioral factors, mental health and chronic diseases across gender and age groups on the usage rate of T2D screening. To analyze the likelihood of the use of T2D screening, we performed weighted binomial logistic regression analyses. Obesity, physical activity and smoking increased the use of T2D screening for females more than for males, and alcohol use increased screenings only for females. Serious psychological distress (SPD) was found to have a positive association with the use of T2D screening for females rather than for males; whereas hypertension and diabetes increased the use of T2D screening for males more than for females. Physical activity was an effective predictor of screening for T2D in the groups of 45-64 years and 65 years or older. Former drinking was positively associated with T2D screening for people aged 65 or older, and smoking was found to increase the odds of screening for T2D for people aged less than 65. Behavioral factors, mental health, and chronic diseases were significantly associated with the use of T2D screening and further demonstrated that gender differences exist in the role of above factors.

Brain MRI lesions and atrophy are associated with employment status in patients with multiple sclerosis.

PubMed

Tauhid, Shahamat; Chu, Renxin; Sasane, Rahul; Glanz, Bonnie I; Neema, Mohit; Miller, Jennifer R; Kim, Gloria; Signorovitch, James E; Healy, Brian C; Chitnis, Tanuja; Weiner, Howard L; Bakshi, Rohit

2015-11-01

Multiple sclerosis (MS) commonly affects occupational function. We investigated the link between brain MRI and employment status. Patients with MS (n = 100) completed a Work Productivity and Activity Impairment (WPAI) (general health version) survey measuring employment status, absenteeism, presenteeism, and overall work and daily activity impairment. Patients "working for pay" were considered employed; "temporarily not working but looking for work," "not working or looking for work due to age," and "not working or looking for work due to disability" were considered not employed. Brain MRI T1 hypointense (T1LV) and T2 hyperintense (T2LV) lesion volumes were quantified. To assess lesional destructive capability, we calculated each subject's ratio of T1LV to T2LV (T1/T2). Normalized brain parenchymal volume (BPV) assessed brain atrophy. The mean (SD) age was 45.5 (9.7) years; disease duration was 12.1 (8.1) years; 75 % were women, 76 % were relapsing-remitting, and 76 % were employed. T1LV, T1/T2, Expanded Disability Status Scale (EDSS) scores, and activity impairment were lower and BPV was higher in the employed vs. not employed group (Wilcoxon tests, p < 0.05). Age, disease duration, MS clinical subtype, and T2LV did not differ between groups (p > 0.05). In multivariable logistic regression modeling, adjusting for age, sex, and disease duration, higher T1LV predicted a lower chance of employment (p < 0.05). Pearson correlations showed that EDSS was associated with activity impairment (p < 0.05). Disease duration, age, and MRI measures were not correlated with activity impairment or other WPAI outcomes (p > 0.05). We report a link between brain atrophy and lesions, particularly lesions with destructive potential, to MS employment status.

Psychometric Testing of the Chinese-Version Glover-Nilsson Smoking Behavioral Questionnaire (GN-SBQ-C) for the Identification of Nicotine Dependence in Adult Smokers in Taiwan.

PubMed

Chen, Shu-Ching; Chen, Hsiu-Fang; Peng, Hsi-Ling; Lee, Li-Yun; Chiang, Ting-Yu; Chiu, Hui-Chuan

2017-04-01

The purposes of this study were to evaluate the psychometric properties, reliability, and validity of the Chinese-version Glover-Nilsson Smoking Behavioral Questionnaire (GN-SBQ-C) and assess the behavioral nicotine dependence among community-dwelling adult smokers in Taiwan. The methods used were survey design, administration, and validation. A total of 202 adult smokers completed a survey to assess behavioral dependence, nicotine dependence, depression, social support, and demographic and smoking characteristics. Data analysis included descriptive statistics, internal consistency reliability, t test, exploratory factor analysis, independent t test, and Pearson product moment correlation. The results showed that (1) the GN-SBQ-C has good internal consistency reliability and stability (2-week test-retest reliability); (2) the extracted one factor explained 41.80 % of the variance, indicating construct validity; (3) the scale has acceptable concurrent validity, with significant positive correlation between the GN-SBQ-C and nicotine dependence, depression, and time smoking and negative correlation between the GN-SBQ-C and age and exercise habit; and (4) the instrument has discriminant validity, supported by significant differences between those with high and low-to-moderate nicotine dependence, smokers greater than 43 years old and those 43 years old and younger, and those who smoked 10 years or less and those smoking more than 10 years. The 11-item GN-SBQ-C has satisfactory psychometric properties when applied in a sample of Taiwanese adult smokers. The scale is feasible and valid to use to assess smoking behavioral dependence.

Age- and stage-dependent variations of muscle-specific gene expression in brown trout Salmo trutta L.

PubMed

Churova, Maria V; Meshcheryakova, Olga V; Ruchev, Mikhail; Nemova, Nina N

2017-09-01

This study was conducted to characterize the features of muscle-specific genes expression during development of brown trout Salmo trutta inhabiting the river Krivoy ruchey (Kola Peninsula, Russia). Gene expression levels of myogenic regulatory factors (MRFs - MyoD1 paralogs (MyoD1a, MyoD1b, MyoD1c), Myf5, myogenin), myostatin paralogs (MSTN-1a, MSTN-1b, MSTN-2a), fast skeletal myosin heavy chain (MyHC) were measured in the white muscles of brown trout parr of ages 0+ (under-yearling), 1+ (yearling) and 2+ (two year old) and smolts of age 2+. Multidirectional changes in MyoD1 and MSTN paralogs expression along with myogenin, Myf 5 and MyHC expression levels in white muscles in parr of trout with age were revealed. The expression of MyoD1c, myogenin, MSTN-2a was the highest in 0+ parr and then decreased. MyoD1a/b expression levels didn't differ between age groups. The simultaneous elevation of MyHC, Myf5, MSTN-1a, and MSTN-1b was found in trout yearlings. In smolts, expression levels of MSTN paralogs, MyHC, Myf5, MyoD1a was lower than in parr. But in contrast, the MyoD1c and myogenin mRNA levels was higher in smolts. The study revealed that there are definite patterns in simultaneous muscle-specific genes expression in age groups of parr and smolts. As MyoD and MSTN paralogs expression changed differently in dependence on age and stage, it was suggested that paralogs of the same gene complementarily control myogenesis during development. Copyright © 2017 Elsevier Inc. All rights reserved.

Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina

PubMed Central

Henning, Yoshiyuki; Szafranski, Karol

2016-01-01

The thyroid hormones (TH) triiodothyronine (T3) and its prohormone thyroxine (T4) are crucial for retinal development and function, and increasing evidence points at TH dysregulation as a cause for retinal degenerative diseases. Thus, precise regulation of retinal TH supply is required for proper retinal function, but knowledge on these mechanisms is still fragmentary. Several transmembrane transporters have been described as key regulators of TH availability in target tissues of which the monocarboxylate transporter 8 (MCT8), a high affinity transporter for T4 and T3, plays an essential role in the central nervous system. Moreover, in the embryonic chicken retina, MCT8 is highly expressed, but the postnatal availability of MCT8 in the mammalian retina was not reported to date. In the present study, spatiotemporal retinal MCT8 availability was examined in mice of different age. For this purpose, we quantified expression levels of Mct8 via Real-Time Reverse-Transcriptase PCR in mouse eyecups (C57BL/6) of juvenile and adult age groups. Additionally, age-dependent MCT8 protein levels were quantified via Western blotting and localized via immunofluorescence confocal microscopy. While no difference in Mct8 expression levels could be detected between age groups, MCT8 protein levels in juvenile animals were about two times higher than in adult animals based on Western blot analyses. Immunohistochemical analyses showed that MCT8 immunoreactivity in the eyecup was restricted to the retina and the retinal pigment epithelium. In juvenile mice, MCT8 was broadly observed along the apical membrane of the retinal pigment epithelium, tightly surrounding photoreceptor outer segments. Distinct immunopositive staining was also detected in the inner nuclear layer and the ganglion cell layer. However, in adult specimens, immunoreactivity visibly declined in all layers, which was in line with Western blot analyses. Since MCT8 was abundantly present in juvenile and about twofold lower in adult retinae, our findings suggest a pivotal role of MCT8 especially during postnatal maturation. The present study provides novel insights into age-dependent retinal TH supply, which might help to understand different aspects regarding retinal development, function, and disorders. PMID:27616981

Arterial blood pressure and serum lipids in a population of children and adolescents from Southern Italy: the Calabrian Sierras Community Study (CSCS).

PubMed

Martino, Francesco; Puddu, Paolo Emilio; Pannarale, Giuseppe; Colantoni, Chiara; Zanoni, Cristina; Martino, Eliana; Barillà, Francesco

2013-09-30

Lipid standards in Italy are lacking in children and adolescents whereas those for blood pressure (BP) were derived from US surveys. In a 14-town community in Southern Italy 1657 (64%) of 2594 children aged 6-14 years were enrolled and anthropometric, BP, lipid and glucose serum levels were obtained. Average systolic BP was 101 ± 11 (60-150) mm Hg and cholesterol (CholT) level was 156 ± 28 (57-264) mg/dl. There were positive (p<0.00001) age-trends for systolic BP and body mass index (BMI) in both genders whereas age-trends for CholT and heart rate were negative (p<0.00001). A negative age-trend in both genders was also seen for non-HDL cholesterol (p<0.03). Based on 95% percentile gender and age distributions, there were 177 (10.68%) hypertensive (HT) and 82 (4.94%) hypercholesterolemic (HC) children or adolescents. Univariately, HT had higher (p<0.00001) height, weight, BMI, arm circumference, hips, waist, diastolic BP and waist/height, whereas HC had higher LDL-, HDL and non-HDL-cholesterol and triglycerides (p<0.01). Systolic BP was predicted (r(2)=0.2810, p=0.00001) by age (t=2.319, p<0.0205), male gender (t=3.179, p<0.0015), glucose (t=2.357, p<0.0186), height (t=2.473, p<0.0135), arm circumference (t=3.313, p<0.0009) and heart rate (t=4.161, p<0.00001). CholT was related inversely (r(2)=0.1399, p=0.00001) to height (t=-3.928, p<0.0001), weight (t=-3.922, p<0.0001) and waist/height (t=-4.797, p<0.00001) and directly to BMI (t=3.064, p<0.0022), waist (t=5.149, p<0.0000), triglycerides (t=11.332, p<0.00001) and female gender (t=-2.041, p<0.0414). In these Southern Italian children and adolescents systolic BP and CholT are related with anthropometric and other variables, not confined to height. BP is lower than previously reported. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Obesity and age as dominant correlates of low testosterone in men irrespective of diabetes status.

PubMed

Ng Tang Fui, M; Hoermann, R; Cheung, A S; Gianatti, E J; Zajac, J D; Grossmann, M

2013-11-01

Although men with type 2 diabetes (T2D) frequently have lowered testosterone levels, it is not well established whether this is ascribable to the diabetic state per se, or because of other factors, such as obesity. Our objective was to determine the prevalence and correlates of low testosterone in middle-aged men with diabetes. We conducted a cross-sectional study in 240 men including 80 men with type 1 diabetes (T1D), 80 men with T2D and 80 men without diabetes. Prevalence of a total testosterone ≤8 nmol/L was low, occurring in none of the men with T1D, 6.2% of men with T2D and 2.5% of men without diabetes. Men with T1D had higher testosterone levels compared with men without diabetes (p < 0.001), even after adjustment for body mass index (BMI) and age (p < 0.02). While men with T2D had lower testosterone compared with controls (p = 0.03), this was no longer significant when BMI and age were taken into account (p = 0.16). In the entire cohort, TT remained inversely associated with BMI independent of age, sex hormone-binding globulin and diabetic status (p = 0.01), whereas calculated free testosterone (cFT) was independently and inversely associated with age (p < 0.001), but not with BMI (p = 0.47). These results suggest that marked reductions in circulating testosterone are uncommon in middle-aged men with diabetes. Increasing BMI and age are dominant drivers of lowered total and cFT, respectively, independent of the presence or absence of diabetes. © 2013 American Society of Andrology and European Academy of Andrology.

Effect of PPARG on AGEs-induced AKT/MTOR signaling-associated human chondrocytes autophagy.

PubMed

Wang, Zhao-Jun; Zhang, Hai-Bin; Chen, Cheng; Huang, Hao; Liang, Jian-Xia

2018-02-17

Accumulation of advanced glycation end products (AGEs) in articular cartilage is thought to represent a major risk factor for osteoarthritis development. In this study we aimed to probe the role of AGEs in human chondrocytes and to determine the impact of the peroxisome proliferator-activated receptor-γ (PPARG) on AGEs-induced cell autophagy. Cell viability was measured after human chondrocytes were treated with different concentrations of AGEs with or without the PPARG inhibitor, T0070907, or agonist, pioglitazone. Autophagy activation markers (MAP2LC3, BECN1 and SQSTM1/P62), expression of PPARG and the phosphorylation levels of Akt/MTOR were determined by Western blotting; autophagosome formation was analyzed by transmission electron microscopy (TEM); autophagic flux was detected with mRFP-GFP-LC3 tandem construct. Low doses of AGEs over a short amount of time stimulated chondrocyte proliferation and autophagy by limiting phosphorylation of Akt/MTOR signaling. The addition of PPARG inhibitor T0070907 lead to defective autophagy. High dose and long exposure to AGEs inhibited cell viability and autophagy by increasing phosphorylation levels of Akt/MTOR signaling. The agonist, pioglitazone, was shown to protect cell autophagy in a dose-dependent manner. Our findings suggest AGEs can downregulate PPARG and that PPARG maintains cell viability by activating the Akt/MTOR signaling pathway as well as inducing chondrocyte autophagy. © 2018 International Federation for Cell Biology.

Quantitative evaluation of cerebral white matter in patients with multiple sclerosis using multicomponent T2 mapping.

PubMed

Baranovicova, Eva; Mlynarik, Vladimir; Kantorova, Ema; Hnilicova, Petra; Dobrota, Dusan

2016-05-01

A standard magnetic resonance imaging (MRI) investigation of white matter (WM) areas with visible or expected pathology does not explain satisfactorily the relation between pathology and clinical outcome. Therefore, we focused on multicomponent T2 mapping of WM with the intention to characterize the WM, including normal-appearing white matter that has normal and prolonged T2 and lesions, including degenerated tissue. Twenty-nine patients with clinically diagnosed MS and 27 healthy controls underwent MRI examination. T2 mapping of the WM across the two whole MRI slices was carried out. The relative abundance of biologically relevant T2 regions was correlated with age and the expanded disability status scale (EDSS). The relative abundance of the T2 values of water trapped in myelin increased with age in both healthy subjects (p < 0.05) and MS patients (p < 0.05). The relative abundance of intermediate T2 assigned to intra- and extracellular water decreased with age in both groups (p < 0.05) and with EDSS (p < 0.005) in the MS patients. The mixed water pools with a T2 above 110 ms were not related to age, but strongly increased with EDSS (p < 0.000005). Our results suggest that multicomponent T2 mapping of the WM can be a useful parameter for monitoring the progression of MS in patients.

Quantitative T2 mapping of white matter: applications for ageing and cognitive decline

NASA Astrophysics Data System (ADS)

Knight, Michael J.; McCann, Bryony; Tsivos, Demitra; Dillon, Serena; Coulthard, Elizabeth; Kauppinen, Risto A.

2016-08-01

In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer’s disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of  T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia.

Influence of marital status on testosterone levels-A ten year follow-up of 1113 men.

PubMed

Holmboe, Stine A; Priskorn, Lærke; Jørgensen, Niels; Skakkebaek, Niels E; Linneberg, Allan; Juul, Anders; Andersson, Anna-Maria

2017-06-01

Based on a large population of 1113 men aged 30-60 at baseline (mean: 44.1 years, standard deviation: 10.5), we investigated whether intra-individual changes in testosterone (T) and related reproductive hormones during a ten year period were dependent of marital status at baseline and follow-up. The studied men were part of a health survey in Denmark, conducted between 1982 and 1984 with a follow-up examination approximately ten years later. Data on reproductive hormones, measured in serum, and lifestyle and marital status were obtained at both time points. As expected, an age-related decline in testosterone was observed. However, independent of age and lifestyle, we observed that men who went from unmarried to married (n=81) during the study period experienced an accelerated age-related decline in testosterone (-6.6nmol/L) whereas men who went from married to unmarried (n=67) experienced an attenuated age-related decline (-2.3nmol/L). Men who were either married or unmarried at both time points (n=167, n=798, respectively) had a testosterone decline in between (-3.7nmol/L and -4.6nmol/L, respectively). Changes in T/LH ratio did not differ according to marital status indicating that the lowered T level is not compensated by increasing LH levels. This could suggest a modification of the gonadostat due to an adaptation to changing life circumstances. Copyright © 2017 Elsevier Ltd. All rights reserved.

Systematic Review of the Epidemiology and Natural History of the Metabolic Vascular Syndrome and its Coincidence with Type 2 Diabetes Mellitus and Cardiovascular Diseases in Different European Countries.

PubMed

Kwasny, Caroline; Manuwald, Ulf; Kugler, Joachim; Rothe, Ulrike

2018-03-01

The objectives of this systematic review were to estimate the incidence, prevalence and natural history of the metabolic (vascular) syndrome (MVS) among adults in different European countries. Furthermore, we assessed its co-incidence with type 2 diabetes (T2DM) and cardiovascular diseases (CVD). PubMed, MedLine, and EMBASE (via Ovid) were searched for relevant studies. After reading 116 full-text articles to find eligible ones, 66 publications met our inclusion criteria. Data for the incidence are based on a study from Portugal, in which the incidence rate for the MVS was 47.2/1000 person-years. Prevalence varied strongly depending on country and definition. The lowest was found in the United Kingdom (3%), the highest in Finland (71.7%). No article that deals with the natural history of the MVS was found. Considering the co-existence of MVS and T2DM, it ranged between 2% (United Kingdom) and 74.4% (Spain). The co-occurrence of MVS and CVD ranged from 2.8% (Italy) up to 52% (Netherlands). Coronary heart disease (CHD) varied between 1.2% and 44.2%. With regard to peripheral artery disease (PAD), values between 3.3% and 59.8% were found. Due to the many different definitions of the MVS, a comparison is very difficult. Overall prevalence ranged between 3% and 71.7% depending on definition, age, and country. An association between MVS and T2DM as well as several CVD can be assumed. © Georg Thieme Verlag KG Stuttgart · New York.

Phosphate (Pi)-regulated heterodimerization of the high-affinity sodium-dependent Pi transporters PiT1/Slc20a1 and PiT2/Slc20a2 underlies extracellular Pi sensing independently of Pi uptake.

PubMed

Bon, Nina; Couasnay, Greig; Bourgine, Annabelle; Sourice, Sophie; Beck-Cormier, Sarah; Guicheux, Jérôme; Beck, Laurent

2018-02-09

Extracellular phosphate (P i ) can act as a signaling molecule that directly alters gene expression and cellular physiology. The ability of cells or organisms to detect changes in extracellular P i levels implies the existence of a P i -sensing mechanism that signals to the body or individual cell. However, unlike in prokaryotes, yeasts, and plants, the molecular players involved in P i sensing in mammals remain unknown. In this study, we investigated the involvement of the high-affinity, sodium-dependent P i transporters PiT1 and PiT2 in mediating P i signaling in skeletal cells. We found that deletion of PiT1 or PiT2 blunted the P i -dependent ERK1/2-mediated phosphorylation and subsequent gene up-regulation of the mineralization inhibitors matrix Gla protein and osteopontin. This result suggested that both PiTs are necessary for P i signaling. Moreover, the ERK1/2 phosphorylation could be rescued by overexpressing P i transport-deficient PiT mutants. Using cross-linking and bioluminescence resonance energy transfer approaches, we found that PiT1 and PiT2 form high-abundance homodimers and P i -regulated low-abundance heterodimers. Interestingly, in the absence of sodium-dependent P i transport activity, the PiT1-PiT2 heterodimerization was still regulated by extracellular P i levels. Of note, when two putative P i -binding residues, Ser-128 (in PiT1) and Ser-113 (in PiT2), were substituted with alanine, the PiT1-PiT2 heterodimerization was no longer regulated by extracellular P i These observations suggested that P i binding rather than P i uptake may be the key factor in mediating P i signaling through the PiT proteins. Taken together, these results demonstrate that P i -regulated PiT1-PiT2 heterodimerization mediates P i sensing independently of P i uptake. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Differential maturation of vesicular glutamate and GABA transporter expression in the mouse auditory forebrain during the first weeks of hearing.

PubMed

Hackett, Troy A; Clause, Amanda R; Takahata, Toru; Hackett, Nicholas J; Polley, Daniel B

2016-06-01

Vesicular transporter proteins are an essential component of the presynaptic machinery that regulates neurotransmitter storage and release. They also provide a key point of control for homeostatic signaling pathways that maintain balanced excitation and inhibition following changes in activity levels, including the onset of sensory experience. To advance understanding of their roles in the developing auditory forebrain, we tracked the expression of the vesicular transporters of glutamate (VGluT1, VGluT2) and GABA (VGAT) in primary auditory cortex (A1) and medial geniculate body (MGB) of developing mice (P7, P11, P14, P21, adult) before and after ear canal opening (~P11-P13). RNA sequencing, in situ hybridization, and immunohistochemistry were combined to track changes in transporter expression and document regional patterns of transcript and protein localization. Overall, vesicular transporter expression changed the most between P7 and P21. The expression patterns and maturational trajectories of each marker varied by brain region, cortical layer, and MGB subdivision. VGluT1 expression was highest in A1, moderate in MGB, and increased with age in both regions. VGluT2 mRNA levels were low in A1 at all ages, but high in MGB, where adult levels were reached by P14. VGluT2 immunoreactivity was prominent in both regions. VGluT1 (+) and VGluT2 (+) transcripts were co-expressed in MGB and A1 somata, but co-localization of immunoreactive puncta was not detected. In A1, VGAT mRNA levels were relatively stable from P7 to adult, while immunoreactivity increased steadily. VGAT (+) transcripts were rare in MGB neurons, whereas VGAT immunoreactivity was robust at all ages. Morphological changes in immunoreactive puncta were found in two regions after ear canal opening. In the ventral MGB, a decrease in VGluT2 puncta density was accompanied by an increase in puncta size. In A1, perisomatic VGAT and VGluT1 terminals became prominent around the neuronal somata. Overall, the observed changes in gene and protein expression, regional architecture, and morphology relate to-and to some extent may enable-the emergence of mature sound-evoked activity patterns. In that regard, the findings of this study expand our understanding of the presynaptic mechanisms that regulate critical period formation associated with experience-dependent refinement of sound processing in auditory forebrain circuits.

Differential maturation of vesicular glutamate and GABA transporter expression in the mouse auditory forebrain during the first weeks of hearing

PubMed Central

Hackett, Troy A.; Clause, Amanda R.; Takahata, Toru; Hackett, Nicholas J.; Polley, Daniel B.

2015-01-01

Vesicular transporter proteins are an essential component of the presynaptic machinery that regulates neurotransmitter storage and release. They also provide a key point of control for homeostatic signaling pathways that maintain balanced excitation and inhibition following changes in activity levels, including the onset of sensory experience. To advance understanding of their roles in the developing auditory forebrain, we tracked the expression of the vesicular transporters of glutamate (VGluT1, VGluT2) and GABA (VGAT) in primary auditory cortex (A1) and medial geniculate body (MGB) of developing mice (P7, P11, P14, P21, adult) before and after ear canal opening (~P11–P13). RNA sequencing, in situ hybridization, and immunohistochemistry were combined to track changes in transporter expression and document regional patterns of transcript and protein localization. Overall, vesicular transporter expression changed the most between P7 and P21. The expression patterns and maturational trajectories of each marker varied by brain region, cortical layer, and MGB subdivision. VGluT1 expression was highest in A1, moderate in MGB, and increased with age in both regions. VGluT2 mRNA levels were low in A1 at all ages, but high in MGB, where adult levels were reached by P14. VGluT2 immunoreactivity was prominent in both regions. VGluT1+ and VGluT2+ transcripts were co-expressed in MGB and A1 somata, but co-localization of immunoreactive puncta was not detected. In A1, VGAT mRNA levels were relatively stable from P7 to adult, while immunoreactivity increased steadily. VGAT+ transcripts were rare in MGB neurons, whereas VGAT immunoreactivity was robust at all ages. Morphological changes in immunoreactive puncta were found in two regions after ear canal opening. In the ventral MGB, a decrease in VGluT2 puncta density was accompanied by an increase in puncta size. In A1, peri-somatic VGAT and VGluT1 terminals became prominent around the neuronal somata. Overall, the observed changes in gene and protein expression, regional architecture, and morphology relate to—and to some extent may enable— the emergence of mature sound-evoked activity patterns. In that regard, the findings of this study expand our understanding of the presynaptic mechanisms that regulate critical period formation associated with experience-dependent refinement of sound processing in auditory forebrain circuits. PMID:26159773

Correlation between three-dimensional morphological changes of the hyoid bone with other skeletal maturation methods in adolescents.

PubMed

Shim, Jocelyne; Heo, Giseon; Lagravère, Manuel O

2013-10-01

The study compares growth changes of hyoid bone in cone-beam computed tomography (CBCT) with conventional skeletal maturation methods to examine their potential implications in the development of a three-dimensional method. Subjects (n = 62, 11-17 years of age) were exposed to CBCT at a six-month interval (T1/T2/T3). Ten-hyoid distances were compared with age, hand wrist skeletal maturation index (SMI), and cervical vertebral maturation stage (CS). The length of greater cornua (GC) was most frequently, moderate to highly correlated with age (right: 0.57/0.53/0.58; left: 0.45/0.50/0.48), SMI (right: 0.52/0.40/0.45; left: 0.42 at T3), and CS (right: 0.52 at T1), followed by the length of the hyoid bone with age (right: 0.50/0.49/0.47; left: 0.44/0.47 at T1/T2), SMI (right: 0.45/0.41 at T1/T2), and CS (right: 0.48 at T1). The width of body of the hyoid (HB) width was correlated with age (0.43/0.44/0.44). The GC-HB gap was correlated with age (right: -0.41 at T3) and SMI (right: -0.42 at T1). Peripubertal hyoid maturation did not yield sufficient diagnostic information for considerations in the development of a 3D-skeletal maturation method. Copyright © 2013 Elsevier Inc. All rights reserved.

Age-Dependent Cell Trafficking Defects in Draining Lymph Nodes Impair Adaptive Immunity and Control of West Nile Virus Infection.

PubMed

Richner, Justin M; Gmyrek, Grzegorz B; Govero, Jennifer; Tu, Yizheng; van der Windt, Gerritje J W; Metcalf, Talibah U; Haddad, Elias K; Textor, Johannes; Miller, Mark J; Diamond, Michael S

2015-07-01

Impaired immune responses in the elderly lead to reduced vaccine efficacy and increased susceptibility to viral infections. Although several groups have documented age-dependent defects in adaptive immune priming, the deficits that occur prior to antigen encounter remain largely unexplored. Herein, we identify novel mechanisms for compromised adaptive immunity that occurs with aging in the context of infection with West Nile virus (WNV), an encephalitic flavivirus that preferentially causes disease in the elderly. An impaired IgM and IgG response and enhanced vulnerability to WNV infection during aging was linked to delayed germinal center formation in the draining lymph node (DLN). Adoptive transfer studies and two-photon intravital microscopy revealed a decreased trafficking capacity of donor naïve CD4+ T cells from old mice, which manifested as impaired T cell diapedesis at high endothelial venules and reduced cell motility within DLN prior to antigen encounter. Furthermore, leukocyte accumulation in the DLN within the first few days of WNV infection or antigen-adjuvant administration was diminished more generally in old mice and associated with a second aging-related defect in local cytokine and chemokine production. Thus, age-dependent cell-intrinsic and environmental defects in the DLN result in delayed immune cell recruitment and antigen recognition. These deficits compromise priming of early adaptive immune responses and likely contribute to the susceptibility of old animals to acute WNV infection.

Projections of type 1 and type 2 diabetes burden in the U.S. population aged <20 years through 2050: dynamic modeling of incidence, mortality, and population growth.

PubMed

Imperatore, Giuseppina; Boyle, James P; Thompson, Theodore J; Case, Doug; Dabelea, Dana; Hamman, Richard F; Lawrence, Jean M; Liese, Angela D; Liu, Lenna L; Mayer-Davis, Elizabeth J; Rodriguez, Beatriz L; Standiford, Debra

2012-12-01

To forecast the number of U.S. individuals aged <20 years with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) through 2050, accounting for changing demography and diabetes incidence. We used Markov modeling framework to generate yearly forecasts of the number of individuals in each of three states (diabetes, no diabetes, and death). We used 2001 prevalence and 2002 incidence of T1DM and T2DM from the SEARCH for Diabetes in Youth study and U.S. Census Bureau population demographic projections. Two scenarios were considered for T1DM and T2DM incidence: 1) constant incidence over time; 2) for T1DM yearly percentage increases of 3.5, 2.2, 1.8, and 2.1% by age-groups 0-4 years, 5-9 years, 10-14 years, and 15-19 years, respectively, and for T2DM a yearly 2.3% increase across all ages. Under scenario 1, the projected number of youth with T1DM rises from 166,018 to 203,382 and with T2DM from 20,203 to 30,111, respectively, in 2010 and 2050. Under scenario 2, the number of youth with T1DM nearly triples from 179,388 in 2010 to 587,488 in 2050 (prevalence 2.13/1,000 and 5.20/1,000 [+144% increase]), with the greatest increase in youth of minority racial/ethnic groups. The number of youth with T2DM almost quadruples from 22,820 in 2010 to 84,131 in 2050; prevalence increases from 0.27/1,000 to 0.75/1,000 (+178% increase). A linear increase in diabetes incidence could result in a substantial increase in the number of youth with T1DM and T2DM over the next 40 years, especially those of minority race/ethnicity.

Temperature dependence of superfluid density in YBa 2Cu 3O 7- δ and Y 0.7Ca 0.3Ba 2Cu 3O 7- δ thin films: A doping dependence study of the linear slope

NASA Astrophysics Data System (ADS)

Lai, L. S.; Juang, J. Y.; Wu, K. H.; Uen, T. M.; Gou, Y. S.

2005-11-01

By using a microstrip ring resonator to measure the temperature dependence of the in-plane magnetic penetration depth λ(T) in YBa2Cu3O7-δ (YBCO) and Y0.7Ca0.3Ba2Cu3O7-δ (Ca-YBCO) epitaxially grown thin films, the linear temperature dependence of the superfluid density ρs/m∗ ≡ 1/λ2(T) was observed from the under- to the overdoped regime at the temperatures below T/Tc ≈ 0.3 . For the underdoped regime of YBCO and Ca-YBCO thin films, the magnitude of the slope d(1/λ2(T))/dT is insensitive to doping, and it can be treated in the framework of projected d-density-wave model. Combining these slope values with the thermal conductivity measurements, the Fermi-liquid correction factor α2 from the Fermi-liquid model, suggested by Wen and Lee, was revealed here with various doping levels.

Effect of Transient Hypothyroidism During Infancy on the Postnatal Ontogeny of Luteinising Hormone Release in the Agonadal Male Rhesus Monkey (Macaca mulatta): Implications for the Timing of Puberty in Higher Primates

PubMed Central

Plant, T. M.; Ramaswamy, S.; Bhat, G. K.; Stah, C. D.; Pohl, C. R.; Mann, D. R.

2010-01-01

The present study examined whether a transient thyroid hormone (T4) deficit during infancy in male monkeys would compromise the arrest of luteinising hormone (LH) secretion during the infant–juvenile transition, and/or interfere with the pubertal resurgence of LH. Animals were orchidectomised and thyroidectomised (n = 3; Tx) or sham Tx (n = 3) within 5 days of birth. T4 replacement was initiated in two Tx monkeys at age 19 weeks to reestablish a euthyroid condition. Blood samples were drawn weekly for hormone assay. Body weight, crown–rump length, and bone age were assessed throughout the study. Within a week of Tx, plasma T4 declined to undetectable levels and, by 6–8 weeks of age, signs of hypothyroidism were evident. Transient hypothyroidism during infancy failed to prevent either arrest of LH secretion during the infant–juvenile transition or the pubertal resurgence of LH secretion, both of which occurred at similar ages to sham Tx animals. Although body weight exhibited complete catch-up with T4 replacement, crown–rump length and bone age did not. Thus, bone age at the time of the pubertal LH resurgence in Tx animals was less advanced than that in shams. Although Tx did not influence qualitatively the pattern of gonadotrophin secretion, LH levels during infancy and after pubertal LH resurgence were elevated in Tx monkeys. This was not associated with changes in LH pulse frequency and amplitude, but half-life (53 versus 65 min) of the slow second phase of LH clearance was greater in Tx animals. These results indicate that hypothalamic mechanisms dictating the pattern of gonadotrophin-releasing hormone release from birth to puberty are not dependent on T4 action during infancy, and fail to support the notion that onset of puberty is causally coupled to skeletal maturation. They also indicate that LH renal clearance mechanisms may be programmed in a T4 dependent manner during infancy. PMID:18673410

Molecular role of TGF-beta, secreted from a new type of CD4+ suppressor T cell, NY4.2, in the prevention of autoimmune IDDM in NOD mice.

PubMed

Han, H S; Jun, H S; Utsugi, T; Yoon, J W

1997-06-01

A new type of CD4+ T cell clone (NY4.2) isolated from pancreatic islet-infiltrated lymphocytes of acutely diabetic non-obese diabetic (NOD) mice prevents the development of insulin-dependent diabetes mellitus (IDDM) in NOD mice, as well as the recurrence of autoimmune diabetes in syngeneic islet-transplanted NOD mice. It has been demonstrated that the cytokine TGF-beta, secreted from the cells of this clone, is the substance which prevents autoimmune IDDM. This investigation was initiated to determine the molecular role TGF-beta plays in the prevention of autoimmune IDDM by determining its effect on IL-2-induced signal transduction in Con A-activated NOD mouse splenocytes and HT-2 cells. First, we determined whether TGF-beta, secreted from NY4.2 T cells, inhibits IL-2-dependent T cell proliferation in HT-2 cells (IL-2-dependent T cell line) and NOD splenocytes. We found that TGF-beta suppresses IL-2-dependent T cell proliferation. Second, we determined whether TGF-beta inhibits the activation of Janus kinases (JAKs), as well as signal transducers and activators of transcription (STAT) proteins, involved in an IL-2-induced signalling pathway that normally leads to the proliferation of T cells. We found that TGF-beta inhibited tyrosine phosphorylation of JAK1, JAK3, STAT3 and STAT5 in Con A blasts from NOD splenocytes and HT-2 cells. Third, we examined whether TGF-beta inhibits the cooperation between STAT proteins and mitogen-activated protein kinase (MAPK), especially extracellular signal-regulated kinase 2 (ERK2). We found that TGF-beta inhibited the association of STAT3 and STAT5 with ERK2 in Con A blasts from NOD splenocytes and HT-2 cells. On the basis of these observations, we conclude that TGF-beta may interfere with signal transduction via inhibition of the IL-2-induced JAK/STAT pathway and inhibition of the association of STAT proteins with ERK2 in T cells from NOD splenocytes, resulting in the inhibition of IL-2-dependent T cell proliferation. TGF-beta-mediated suppression of T cell activation may be responsible for the prevention of effector T cell-mediated autoimmune IDDM in NOD mice by TGF-beta-producing CD4+ suppressor T cells.

Surface Gravities for 228 M, L, and T Dwarfs in the NIRSPEC Brown Dwarf Spectroscopic Survey

NASA Astrophysics Data System (ADS)

Martin, Emily C.; Mace, Gregory N.; McLean, Ian S.; Logsdon, Sarah E.; Rice, Emily L.; Kirkpatrick, J. Davy; Burgasser, Adam J.; McGovern, Mark R.; Prato, Lisa

2017-03-01

We combine 131 new medium-resolution (R ˜ 2000) J-band spectra of M, L, and T dwarfs from the Keck NIRSPEC Brown Dwarf Spectroscopic Survey (BDSS) with 97 previously published BDSS spectra to study surface-gravity-sensitive indices for 228 low-mass stars and brown dwarfs spanning spectral types M5-T9. Specifically, we use an established set of spectral indices to determine surface gravity classifications for all of the M6-L7 objects in our sample by measuring the equivalent widths (EW) of the K I lines at 1.1692, 1.1778, and 1.2529 μm, and the 1.2 μm FeH J absorption index. Our results are consistent with previous surface gravity measurements, showing a distinct double peak—at ˜L5 and T5—in K I EW as a function of spectral type. We analyze the K I EWs of 73 objects of known ages and find a linear trend between log(Age) and EW. From this relationship, we assign age ranges to the very low gravity, intermediate gravity, and field gravity designations for spectral types M6-L0. Interestingly, the ages probed by these designations remain broad, change with spectral type, and depend on the gravity-sensitive index used. Gravity designations are useful indicators of the possibility of youth, but current data sets cannot be used to provide a precise age estimate. The data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation.

Stroke Onset Time Determination Using MRI Relaxation Times without Non-Ischaemic Reference in A Rat Stroke Model

PubMed Central

Knight, Michael J.; McGarry, Bryony M.; Jokivarsi, Kimmo T.; Gröhn, Olli H.J.; Kauppinen, Risto A.

2017-01-01

Background Objective timing of stroke in emergency departments is expected to improve patient stratification. Magnetic resonance imaging (MRI) relaxations times, T2 and T1ρ, in abnormal diffusion delineated ischaemic tissue were used as proxies of stroke time in a rat model. Methods Both ‘non-ischaemic reference’-dependent and -independent estimators were generated. Apparent diffusion coefficient (ADC), T2 and T1ρ, were sequentially quantified for up to 6 hours of stroke in rats (n = 8) at 4.7T. The ischaemic lesion was identified as a contiguous collection of voxels with low ADC. T2 and T1ρ in the ischaemic lesion and in the contralateral non-ischaemic brain tissue were determined. Differences in mean MRI relaxation times between ischaemic and non-ischaemic volumes were used to create reference-dependent estimator. For the reference-independent procedure, only the parameters associated with log-logistic fits to the T2 and T1ρ distributions within the ADC-delineated lesions were used for the onset time estimation. Result The reference-independent estimators from T2 and T1ρ data provided stroke onset time with precisions of ±32 and ±27 minutes, respectively. The reference-dependent estimators yielded respective precisions of ±47 and ±54 minutes. Conclusions A ‘non-ischaemic anatomical reference’-independent estimator for stroke onset time from relaxometric MRI data is shown to yield greater timing precision than previously obtained through reference-dependent procedures. PMID:28685128

Maternal Nutritional Deficiencies and Small-for-Gestational-Age Neonates at Birth of Women Who Have Undergone Bariatric Surgery

PubMed Central

Le Guennec, D.; Accoceberry, M.; Lemery, D.; Mulliez, A.; Farigon, N.; Lahaye, C.; Miolanne-Debouit, M.; Boirie, Y.

2017-01-01

The aim is to compare the prevalence of maternal deficiencies in micronutrients, the obstetrical and neonatal complications after bariatric surgery according to surgical techniques, the time between surgery and conception, and BMI at the onset of pregnancy. A retrospective cohort study concerned 57 singleton pregnancies between 2011 and 2016 of 48 adult women who have undergone bariatric surgery. Small-for-gestational-age neonates were identified in 36.0% of pregnancies. With supplements intake (periconceptional period: 56.8%, trimester 1 (T1): 77.8%, T2: 96.3%, and T3: 100.0%), nutritional deficiencies involved vitamins A (T1: 36.4%, T2: 21.1%, and T3: 40.0%), D (T1: 33.3%, T2: 26.3%, and T3: 8.3%), C (T1: 66.7%, T2: 41.2%, and T3: 83.3%), B1 (T1: 45.5%, T2: 15.4%, and T3: 20.0%), and B9 (T1: 14.3%, T2: 0%, and T3: 9.1%) and selenium (T1: 77.8%, T2: 22.2%, and T3: 50.0%). There was no significant difference in the prevalence of nutritional deficiencies and complications according to surgery procedures and in the prevalence of pregnancy issues according to BMI at the beginning of the pregnancy and time between surgery and pregnancy. Prevalence of micronutritional deficiencies and small-for-gestational-age neonates is high in pregnant women following bariatric surgery. Specific nutritional programmes should be recommended for these women. PMID:29082043

Maternal Nutritional Deficiencies and Small-for-Gestational-Age Neonates at Birth of Women Who Have Undergone Bariatric Surgery.

PubMed

Hazart, J; Le Guennec, D; Accoceberry, M; Lemery, D; Mulliez, A; Farigon, N; Lahaye, C; Miolanne-Debouit, M; Boirie, Y

2017-01-01

The aim is to compare the prevalence of maternal deficiencies in micronutrients, the obstetrical and neonatal complications after bariatric surgery according to surgical techniques, the time between surgery and conception, and BMI at the onset of pregnancy. A retrospective cohort study concerned 57 singleton pregnancies between 2011 and 2016 of 48 adult women who have undergone bariatric surgery. Small-for-gestational-age neonates were identified in 36.0% of pregnancies. With supplements intake (periconceptional period: 56.8%, trimester 1 (T1): 77.8%, T2: 96.3%, and T3: 100.0%), nutritional deficiencies involved vitamins A (T1: 36.4%, T2: 21.1%, and T3: 40.0%), D (T1: 33.3%, T2: 26.3%, and T3: 8.3%), C (T1: 66.7%, T2: 41.2%, and T3: 83.3%), B1 (T1: 45.5%, T2: 15.4%, and T3: 20.0%), and B9 (T1: 14.3%, T2: 0%, and T3: 9.1%) and selenium (T1: 77.8%, T2: 22.2%, and T3: 50.0%). There was no significant difference in the prevalence of nutritional deficiencies and complications according to surgery procedures and in the prevalence of pregnancy issues according to BMI at the beginning of the pregnancy and time between surgery and pregnancy. Prevalence of micronutritional deficiencies and small-for-gestational-age neonates is high in pregnant women following bariatric surgery. Specific nutritional programmes should be recommended for these women.

Longitudinal change of selected human milk oligosaccharides and association to infants’ growth, an observatory, single center, longitudinal cohort study

PubMed Central

Lee, Le Ye; De Castro, Carlos Antonio; Steenhout, Philippe; Thakkar, Sagar K.

2017-01-01

Background Human milk is the recommended and sole nutrient source for newborns. One of the largest components of human milk is oligosaccharides (HMOs) with major constituents determined by the mother genotype for the fucosyltransferase 2 (FUT2, secretor) gene. HMO variation has been related with infant microbiota establishment, diarrhea incidence, morbidity and mortality, IgE associated eczema and body composition. Objectives We investigated the (i) dependence of several major representative HMOs on the FUT2 status assessed through breast milk 2’Fucosyllactose (2’FL) and (ii) the relation of the 2’FL status with infant growth up to 4 months of life. Design From an open observatory, single center, longitudinal cohort study with quantitative human milk collection at 30, 60, and 120 days postpartum from 50 mothers, who gave birth to 25 female and 25 male singleton infants, we collected a representative sample of human milk. We quantified the following 5 representative HMOs: 2’FL, Lacto-N-tetraose (LNT), Lacto-N-neotetraose (LNnT), 3’Sialyllactose (3’SL) and 6’Sialyllactose (6’SL). We grouped the milk samples and corresponding infants according to the measured milk 2’FL concentrations at 30 days of lactation, which clustered around low concentrations (95% CI of mean 12–42 mg/L) and high concentrations (95% CI of mean 1880–2460 mg/L) with the former likely representing Secretor negative mothers. Infant anthropometric measures were recorded at birth, 1, 2 and 4 months of age. Relations among the quantified HMOs and the relation of the high and low 2’FL HMOs groups with infant growth parameters were investigated via linear mixed models. Results The milk samples with low 2’FL concentration had higher LNT and lower LNnT concentrations compared to the samples with high 2’FL. The milk 3’- and 6’SL concentrations were independent of 2’FL. Over lactation time we observed a drop in the concentration of 2’FL, LNT, LNnT and 6’SL, especially from 1 to 2 months, while 3’SL remained at relatively constant concentration from 1 month onwards. Up to 4 months of age, we did not observe significant differences in body weight, body length, body mass index and head circumference of the infants who consumed breast milk with low or high FUT2 associated HMO concentrations and composition. Conclusions Our findings on HMO concentrations over time of lactation and clusters based on 2’FL concentrations confirm previous observations and suggest that LNnT and LNT are ‘co-regulated’ with the FUT2 dependent 2’FL concentration, with LNnT showing a positive and LNT a negative relation. Further, our findings also suggest that the relatively substantial variation in HMOs between the high and low 2’FL clusters do not impact infant growth of either sex up to 4 months of age. The study was registered in www.ClinicalTrial.gov (NCT01805011). PMID:28182762

Initial Isotopic Heterogeneities in ZAGAMI: Evidence of a Complex Magmatic History

NASA Technical Reports Server (NTRS)

Nyquist, L. E.; Shih, C.-Y.; Reese, Y. D.

2006-01-01

Interpretations of Zagami s magmatic history range from complex [1,2] to relatively simple [3]. Discordant radiometric ages led to a suggestion that the ages had been reset [4]. In an attempt to identify the mechanism, Rb-Sr isochrons were individually determined for both fine-grained and coarse-grained Zagami [5]. Ages of approx.180 Ma were obtained from both lithologies, but the initial Sr-87/Sr-86 (ISr) of the fine-grained lithology was higher by 8.6+/-0.4 e-units. Recently, a much older age of approx.4 Ga has been advocated [6]. Here, we extend our earlier investigation [5]. Rb-Sr Data: In [5] we applied identical, simplified, procedures to both lithologies to test whether a grain-size dependent process such as thermally-driven subsolidus isotopic reequilibration had caused age-resetting. Minerals were separated only by density. In the present experiment, purer mineral separates were analysed with improved techniques. Combined Rb-Sr results give ages (T) = 166+/-12 Ma and 177+/-9 Ma and I(subSr) = 0.72174+/-9 and 0.72227+/-7 for the coarse-grained and fine-grained lithologies, respectively. ISr in the fine-grained sample is thus higher than in the coarse-grained sample by 7.3+/-1.6 e-units. The results for the coarse-grained lithology are in close agreement with T = 166+/-6 Ma, ISr = 0.72157+/-8 for an adjacent sample [7] and T = 178+/-4 Ma, ISr = 0.72151+/-5 [4, adjusted] for a separate sample. Thus, fine-grained Zagami appears on average to be less typical of the bulk than coarse-grained Zagami.

Hyperandrogenism induces a proinflammatory TNFα response to glucose ingestion in a receptor-dependent fashion.

PubMed

González, Frank; Sia, Chang Ling; Bearson, Dawn M; Blair, Hilary E

2014-05-01

Hyperandrogenism and inflammation are related in polycystic ovary syndrome (PCOS). Hyperandrogenemia can induce inflammation in reproductive-age women, but the mechanism for this phenomenon is unclear. We examined the in vivo and in vitro effects of hyperandrogenism on mononuclear cell (MNC)-derived androgen receptor (AR) status and TNFα release. This study combined a randomized, controlled, double-blind protocol with laboratory-based cell culture experiments. This work was performed in an academic medical center. Lean, healthy, reproductive-age women were treated with 130 mg of dehydroepiandrosterone (DHEA) or placebo (n = 8 subjects each) for 5 days and also provided untreated fasting blood samples (n = 12 subjects) for cell culture experiments. AR mRNA content and TNFα release were measured before and after DHEA administration in the fasting state and 2 hours after glucose ingestion. TNFα release in the fasting state was also measured in cultured MNCs exposed to androgens with or without flutamide preincubation. At baseline, subjects receiving DHEA or placebo exhibited no significant difference in androgens and TNFα release from MNCs before and after glucose ingestion. Compared with placebo, DHEA administration raised levels of T, androstenedione, and DHEA sulfate, and increased MNC-derived AR mRNA content and TNFα release in the fasting state and in response to glucose ingestion. Compared with MNC exposure to baseline concentrations of DHEA (175 ng/dL) or T (50 ng/dL), the absolute change in TNFα release increased after exposure to T concentrations of 125 and 250 ng/dL and a DHEA concentration of 1750 ng/dL. Preincubation with flutamide reduced the TNFα response by ≥ 60% across all T concentrations. Androgen excess in vivo and in vitro comparable to what is present in PCOS increases TNFα release from MNCs of lean healthy reproductive-age women in a receptor-dependent fashion. Hyperandrogenemia activates and sensitizes MNCs to glucose in this population.

Early language mediates the relations between preschool inattention and school-age reading achievement.

PubMed

O'Neill, Sarah; Thornton, Veronica; Marks, David J; Rajendran, Khushmand; Halperin, Jeffrey M

2016-05-01

Early inattention is associated with later reading problems in children, but the mechanism by which this occurs is unclear. We investigated whether the negative relation between preschoolers' ADHD symptoms and 8-year-old reading achievement is directly related to the severity of inattention or is mediated by early language skills. Children (n = 150; 76% boys) were evaluated at 3 time points: preschool (T1), mean (SD) age = 4.24 (.49) years; 1 year later (T2), mean (SD) age = 5.28 (.50) years; and during school age (T3), mean (SD) age = 8.61 (.31) years. At T1, parents' Kiddie-SADS responses were dimensionalized to reflect ADHD severity. Children completed the Language domain of the NEPSY (i.e., A Developmental Neuropsychological Assessment) at T1 and again at T2. At T3, children completed the Wechsler Individual Achievement Test, Second Edition Word Reading, Pseudoword Decoding, Reading Comprehension, and Spelling subtests, and their teachers completed ratings of Reading and Written Expression performance in school. The mediating effect of T2 Language on the relation between preschool Inattention and age 8 Reading was examined using the nonparametric bootstrapping procedure, while controlling for T1 Language. Language ability at T2 mediated the path from preschool inattention (but not hyperactivity/impulsivity) to 8-year-old reading achievement (both test scores and ratings) after controlling for preschoolers' language ability. Early attentional deficits may negatively impact school-age reading outcomes by compromising the development of language skills, which in turn imperils later reading achievement. Screening children with attentional problems for language impairment, as well as implementing early intervention for both attentional and language problems may be critical to promote reading achievement during school years. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Pressure dependence of coherence-incoherence crossover behavior in KFe 2 As 2 observed by resistivity and As 75 -NMR/NQR

DOE PAGES

Wiecki, P.; Taufour, V.; Chung, D. Y.; ...

2018-02-13

We present the results of 75As nuclear magnetic resonance (NMR), nuclear quadrupole resonance (NQR), and resistivity measurements in KF e2 As 2 under pressure (p). The temperature dependence of the NMR shift, nuclear spin-lattice relaxation time (T 1), and resistivity show a crossover between a high-temperature incoherent, local-moment behavior and a low-temperature coherent behavior at a crossover temperature (T*). T* is found to increase monotonically with pressure, consistent with increasing hybridization between localized 3d orbital-derived bands with the itinerant electron bands. No anomaly in T* is seen at the critical pressure p c= 1.8 GPa where a change of slopemore » of the superconducting (SC) transition temperature T c( p ) has been observed. In contrast, T c( p ) seems to correlate with antiferromagnetic spin fluctuations in the normal state as measured by the NQR 1/T 1 data, although such a correlation cannot be seen in the replacement effects of A in the AFe 2As 2 (A=K,Rb,Cs) family. In the superconducting state, two T 1 components are observed at low temperatures, suggesting the existence of two distinct local electronic environments. The temperature dependence of the short T 1s indicates a nearly gapless state below T c. On the other hand, the temperature dependence of the long component 1/T 1Limplies a large reduction in the density of states at the Fermi level due to the SC gap formation. These results suggest a real-space modulation of the local SC gap structure in KFe 2As 2 under pressure.« less

Pressure dependence of coherence-incoherence crossover behavior in KFe 2 As 2 observed by resistivity and As 75 -NMR/NQR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiecki, P.; Taufour, V.; Chung, D. Y.

We present the results of 75As nuclear magnetic resonance (NMR), nuclear quadrupole resonance (NQR), and resistivity measurements in KF e2 As 2 under pressure (p). The temperature dependence of the NMR shift, nuclear spin-lattice relaxation time (T 1), and resistivity show a crossover between a high-temperature incoherent, local-moment behavior and a low-temperature coherent behavior at a crossover temperature (T*). T* is found to increase monotonically with pressure, consistent with increasing hybridization between localized 3d orbital-derived bands with the itinerant electron bands. No anomaly in T* is seen at the critical pressure p c= 1.8 GPa where a change of slopemore » of the superconducting (SC) transition temperature T c( p ) has been observed. In contrast, T c( p ) seems to correlate with antiferromagnetic spin fluctuations in the normal state as measured by the NQR 1/T 1 data, although such a correlation cannot be seen in the replacement effects of A in the AFe 2As 2 (A=K,Rb,Cs) family. In the superconducting state, two T 1 components are observed at low temperatures, suggesting the existence of two distinct local electronic environments. The temperature dependence of the short T 1s indicates a nearly gapless state below T c. On the other hand, the temperature dependence of the long component 1/T 1Limplies a large reduction in the density of states at the Fermi level due to the SC gap formation. These results suggest a real-space modulation of the local SC gap structure in KFe 2As 2 under pressure.« less

Effects of sevelamer carbonate on advanced glycation end products and antioxidant/pro-oxidant status in patients with diabetic kidney disease.

PubMed

Yubero-Serrano, Elena M; Woodward, Mark; Poretsky, Leonid; Vlassara, Helen; Striker, Gary E

2015-05-07

The primary goals were to re-examine whether sevelamer carbonate (SC) reduces advanced glycation end products (AGEs) (methylglyoxal and carboxymethyllysine [CML]), increases antioxidant defenses, reduces pro-oxidants, and improves hemoglobin A1c (HbA1c) in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Secondary goals examined albuminuria, age, race, sex, and metformin prescription. This two-center, randomized, intention-to-treat, open-label study evaluated 117 patients with T2DM (HbA1c >6.5%) and stages 2-4 DKD (urinary albumin/creatinine ratio ≥200 mg/g) treated with SC (1600 mg) or calcium carbonate (1200 mg), three times a day, without changing medications or diet. Statistical analyses used linear mixed models adjusted for randomization levels. Preselected subgroup analyses of sex, race, age, and metformin were conducted. SC lowered serum methylglyoxal (95% confidence interval [CI], -0.72 to -0.29; P<0.001), serum CML (95% CI, -5.08 to -1.35; P≤0.001), and intracellular CML (95% CI, -1.63 to -0.28; P=0.01). SC increased anti-inflammatory defenses, including nuclear factor like-2 (95% CI, 0.58 to 1.29; P=0.001), AGE receptor 1 (95% CI, 0.23 to 0.96; P=0.001), NAD-dependent deacetylase sirtuin-1 (95% CI, 0.20 to 0.86; P=0.002), and estrogen receptor α (95% CI, 1.38 to 2.73; P ≤0.001). SC also decreased proinflammatory factors such as TNF receptor 1 (95% CI, -1.56 to -0.72; P≤0.001) and the receptor for AGEs (95% CI, -0.58 to 1.53; P≤0.001). There were no differences in HbA1c, GFR, or albuminuria in the overall group. Subanalyses showed that SC lowered HbA1c in women (95% CI, -1.71 to -0.27; P=0.01, interaction P=0.002), and reduced albuminuria in those aged <65 years (95% CI, -1.15 to -0.07; P=0.03, interaction P=0.02) and non-Caucasians (95% CI, -1.11 to -0.22; P=0.003, interaction P≤0.001), whereas albuminuria increased after SC and calcium carbonate in Caucasians. SC reduced circulating and cellular AGEs, increased antioxidants, and decreased pro-oxidants, but did not change HbA1c or the albumin/creatinine ratio overall in patients with T2DM and DKD. Because subanalyses revealed that SC may reduce HbA1c and albuminuria in some patients with T2DM with DKD, further studies may be warranted. Copyright © 2015 by the American Society of Nephrology.

Disorder dependence electron phonon scattering rate of V82Pd18 - xFex alloys at low temperature

NASA Astrophysics Data System (ADS)

Jana, R. N.; Meikap, A. K.

2018-04-01

We have systematically investigated the disorder dependence electron phonon scattering rate in three dimensional disordered V82Pd18 - xFex alloys. A minimum in temperature dependence resistivity curve has been observed at low temperature T =Tm. In the temperature range 5 K ≤ T ≤Tm the resistivity correction follows ρo 5 / 2T 1 / 2 law. The dephasing scattering time has been calculated from analysis of magnetoresistivity by weak localization theory. The electron dephasing time is dominated by electron-phonon scattering and follows anomalous temperature (T) and disorder (ρ0) dependence behaviour like τe-ph-1 ∝T2 /ρ0, where ρ0 is the impurity resistivity. The magnitude of the saturated dephasing scattering time (τ0) at zero temperature decreases with increasing disorder of the samples. Such anomalous behaviour of dephasing scattering rate is still unresolved.

Tax-dependent stimulation of G1 phase-specific cyclin-dependent kinases and increased expression of signal transduction genes characterize HTLV type 1-transformed T cells.

PubMed

Haller, K; Ruckes, T; Schmitt, I; Saul, D; Derow, E; Grassmann, R

2000-11-01

Human T cell leukemia virus protein induces T cells to permanent IL-2-dependent growth. These cells occasionally convert to factor independence. The viral oncoprotein Tax acts as an essential growth factor of transformed lymphocytes and stimulates the cell cycle in the G(1) phase. In T cells and fibroblasts Tax enhances the activity of the cyclin-dependent kinases (CDK) CDK4 and CDK6. These kinases, which require binding to cyclin D isotypes for their activity, control the G(1) phase. Coimmunoprecipitation from these cells revealed that Tax associates with cyclin D3/CDK6, suggesting a direct activation of this kinase. The CDK stimulation may account in part for the mitogenic Tax effect, which causes IL-2-dependent T cell growth by Tax. To address the conversion to IL-2-independent proliferation and to identify overexpressed genes, which contribute to the transformed growth, the gene expression patterns of HTLV-1-transformed T cells were compared with that of peripheral blood lymphocytes. Potentially overexpressed cDNAs were cloned, sequenced, and used to determine the RNA expression. Genes found to be up-regulated are involved in signal transduction (STAT5a, cyclin G(1), c-fgr, hPGT) and also glycoprotein synthesis (LDLC, ribophorin). Many of these are also activated during T cell activation and implicated in the regulation of growth and apoptosis. The transcription factor STAT5a, which is involved in IL-2 signaling, was strongly up-regulated only in IL-2-independent cells, thus suggesting that it contributes to factor-independent growth. Thus, the differentially expressed genes could cooperate with the Tax-induced cell cycle stimulation in the maintenance of IL-2-dependent and IL-2-independent growth of HTLV-transformed lymphocytes.

A scaling law for the critical current of Nb3Sn stands based on strong-coupling theory of superconductivity

NASA Astrophysics Data System (ADS)

Oh, Sangjun; Kim, Keeman

2006-02-01

We study the transition temperature Tc, the thermodynamic critical field Bc, and the upper critical field Bc2 of Nb3Sn with Eliashberg theory of strongly coupled superconductors using the Einstein spectrum α2(ω)F(ω)=λ<ω2>1/2δ(ω-<ω2>1/2). The strain dependences of λ(ɛ) and <ω2>1/2(V) are introduced from the empirical strain dependence of Tc(V) for three model cases. It is found that the empirical relation Tc(V)/Tc(0)=[Bc2(4.2 K,V)/Bc2(4.2 K,0)]1/w (w~3) is mainly due to the low-energy-phonon mode softening. We derive analytic expressions for the strain and temperature dependences of Bc(T,V) and Bc2(T,V) and the Ginzburg-Landau parameter κ(T,V) from the numerical calculation results. The Summers refinement on the temperature dependence of κ(T) shows deviation from our calculation results. We propose a unified scaling law of flux pinning in Nb3Sn strands in the form of the Kramer model with the analytic expressions of Bc2(T,V) and κ(T,V) derived in this work. It is shown that the proposed scaling law gives a reasonable fit to the reported data with only eight fitting parameters.

The relationships between sex hormones and sexual function in middle-aged and older European men.

PubMed

O'Connor, Daryl B; Lee, David M; Corona, Giovanni; Forti, Gianni; Tajar, Abdelouahid; O'Neill, Terence W; Pendleton, Neil; Bartfai, Gyorgy; Boonen, Steven; Casanueva, Felipe F; Finn, Joseph D; Giwercman, Aleksander; Han, Thang S; Huhtaniemi, Ilpo T; Kula, Krzysztof; Labrie, Fernand; Lean, Michael E J; Punab, Margus; Silman, Alan J; Vanderschueren, Dirk; Wu, Frederick C W

2011-10-01

Limited data are available exploring the associations between sex hormones, multiple domains of sexual functioning, and sexual function-related distress in nonpatient samples in Europe. The aim of the study was to investigate the relationships between serum testosterone (T), estradiol (E2), and dihydrotestosterone (DHT) and sexual function in a multicenter population-based study of aging in men. Using stratified random sampling, 2838 men aged 40-79 yr completed the European Male Ageing Study-Sexual Function Questionnaire and provided a blood sample for hormone measurements. T, E2, and DHT were measured using gas chromatography-mass spectrometry. We conducted a community-based population survey in eight European centers. Self-reported sexual function (overall sexual function, sexual function-related distress, erectile dysfunction, masturbation) was measured. Total and free T, but not E2 or DHT, was associated with overall sexual function in middle-aged and older men. E2 was the only hormone associated with sexual function-related distress such that higher levels were related to greater distress. Free T levels were associated with masturbation frequency and erectile dysfunction in the fully adjusted models, such that higher T was associated with less dysfunction and greater frequency. Moreover, there was a T threshold for the relationship between total T, sexual function, and erectile dysfunction. At T concentrations of 8 nmol/liter or less, T was associated with worse sexual functioning, whereas at T levels over 8 nmol/liter, the relationship came to a plateau. These findings suggest that different hormonal mechanisms may regulate sexual functioning (T) vs. the psychological aspects (E2) of male sexual behavior. Moreover, there was a T threshold for overall sexual function such that at levels greater than 8 nmol/liter the relationship between T and sexual function did not become stronger.

Effects of T-2 Toxin on Pacific White Shrimp Litopenaeus vannamei: Growth, and Antioxidant Defenses and Capacity and Histopathology in the Hepatopancreas.

PubMed

Deng, Yijia; Wang, Yaling; Zhang, Xiaodi; Sun, Lijun; Wu, Chaojin; Shi, Qi; Wang, Rundong; Sun, Xiaodong; Bi, Siyuan; Gooneratne, Ravi

2017-03-01

Modified-masked T-2 toxin (mT-2) formed during metabolism in edible aquatic animals may go undetected by traditional analytical methods, thereby underestimating T-2 toxicity. The effects of T-2 on growth and antioxidant capacity and histopathological changes in the hepatopancreas were studied in Pacific white shrimp Litopenaeus vannamei exposed for 20 d to 0, 0.5, 1.2, 2.4, 4.8, and 12.2 mg/kg of T-2 in their feed. The concentration of mT-2 in the hepatopancreas was detected by liquid chromatography-tandem mass spectrophotometry before and after trifluoroacetic acid (TFA) treatment that converted mT-2 to free T-2. A dose-dependent increase in mT-2 concentration was observed in the hepatopancreas. Dietary exposure to T-2 significantly decreased (P < 0.05) shrimp growth and survival rate compared with the controls. The malondialdehyde (MDA) concentration was significantly increased in shrimp exposed to feed with ≥2.4 mg/kg T-2 (P < 0.05). The antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx), total antioxidant capacity (T-AOC), and also glutathione (GSH) content increased in shrimp dosed with 2.4-4.8 mg/kg T-2 but declined at the highest dose (12.2 mg/kg), probably indicating an inability to cope with high concentrations of reactive oxygen species (ROS) as evident from a marked increase in MDA (P < 0.05) culminating in cellular toxicity. Histopathological changes in the hepatopancreas were dose dependent, with cell autophagy evident at the highest exposure dose. This is the first report in shrimp of a dose-dependent increase in ROS, SOD enzyme activity, and T-AOC at low T-2 exposures, and associated histopathological changes in the hepatopancreas, in response to dietary T-2. Received January 26, 2016; accepted October 9, 2016.

Cancer cachexia and diabetes: similarities in metabolic alterations and possible treatment.

PubMed

Chevalier, Stéphanie; Farsijani, Samaneh

2014-06-01

Cancer cachexia is a metabolic syndrome featuring many alterations typical of type 2 diabetes (T2D). While muscle wasting is a hallmark of cachexia, epidemiological evidence also supports an accelerated age-related muscle loss in T2D. Insulin resistance manifests in both conditions and impairs glucose disposal and protein anabolism by tissues. A greater contribution of gluconeogenesis to glucose production may limit amino acid availability for muscle protein synthesis, further aggravating muscle loss. In the context of inter-dependence between glucose and protein metabolism, the present review summarizes the current state of knowledge on alterations that may lead to muscle wasting in human cancer. By highlighting the similarities with T2D, a disease that has been more extensively studied, the objective of this review is to provide a better understanding of the pathophysiology of cancer cachexia and to consider potential treatments usually targeted for T2D. Nutritional approaches aimed at stimulating protein anabolism might include specially formulated food with optimal protein and amino acid composition. Because the gradual muscle loss in T2D may be attenuated by diabetes treatment, anti-diabetic drugs might be considered in cachexia treatment. Metformin emerges as a choice candidate as it acts both on reducing gluconeogenesis and improving insulin sensitivity, and has demonstrated tumour suppressor properties in multiple cancer types. Such a multimodal approach to slow or reverse muscle wasting in cachexia warrants further investigation.

Age-associated Epstein–Barr virus-specific T cell responses in seropositive healthy adults

PubMed Central

Cárdenas Sierra, D; Vélez Colmenares, G; Orfao de Matos, A; Fiorentino Gómez, S; Quijano Gómez, S M

2014-01-01

Epstein–Barr virus (EBV) is present in 95% of the world's adult population. The immune response participates in immune vigilance and persistent infection control, and this condition is maintained by both a good quality (functionality) and quantity of specific T cells throughout life. In the present study, we evaluated EBV-specific CD4+ and CD8+ T lymphocyte responses in seropositive healthy individuals younger and older than 50 years of age. The assessment comprised the frequency, phenotype, functionality and clonotypic distribution of T lymphocytes. We found that in both age groups a similar EBV-specific T cell response was found, with overlapping numbers of tumour necrosis factor (TNF)-α+ T lymphocytes (CD4+ and CD8+) within the memory and effector cell compartments, in addition to monofunctional and multi-functional T cells producing interleukin (IL)-2 and/or interferon (IFN)-γ. However, individuals aged more than 50 years showed significantly higher frequencies of IL-2-producing CD4+ T lymphocytes in association with greater production of soluble IFN-γ, TNF-α and IL-6 than subjects younger than 50 years. A polyclonal T cell receptor (TCR)-variable beta region (Vβ) repertoire exists in both age groups under basal conditions and in response to EBV; the major TCR families found in TNF-α+/CD4+ T lymphocytes were Vβ1, Vβ2, Vβ17 and Vβ22 in both age groups, and the major TCR family in TNF-α+/CD8+ T cells was Vβ13·1 for individuals younger than 50 years and Vβ9 for individuals aged more than 50 years. Our findings suggest that the EBV-specific T cell response (using a polyclonal stimulation model) is distributed throughout several T cell differentiation compartments in an age-independent manner and includes both monofunctional and multi-functional T lymphocytes. PMID:24666437

Restoration of the antibody response upon rabies vaccination in HIV-infected patients treated with HAART.

PubMed

Gelinck, Luc B S; Jol-van der Zijde, Cornelia M; Jansen-Hoogendijk, Anja M; Brinkman, Daniëlle M C; van Dissel, Jaap T; van Tol, Maarten J D; Kroon, Frank P

2009-11-27

Rabies vaccine was used as a T-cell-dependent neoantigen to investigate several aspects of the primary and booster immune response in vivo in HIV-infected individuals receiving antiretroviral treatment. Study participants received rabies vaccination twice, within a 3-month interval. Serum samples were taken before and 1, 2 and 4 weeks after both vaccinations and 1 and 5 years after the primary vaccination. Antirabies antibodies [immunoglobulin G (IgG), IgG subclasses, immunoglobulin A (IgA) and immunoglobulin M (IgM)] were determined; antibody avidity was measured after both vaccinations. T-cell subsets were characterized by flow cytometry. Eighteen healthy controls and 30 HIV-infected adults, treated with HAART for almost 4 years, with a median CD4(+) T-cell count of 537 cells/microl, were immunized. The postvaccination concentrations of antirabies IgG and IgM were significantly lower in HIV-infected individuals as compared with controls. Three T-cell-dependent processes, a true booster response, a class switch from IgM to IgG and avidity maturation were present in both healthy controls and HIV-infected individuals. Higher age was associated with lower postvaccination antirabies IgG and IgM titers. Five years after the primary vaccination, 63% of the HIV-infected individuals still had antibody titers above the protection threshold. Immune restoration in HIV-infected individuals treated with HAART, resulting in a CD4(+) T-cell count greater than 500 cells/microl, is incomplete. However, the majority of HIV-infected individuals are capable of mounting a long-lasting immune response, including several pivotal T-cell-dependent processes, upon vaccination with a neoantigen such as the rabies vaccine.

The Stellar Population Histories of Elliptical Galaxies

NASA Astrophysics Data System (ADS)

Trager, Scott Charles

1997-08-01

This dissertation sets out to probe the stellar population histories of local field and distant cluster elliptical galaxies. Absorption-line strengths of the centers of 381 early-type galaxies and 38 globular clusters measured from the Lick Image Dissector Scanner (Lick/IDS) are presented. Error estimation and corrections for velocity-dispersion broadening are described in detail. Monte Carlo simulations show that the Lick/IDS data are not accurate enough to infer ages and abundances of individual ellipticals with confidence. The excellent data of Gonzalez (1993) are therefore used to infer the stellar population ages and abundances of the centers of local field ellipticals. Elliptical galaxy nuclei follow three relations in this sample. (1) The t-Z relation. Elliptical nuclei have an age-abundance relation at fixed velocity dispersion σ that follows the Worthey (1994) '3/2 rule.' Ellipticals therefore have fixed color and metal-line strengths at fixed σ. (2) The σ-Z relation. The abundance zeropoint of the t-Z relation increases with increasing σ. Taken together, (1) and (2) predict scaling relations like the Mg2-σ and color-magnitude relations. (3) The σ- (Mg/Fe) relation. The abundance ratio (Mg/Fe) increases with increasing σ, as the σ-Z relation for Mg has twice the slope of the σ-Z relation for Fe. Relations (1)-(3) can be expressed as a pair of planes in t-Z-σ space, one for Fe and one for Mg, with similar age dependences but different σ-dependences. Scenarios for the possible origins of these relations are presented. Absorption-line strengths of eighteen early-type galaxies in two rich clusters at z = 0.41 (CL0939 + 4713) and z = 0.76 (CL1322 + 3027) have been measured from Keck LRIS spectra. The Balmer-line strengths of ellipticals at z = 0.41 are consistent with passive evolution of local field ellipticals but seem too metal-rich. Both Balmer- and metal-line strengths of ellipticals at z = 0.76 are consistent with passive evolution of local field ellipticals. Spectra of four z $>$ 3 objects discovered serendipitiously are presented. They are small (r1/2 ~ 10 kpc), bright (LB ~ 1-10 LB*), lumpy, and are most likely gravitationally lensed. They are metal-poor (Z/ ~/ 2 Msolar yr-1). A model for their evolution is presented. It is suggested that they are the progenitors of the Population II component of local spheroids.

Cardiovascular disease and type 1 diabetes: prevalence, prediction and management in an ageing population

PubMed Central

Lee, Siang Ing; Patel, Mitesh; Jones, Christopher M.; Narendran, Parth

2015-01-01

Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes mellitus (T1D). However, evidence of its risks and management is often extrapolated from studies in type 2 diabetic (T2D) patients or the general population. This approach is unsatisfactory given that the underlying pathology, demographics and natural history of the disease differ between T1D and T2D. Furthermore, with a rising life expectancy, a greater number of T1D patients are exposed to the cardiovascular (CV) risk factors associated with an ageing population. The aim of this review is to examine the existing literature around CVD in T1D. We pay particular attention to CVD prevalence, how well we manage risk, potential biomarkers, and whether the studies included the older aged patients (defined as aged over 65). We also discuss approaches to the management of CV risk in the older aged. The available data suggest a significant CVD burden in patients with T1D and poor management of CV risk factors. This is underpinned by a poor evidence base for therapeutic management of CV risk specifically for patients with T1D, and in the most relevant population – the older aged patients. We would suggest that important areas remain to be addressed, particularly exploring the risks and benefits of therapeutic approaches to CVD management in the older aged. PMID:26568811

An OX40/OX40L interaction directs successful immunity to hepatitis B virus

PubMed Central

Publicover, Jean; Gaggar, Anuj; Jespersen, Jillian M.; Halac, Ugur; Johnson, Audra J.; Goodsell, Amanda; Avanesyan, Lia; Nishimura, Stephen L.; Holdorf, Meghan; Mansfield, Keith G.; Judge, Joyce Bousquet; Koshti, Arya; Croft, Michael; Wakil, Adil E.; Rosenthal, Philip; Pai, Eric; Cooper, Stewart; Baron, Jody L.

2018-01-01

Depending on age of acquisition, hepatitis B virus (HBV) can induce a cell-mediated immune response that results in either cure or progressive liver injury. In adult-acquired infection, HBV antigens are usually cleared, whereas in infancy-acquired infection, they persist. Individuals infected during infancy therefore represent the majority of patients chronically infected with HBV (CHB). A therapy that can promote viral antigen clearance in most CHB patients has not been developed and would represent a major health care advance and cost mitigator. Using an age-dependent mouse model of HBV clearance and persistence in conjunction with human blood and liver tissue, we studied mechanisms of viral clearance to identify new therapeutic targets. We demonstrate that age-dependent expression of the costimulatory molecule OX40 ligand (OX40L) by hepatic innate immune cells is pivotal in determining HBV immunity, and that treatment with OX40 agonists leads to improved HBV antigen clearance in young mice, as well as increased strength of T cell responses in young mice and adult mice that were exposed to HBV when they were young and developed a CHB serological profile. Similarly, in humans, we show that hepatic OX40L transcript expression is age-dependent and that increased OX40 expression on peripheral CD4+ T cells in adults is associated with HBV clearance. These findings provide new mechanistic understanding of the immune pathways and cells necessary for HBV immunity and identify potential therapeutic targets for resolving CHB. PMID:29563320

Effect of Li level, artificial aging, and TiB2 reinforcement on the modulus of Weldalite (tm) 049

NASA Technical Reports Server (NTRS)

1991-01-01

The dynamic Young's Modulus (E) was determined for (1) alloys 049(1.3)(heat 072), (2) 049(1.9), and (3) 049(1.3) TiB2 in the T3 temper and after aging at 160 C were made on a single 0.953 cm (0.375 in) cube to reduce scatter from microstructural inhomogeneities. Both shear and transverse wave velocities were measured for the L, LT, and ST directions by a pulse echo technique. These velocities were then used to calculate modulus. The change is shown in E with aging time at 160 C (320 F) for the three alloys. It is clear from the plots that aging has a minor, but measurable, influence on the E of alloys 049(1.3) and 049(1.9): E decreases by -2.5 pct. for 2 and 3 during the initial stages of artificial aging. This decrease in E generally follows the strength reversion. On further aging beyond the reversion well, E increases and then decreases again as the alloy overage. The slightly higher modulus in the T8 than in the T3 temper is consistent with the presence of the high modulus T sub 1 phase in the T8 temper. A similar change in E was observed on aging for the TiB2 reinforced variant that also follows the aging curve.

Clinical characteristics of polycystic ovary syndrome: investigating differences in White and South Asian women.

PubMed

Mani, Hamidreza; Davies, Melanie J; Bodicoat, Danielle H; Levy, Miles J; Gray, Laura J; Howlett, Trevor A; Khunti, Kamlesh

2015-10-01

To understand the phenotypic presentation of women with polycystic ovary syndrome (PCOS) of different ethnicities and at different ages. Cross-sectional, retrospective data analysis (1988 - 2009). Specialist clinic in a University Hospital, Leicestershire, UK. Women with PCOS, n = 1310 (mean age 26·2 years), 70·9% White and 29·1% South Asian (SA) attending a speciality clinic in Leicester UK. Clinical and demographic characteristics of women with PCOS including age at first clinic appointment, signs and symptoms, body mass index (BMI) and blood pressure (BP). Compared to White women, the SA were younger (24·3 vs 27·1 years, P < 0·001), less likely to smoke (3·7% vs 17·9% P < 0·001) and had a higher prevalence of acanthosis nigricans (AN) (16·8% vs 3·1% P < 0·001), type 2 diabetes (T2DM) (8·1% vs 5·6%, P < 0·01) and hirsutism (88·5% vs 77·4%, P < 0·001), with lower systolic (126·5 vs 133·0 mmHg, P < 0·001), diastolic BP (71·8 vs 75·1 mmHg P = 0·008) and BMI (29·3 vs 31·5 kg/m(2) P = 0·002). Differences in body weight remained when participants were classified as obese, overweight and normal according to ethnicity-specific cut-off points (P = 0·048). In both ethnicities, those aged ≥30 years old had higher rates of obesity, T2DM, hypertension and infertility, and less acne, and oligomenorrhoea. Obesity was associated with increased T2DM, AN, systolic/diastolic BP, hirsutism and infertility. The phenotypic and metabolic presentations of women with PCOS appear to be significantly different depending on ethnicity, obesity and age. This has implications for management strategies in these groups. © 2015 John Wiley & Sons Ltd.

Temperature Dependence of the Upper Critical Field in Disordered Hubbard Model with Attraction

NASA Astrophysics Data System (ADS)

Kuchinskii, E. Z.; Kuleeva, N. A.; Sadovskii, M. V.

2017-12-01

We study disorder effects upon the temperature behavior of the upper critical magnetic field in an attractive Hubbard model within the generalized DMFT+Σ approach. We consider the wide range of attraction potentials U—from the weak coupling limit, where superconductivity is described by BCS model, up to the strong coupling limit, where superconducting transition is related to Bose-Einstein condensation (BEC) of compact Cooper pairs, formed at temperatures significantly higher than superconducting transition temperature, as well as the wide range of disorder—from weak to strong, when the system is in the vicinity of Anderson transition. The growth of coupling strength leads to the rapid growth of H c2( T), especially at low temperatures. In BEC limit and in the region of BCS-BEC crossover H c2( T), dependence becomes practically linear. Disordering also leads to the general growth of H c2( T). In BCS limit of weak coupling increasing disorder lead both to the growth of the slope of the upper critical field in the vicinity of the transition point and to the increase of H c2( T) in the low temperature region. In the limit of strong disorder in the vicinity of the Anderson transition localization corrections lead to the additional growth of H c2( T) at low temperatures, so that the H c2( T) dependence becomes concave. In BCS-BEC crossover region and in BEC limit disorder only slightly influences the slope of the upper critical field close to T c . However, in the low temperature region H c2 ( T may significantly grow with disorder in the vicinity of the Anderson transition, where localization corrections notably increase H c2 ( T = 0) also making H c2( T) dependence concave.

Differences in regional adiposity, bone mineral density, and physical exercise participation based on exercise self-efficacy among senior adults.

PubMed

Glenn, J M; Gray, M; Vincenzo, J L

2015-10-01

The impact of exercise self-efficacy levels (ESE) on exercise participation, levels of body fat (BF), and bone mineral density (BMD) are unclear in senior-aged adults. The purpose of this study was to investigate effects of ESE on exercise participation, regional distribution of BF, and BMD among seniors. Senior adults (N.=76; 36 males, 40 females) were separated into tertiles (T1, age=60.4±1.4; T2, age=61.3±1.4; T3, age=60.4±1.5) based on self-reported levels of ESE. BMD and regional BF were measured using dual-energy x-ray absorptiometry and exercise participation levels were measured using the Rapid Physical-Activity Questionnaire. MANOVA revealed a significant Wilks Lambda (p < 0.001) and univariate analysis was completed for exercise participation levels, android BF, gynoid BF, and spinal BMD. ANOVA revealed T3 was significantly lower for android BF (p=0.002) than T1 and T2 (30% and 26%, respectively) while gynoid BF was significantly lower (p=0.012) for T3 (24%) compared to T1. When evaluating exercise participation levels, T3 was significantly higher (p < 0.001) than T1 or T2. Spinal BMD was significantly higher (p=0.030) between T2 (10%) and T1. ESE is an important factor in senior adults ability to maintain longitudinal health.

Myocardial strain in healthy adults across a broad age range as revealed by cardiac magnetic resonance imaging at 1.5 and 3.0T: Associations of myocardial strain with myocardial region, age, and sex.

PubMed

Mangion, Kenneth; Clerfond, Guillaume; McComb, Christie; Carrick, David; Rauhalammi, Samuli M; McClure, John; Corcoran, David S; Woodward, Rosemary; Orchard, Vanessa; Radjenovic, Aleksandra; Zhong, Xiaodong; Berry, Colin

2016-11-01

To assess myocardial strain using cine displacement encoding with stimulated echoes (DENSE) using 1.5T and 3.0T MRI in healthy adults. Healthy adults without any history of cardiovascular disease underwent magnetic resonance imaging (MRI) at 1.5T and 3.0T within 2 days. The MRI protocol included balanced steady-state free-precession (b-SSFP), 2D cine-echo planar imaging (EPI)-DENSE, and late gadolinium enhancement in subjects >45 years. Acquisitions were divided into six segments; global and segmental peak longitudinal and circumferential strain were derived and analyzed by field strength, age, and gender. In all, 89 volunteers (mean age 44.8 ± 18.0 years, range: 18-87 years) underwent MRI at 1.5T, and 88 of these subjects underwent MRI at 3.0T (1.4 ± 1.4 days between the scans). Compared with 3.0T, the magnitudes of global circumferential (-19.5 ± 2.6% vs. -18.47 ± 2.6%; P = 0.001) and longitudinal (-12.47 ± 3.2% vs. -10.53 ± 3.1%; P = 0.004) strain were greater at 1.5T. At 1.5T, longitudinal strain was greater in females than in males: -10.17 ± 3.4% vs. -13.67 ± 2.4%; P = 0.001. Similar observations occurred for circumferential strain at 1.5T (-18.72 ± 2.2% vs. -20.10 ± 2.7%; P = 0.014) and at 3.0T (-17.92 ± 1.8% vs. -19.1 ± 3.1%; P = 0.047). At 1.5T, longitudinal and circumferential strain were not associated with age after accounting for sex (longitudinal strain P = 0.178, circumferential strain P = 0.733). At 3.0T, longitudinal and circumferential strain were associated with age (P < 0.05). Longitudinal strain values were greater in the apico-septal, basal-lateral, and mid-lateral segments and circumferential strain in the inferior, infero-lateral, and antero-lateral LV segments. Myocardial strain parameters as revealed by cine-DENSE at different MRI field strengths were associated with myocardial region, age, and sex. J. Magn. Reson. Imaging 2016;44:1197-1205. © 2016 The Authors Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

[Hypogonadism and the quality of life in male patients with type-2 diabetes mellitus].

PubMed

Zhang, Lu-Yao; He, Wei; Wan, Jian-Xin; Yin, Qi-Qi; Cheng, Zhen; Chen, Guan-Ming; Ji, Wen; Li, Hai; Li, Yan-Bing; Liao, Zhi-Hong

2016-12-01

To compare the level of testosterone between type-2 diabetes mellitus (T2DM) patients and healthy controls and to investigate the status of hypogonadism and the influence of hypopgonadism on the quality of life. We collected serum total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), and other clinical data from 166 T2DM patients aged over 30 years and 186 age-matched healthy controls. We investigated the quality of life (QoL) of the two groups of subjects using the questionnaires of Androgen Deficiency in Aging Males (ADAM), Aging Male Symptoms (AMS), 36-Item Short-Form Health Survey (SF-36), and Special Quality of Life for Diabetes Mellitus (DSQL). The level of calculated FT (cFT) was remarkably lower in the T2DM patients than in the healthy controls (P<0.05), but no statistically significant differences were observed between the two groups in the levels of TT, bio-available testosterone (Bio-T), and SHBG. The T2DM males with hypogonadism showed significant differences from those without in age, height, systolic blood pressure, and creatinine (P<0.05). Based on the criteria of cFT <0.3 nmol/L and AMS score ≥27, the incidence rate of hypogonadism was 51.81% in the T2DM patients, 31.58% in the 30－39 yr group, 32.50% in the 40－49 yr group, 50% in the 50－59 yr group, 69.23% in the 60－69 yr group, and 77.27% in the ≥70 yr group, elevated by 77.4% with the increase of 10 years of age (OR = 1.774, P<0.001). The AMS score was significantly correlated with the scores of DSQL (r = 0.557, P<0.001) and SF-36 (r = －0.739, P<0.001) in the T2DM patients. T2DM patients have lower levels of cFT than healthy men, accompanied with a higher incidence of hypogonadism. Age is a main risk factor of hypogonadism. Severer testosterone deficiency symptoms are associated with lower scores of QoL in T2DM males.

Sex, age, pubertal development and use of oral contraceptives in relation to serum concentrations of DHEA, DHEAS, 17α-hydroxyprogesterone, Δ4-androstenedione, testosterone and their ratios in children, adolescents and young adults.

PubMed

Søeborg, Tue; Frederiksen, Hanne; Mouritsen, Annette; Johannsen, Trine Holm; Main, Katharina Maria; Jørgensen, Niels; Petersen, Jørgen Holm; Andersson, Anna-Maria; Juul, Anders

2014-11-01

The influence of sex, age, pubertal development and oral contraceptives on dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), 17α-hydroxyprogesterone (17-OHP), Δ4-androstenedione (Adione), testosterone (T), calculated free testosterone (fT), free androgen index (FAI) and selected ratios in 1798 serum samples from healthy children, adolescents and young adults was evaluated. Samples were analyzed by Turboflow-LC-MS/MS. Sex hormone-binding globulin was analyzed by immunoassay. All steroid metabolite concentrations were positively associated with age and pubertal development in both sexes and generally higher in males than in females except for Adione. The pubertal rise in T in males was more pronounced compared to females, reflecting contribution from the testes. Ratios between steroid metabolites varied and depended on sex and age. All ratios were lower during infancy compared to later in life. Use of oral contraceptives significantly lowered serum concentrations of all steroid metabolites, fT, FAI, the 17-OHP/Adione, the Adione/T and the DHEA/Adione ratios, but not the DHEA/DHEAS ratio. We provide reference ranges for DHEA, DHEAS, 17-OHP, Adione, T, fT, FAI and selected ratios in relation to sex, age and pubertal development. Use of oral contraceptives strongly influences adrenal steroidogenesis and should be considered when diagnosing and monitoring treatment of patients with disorders of sex development. Copyright © 2014 Elsevier B.V. All rights reserved.

R2* mapping for brain iron: associations with cognition in normal aging.

PubMed

Ghadery, Christine; Pirpamer, Lukas; Hofer, Edith; Langkammer, Christian; Petrovic, Katja; Loitfelder, Marisa; Schwingenschuh, Petra; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Schmidt, Helena; Fazekas, Franz; Mangin, Jean-Francois; Chabriat, Hugues; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

2015-02-01

Brain iron accumulates during aging and has been associated with neurodegenerative disorders including Alzheimer's disease. Magnetic resonance (MR)-based R2* mapping enables the in vivo detection of iron content in brain tissue. We investigated if during normal brain aging iron load relates to cognitive impairment in region-specific patterns in a community-dwelling cohort of 336 healthy, middle aged, and older adults from the Austrian Stroke Prevention Family Study. MR imaging and R2* mapping in the basal ganglia and neocortex were done at 3T. Comprehensive neuropsychological testing assessed memory, executive function, and psychomotor speed. We found the highest iron concentration in the globus pallidus, and pallidal and putaminal iron was significantly and inversely associated with cognitive performance in all cognitive domains, except memory. These associations were iron load dependent. Vascular brain lesions and brain volume did not mediate the relationship between iron and cognitive performance. We conclude that higher R2*-determined iron in the basal ganglia correlates with cognitive impairment during brain aging independent of concomitant brain abnormalities. The prognostic significance of this finding needs to be determined. Copyright © 2015 Elsevier Inc. All rights reserved.

[Relationship between body weight status in early adulthood and body weight change at middle age in adults and type 2 diabetes mellitus].

PubMed

Zhou, Long; Zhao, Liancheng; Li, Ying; Guo, Min; Wu, Yangfeng

2016-03-01

To explore the relationship between weight status in early adulthood and body weight change at middle age in adults and type 2 diabetes mellitus (T2DM). The data of 14 population samples from China Multicenter Collaborative Study of Cardiovascular Epidemiology conducted in 1998 were used. Approximately 1 000 men and women in each sample were surveyed for cardiovascular disease risk factors, including body weight at age 25 years. The body mass index (BMI) at the age 25 years was calculated. The association between body weight in early adulthood and body weight change at middle age and T2DM was examined by using logistic regression model. The incidence of T2DM in low weight group (BMI<18.5 kg/m(2)), normal weight group (BMI: 18.5-23.9 kg/m(2)), overweight group (BMI: 24.0-27.9 kg/m(2)) and obese group (BMI:≥28.0 kg/m(2)) at 25 years old were 2.4%(30/1263), 2.8%(266/9562), 4.0%(70/1739) and 6.4% (7/110), respectively (P value for trend<0.01). The incidence of T2DM for adults with weight change <-7.5 kg, -7.5--2.6 kg, -2.5-2.5 kg, 2.6-7.5 kg, 7.6-12.5 kg and >12.5 kg at middle age were 2.5% (18/712), 1.3%(21/1629), 2.1%(48/2330), 2.3%(59/2585), 3.7%(94/2518), and 4.6% (133/2900) respectively. (P value for trend <0.01), Multivariate logistic regression analysis showed that overweight and obesity at age 25 years and subsequent weight gain were positively correlated with T2DM after adjusted other risk factors (all P values for trend <0.01). Overweight and obesity in early adulthood and weight gain at middle age were both independently associated with the increased risk of T2DM in middle-aged men and women.

F61. THE RELATIONSHIP OF AGE AND SYMPTOMS WITH COGNITIVE PLANNING IN SCHIZOPHRENIA

PubMed Central

Kontis, Dimitrios; Giannakopoulou, Alexandra; Theochari, Eirini; Andreopoulou, Angeliki; Vassilouli, Spyridoula; Giannakopoulou, Dimitra; Siettou, Eleni; Tsaltas, Eleftheria

2018-01-01

Abstract Background The relationship of age and symptoms with the performance on non-verbal cognitive planning tasks in schizophrenia could be useful for the development of cognitive remediation programmes. Methods During a cross-sectional study, 97 medicated and stabilized patients with chronic schizophrenia (61 males and 36 females, mean age=43.74 years, standard deviation-SD=11.59), which were consecutively referred to our Unit, were assessed using the Stockings of Cambridge (SOC) task of the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Positive and Negative Syndrome Scale (PANSS). Linear regression analyses were conducted in order to investigate the correlations of symptoms and age with SOC performance. Results Age and PANSS total scores negatively correlated with optimal SOC solutions (problems solved in minimum moves) (age: B=-0.05, 95% CI=-0.089, -0–012, df=86, t=-2.599, p=0.011, symptoms: B=-0.047, 95%CI=-0.071, -0.024, df=86, t=-3.982, p<0.001). The effects of total symptoms were driven by positive (B=-0.149, 95%CI=-0.229, -0.068, df=86 t=-3.672, p<0.001), negative (B=-0.087, 95%CI=-0.150, -0.023, df=86, t=-2.717, p=0.008) and general psychopathology symptoms (B=-0.065, 95%CI=-0.108, -0.023, df=86, t=-3.045, p=0.03). PANSS total scores positively correlated with mean excess moves in 2- (B=0.007, 95%CI=0.002, 0.012, df=86, t=2.656, p=0.009), 3- (B=0.014, 95%CI=0.005, 0.023, df=86, t=2.951, p=0.004) and 5-move (B=0.026, 95%CI=0.008, 0.044, df=86, t=2.923, p=0.004) problems and age only in 4- (B=0.026, 95%CI=0.006, 0.046, df=86, t=2.571, p=0.012) and 5-move (B=0.032, 95%CI=0.002, 0.061, df=86, t=2.152, p=0.034) problems. We could not find any association between PANSS scores and age with initial or subsequent thinking times during the SOC task. Discussion Cognitive planning deficits in schizophrenia are associated with patients’ symptoms and age. Whereas the effect of symptoms appears to be independent of task difficulty, the age effect emerges when the planning tasks become more complex. The role of drugs remains to be examined in future analyses.

Functional assessment of older obese patients candidates for bariatric surgery.

PubMed

Pajecki, Denis; Santo, Marco Aurélio; Kanagi, Ana Lumi; Riccioppo, Daniel; de Cleva, Roberto; Cecconello, Ivan

2014-01-01

Obesity in the elderly is associated with exacerbation of functional decline (dependency), that occurs with aging, because of decreased muscle mass and strength, and increased joint dysfunction. Consequently, there is progressive loss of independence, autonomy, chronic pain and impaired quality of life. The weight loss can bring benefits in all these aspects, especially when accompanied by exercises. Elderly patients with morbid obesity may be submitted to surgical treatment, taking into account that the massive weight loss, eventually caused by bariatric surgery, may exacerbate the loss of muscle mass and nutritional complications that may bring harm to the overall health and quality of life of these patients. The functional assessment of elderly patients, candidates for bariatric surgery and the extent to which surgery can bring benefits to the patients, in the field of functionality, has still to be determined. To describe profile functionality in obese elderly referred to a bariatric surgery program. Patients with age ≥ 60 and BMI ≥ 35 underwent comprehensive geriatric assessment that evaluates co morbidities, medication use, ability to perform basic activities of daily living and instrumental activities of daily living, and the "Timedupandgo" test to evaluate mobility, whose cut-off point was ≤ 10 seconds. Statistical analysis was performed in order to see if there is a positive correlation of dependency with BMI and age (over or under 65 years). Results Forty subjects have completed evaluation. The mean age was 64.1 years (60-72) and 75% were women. They had an average weight of 121.1 kg (72.7-204) and a mean BMI of 47.2 kg/m2 (35.8-68.9). 16 patients (40%) have shown dependency for activities of daily living, 19 (47,5%) for instrumental activities of daily living and 20 patients (50%) had a "Timedupandgo" test over 10 seconds. Statistical analysis (t-Student, Mann-Whitney, Binary Logistic Regression) has shown positive correlation of dependency in activities of daily living for BMI >49 kg/m2, dependency in instrumental activities of daily living for BMI >46,5 kg/m2, and "Timedupandgo" test greater than 10 seconds for BMI >51 kg/m2 (P<0,05). No dependency difference was observed for patients over or under 65 years age. Functional decline is observed in almost half of the morbid obese patients over 60 years old. It is related to increasing BMI (BMI >46,5 kg/m2) but not related to age (60 to 65 years or over 65 years). Functional decline should be considered a co-morbidity in the elderly obese patients and should be assessed before bariatric surgery in this population.

F29. HIGH-RISK SYMPTOMS FOR PSYCHOSIS IN ADOLESCENTS AND ITS RELATIONSHIP WITH FAMILY BURDEN

PubMed Central

Puig-Navarro, Olga; De la Serna, Elena; Tor, Jordina; Sintes, Anna; Sugranyes, Gisela; Redondo, Marina; Pardo, Marta; Dolz, Montse; Baeza, Inmaculada

2018-01-01

Abstract Background High-risk symptoms for psychosis (HRS) and substantial functional impairment occurs early in the course of psychosis (Fusar-Poli et al., 2015). Many patients with HRS are adolescents who are still living at home and are highly reliant on their relatives for support. Objectives: (1) To compare the family burden of caregivers of adolescents with HRS with carers of an age and gender matched healthy control group (HC), (2) to examine the relationships between different family burden aspects and high-risk symptoms for psychosis in the HRS sample. Methods Sample: 68 HRS subjects (15.3 ± 1.7 years, 66% females) and 42 HC subjects (15.5 ± 1.5 years, 66% females) from a prospective longitudinal study including help-seeking subjects who met HRS criteria (Child and Adolescent Psychiatry and Psychology departments of Hospital Clínic and Sant Joan de Déu, Barcelona, Spain). Inclusion criteria: age 10–17 years, meeting criteria for 1) attenuated positive or negative symptoms in the previous 12-months, 2) brief intermittent psychotic symptoms, 3) first or second degree relative with schizophrenia or schizotypical disorder plus impairment of functioning. Exclusion criteria: IQ<70, having a diagnosis of ASD. For HC subjects, exclusion criteria were having 1st or 2nd degree familiar with a psychotic disorder; a diagnosis of ASD and/or IQ<70. Instruments: the Semistructured Interview for Prodromal Syndromes and Scale of Prodromal Symptoms (SIPS/SOPS), the Hamilton Depression Scale and the Young Mania Scale for affective symptoms, a cognitive battery and the Caregiver Burden Inventory (CBI) which is a measure of family burden that has been validated in first-episode patients (McCleery et al., 2007). Caregivers’ responses are rated on a Likert scale from 0 (not at all descriptive) to 4 (very descriptive) and distributed in 5 factors: Time-Dependence Burden (T-Db), Developmental Burden (Db), Physical Burden (Pb), Social Burden (Sb), and Emotional Burden (Eb). High scores indicate greater perceived burden. Results HRS and HC subjects did not significantly differ in age (t=0.68, p=0.497) and sex (X2=0.003, p=0.958). Intellectual quotient was higher in HC (mean=105.4 ± 11.28) than in HRS subjects (98.63 ± 14.27, t=2.53, p=0.013). Mean scores of high-risk symptoms in HRS subjects were higher than in HC subjects (t>-9.35, p<0.001): positive: 9.12 ± 4.76, negative:11.16 ± 5.49, disorganitzation:4.96 ± 3.03, general: 8.22 ± 3.83, and total symptoms:33.24 ± 12.59. HRS subjects had also higher scores in depressive (10.54 ± 7.54, t=-9.75, p<0.001) and manic symptoms (3.61 ± 4.53, t=-5.10, p<0.001). Caregivers of HRS subjects showed higher scores than caregivers of HC in all CBI subscales (t>-5.59, p<0.001; T-Db: 6.36 ± 5.01 vs 1.02 ± 1.60, Db: 7.42 ± 6.51 vs 0.45 ± 1.23, Pb: 7.00 ± 6.13 vs 0.58 ± 1.80, Sb: 4.77 ± 4.66 vs 0.64 ± 1.95, Eb: 4.86 ± 4.64 vs 0.93 ± 2.66). Time-Dependence burden reported by caregivers of HRS patients was significantly correlated with the SOPS total score (r=0.303, p=0.014) and with the negative SOPS subscale score (r=0.308, p=0.012). The relationship between negative SOPS symptoms and time-dependence burden remained after controlling for affective symptoms (F=5.07, p0.028) and intelligence quotient (F=7.27, p=0.009). This factor represents objective aspects of burden arising from demands on the caregiver’s time. Discussion Caregivers of adolescents meeting criteria for HRS showed high perceived burden compared with caregivers of healthy adolescents. Time-dependence burden reported by caregivers was related to negative prodromal symptoms of HRS subjects. These findings highlighted that family burden occurs early in the course of psychosis. Acknowledgments: ISC-III/FIS, FEDER.

Age-dependent divergent effects of OX40L treatment on the development of diabetes in NOD mice

PubMed Central

Haddad, Christine S.; Bhattacharya, Palash; Alharshawi, Khaled; Marinelarena, Alejandra; Kumar, Prabhakaran; El-Sayed, Osama; Elshabrawy, Hatem A.; Epstein, Alan L.; Prabhakar, Bellur S.

2016-01-01

Earlier, we have shown that GM-CSF derived bone marrow dendritic cells (G-BMDCs) can expand Foxp3+ regulatory T-cells (Tregs) through a TCR-independent, but IL-2 dependent mechanism that required OX40L/OX40 interaction. While some reports have shown suppression of autoimmunity upon treatment with an OX40 agonist, others have shown exacerbation of autoimmune disease instead. To better understand the basis for these differing outcomes, we compared the effects of OX40L treatment in 6-week-old pre-diabetic and 12-week-old near diabetic NOD mice. Upon treatment with OX40L, 6-week-old NOD mice remained normoglycemic and showed a significant increase in Tregs in their spleen and lymph nodes, while 12-week-old NOD mice very rapidly developed hyperglycemia and failed to show Treg increase in spleen or LN. Interestingly, OX40L treatment increased Tregs in the thymus of both age groups. However, it induced Foxp3+CD103+CD38− stable-phenotype Tregs in the thymus and reduced the frequency of autoreactive Teff cells in 6-week-old mice; while it induced Foxp3+CD103−CD38+ labile-phenotype Tregs in the thymus and increased autoreactive CD4+ T cells in the periphery of 12-week-old mice. This increase in autoreactive CD4+ T cells was likely due to either a poor suppressive function or conversion of labile Tregs into Teff cells. Using ex vivo cultures, we found that the reduction in Treg numbers in 12-week-old mice was likely due to IL-2 deficit, and their numbers could be increased upon addition of exogenous IL-2. The observed divergent effects of OX40L treatment were likely due to differences in the ability of 6- and 12-week-old NOD mice to produce IL-2. PMID:27245356

Influence of the Vitreoretinal Interface on the Treatment with Anti-VEGF for Exudative Age-Related Macular Degeneration.

PubMed

Gil, Pedro; Gil, João; Oliveira, Nuno; Laíns, Inês; Camilo, Eduardo Nery Rossi; Fonseca, Cristina; Raimundo, Miguel; Cachulo, Maria da Luz; Silva, Rufino

2018-05-07

To investigate the influence of the vitreoretinal interface on the outcomes of different ranibizumab regimens for exudative age-related macular degeneration. We conducted a retrospective subanalysis of 2 prospective clinical trials. Patients were treated with ranibizumab for 12 months according to 3 different regimens: pro-re-nata (PRN), treat and extend (T&E), and monthly. Vitreoretinal interface was assessed for absence (group ON) or presence (group OFF) of posterior vitreous detachment (PVD). We included 64 eyes from 64 patients. Visual improvement was poorer for group ON (0.3 ± 10.7 letters) than for group OFF (9.2 ± 13.3; p = 0.007). A significant difference in letters of improvement between groups was observed in the PRN cohort (ON: -5.0 ± 12.9; OFF: 11.4 ± 11.9; p = 0.003), but not in the cohorts with monthly (ON: 5.7 ± 7.8; OFF: 7.9 ± 15.2; p = 0.735) or T&E (ON: 4.3 ± 4.3; OFF: 7.8 ± 11.1; p = 0.424) treatment. The negative impact of absence of PVD is regimen dependent, with monthly dosing providing similar outcomes to PVD patients. In the absence of PVD (group ON), PRN should be avoided, and T&E might be an alternative. © 2018 S. Karger AG, Basel.

Cuscuta chinensis seeds water extraction protecting murine osteoblastic MC3T3-E1 cells against tertiary butyl hydroperoxide induced injury.

PubMed

Gao, Jian-mei; Li, Ran; Zhang, Lei; Jia, Li-long; Ying, Xi-xiang; Dou, De-qiang; Li, Jian-chun; Li, Hai-bo

2013-07-09

Cuscuta chinensis (C. chinensis) is a well-known traditional Chinese herb that has been used to treat heart disease, diabetes, liver injury, cancer, and aging. Murine osteoblastic MC3T3-E1 cells were treated with various concentrations of C. chinensis water extraction at different time intervals. The antioxidant effect of C. chinensis on MC3T3-E1 cells was evaluated using MTT and TUNEL assays. The effect of C. chinensis on cell cycle was analyzed by flow cytometry with propidium iodide. Lipid peroxidation was measured by the HPLC method. The cellular redox status was determined from the reduced glutathione to oxidized glutathione ratio (GSH/GSSG) and the enzymes involved in glutathione metabolism, including glutathione reductase (GR), Glutathione S-transferase (GST), and Glucose-6-phosphate dehydrogenase (G6PD). The changes in relative mitochondrial transmembrane potential (ΔΨm) in the MC3T3-E1 cells were analyzed with rhodamine 123 staining. Western blot analysis was used to evaluate the levels of cytochrome c (cyto c), Bax, Bcl-2, caspase 3, Sirt3, and IDH2 expressions. The C. chinensis water extraction protects tertiary butyl hydroperoxide (TBHP)-treated MC3T3-E1 cells from death in a dose-dependent manner. C. chinensis treatment significantly inhibited the reactive oxygen species (ROS) generation, malondialdehyde (MDA) production, and increased the activity of superoxide dismutase (SOD), GR, GST, and G6PD. The release of cyto c from mitochondria was reduced by C. chinensis, which increased the expression of antiapoptotic IDH2, Sirt3, and Bcl-2 and decreased the expression of Bax, cyto c, and caspase 3. C. chinensis modulated the oxidative stress-induced apoptosis in MC3T3-E1 cells, probably due to its antioxidant activity and functioning via mitochondria-dependent pathways. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Detection and differentiation of early acute and following age stages of myocardial infarction with quantitative post-mortem cardiac 1.5T MR.

PubMed

Schwendener, Nicole; Jackowski, Christian; Persson, Anders; Warntjes, Marcel J; Schuster, Frederick; Riva, Fabiano; Zech, Wolf-Dieter

2017-01-01

Recently, quantitative MR sequences have started being used in post-mortem imaging. The goal of the present study was to evaluate if early acute and following age stages of myocardial infarction can be detected and discerned by quantitative 1.5T post-mortem cardiac magnetic resonance (PMCMR) based on quantitative T1, T2 and PD values. In 80 deceased individuals (25 female, 55 male), a cardiac MR quantification sequence was performed prior to cardiac dissection at autopsy in a prospective study. Focal myocardial signal alterations detected in synthetically generated MR images were MR quantified for their T1, T2 and PD values. The locations of signal alteration measurements in PMCMR were targeted at autopsy heart dissection and cardiac tissue specimens were taken for histologic examinations. Quantified signal alterations in PMCMR were correlated to their according histologic age stage of myocardial infarction. In PMCMR seventy-three focal myocardial signal alterations were detected in 49 of 80 investigated hearts. These signal alterations were diagnosed histologically as early acute (n=39), acute (n=14), subacute (n=10) and chronic (n=10) age stages of myocardial infarction. Statistical analysis revealed that based on their quantitative T1, T2 and PD values, a significant difference between all defined age groups of myocardial infarction can be determined. It can be concluded that quantitative 1.5T PMCMR quantification based on quantitative T1, T2 and PD values is feasible for characterization and differentiation of early acute and following age stages of myocardial infarction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of aging at 1040 C (1900 F) on the ductility and structure of a tantalum alloy, T-111

NASA Technical Reports Server (NTRS)

Watson, G. K.; Stephens, J. R.

1972-01-01

The post-aging embrittlement of T-111 (tantalum - 8-percent tungsten - 2-percent hafnium) following exposure for up to about 10,000 hours at 1040 C in either vacuum or liquid lithium was investigated for sheet and tubing samples. This thermal aging was shown to greatly increase the sensitivity of T-111 to hydrogen embrittlement during subsequent room temperature specimen processing or testing. The hydrogen embrittlement problem can be avoided by preventing exposure to the T-111 to moisture during post-aging processing or testing. Aging at 1040 C also resulted in formation of HfO2 particles at grain boundaries, which may contribute to the observed embrittlement.

Phonons on fcc (100), (110), and (111) surfaces using Lennard-Jones potentials. II. Temperature dependence of surface phonons studied with molecular dynamics

NASA Astrophysics Data System (ADS)

Koleske, D. D.; Sibener, S. J.

In this paper we present temperature dependent studies of the surface phonon dispersion relations for fcc (100), (110), and (111) faces using molecular dynamics (MD) simulations and Lennard-Jones potentials. This study was conducted in order to investigate how anharmonic potential terms influence the dynamical properties of the surface. This was accomplished by examining the temperature dependence of the Q-resolved phonon spectral density function. All phonon frequencies were found to decrease linearly in T as the temperature was increased, while at low temperatures the phonon linewidths increased linearly with T. At higher temperatures, some of the phonon linewidths changed from having a linear to a quadratic dependence on T. The temperature at which this T to T2 change occurs is surface dependent and occurs at the lowest temperature on the (110) surface. The T2 dependence arises from the increasing importance of higher-order phonon-phonon scattering terms. The phonons which exhibit T2 dependence tend to be modes which propagate perpendicularly or nearly perpendicularly to the direction of maximum root-mean-squared displacement (RMSD). This is especially true for the linewidth of the S 1 mode at overlineX on the (110) surface where, at T ≈ 15-23% of the melting temperature, the RMSD perpendicular to the atomic rows become larger than the RMSD normal to the surface. Our results indicate that the dynamics on the (110) surface may be significantly influenced by anharmonic potential terms at temperatures as low as 15% of the melting temperature.

Adolescent oligomenorrhea in a biracial schoolgirl cohort: a simple clinical parameter predicting impaired fasting glucose plus type 2 diabetes mellitus, insulin, glucose, insulin resistance, and centripetal obesity from age 19 to 25 years.

PubMed

Morrison, John A; Glueck, Charles J; Daniels, Stephen; Wang, Ping; Stroop, Davis

2011-09-01

We hypothesized that adolescent oligomenorrhea (ages 14-19) would independently predict impaired fasting glucose (IFG; ≥110 to <126 mg/dL) plus type 2 diabetes mellitus (T2DM; ≥126 mg/dL), insulin and glucose levels, and insulin resistance (IR) in young adulthood (ages 19-25). A prospective 15-year follow-up of 370 schoolgirls starting at age 10 was performed. Age 14 waist circumference was the most important explanatory variable for IFG + T2DM during ages 19 to 24 (P = .002; odds ratio, 1.06; 95% confidence interval, 1.02-1.10), along with oligomenorrhea category from ages 14 to 19 (0, 1, 2, ≥3 reports over 6 years; P = .032; odds ratio, 1.82; 95% confidence interval, 1.05-3.14). Impaired fasting glucose + T2DM at ages 19 to 24 were more common in girls having 1 (6%), 2 (11%), and ≥3 (38%) oligomenorrhea reports from ages 14 to 19 than in girls without oligomenorrhea (3%; P = .0003). Positive explanatory variables (all Ps ≤ .05) for homeostasis model assessment of IR at ages 19 to 24 included age 14 waist (partial R(2) = 30.1%), oligomenorrhea with hyperandrogenism (polycystic ovary syndrome; partial R(2) = 4.1%), black race (3.8%), and oligomenorrhea frequency during ages 14 to 19 (0.8%); sex hormone binding globulin was a negative explanatory variable (0.7%). This is the first prospective study to report an independent association of adolescent oligomenorrhea with young adult IFG + T2DM, with insulin and glucose levels, and with IR. Age 14 waist circumference, oligomenorrhea with hyperandrogenism (polycystic ovary syndrome), black race, oligomenorrhea frequency at ages 14 to 19, and age 14 sex hormone binding globulin were independently associated with IR at ages 19 to 24, potentially facilitating primary prevention of IFG, T2DM, and hyperinsulinemia. Copyright © 2011 Elsevier Inc. All rights reserved.

High Prevalence of Polycystic Ovary Syndrome in Type 1 Diabetes Mellitus Adolescents: Is There a Difference Depending on the NIH and Rotterdam Criteria?

PubMed

Busiah, Kanetee; Colmenares, Ana; Bidet, Maud; Tubiana-Rufi, Nadia; Levy-Marchal, Claire; Delcroix, Christine; Jacquin, Paul; Martin, Delphine; Benadjaoud, Lila; Jacqz-Aigrain, Evelyne; Laborde, Kathleen; Robert, Jean-Jacques; Samara-Boustani, Dinane; Polak, Michel

2017-01-01

Polycystic ovary syndrome (PCOS) is more frequently observed in type 1 diabetes mellitus (T1DM) adult women than in nondiabetic women. No such prevalence has yet been studied in adolescent girls with T1DM. The aim of this study was to evaluate the prevalence of PCOS in adolescent girls with T1DM and to determine the clinical and hormonal features associated with the disorder. A cross-sectional study of 53 adolescent girls (gynecological age >2 years) referred for routine evaluation for T1DM was conducted. We diagnosed PCOS using the National Institutes of Health (NIH) and Rotterdam criteria. 26.4 and 47.9% of adolescents had PCOS according to NIH (NIH-PCOS) and Rotterdam (Rotterdam-PCOS) criteria. 66.7% of NIH-PCOS adolescents had a complete phenotype associated with hyperandrogenism, oligomenorrhea, and polycystic ovarian morphology, unlike only 33.3% of the Rotterdam-PCOS adolescents. A family history of type 2 diabetes mellitus (T2DM) was more frequent in PCOS than in non-PCOS girls, whichever criteria were used. Late pubertal development and a T1DM diagnosis close to puberty were factors associated with NIH-PCOS. Adolescents with T1DM had a high prevalence of PCOS. More differences between PCOS and non-PCOS patients were found using the NIH criteria, suggesting that clinical characteristics might be more accurate for diagnosing PCOS in girls with T1DM. A family history of T2DM is associated with a high risk of PCOS. © 2017 S. Karger AG, Basel.

T cell developmental arrest in former premature infants increases risk of respiratory morbidity later in infancy

PubMed Central

Scheible, Kristin M.; Emo, Jason; Laniewski, Nathan; Baran, Andrea M.; Peterson, Derick R.; Bandyopadhyay, Sanjukta; Straw, Andrew G.; Huyck, Heidie; Ashton, John M.; Tripi, Kelly Schooping; Arul, Karan; Werner, Elizabeth; Scalise, Tanya; Maffett, Deanna; Caserta, Mary; Ryan, Rita M.; Reynolds, Anne Marie; Ren, Clement L.; Topham, David J.; Mariani, Thomas J.; Pryhuber, Gloria S.

2018-01-01

The inverse relationship between gestational age at birth and postviral respiratory morbidity suggests that infants born preterm (PT) may miss a critical developmental window of T cell maturation. Despite a continued increase in younger PT survivors with respiratory complications, we have limited understanding of normal human fetal T cell maturation, how ex utero development in premature infants may interrupt normal T cell development, and whether T cell development has an effect on infant outcomes. In our longitudinal cohort of 157 infants born between 23 and 42 weeks of gestation, we identified differences in T cells present at birth that were dependent on gestational age and differences in postnatal T cell development that predicted respiratory outcome at 1 year of age. We show that naive CD4+ T cells shift from a CD31–TNF-α+ bias in mid gestation to a CD31+IL-8+ predominance by term gestation. Former PT infants discharged with CD31+IL8+CD4+ T cells below a range similar to that of full-term born infants were at an over 3.5-fold higher risk for respiratory complications after NICU discharge. This study is the first to our knowledge to identify a pattern of normal functional T cell development in later gestation and to associate abnormal T cell development with health outcomes in infants. PMID:29467329

Are Neurocognitive Speed and Inconsistency Similarly Affected in Type 2 Diabetes?

PubMed Central

Whitehead, Bonnie P.; Dixon, Roger A.; Hultsch, David F.; MacDonald, Stuart W.S.

2011-01-01

Type 2 diabetes (T2D) is a disease of aging with indirect but detectable and cumulative neurological implications. We systematically tested whether neurocognitive speed (mean rate) or inconsistency (intraindividual variability) was the more sensitive clinical marker of T2D. Three of four research questions used a cross-sectional wave of the Victoria Longitudinal Study (VLS) divided into T2D (age 55-81 years) and control (age = 53-91 years) groups. The fourth question addressed relative two-wave longitudinal changes. Each of four speeded tasks produced intraindividual mean rate (IM) and intraindividual standard deviation (ISD) scores. First, the T2D group performed more slowly than the controls. Second, this deficit extended to inconsistency, but less uniformly. Third, based on logistic regression analyses, IM was the more effective predictor of T2D status. Fourth, we observed similar longitudinal change patterns for IM and ISD. Results are linked to the theoretical location of T2D on an adjusted neural vulnerability continuum. PMID:21416426

Metallothionein Is Downstream of Nrf2 and Partially Mediates Sulforaphane Prevention of Diabetic Cardiomyopathy.

PubMed

Gu, Junlian; Cheng, Yanli; Wu, Hao; Kong, Lili; Wang, Shudong; Xu, Zheng; Zhang, Zhiguo; Tan, Yi; Keller, Bradley B; Zhou, Honglan; Wang, Yuehui; Xu, Zhonggao; Cai, Lu

2017-02-01

We have reported that sulforaphane (SFN) prevented diabetic cardiomyopathy in both type 1 and type 2 diabetes (T2DM) animal models via the upregulation of nuclear transcription factor erythroid 2-related factor 2 (Nrf2) and metallothionein (MT). In this study, we tested whether SFN protects the heart from T2DM directly through Nrf2, MT, or both. Using Nrf2-knockout (KO), MT-KO, and wild-type (WT) mice, T2DM was induced by feeding a high-fat diet for 3 months followed by a small dose of streptozotocin. Age-matched controls were given a normal diet. Both T2DM and control mice were then treated with or without SFN for 4 months by continually feeding a high-fat or normal diet. SFN prevented diabetes-induced cardiac dysfunction as well as diabetes-associated cardiac oxidative damage, inflammation, fibrosis, and hypertrophy, with increases in Nrf2 and MT expressions in the WT mice. Both Nrf2-KO and MT-KO diabetic mice exhibited greater cardiac damage than WT diabetic mice. SFN did not provide cardiac protection in Nrf2-KO mice, but partially or completely protected the heart from diabetes in MT-KO mice. SFN did not induce MT expression in Nrf2-KO mice, but stimulated Nrf2 function in MT-KO mice. These results suggest that Nrf2 plays the indispensable role for SFN cardiac protection from T2DM with significant induction of MT and other antioxidants. MT expression induced by SFN is Nrf2 dependent, but is not indispensable for SFN-induced cardiac protection from T2DM. © 2017 by the American Diabetes Association.

Forecasting future prevalence of type 2 diabetes mellitus in Syria.

PubMed

Al Ali, Radwan; Mzayek, Fawaz; Rastam, Samer; M Fouad, Fouad; O'Flaherty, Martin; Capewell, Simon; Maziak, Wasim

2013-05-25

Type 2 diabetes mellitus (T2DM) is increasingly becoming a major public health problem worldwide. Estimating the future burden of diabetes is instrumental to guide the public health response to the epidemic. This study aims to project the prevalence of T2DM among adults in Syria over the period 2003-2022 by applying a modelling approach to the country's own data. Future prevalence of T2DM in Syria was estimated among adults aged 25 years and older for the period 2003-2022 using the IMPACT Diabetes Model (a discrete-state Markov model). According to our model, the prevalence of T2DM in Syria is projected to double in the period between 2003 and 2022 (from 10% to 21%). The projected increase in T2DM prevalence is higher in men (148%) than in women (93%). The increase in prevalence of T2DM is expected to be most marked in people younger than 55 years especially the 25-34 years age group. The future projections of T2DM in Syria put it amongst countries with the highest levels of T2DM worldwide. It is estimated that by 2022 approximately a fifth of the Syrian population aged 25 years and older will have T2DM.

Testosterone in advance age: a New Zealand longitudinal cohort study: Life and Living in Advanced Age (Te Puāwaitanga o Ngā Tapuwae Kia Ora Tonu)

PubMed Central

Connolly, Martin J; Kerse, Ngaire; Wilkinson, Tim; Menzies, Oliver; Rolleston, Anna; Chong, Yih Harng; Broad, Joanna B; Moyes, Simon A; Jatrana, Santosh; Teh, Ruth

2017-01-01

Objectives Serum testosterone (T) levels in men decline with age. Low T levels are associated with sarcopenia and frailty in men aged >80 years. T levels have not previously been directly associated with disability in older men. We explored associations between T levels, frailty and disability in a cohort of octogenarian men. Setting Data from all men from Life and Living in Advanced Age Cohort Study in New Zealand, a longitudinal cohort study in community-dwelling older adults. Participants Community-dwelling (>80 years) adult men excluding those receiving T treatment or with prostatic carcinoma. Outcomes measures Associations between baseline total testosterone (TT) and calculated free testosterone (fT), frailty (Fried scale) and disability (Nottingham Extended Activities of Daily Living scale (NEADL)) (baseline and 24 months) were examined using multivariate regression and Wald’s χ2 techniques. Subjects with the lowest quartile of baseline TT and fT values were compared with those in the upper three quartiles. Results Participants: 243 men, mean (SD) age 83.7 (2.0) years. Mean (SD) TT=17.6 (6.8) nmol/L and fT=225.3 (85.4) pmol/L. On multivariate analyses, lower TT levels were associated with frailty: β=0.41, p=0.017, coefficient of determination (R2)=0.10 and disability (NEADL) (β=−1.27, p=0.017, R2=0.11), low haemoglobin (β=−7.38, p=0.0016, R2=0.05), high fasting glucose (β=0.38, p=0.038, R2=0.04) and high C reactive protein (CRP) (β=3.57, p=0.01, R2=0.06). Low fT levels were associated with frailty (β=0.39, p=0.024, R2=0.09) but not baseline NEADL (β=−1.29, p=0.09, R2=0.09). Low fT was associated with low haemoglobin (β=−7.83, p=0.0008, R2=0.05) and high CRP (β=2.86, p=0.04, R2=0.05). Relationships between baseline TT and fT, and 24-month outcomes of disability and frailty were not significant. Conclusions In men over 80 years, we confirm an association between T levels and baseline frailty scores. The new finding of association between T levels and disability is potentially relevant to debates on T supplementation in older men, though, as associations were not present at 24 months, further work is needed. PMID:29133315

Transverse relaxation in the rotating frame induced by chemical exchange.

PubMed

Michaeli, Shalom; Sorce, Dennis J; Idiyatullin, Djaudat; Ugurbil, Kamil; Garwood, Michael

2004-08-01

In the presence of radiofrequency irradiation, relaxation of magnetization aligned with the effective magnetic field is characterized by the time constant T1rho. On the other hand, the time constant T2rho characterizes the relaxation of magnetization that is perpendicular to the effective field. Here, it is shown that T2rho can be measured directly with Carr-Purcell sequences composed of a train of adiabatic full-passage (AFP) pulses. During adiabatic rotation, T2rho characterizes the relaxation of the magnetization, which under adiabatic conditions remains approximately perpendicular to the time-dependent effective field. Theory is derived to describe the influence of chemical exchange on T2rho relaxation in the fast-exchange regime, with time constant defined as T2rho,ex. The derived theory predicts the rate constant R2rho,ex (= 1/T2rho,ex) to be dependent on the choice of amplitude- and frequency-modulation functions used in the AFP pulses. Measurements of R2rho,ex of the water/ethanol exchanging system confirm the predicted dependence on modulation functions. The described theoretical framework and adiabatic methods represent new tools to probe exchanging systems. Copyright 2004 Elsevier Inc.

A study of electron and thermal transport in layered titanium disulphide single crystals

NASA Astrophysics Data System (ADS)

Suri, Dhavala; Siva, Vantari; Joshi, Shalikram; Senapati, Kartik; Sahoo, P. K.; Varma, Shikha; Patel, R. S.

2017-12-01

We present a detailed study of thermal and electrical transport behavior of single crystal titanium disulphide flakes, which belong to the two dimensional, transition metal dichalcogenide class of materials. In-plane Seebeck effect measurements revealed a typical metal-like linear temperature dependence in the range of 85-285 K. Electrical transport measurements with in-plane current geometry exhibited a nearly T 2 dependence of resistivity in the range of 42-300 K. However, transport measurements along the out-of-plane current geometry showed a transition in temperature dependence of resistivity from T 2 to T 5 beyond 200 K. Interestingly, Au ion-irradiated TiS2 samples showed a similar T 5 dependence of resistivity beyond 200 K, even in the current-in-plane geometry. Micro-Raman measurements were performed to study the phonon modes in both pristine and ion-irradiated TiS2 crystals.

Serum testosterone, dihydrotestosterone and estradiol concentrations in older men self-reporting very good health: the healthy man study.

PubMed

Sartorius, Gideon; Spasevska, Sasa; Idan, Amanda; Turner, Leo; Forbes, Elise; Zamojska, Anna; Allan, Carolyn A; Ly, Lam P; Conway, Ann J; McLachlan, Robert I; Handelsman, David J

2012-11-01

To determine serum concentrations, intra-individual variability and impact of age-related co-morbidities on serum testosterone (T), dihydrotestosterone (DHT), estradiol (E(2)) and estrone (E(1)) in older men. Observational, repeated measures study. Men (n = 325) with 40 years and older self-reporting very good or excellent health. Standardized history, physical examination and collection of nine blood samples at fixed time intervals were measured over 3 months (three at 20 min intervals on days 1 (fasting) and 2 (non-fasting), one at days 7, 30 and 90). Serum T, DHT, E(2) and E(1) (n = 2900, > 99% of scheduled samples) measured by liquid chromatography-tandem mass spectrometry (LC-MS) were analysed by linear mixed model analysis with fasting, age and obesity as covariables. Mean serum T did not vary with age (P = 0·76) but obesity (-0·35 nM per body mass index (BMI) unit, P < 0·0001) and ex-smoker status (-1·6 nM, P < 0·001) had significant effects. Serum DHT was increased with age (+0·011 nM per year, P = 0·001) but decreased with obesity (-0·05 nM per BMI unit, P < 0·0001). Serum E(2) did not vary with age (P = 0·31) or obesity (P = 0·12). Overnight fasting increased (by 9-16%, all P < 0·001) and reduced variability in morning serum T, DHT, E(2) and E(1). Non-fasting serum T and DHT were stable over time (day, week, month or 3 months; P > 0·28). Serum T, DHT and E(2) displayed no decrease associated with age among men over 40 years of age who self-report very good or excellent health although obesity and ex-smoking status were associated with decreased serum androgens (T and DHT) but not E(2). These findings support the interpretation that the age-related decline in blood T accompanying non-specific symptoms in older men may be due to accumulating age-related co-morbidities rather than a symptomatic androgen deficiency state. © 2012 Blackwell Publishing Ltd.

Refraction in Adults with Diabetes

PubMed Central

Klein, Barbara E. K.; Lee, Kristine E.; Klein, Ronald

2010-01-01

Objective(s) Examine refraction, change in refraction, and risk factors for change in refraction in adults with type 1 and type 2 diabetes. Methods Population based study. Modified Early Treatment of Diabetic Retinopathy Study refractions and a standard history were obtained for all participants. Baseline and ten-year follow-up data were available. Results Age was significantly associated with refraction in persons with younger-onset diabetes (T1D) and those with older-onset diabetes (T2D); refractions were similar for both groups. Persons of similar age with T1D were likely to be more myopic than those with T2D (P<.01). Years of education were significantly associated with more myopic refraction (P<.0001). In those with T1D on average there was a −.35 diopter (D) change in refraction over 10 years. However, there was a systematic decrease in myopic shift with increasing age at baseline. Those with longer duration of diabetes and with proliferative retinopathy were more likely to have hyperopic shifts in refraction. In those with T2D there was, on average, a +.25D change in refraction over the 10 years but there was little consistency in the amount of change by age at baseline. There were no other significant effects on change in refraction in this group. Conclusions In persons of similar age, those with T1D are likely to be slightly more myopic than those with T2D. Overall, mean refractions and the important risk factors of age and education are similar to those reported in non-diabetic populations. PMID:21220629

Impaired osteogenic differentiation and enhanced cellular receptor of advanced glycation end products sensitivity in patients with type 2 diabetes.

PubMed

Phimphilai, Mattabhorn; Pothacharoen, Peraphan; Kongtawelert, Prachya; Chattipakorn, Nipon

2017-11-01

Preclinical studies have demonstrated impaired osteoblast differentiation in type 2 diabetes (T2DM), which is related to skeletal accumulation of advanced glycation end products (AGEs). However, the role of AGE in osteoblast differentiation in patients with T2DM is unclear. This cross-sectional study was performed to investigate osteoblast differentiation and its association with serum pentosidine and soluble receptor of AGEs (sRAGE). Twenty-seven patients with T2DM and 15 age-matched controls were included to measure sRAGE and osteogenic differentiation in mononuclear cells derived from peripheral blood. The mononuclear cells isolated from patients with T2DM showed a significantly lower rate of osteogenic differentiation (7.4% vs 86.7%, p < 0.0001) with a lower level of ALPL, COL1A1, and BGLAP expression than those of controls by 11-, 44-, and 15-fold respectively, together with nonvisualized mineralization by alizarin red S staining. The levels of pentosidine and sRAGE were comparable in both groups. AGER expression was significantly higher in the T2DM group. BAX expression was also significantly higher in the T2DM group, and showed a strong correlation with AGER expression (r = 0.86, p < 0.0001). Fasting plasma glucose (FPG) level, AGER expression, and BAX expression showed a strong correlation with osteogenic differentiation defects on univariate analysis. However, only FPG showed a correlation with this defect in a multivariate analysis. In conclusion, patients with T2DM showed impairment of osteoblast differentiation, and FPG was an independent risk factor for this impairment. Moreover, T2DM showed a higher cellular sensitivity for activation of receptor of AGEs and higher cellular apoptosis, which may contribute to the defect in osteoblast differentiation.

Commentary on "integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer." Weischenfeldt J, Simon R, Feuerbach L, Schlangen K, Weichenhan D, Minner S, Wuttig D, Warnatz HJ, Stehr H, Rausch T, Jäger N, Gu L, Bogatyrova O, Stütz AM, Claus R, Eils J, Eils R, Gerhäuser C, Huang PH, Hutter B, Kabbe R, Lawerenz C, Radomski S, Bartholomae CC, Fälth M, Gade S, Schmidt M, Amschler N, Haß T, Galal R, Gjoni J, Kuner R, Baer C, Masser S, von Kalle C, Zichner T, Benes V, Raeder B, Mader M, Amstislavskiy V, Avci M, Lehrach H, Parkhomchuk D, Sultan M, Burkhardt L, Graefen M, Huland H, Kluth M, Krohn A, Sirma H, Stumm L, Steurer S, Grupp K, Sültmann H, Sauter G, Plass C, Brors B, Yaspo ML, Korbel JO, Schlomm T, Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.: Cancer Cell 2013;23(2):159-70.

PubMed

Olumi, Aria F

2014-02-01

Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of>10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic "androgen-type" pathomechanism in EO-PCA. Copyright © 2014 Elsevier Inc. All rights reserved.

Serum adiponectin helps to differentiate type 1 and type 2 diabetes among young Asian Indians.

PubMed

Gokulakrishnan, Kuppan; Aravindhan, Vivekanandhan; Amutha, Anandakumar; Abhijit, Shiny; Ranjani, Harish; Anjana, Ranjit Mohan; Unnikrishnan, Ranjith; Miranda, Priya; Narayan, K M Venkat; Mohan, Viswanathan

2013-08-01

This study assessed whether serum adiponectin could be used as a biochemical marker to differentiate type 1 diabetes mellitus (T1DM) from type 2 diabetes mellitus (T2DM) among young Asian Indians. We recruited age- and sex-matched individuals with physician-diagnosed T1DM (n=70) and T2DM (n=72). All were 12-27 years of age with a duration of diabetes of >2 years, at a large tertiary-care diabetes center in Chennai, southern India. Age- and sex-matched individuals with normal glucose tolerance (NGT) (n=68) were selected from an ongoing population study. NGT was defined using World Health Organization criteria. Serum total adiponectin was measured by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curves were used to identify adiponectin cut points for discriminating T1DM from T2DM. Adiponectin levels were higher in T1DM and lower in T2DM compared with the NGT group (9.89, 3.88, and 6.84 μg/mL, respectively; P<0.001). In standardized polytomous regression models, adiponectin was associated with T1DM (odds ratio [OR]=1.131 per SD; 95% confidence interval [CI], 1.025-1.249) and T2DM (OR=0.628 per SD; 95% CI, 0.504-0.721) controlled for age, gender, waist circumference, body mass index, hypertension, glycated hemoglobin, total cholesterol, serum triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, family history of T2DM, and estimated glomerular filtration rate. Using ROC analysis, an adiponectin cut point of 5.1 μg/mL had a C statistic of 0.886 (95% CI, 0.836-0.953), sensitivity of 80.6%, and specificity of 80.6% to differentiate T1DM from T2DM. Using the 5.1 μg/mL cut point, 80.6% of T1DM and 81.8% of T2DM would be correctly classified. Serum adiponectin is a useful biochemical marker for differentiating T1DM and T2DM among young Asian Indians.

Kaon and lambda production at intermediate pT: Insights into the hadronization of the bulk partonic matter created in Au+Au collisions at RHIC

NASA Astrophysics Data System (ADS)

Sorensen, Paul Richard

2003-06-01

Measurements of identified particles over a broad transverse momentum pT range may provide particularly strong evidence for the existence of a thermalized partonic state in heavy-ion collisions ( i.e. a quark-gluon plasma). Of particular interest are the centrality dependence and the azimuthal anisotropy in the yield of baryons and mesons at intermediate pT. The first measurements of v2---an event-by-event azimuthal anisotropy parameter---and the nuclear modification factor RCP for mid-rapidity K0S and Λ + L¯ production in Au+Au collisions at ultra-relativistic energy are presented. The K0S , Λ and L¯ candidates are selected based on characteristics of their decays in the STAR Time Projection Chamber (TPC). A statistical treatment is used to extract v2(pT) and RCP(pT) from their invariant mass distributions. These measurements establish the particle type dependence of v2 and RCP in the kinematic region 0.4 < pT < 6.0 and |y| < 1.0. In the low pT region (pT < 1.0 GeV/c) the v2 values for different particles are increasing with pT and follow a mass dependence similar to that expected from hydrodynamical models of Au+Au collisions---where, at a given pT, the particle with the larger mass will have a smaller v2. At higher p T however, v2 of the heavier Λ hyperon continues to increase while v2 of the lighter K0S meson saturates at v2 ˜ 0.13 for 2.0 < pT < 5.0 GeV/c. At intermediate pT the v2 of K0S and Λ + L¯ are shown to follow a number-of-constituent-quark scaling with vkaon2pT /22≈v lambda2pT/3 3 . The binary collision scaled centrality ratio RCP shows that Λ + L¯ production at intermediate pT increases more rapidly with system size than kaon production: This is consistent with a scenario where multi-parton dynamics play an important role in particle production. At pT ≈ 5.5 GeV/c Λ + L¯ , K0S , and charged hadron production are all suppressed by a similar amount: a factor of three below expectations from binary nucleon-nucleon collision scaling (i.e. RCP ≈ 0.33). This p T value establishes the extent to which the centrality dependent enhancement of baryon production persists. The particle-type dependence of v2 and RCP provides a stringent test for models of heavy-ion collisions. In particular the larger values of Λ + L¯ v2 compared to their smaller suppression manifested in RCP suggests that for p T < 4.0 GeV/c a particle production mechanism beyond the framework of energy loss and fragmentation exists in central Au+Au collisions. The particle- and pT-dependence of v 2, and RCP are consistent, however, with expectations based on the hadronization of a bulk partonic matter by coalescence or recombination. As such, the constituent-quark-number scaled v 2 reflects the anisotropy established in a partonic stage and provides strong evidence for the existence of a quark-gluon plasma in Au+Au collisions at RHIC.

Diffusion of new medication across different income groups under a universal health insurance program: an example involving newly enlisted nonsteroidal anti-inflammatory drugs for elderly osteoarthritis patients.

PubMed

Wang, Pen-Jen; Chou, Yiing-Jenq; Lee, Cheng-Hua; Pu, Christy

2010-10-01

The aim of this research was to determine whether socioeconomic status, as measured by income level, impacts on the diffusion to patients of newly reimbursed nonsteroidal anti-inflammatory drugs (NSAIDs) under the National Health Insurance program in Taiwan. We used income tax records to identify the income levels of 324 male and 551 female randomly sampled osteoarthritis patients aged over 60 years in 2000. The study period was 2 years (t (1) = April 2001-March 2002 and t (2) = April 2002-March 2003). Generalized estimating equation models were used to analyze the impact of income level on being prescribed one of the newly reimbursed NSAIDs. The impact of income level on being treated with the new drug was positive and significant for females (OR = 2.11, p < 0.01) but not for males. The interaction term between income groups and the time trend was insignificant. Other factors associated with being treated with the new drug include age, habit of health-care utilization, and residential characteristics. Diffusion of new drugs still depends on income level despite the presence of a universal national health insurance system in Taiwan.

My starting point: the discovery of an NMR method for measuring blood oxygenation using the transverse relaxation time of blood water.

PubMed

Thulborn, Keith R

2012-08-15

This invited personal story, covering the period from 1979 to 2010, describes the discovery of the dependence of the transverse relaxation time of water in blood on the oxygenation state of hemoglobin in the erythrocytes. The underlying mechanism of the compartmentation of the different magnetic susceptibilities of hemoglobin in its different oxygenation states also explains the mechanism that underlies blood oxygenation level dependent contrast used in fMRI. The story begins with the initial observation of line broadening during ischemia in small rodents detected by in vivo 31P NMR spectroscopy at high field. This spectroscopic line broadening or T2* relaxation effect was demonstrated to be related to the oxygenation state of blood. The effect was quantified more accurately using T2 values measured by the Carr-Purcell-Meiboom-Gill method. The effect was dependent on the integrity of the erythrocytes to compartmentalize the different magnetic susceptibilities produced by the changing spin state of the ferrous iron of hemoglobin in its different oxygenation states between the erythrocytes and the suspending solution. The hematocrit and magnetic field dependence, the requirement for erythrocyte integrity and lack of T1 dependence confirmed that the magnetic susceptibility effect explained the oxygenation state dependence of T2* and T2. This T2/T2* effect was combined with T1 based measurements of blood flow to measure oxygen consumption in animals. This blood oxygenation assay and its underlying magnetic susceptibility gradient mechanism was published in the biochemistry literature in 1982 and largely forgotten. The observation was revived to explain evolving imaging features of cerebral hematoma as MR imaging of humans increased in field strength to 1.5 T by the mid 1980s. Although the imaging version of this assay was used to measure a global metabolic rate of cerebral oxygen consumption in humans at 1.5-T by 1991, the global measurement had little clinical value. By contrast, a decade after the spectroscopic observation, imaging experiments performed on rodents at 7 T by Ogawa and colleagues identified the extravascular T2* imaging characteristics of the blood oxygenation effect and, most importantly, associated that change with brain functional states. Ogawa appropriately branded this blood oxygenation level dependent mechanism as BOLD contrast. This mechanism was subsequently shown to be the basis of localized MR signal changes associated with local brain function. This connection led to the fMRI revolution in human brain mapping. Copyright © 2012. Published by Elsevier Inc.

Mesoscopic fluctuations and intermittency in aging dynamics

NASA Astrophysics Data System (ADS)

Sibani, P.

2006-01-01

Mesoscopic aging systems are characterized by large intermittent noise fluctuations. In a record dynamics scenario (Sibani P. and Dall J., Europhys. Lett., 64 (2003) 8) these events, quakes, are treated as a Poisson process with average αln (1 + t/tw), where t is the observation time, tw is the age and α is a parameter. Assuming for simplicity that quakes constitute the only source of de-correlation, we present a model for the probability density function (PDF) of the configuration autocorrelation function. Beside α, the model has the average quake size 1/q as a parameter. The model autocorrelation PDF has a Gumbel-like shape, which approaches a Gaussian for large t/tw and becomes sharply peaked in the thermodynamic limit. Its average and variance, which are given analytically, depend on t/tw as a power law and a power law with a logarithmic correction, respectively. Most predictions are in good agreement with data from the literature and with the simulations of the Edwards-Anderson spin-glass carried out as a test.

Empirical calibration of the near-infrared CaII triplet - IV. The stellar population synthesis models

NASA Astrophysics Data System (ADS)

Vazdekis, A.; Cenarro, A. J.; Gorgas, J.; Cardiel, N.; Peletier, R. F.

2003-04-01

We present a new evolutionary stellar population synthesis model, which predicts spectral energy distributions for single-age single-metallicity stellar populations (SSPs) at resolution 1.5 Å (FWHM) in the spectral region of the near-infrared CaII triplet feature. The main ingredient of the model is a new extensive empirical stellar spectral library that has been recently presented by Cenarro et al., which is composed of more than 600 stars with an unprecedented coverage of the stellar atmospheric parameters. Two main products of interest for stellar population analysis are presented. The first is a spectral library for SSPs with metallicities -1.7 < [Fe/H] < +0.2, a large range of ages (0.1-18 Gyr) and initial mass function (IMF) types. They are well suited to modelling galaxy data, since the SSP spectra, with flux-calibrated response curves, can be smoothed to the resolution of the observational data, taking into account the internal velocity dispersion of the galaxy, allowing the user to analyse the observed spectrum in its own system. We also produce integrated absorption-line indices (namely CaT*, CaT and PaT) for the same SSPs in the form of equivalent widths. We find the following behaviour for the CaII triplet feature in old-aged SSPs: (i) the strength of the CaT* index does not change much with time for all metallicities for ages larger than ~3 Gyr; (ii) this index shows a strong dependence on metallicity for values below [M/H]~-0.5 and (iii) for larger metallicities this feature does not show a significant dependence either on age or on the metallicity, being more sensitive to changes in the slope of power-like IMF shapes. The SSP spectra have been calibrated with measurements for globular clusters by Armandroff & Zinn, which are well reproduced, probing the validity of using the integrated CaII triplet feature for determining the metallicities of these systems. Fitting the models to two early-type galaxies of different luminosities (NGC 4478 and 4365), we find that the CaII triplet measurements cannot be fitted unless a very dwarf-dominated IMF is imposed, or if the Ca abundance is even lower than the Fe abundance. More details can be found in work by Cenarro et al.

Simultaneous T1 and T2 Brain Relaxometry in Asymptomatic Volunteers using Magnetic Resonance Fingerprinting.

PubMed

Badve, Chaitra; Yu, Alice; Rogers, Matthew; Ma, Dan; Liu, Yiying; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Gulani, Vikas

2015-12-01

Magnetic resonance fingerprinting (MRF) is a method of image acquisition that produces multiple MR parametric maps from a single scan. Here, we describe the normal range and progression of MRF-derived relaxometry values with age in healthy individuals. 56 normal volunteers (ages 11-71 years, M:F 24:32) were scanned. Regions of interest were drawn on T 1 and T 2 maps in 38 areas, including lobar and deep white matter, deep gray nuclei, thalami and posterior fossa structures. Relaxometry differences were assessed using a forward stepwise selection of a baseline model including either gender, age, or both, where variables were included if they contributed significantly (p<0.05). Additionally, differences in regional anatomy, including comparisons between hemispheres and between anatomical subcomponents, were assessed by paired t-tests. Using this protocol, MRF-derived T 1 and T 2 in frontal WM regions were found to increase in with age, while occipital and temporal regions remained relatively stable. Deep gray nuclei, including substantia nigra, were found to have age-related decreases in relaxometry. Gender differences were observed in T 1 and T 2 of temporal regions, cerebellum and pons. Males were also found to have more rapid age-related changes in frontal and parietal WM. Regional differences were identified between hemispheres, between genu and splenium of corpus callosum, and between posteromedial and anterolateral thalami. In conclusion, MRF quantification can measure relaxometry trends in healthy individuals that are in agreement with current understanding of neuroanatomy and neurobiology, and has the ability to uncover additional patterns that have not yet been explored.

Simultaneous T1 and T2 Brain Relaxometry in Asymptomatic Volunteers using Magnetic Resonance Fingerprinting

PubMed Central

Badve, Chaitra; Yu, Alice; Rogers, Matthew; Ma, Dan; Liu, Yiying; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Gulani, Vikas

2016-01-01

Magnetic resonance fingerprinting (MRF) is a method of image acquisition that produces multiple MR parametric maps from a single scan. Here, we describe the normal range and progression of MRF-derived relaxometry values with age in healthy individuals. 56 normal volunteers (ages 11-71 years, M:F 24:32) were scanned. Regions of interest were drawn on T1 and T2 maps in 38 areas, including lobar and deep white matter, deep gray nuclei, thalami and posterior fossa structures. Relaxometry differences were assessed using a forward stepwise selection of a baseline model including either gender, age, or both, where variables were included if they contributed significantly (p<0.05). Additionally, differences in regional anatomy, including comparisons between hemispheres and between anatomical subcomponents, were assessed by paired t-tests. Using this protocol, MRF-derived T1 and T2 in frontal WM regions were found to increase in with age, while occipital and temporal regions remained relatively stable. Deep gray nuclei, including substantia nigra, were found to have age-related decreases in relaxometry. Gender differences were observed in T1 and T2 of temporal regions, cerebellum and pons. Males were also found to have more rapid age-related changes in frontal and parietal WM. Regional differences were identified between hemispheres, between genu and splenium of corpus callosum, and between posteromedial and anterolateral thalami. In conclusion, MRF quantification can measure relaxometry trends in healthy individuals that are in agreement with current understanding of neuroanatomy and neurobiology, and has the ability to uncover additional patterns that have not yet been explored. PMID:26824078

Epidemiological and Mendelian Randomization Studies of Dihydrotestosterone and Estradiol and Leukocyte Telomere Length in Men.

PubMed

Yeap, Bu B; Knuiman, Matthew W; Divitini, Mark L; Hui, Jennie; Arscott, Gillian M; Handelsman, David J; McLennan, Susan V; Twigg, Stephen M; McQuillan, Brendan; Hung, Joseph; Beilby, John P

2016-03-01

Advancing age is accompanied by an accumulation of ill health and shortening of chromosomal telomeres signifying biological aging. T is metabolized to DHT by 5α-reductase (SRD5A2) and to estradiol (E2) by aromatase (CYP19A1). Telomerase preserves telomeres, and T and E2 regulate telomerase expression and activity in vitro. The objective of the study was to establish whether circulating T or its metabolites, DHT or E2, and single-nucleotide polymorphisms in SRD5A2 or CYP19A1 associate with leucocyte telomere length (LTL) in men. Early-morning serum T, DHT, and E2 were assayed using mass spectrometry, and SRD5A2 and CYP19A1 single-nucleotide polymorphisms and LTL analyzed by PCR in 980 men from the Western Australian Busselton Health Survey who participated in the study. LTL was expressed as the T/S ratio. Men were aged (mean ± SD) 53.7 ± 15.6 years. LTL decreased linearly with age, from the T/S ratio of 1.89 ± 0.41 at younger than 30 years to 1.50 ± 0.49 at 70 to younger than 80 years (r = -0.225, P < .0001). After adjustment for age, DHT and E2 were positively correlated with LTL (DHT, r = 0.069, P = .030; E2, r = 0.068, P = .034). The SRD5A2 rs9282858 polymorphism was associated with serum DHT but not with LTL. Three dominant alleles of CYP19A1 were each associated with lower serum E2 and shorter LTL: rs2899470 T (E2, 59.3 vs 68.6 pmol/L, P < .0001; T/S ratio, 1.54 vs 1.62, P = .045), rs10046 C (60.5 vs 68.1 pmol/L, P = .0005, 1.54 vs 1.62, P = .035), and rs700518 A (59.9 vs 68.9 pmol/L, P < .0001, 1.54 vs 1.63, P = .020). A single-copy haplotype C/T/I/A/T rs10046/rs2899470/rs11575899/rs700518/rs17703883 (52% prevalence) was associated with both lower E2 and shorter LTL. In men, serum DHT and E2 correlate with LTL independently of age. Aromatase gene polymorphisms include three dominant alleles that are associated with both lower serum E2 and shorter LTL. E2 influences telomere length in vivo, thus warranting further studies to examine whether hormonal interventions might slow biological aging in men.

Physical activity, smoking, and alcohol consumption in association with incidence of type 2 diabetes among middle-aged and elderly Chinese men.

PubMed

Shi, Liang; Shu, Xiao-Ou; Li, Honglan; Cai, Hui; Liu, Qiaolan; Zheng, Wei; Xiang, Yong-Bing; Villegas, Raquel

2013-01-01

Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease worldwide. The prevalence of T2DM is increasing rapidly in China. Understanding the contribution of modifiable lifestyle factors on T2DM risk is imperative to prevent the development of T2DM in China. We examined associations between lifestyle factors including physical activity, smoking and alcohol consumption with incidence of T2DM among middle-aged and elderly men in urban Shanghai. Information on socio-demographics, lifestyle habits, dietary habits, and disease history was collected via in-person interviews. Anthropometric measurements were taken. A total of 51 464 Chinese men aged 40-74 years free of T2DM, coronary heart disease (CHD), and stroke at baseline were included in the current study. Incident T2DM was identified through follow-up surveys conducted every 2-3 years. Cox proportional hazard analyses were conducted to evaluate associations between lifestyle risk factors and incidence of T2DM. We documented 1304 new cases of T2DM during 276 929 person-years of follow-up (average: 5.4 years). Physical activity was inversely associated with T2DM risk. Daily living, commuting, and total physical activity METs had inverse negative dose-response relationships with T2DM (P-trend = 0.0033, 0.0022, and <0.0001, respectively). Regular participation in exercise or sports reduced T2DM risk (HR = 0.86, 95%CI: 0.76-0.98). Moderate alcohol intake (1-3 drinks/day) was inversely related to T2DM risk (HR = 0.80, 95%CI: 0.67-0.94). Cigarette smoking, on the other hand, was associated with increased T2DM risk; HRs were 1.25 (95%CI: 1.00-1.56) for smoking more than 20 cigarettes per day and 1.28 (95%CI: 1.04-1.57) for smoking more than 40 pack-years. Physical activity and moderate alcohol intake are inversely associated with T2DM risk, whereas smoking was positively associated with T2DM risk among middle-age and elderly Chinese men. Preventive measures should be developed to focus on these modifiable lifestyle habits to reduce the upward trend of T2DM.

Correlated time-variation of bulk microstructure and rheology in asphalt binders.

PubMed

Ramm, A; Sakib, N; Bhasin, A; Downer, M C

2018-05-22

We use near-infrared dark-field optical microscopy to probe isothermal time variation of the volume fraction of naturally-occurring, subsurface microstructures in PG 64-22 asphalt binders at temperature T=30∘C, following a rapid heating (cooling) increment |ΔT|=20∘C from initial temperature T0=10∘C(50∘C). We compare these microstructure variations with isothermal time variations of the magnitude |G30∗(t)| of the bulk complex shear modulus measured for identical sample conditions with a Dynamic Shear Rheometer. The main findings are: (1) Microstructure volume fraction (inferred from intensity I(t) of near-infrared optical scatter) and |G∗(t)| both continue to change appreciably long after measurable changes of binder temperature cease. Moreover, delayed time variations in I(t) and |G∗(t)| (2) correlate closely with each other; (3) evolve on three distinct time scales - several minutes, ∼1 h, >1 day; (4) depend on binder aging; (5) are more pronounced after a cooling step (ΔT=-20∘C) than after a heating step (ΔT=+20∘C); and (6) account for hysteresis in I(t) and |G∗(t)| curves observed during heating-cooling cycles. © 2018 The Authors Journal of Microscopy © 2018 Royal Microscopical Society.

Washington photometry of 14 intermediate-age to old star clusters in the Small Magellanic Cloud

NASA Astrophysics Data System (ADS)

Piatti, Andrés E.; Clariá, Juan J.; Bica, Eduardo; Geisler, Doug; Ahumada, Andrea V.; Girardi, Léo

2011-10-01

We present CCD photometry in the Washington system C, T1 and T2 passbands down to T1˜ 23 in the fields of L3, L28, HW 66, L100, HW 79, IC 1708, L106, L108, L109, NGC 643, L112, HW 84, HW 85 and HW 86, 14 Small Magellanic Cloud (SMC) clusters, most of them poorly studied objects. We measured T1 magnitudes and C-T1 and T1-T2 colours for a total of 213 516 stars spread throughout cluster areas of 14.7 × 14.7 arcmin2 each. We carried out an in-depth analysis of the field star contamination of the colour-magnitude diagrams (CMDs) and statistically cleaned the cluster CMDs. Based on the best fits of isochrones computed by the Padova group to the (T1, C-T1) CMDs, as well as from the δ(T1) index and the standard giant branch procedure, we derived ages and metallicities for the cluster sample. With the exception of IC 1708, a relatively metal-poor Hyades-age cluster, the remaining 13 objects are between intermediate and old age (from 1.0 to 6.3 Gyr), their [Fe/H] values ranging from -1.4 to -0.7 dex. By combining these results with others available in the literature, we compiled a sample of 43 well-known SMC clusters older than 1 Gyr, with which we produced a revised age distribution. We found that the present clusters' age distribution reveals two primary excesses of clusters at t˜ 2 and 5 Gyr, which engraves the SMC with clear signs of enhanced formation episodes at both ages. In addition, we found that from the birth of the SMC cluster system until approximately the first 4 Gyr of its lifetime, the cluster formation resembles that of a constant formation rate scenario.

Relationship between Carotenoids, Retinol, and Estradiol Levels in Older Women

PubMed Central

Maggio, Marcello; de Vita, Francesca; Lauretani, Fulvio; Bandinelli, Stefania; Semba, Richard D.; Bartali, Benedetta; Cherubini, Antonio; Cappola, Anne R.; Ceda, Gian Paolo; Ferrucci, Luigi

2015-01-01

Background. In vitro evidence suggests anti-estrogenic properties for retinol and carotenoids, supporting a chemo-preventive role of these phytochemicals in estrogen-dependent cancers. During aging there are significant reductions in retinol and carotenoid concentrations, whereas estradiol levels decline during menopause and progressively increase from the age of 65. We aimed to investigate the hypothesis of a potential relationship between circulating levels of retinol, carotenoids, and estradiol (E2) in a cohort of late post-menopausal women. Methods. We examined 512 women ≥ 65 years from the InCHIANTI study. Retinol, α-caroten, β-caroten, β-criptoxantin, lutein, zeaxanthin, and lycopene levels were assayed at enrollment (1998–2000) by High-Performance Liquid Chromatography. Estradiol and testosterone (T) levels were assessed by Radioimmunometry (RIA) and testosterone-to-estradiol ratio (T/E2), as a proxy of aromatase activity, was also calculated. General linear models adjusted for age (Model 1) and further adjusted for other confounders including Body Mass Index (BMI) BMI, smoking, intake of energy, lipids, and vitamin A; C-Reactive Protein, insulin, total cholesterol, liver function, and testosterone (Model 2) were used to investigate the relationship between retinol, carotenoids, and E2 levels. To address the independent relationship between carotenoids and E2 levels, factors significantly associated with E2 in Model 2 were also included in a fully adjusted Model 3. Results. After adjustment for age, α-carotene (β ± SE = −0.01 ± 0.004, p = 0.02) and β-carotene (β ± SE = −0.07 ± 0.02, p = 0.0007) were significantly and inversely associated with E2 levels. α-Carotene was also significantly and positively associated with T/E2 ratio (β ± SE = 0.07 ± 0.03, p = 0.01). After adjustment for other confounders (Model 2), the inverse relationship between α-carotene (β ± SE = −1.59 ± 0.61, p = 0.01), β-carotene (β ± SE = −0.29 ± 0.08, p = 0.0009), and E2 persisted whereas the relationship between α-carotene and T/E2 ratio was attenuated (β ± SE = 0.22 ± 0.12, p = 0.07). In a fully adjusted model (Model 3), only β-carotene (β ± SE = −0.05 ± 0.02, p = 0.03) was significantly and inversely associated with E2 levels independent of α-carotene. No association was found between retinol, total non-pro-vitamin A carotenoids, lutein, zeaxanthin, and lycopene, and E2 levels. Conclusions: In older women, β-carotene levels are independently and inversely associated with E2. PMID:26251919

Relationship between Carotenoids, Retinol, and Estradiol Levels in Older Women.

PubMed

Maggio, Marcello; de Vita, Francesca; Lauretani, Fulvio; Bandinelli, Stefania; Semba, Richard D; Bartali, Benedetta; Cherubini, Antonio; Cappola, Anne R; Ceda, Gian Paolo; Ferrucci, Luigi

2015-08-05

In vitro evidence suggests anti-estrogenic properties for retinol and carotenoids, supporting a chemo-preventive role of these phytochemicals in estrogen-dependent cancers. During aging there are significant reductions in retinol and carotenoid concentrations, whereas estradiol levels decline during menopause and progressively increase from the age of 65. We aimed to investigate the hypothesis of a potential relationship between circulating levels of retinol, carotenoids, and estradiol (E2) in a cohort of late post-menopausal women. We examined 512 women ≥ 65 years from the InCHIANTI study. Retinol, α-caroten, β-caroten, β-criptoxantin, lutein, zeaxanthin, and lycopene levels were assayed at enrollment (1998-2000) by High-Performance Liquid Chromatography. Estradiol and testosterone (T) levels were assessed by Radioimmunometry (RIA) and testosterone-to-estradiol ratio (T/E2), as a proxy of aromatase activity, was also calculated. General linear models adjusted for age (Model 1) and further adjusted for other confounders including Body Mass Index (BMI) BMI, smoking, intake of energy, lipids, and vitamin A; C-Reactive Protein, insulin, total cholesterol, liver function, and testosterone (Model 2) were used to investigate the relationship between retinol, carotenoids, and E2 levels. To address the independent relationship between carotenoids and E2 levels, factors significantly associated with E2 in Model 2 were also included in a fully adjusted Model 3. After adjustment for age, α-carotene (β ± SE = -0.01 ± 0.004, p = 0.02) and β-carotene (β ± SE = -0.07 ± 0.02, p = 0.0007) were significantly and inversely associated with E2 levels. α-Carotene was also significantly and positively associated with T/E2 ratio (β ± SE = 0.07 ± 0.03, p = 0.01). After adjustment for other confounders (Model 2), the inverse relationship between α-carotene (β ± SE = -1.59 ± 0.61, p = 0.01), β-carotene (β ± SE = -0.29 ± 0.08, p = 0.0009), and E2 persisted whereas the relationship between α-carotene and T/E2 ratio was attenuated (β ± SE = 0.22 ± 0.12, p = 0.07). In a fully adjusted model (Model 3), only β-carotene (β ± SE = -0.05 ± 0.02, p = 0.03) was significantly and inversely associated with E2 levels independent of α-carotene. No association was found between retinol, total non-pro-vitamin A carotenoids, lutein, zeaxanthin, and lycopene, and E2 levels. In older women, β-carotene levels are independently and inversely associated with E2.

Bacterial superantigens bypass Lck-dependent T cell receptor signaling by activating a Galpha11-dependent, PLC-beta-mediated pathway.

PubMed

Bueno, Clara; Lemke, Caitlin D; Criado, Gabriel; Baroja, Miren L; Ferguson, Stephen S G; Rahman, A K M Nur-Ur; Tsoukas, Constantine D; McCormick, John K; Madrenas, Joaquin

2006-07-01

The paradigm to explain antigen-dependent T cell receptor (TCR) signaling is based on the activation of the CD4 or CD8 coreceptor-associated kinase Lck. It is widely assumed that this paradigm is also applicable to signaling by bacterial superantigens. However, these bacterial toxins can activate human T cells lacking Lck, suggesting the existence of an additional pathway of TCR signaling. Here we showed that this alternative pathway operates in the absence of Lck-dependent tyrosine-phosphorylation events and was initiated by the TCR-dependent activation of raft-enriched heterotrimeric Galpha11 proteins. This event, in turn, activated a phospholipase C-beta and protein kinase C-mediated cascade that turned on the mitogen-activated protein kinases ERK-1 and ERK-2, triggered Ca(2+) influx, and translocated the transcription factors NF-AT and NF-kappaB to the nucleus, ultimately inducing the production of interleukin-2 in Lck-deficient T cells. The triggering of this alternative pathway by superantigens suggests that these toxins use a G protein-coupled receptor as a coreceptor on T cells.

Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: Redundant roles for PiT-1 and PiT-2

PubMed Central

Crouthamel, Matthew H.; Lau, Wei Ling; Leaf, Elizabeth M.; Chavkin, Nick; Wallingford, Mary C.; Peterson, Danielle F.; Li, Xianwu; Liu, Yonggang; Chin, Michael T.; Levi, Moshe; Giachelli, Cecilia M.

2014-01-01

Objective Elevated serum phosphate has emerged as a major risk factor for vascular calcification. The sodium-dependent phosphate cotransporter, PiT-1, was previously shown to be required for phosphate-induced osteogenic differentiation and calcification of cultured human VSMCs, but its importance in vascular calcification in vivo, as well as the potential role of its homologue, PiT-2, have not been determined. We investigated the in vivo requirement for PiT-1 in vascular calcification using a mouse model of chronic kidney disease, and the potential compensatory role of PiT-2 using in vitro knockdown and over-expression strategies. Approach and Results Mice with targeted deletion of PiT-1 in VSMCs were generated (PiT-1Δsm). PiT-1 mRNA levels were undetectable whereas PiT-2 mRNA levels were increased 2 fold in the vascular aortic media of PiT-1Δsm compared to PiT-1flox/flox control. When arterial medial calcification was induced in PiT-1Δsm and PiT-1flox/flox by chronic kidney disease followed by dietary phosphate loading, the degree of aortic calcification was not different between genotypes, suggesting compensation by PiT-2. Consistent with this possibility, VSMCs isolated from PiT-1Δsm mice had no PiT-1 mRNA expression, increased PiT-2 mRNA levels, and no difference in sodium-dependent phosphate uptake or phosphate-induced matrix calcification compared to PiT-1flox/flox VSMCs. Knockdown of PiT-2 decreased phosphate uptake and phosphate-induced calcification of PiT-1Δsm VSMCs. Furthermore, over-expression of PiT-2 restored these parameters in human PiT-1-deficient VSMCs. Conclusions PiT-2 can mediate phosphate uptake and calcification of VSMCs in the absence of PiT-1. Mechanistically, PiT-1 and PiT-2 appear to serve redundant roles in phosphate-induced calcification of vascular smooth muscle cells. PMID:23968976

[Characteristics of smoking, nicotine dependence and motivation for change in specialists training in health sciences (residents) in Andalusia (Spain)].

PubMed

Juárez-Jiménez, M V; Valverde-Bolívar, F J; Pérez-Milena, A; Moreno-Corredor, A

2015-09-01

As there are few studies on the smoking habits of specialists training in health sciences (residents), it is of interest to determine the prevalence of smoking, nicotine dependence and motivation for change, and their relationship with other variables (personal, work and consumption of other drugs). A multicentre, cross-sectional study using a questionnaire was conducted in 2012. All the residents who were studying in Teaching Health Centres in Andalusia (Spain) completed a questionnaire, which was sent by e-mail, collecting: age, sex, specialty, country of origin, qualitative-quantitative consumption of tobacco, age of onset/cessation, Fagerström test and stage of change (Proschaka). A total of 2667 residents (63% of total) completed the questionnaire. The mean age was 29.1 years (± 5.2), 69% female, 89% Spanish, and 86% physicians. Of the 17% who smoked (daily pattern-47%, intermittently-41%, related to leisure-3%), starting at 17.4 years (±3.5) and mean of 7.5 cigarettes per day (±7.1), higher medical specialties (P=.067 ANOVA), and in men (P=.074, Student-t). More than three-quarters (82%) had a low nicotine dependence, being higher in hospital medical specialties (P=.078 χ(2)). Of the total, 7% were former smokers, and 48% wanted to quit smoking (contemplation 38%, preparation 10%). In the multivariate analysis there was a link between smoking and alcohol consumption (OR 2.84) and illegal drugs (OR 3.57). There were no differences by age or country. The consumption of tobacco in residents is less than the general population, with a low dependence and better willingness to change. The period of specialised training is a good time to offer tobacco interventions. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Does tinnitus distress depend on age of onset?

PubMed

Schlee, Winfried; Kleinjung, Tobias; Hiller, Wolfgang; Goebel, Gerhard; Kolassa, Iris-Tatjana; Langguth, Berthold

2011-01-01

Tinnitus is the perception of a sound in the absence of any physical source of it. About 5-15% of the population report hearing such a tinnitus and about 1-2% suffer from their tinnitus leading to anxiety, sleep disorders or depression. It is currently not completely understood why some people feel distressed by their tinnitus, while others don't. Several studies indicate that the amount of tinnitus distress is associated with many factors including comorbid anxiety, comorbid depression, personality, the psychosocial situation, the amount of the related hearing loss and the loudness of the tinnitus. Furthermore, theoretical considerations suggest an impact of the age at tinnitus onset influencing tinnitus distress. Based on a sample of 755 normal hearing tinnitus patients we tested this assumption. All participants answered a questionnaire on the amount of tinnitus distress together with a large variety of clinical and demographic data. Patients with an earlier onset of tinnitus suffer significantly less than patients with an onset later in life. Furthermore, patients with a later onset of tinnitus describe their course of tinnitus distress as more abrupt and distressing right from the beginning. We argue that a decline of compensatory brain plasticity in older age accounts for this age-dependent tinnitus decompensation.

Retrospective database analysis of cancer risk in patients with type 2 diabetes mellitus in China.

PubMed

He, Xiaoning; Shi, Lizheng; Wu, Jing

2018-01-18

To investigate the association between type 2 diabetes (T2D) and the risk of overall cancer and site-specific cancers in a Chinese population. Tianjin Urban Employee Basic Medical Insurance database (2003-2014) was used to identify patients with newly onset T2D in 2009, patients with prevalent T2D prior to 2009, and general individuals without T2D. Overall and site-specific cancer incidence rates and incidence rate ratios relative to general population were calculated for both incident and prevalent T2D cohorts. Multivariate Cox proportional hazards models adjusting for baseline characteristics and potential bias were conducted. Subgroup analyses based on gender and age were further conducted. For the year 2009, 21,208 patients with onset T2D (mean age 58.8 years; 48.1% female), 28,248 patients with prevalent T2D (mean age 63.7 years; 50.2% female) and 744,339 general individuals (mean age 43.2 years; 47.7% female) were identified. Controlling for confounders, diabetic patients had an overall 56%-59% higher risk of developing cancer, among which the highest risks by site were liver (adjusted hazard ratio [aHR] = 1.80-2.48), colorectal (aHR = 2.41-2.69) and stomach (aHR = 2.02-2.51) cancers (all p < .05). Patients with prevalent T2D had increased cancer risk in the pancreas (aHR = 4.52, p < .001). Female diabetic patients had increased risk in the kidneys (aHR = 3.22-3.31, p < .01). Patients aged between 50 and 59 years had the highest relative risk (90% higher), while the relative risk was the lowest among patients ≥70 (45% higher). Type 2 diabetes was associated with increased overall cancer risk led by liver, colorectal and stomach cancers. Patients with longer diabetes duration were associated with higher pancreatic cancer risk and female diabetic patients had a higher risk of kidney cancer.

Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory.

PubMed

Sindreu, Carlos; Palmiter, Richard D; Storm, Daniel R

2011-02-22

The physiological role of vesicular zinc at central glutamatergic synapses remains poorly understood. Here we show that mice lacking the synapse-specific vesicular zinc transporter ZnT3 (ZnT3KO mice) have reduced activation of the Erk1/2 MAPK in hippocampal mossy fiber terminals, disinhibition of zinc-sensitive MAPK tyrosine phosphatase activity, and impaired MAPK signaling during hippocampus-dependent learning. Activity-dependent exocytosis is required for the effect of zinc on presynaptic MAPK and phosphatase activity. ZnT3KO mice have complete deficits in contextual discrimination and spatial working memory. Local blockade of zinc or MAPK in the mossy fiber pathway of wild-type mice impairs contextual discrimination. We conclude that ZnT3 is important for zinc homeostasis modulating presynaptic MAPK signaling and is required for hippocampus-dependent memory.

Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory

PubMed Central

Sindreu, Carlos; Palmiter, Richard D.; Storm, Daniel R.

2011-01-01

The physiological role of vesicular zinc at central glutamatergic synapses remains poorly understood. Here we show that mice lacking the synapse-specific vesicular zinc transporter ZnT3 (ZnT3KO mice) have reduced activation of the Erk1/2 MAPK in hippocampal mossy fiber terminals, disinhibition of zinc-sensitive MAPK tyrosine phosphatase activity, and impaired MAPK signaling during hippocampus-dependent learning. Activity-dependent exocytosis is required for the effect of zinc on presynaptic MAPK and phosphatase activity. ZnT3KO mice have complete deficits in contextual discrimination and spatial working memory. Local blockade of zinc or MAPK in the mossy fiber pathway of wild-type mice impairs contextual discrimination. We conclude that ZnT3 is important for zinc homeostasis modulating presynaptic MAPK signaling and is required for hippocampus-dependent memory. PMID:21245308

The thermopower in the temperature range T(sub c)-1000K and the bank spectrum of Bi-based superconductors

NASA Technical Reports Server (NTRS)

Gasumyants, V. E.; Vladimirskaya, E. V.; Smirnov, V. I.; Kazanskiy, S. V.

1995-01-01

The temperature dependencies of thermopower, S, in the range T = T(sub c)-1000K as well as of resistivity and Hall coefficient in the range T = T(sub c)-300K for the single-phase ceramic samples Bi2Sr2Ca(1-x)Nd(x)Cu2O(y) have been measured. It was found that the S(T) dependencies in normal phase have three characteristic regions. Despite the fact that the S(T) dependencies in Bi-based high-T(sub c) superconductors (HTSC) differ essentially from ones in Y-based HTSC at T = T(sub c)-300K, the main feature of theirs (S(T) = const at high temperatures) retains in samples investigated at T is greater than 620K. The results obtained have been analyzed on the basis of the narrow-band model with the use of assumption of slight asymmetry of the conductive band. The band spectrum parameters of the samples studied have been calculated. An analysis of the tendencies in these parameters changes with samples composition varying enables to make the conclusion about the similarity of the main features of the conductive band structure in Y- and Bi-based HTSC.

Pressure dependence of coherence-incoherence crossover behavior in KFe2As2 observed by resistivity and 75As-NMR/NQR

NASA Astrophysics Data System (ADS)

Wiecki, P.; Taufour, V.; Chung, D. Y.; Kanatzidis, M. G.; Bud'ko, S. L.; Canfield, P. C.; Furukawa, Y.

2018-02-01

We present the results of 75As nuclear magnetic resonance (NMR), nuclear quadrupole resonance (NQR), and resistivity measurements in KFe2As2 under pressure (p ). The temperature dependence of the NMR shift, nuclear spin-lattice relaxation time (T1), and resistivity show a crossover between a high-temperature incoherent, local-moment behavior and a low-temperature coherent behavior at a crossover temperature (T*). T* is found to increase monotonically with pressure, consistent with increasing hybridization between localized 3 d orbital-derived bands with the itinerant electron bands. No anomaly in T* is seen at the critical pressure pc=1.8 GPa where a change of slope of the superconducting (SC) transition temperature Tc(p ) has been observed. In contrast, Tc(p ) seems to correlate with antiferromagnetic spin fluctuations in the normal state as measured by the NQR 1 /T1 data, although such a correlation cannot be seen in the replacement effects of A in the A Fe2As2 (A =K , Rb, Cs) family. In the superconducting state, two T1 components are observed at low temperatures, suggesting the existence of two distinct local electronic environments. The temperature dependence of the short T1 s indicates a nearly gapless state below Tc. On the other hand, the temperature dependence of the long component 1 /T1 L implies a large reduction in the density of states at the Fermi level due to the SC gap formation. These results suggest a real-space modulation of the local SC gap structure in KFe2As2 under pressure.

Type 2 diabetes mellitus in children and adolescents is still a rare disease in Germany: a population-based assessment of the prevalence of type 2 diabetes and MODY in patients aged 0-20 years.

PubMed

Neu, Andreas; Feldhahn, Lutz; Ehehalt, Stefan; Hub, Regine; Ranke, Michael B

2009-11-01

To assess the prevalence of type 2 diabetes mellitus (T2DM) and maturity onset diabetes of the young (MODY) in children and adolescents aged 0-20 yr in Baden-Württemberg (BW), Germany, and to compare our results with those from other European countries. Our study involved every children's hospital (n = 31), each diabetologist in private practice (n = 122), and every internal medicine unit (n = 164) in BW. A written questionnaire and a telephone survey were used to identify children with T2DM and MODY who had been examined at any of these institutions between 2004 and 2005. Population data were drawn from the national census of 1987 and the subsequent annual updates. The prevalence of T2DM for the age range from 0 to 20 yr is 2.30/100 000, whereas the prevalence of MODY in the same age range is 2.39/100 000. The median age of patients with T2DM was 15.8 yr, and 13.9 yr for MODY patients. The majority of patients with either T2DM or MODY were treated in children's hospitals and by consultant diabetologists. A molecular genetic analysis was done to substantiate the clinical diagnosis in less than half of the recruits (14.3% of T2DM and 44.8% of MODY patients). The prevalence of T2DM and MODY is considerably lower than the prevalence of type 1 diabetes. Type 2 diabetes thus continues to be a rare disease in children and adolescents in Germany, as is also the case in other European countries.

Nonmonotonic pressure evolution of the upper critical field in superconducting FeSe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaluarachchi, Udhara S.; Taufour, Valentin; Böhmer, Anna E.

2016-02-01

The pressure dependence of the upper critical field, H c2,c, of single crystalline FeSe was studied using measurements of the interplane resistivity, ρ c, in magnetic fields parallel to tetragonal c axis. H c2,c(T) curves obtained under hydrostatic pressures up to 1.56 GPa, the range over which the superconducting transition temperature, T c, of FeSe exhibits a nonmonotonic dependence with local maximum at p 1 ≈ 0.8 GPa and local minimum at p 2 ≈ 1.2 GPa. The slope of the upper critical field at T c,(dH c2,c/dT)T c, also exhibits a nonmonotonic pressure dependence with distinct changes at pmore » 1 and p 2. For p < p 1 the slope can be described within a multiband orbital model. For both p 1 < p < p 2 and p > p 2 the slope is in good semiquantitative agreement with a single band, orbital Helfand-Werthamer theory with Fermi velocities determined from Shubnikov–de Haas measurements. Lastly, this finding indicates that Fermi surface changes are responsible for the local minimum of T c(p) at p 2 ≈ 1.2 GPa.« less

Association between type 1 and type 2 diabetes with periodontal disease and tooth loss.

PubMed

Kaur, Gaganpreet; Holtfreter, Birte; Rathmann, Wolfgang; Rathmann, Wolfgan G; Schwahn, Christian; Wallaschofski, Henry; Schipf, Sabine; Nauck, Matthias; Kocher, Thomas

2009-09-01

The aim of this study was to determine whether both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) are associated with increased prevalence and extent of periodontal disease and tooth loss compared with non-diabetic subjects within a homogeneous adult study population. T1DM, T2DM and non-diabetic subjects were recruited from the population-based Study of Health in Pomerania. Additionally, T1DM subjects were retrieved from a Diabetes Centre. The total study population comprised 145 T1DM and 2647 non-diabetic subjects aged 20-59 years, and 182 T2DM and 1314 non-diabetic subjects aged 50-81 years. Periodontal disease was assessed by attachment loss (AL) and the number of missing teeth. Multivariable regression revealed an association between T1DM (p<0.001) and T2DM (p<0.01) with mean AL after full adjustment. After age stratification (p=0.04 for interaction), the effect of T2DM was only statistically significant in the 60-69-year-old subjects (B=0.90 (95% confidence intervals [95% CI]; 0.49, 1.31). T1DM was positively associated with tooth loss (adjusted, p<0.001). The association between T2DM and tooth loss was statistically significant only for females (odds ratios=1.60 [95% CI: 1.10, 2.33]). Our study confirmed an association between both T1DM and T2DM with periodontitis and tooth loss. Therefore, oral health education should be promoted in diabetic subjects.

Prediction of Cardiovascular Disease Risk by Cardiac Biomarkers in 2 United Kingdom Cohort Studies: Does Utility Depend on Risk Thresholds For Treatment?

PubMed

Welsh, Paul; Hart, Carole; Papacosta, Olia; Preiss, David; McConnachie, Alex; Murray, Heather; Ramsay, Sheena; Upton, Mark; Watt, Graham; Whincup, Peter; Wannamethee, Goya; Sattar, Naveed

2016-02-01

We tested the predictive ability of cardiac biomarkers N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T, and midregional pro adrenomedullin for cardiovascular disease (CVD) events using the British Regional Heart Study (BRHS) of men aged 60 to 79 years, and the MIDSPAN Family Study (MFS) of men and women aged 30 to 59 years. They included 3757 and 2226 participants, respectively, and during median 13.0 and 17.3 years follow-up the primary CVD event rates were 16.6 and 5.3 per 1000 patient-years, respectively. In Cox models adjusted for basic classical risk factors, 1 SD increases in log-transformed NT-proBNP, high-sensitivity troponin T, and midregional pro adrenomedullin were generally associated with increased primary CVD risk in both the studies (P<0.006) except midregional pro adrenomedullin in MFS (P=0.10). In BRHS, QRISK2 risk factors yielded a C-index of 0.657, which was improved by 0.017 (P=0.005) by NT-proBNP, but not by other biomarkers. Using 28% 14-year risk as a proxy for 20% 10-year risk, NT-proBNP improved risk classification for primary CVD cases (case net reclassification index, 5.9%; 95% confidence interval, 2.8%-9.2%), but only improved classification of noncases at a 14% 14-year risk threshold (4.6%; 2.9%-6.3%). In MFS, ASSIGN risk factors yielded a C-index of 0.752 for primary CVD; none of the cardiac biomarkers improved the C-index. Improvements in risk classification were only seen using NT-proBNP and high-sensitivity troponin T among cases using the 28% 14-year risk threshold (4.7%; 1.0%-9.2% and 2.6%; 0.0%-5.8%, respectively). In conclusion, the improvement in treatment allocation gained by adding cardiac biomarkers to risk scores seems to depend on the risk threshold chosen for commencing preventative treatments. © 2015 The Authors.

Arsenic Exposure and Calpain-10 Polymorphisms Impair the Function of Pancreatic Beta-Cells in Humans: A Pilot Study of Risk Factors for T2DM

PubMed Central

Díaz-Villaseñor, Andrea; Cruz, Laura; Cebrián, Arturo; Hernández-Ramírez, Raúl U.; Hiriart, Marcia; García-Vargas, Gonzálo; Bassol, Susana; Sordo, Monserrat; Gandolfi, A. Jay; Klimecki, Walter T.; López-Carillo, Lizbeth; Cebrián, Mariano E.; Ostrosky-Wegman, Patricia

2013-01-01

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide and diverse environmental and genetic risk factors are well recognized. Single nucleotide polymorphisms (SNPs) in the calpain-10 gene (CAPN-10), which encodes a protein involved in the secretion and action of insulin, and chronic exposure to inorganic arsenic (iAs) through drinking water have been independently associated with an increase in the risk for T2DM. In the present work we evaluated if CAPN-10 SNPs and iAs exposure jointly contribute to the outcome of T2DM. Insulin secretion (beta-cell function) and insulin sensitivity were evaluated indirectly through validated indexes (HOMA2) in subjects with and without T2DM who have been exposed to a gradient of iAs in their drinking water in northern Mexico. The results were analyzed taking into account the presence of the risk factor SNPs SNP-43 and -44 in CAPN-10. Subjects with T2DM had significantly lower beta-cell function and insulin sensitivity. An inverse association was found between beta-cell function and iAs exposure, the association being more pronounced in subjects with T2DM. Subjects without T2DM who were carriers of the at-risk genotype SNP-43 or -44, also had significantly lower beta-cell function. The association of SNP-43 with beta-cell function was dependent on iAs exposure, age, gender and BMI, whereas the association with SNP-44 was independent of all of these factors. Chronic exposure to iAs seems to be a risk factor for T2DM in humans through the reduction of beta-cell function, with an enhanced effect seen in the presence of the at-risk genotype of SNP-43 in CAPN-10. Carriers of CAPN-10 SNP-44 have also shown reduced beta-cell function. PMID:23349674

T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic programming

PubMed Central

Yang, Kai; Shrestha, Sharad; Zeng, Hu; Karmaus, Peer W.F.; Neale, Geoffrey; Vogel, Peter; Guertin, David A.; Lamb, Richard F.; Chi, Hongbo

2014-01-01

SUMMARY Naïve T cells respond to antigen stimulation by exiting from quiescence and initiating clonal expansion and functional differentiation, but the control mechanism is elusive. Here we describe that Raptor-mTORC1-dependent metabolic programming is a central determinant of this transitional process. Loss of Raptor abrogated T cell priming and Th2 cell differentiation, although Raptor function is less important for continuous proliferation of actively cycling cells. mTORC1 coordinated multiple metabolic programs in T cells including glycolysis, lipid synthesis and oxidative phosphorylation to mediate antigen-triggered exit from quiescence. mTORC1 further linked glucose metabolism to the initiation of Th2 cell differentiation by orchestrating cytokine receptor expression and cytokine responsiveness. Activation of Raptor-mTORC1 integrated T cell receptor and CD28 co-stimulatory signals in antigen-stimulated T cells. Our studies identify a Raptor-mTORC1-dependent pathway linking signal-dependent metabolic reprogramming to quiescence exit, and this in turn coordinates lymphocyte activation and fate decisions in adaptive immunity. PMID:24315998

Increased minimum legal age for the sale of alcohol in the Netherlands as of 2014: The effect on alcohol sellers' compliance after one and two years.

PubMed

Schelleman-Offermans, Karen; Roodbeen, Ruud T J; Lemmens, Paul H H M

2017-11-01

As of January 2014, the Dutch minimum legal age for the sale and purchase of all alcoholic beverages has increased from 16 to 18 years of age. The effectiveness of a minimum legal age policy in controlling the availability of alcohol for adolescents depends on the extent to which this minimum legal age is complied with in the field. The main aim of the current study is to investigate, for a country with a West-European drinking culture, whether raising the minimum legal age for the sale of alcohol has influenced compliance rates among Dutch alcohol vendors. A total of 1770 alcohol purchase attempts by 15-year-old mystery shoppers were conducted in three independent Dutch representative samples of on- and off-premise alcohol outlets in 2013 (T0), 2014 (T1), and 2016 (T2). The effect of the policy change was estimated controlling for gender and age of the vendor. Mean alcohol sellers' compliance rates significantly increased for 15-year-olds from 46.5% before to 55.7% one year and to 73.9% two years after the policy change. Two years after the policy change, alcohol vendors were up to 3 times more likely to comply with the alcohol age limit policy. After the policy change, mean alcohol compliance rates significantly increased when 15-year-olds attempted to purchase alcohol, an effect which seems to increase over time. Nevertheless, a rise in the compliance rate was already present in the years preceding the introduction of the new minimum legal age. This perhaps signifies a process in which a lowering in the general acceptability of juvenile drinking already started before the increased minimum legal age was introduced and alcohol vendors might have been anticipating this formal legal change. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Australia's Walk to Work Day campaign on adults' active commuting and physical activity behavior.

PubMed

Merom, Dafna; Miller, Yvette; Lymer, Sharyn; Bauman, Adrian

2005-01-01

To determine whether Australia's Walk to Work Day media campaign resulted in behavioral change among targeted groups. Pre- and postcampaign telephone surveys of a cohort of adults aged 18 to 65 years (n = 1100, 55% response rate) were randomly sampled from Australian major metropolitan areas. Tests for dependent samples were applied (McNemar chi2 or paired t-test). Among participants who did not usually actively commute to work was a significant decrease in "car only" use and an increase in walking combined with public transport. Among those who were employed was a significant increase in total time walking (+ 16 min/wk; t [780] = 2.04, p < .05) and in other moderate physical activity (+120 min/wk; t [1087] = 4.76, p < .005), resulting in a significant decrease in the proportion who were "inactive" (chi2 (1) = 6.1, p <.05). Although nonexperimental, the Walk to Work Day initiative elicited shortterm changes in targeted behaviors among target groups. Reinforcement by integrating worksite health promotion strategies may be required for sustained effects.

The thoracic surface anatomy of adult black South Africans: A reappraisal from CT scans.

PubMed

Keough, N; Mirjalili, S A; Suleman, F E; Lockhat, Z I; van Schoor, A

2016-11-01

Surface landmarks or planes taught in anatomy curricula derive from standard anatomical textbooks. Although many surface landmarks are valid, clear age, sex, and population differences exist. We reappraise the thoracic surface anatomy of black South Africans. We analyzed 76 (female = 42; male = 34) thoracoabdominal CT-scans. Patients were placed in a supine position with arms abducted. We analyzed the surface anatomy of the sternal angle, tracheal, and pulmonary trunk bifurcation, azygos vein termination, central veins, heart apex, diaphragm, xiphisternal joint, and subcostal plane using standardized definitions. Surface anatomy landmarks were mostly within the normal variation limits described in previous studies. Variation was observed where the esophagus (T9) and inferior vena cava (IVC) (T8/T9/T10) passed through the diaphragm. The bifurcations of the trachea and pulmonary trunk were inferior to the sternal angle. The subcostal plane level was positioned at L1/L2. The origin of inferior mesenteric artery was mostly inferior to the subcostal plane. Sex differences were noted for the plane of the xiphisternal joint (P = 0.0082), with males (36%) intersecting at T10 and females (36%) intersecting at T9. We provide further evidence for population variations in surface anatomy. The clinical relevance of surface anatomical landmarks depends on descriptions of normal variation. Accurate descriptions of population, sex, age, and body type differences are essential. Clin. Anat. 29:1018-1024, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Magnetic resonance imaging of third molars: developing a protocol suitable for forensic age estimation.

PubMed

De Tobel, Jannick; Hillewig, Elke; Bogaert, Stephanie; Deblaere, Karel; Verstraete, Koenraad

2017-03-01

Established dental age estimation methods in sub-adults study the development of third molar root apices on radiographs. In living individuals, however, avoiding ionising radiation is expedient. Studying dental development with magnetic resonance imaging complies with this requirement, adding the advantage of imaging in three dimensions. To elaborate the development of an MRI protocol to visualise all third molars for forensic age estimation, with particular attention to the development of the root apex. Ex vivo scans of porcine jaws and in vivo scans of 10 volunteers aged 17-25 years were performed to select adequate sequences. Studied parameters were T1 vs T2 weighting, ultrashort echo time (UTE), fat suppression, in plane resolution, slice thickness, 3D imaging, signal-to-noise ratio, and acquisition time. A bilateral four-channel flexible surface coil was used. Two observers evaluated the suitability of the images. T2-weighted images were preferred to T1-weighted images. To clearly distinguish root apices in (almost) fully developed third molars an in plane resolution of 0.33 × 0.33 mm 2 was deemed necessary. Taking acquisition time limits into account, only a T2 FSE sequence with slice thickness of 2 mm generated images with sufficient resolution and contrast. UTE, thinner slice T2 FSE and T2 3D FSE sequences could not generate the desired resolution within 6.5 minutes. Three Tesla MRI of the third molars is a feasible technique for forensic age estimation, in which a T2 FSE sequence can provide the desired in plane resolution within a clinically acceptable acquisition time.

Long-term weight-change slope, weight fluctuation and risk of type 2 diabetes mellitus in middle-aged Japanese men and women: findings of Aichi Workers' Cohort Study.

PubMed

Zhang, Y; Yatsuya, H; Li, Y; Chiang, C; Hirakawa, Y; Kawazoe, N; Tamakoshi, K; Toyoshima, H; Aoyama, A

2017-03-20

This study aims to investigate the association of long-term weight-change slopes, weight fluctuation and the risk of type 2 diabetes mellitus (T2DM) in middle-aged Japanese men and women. A total of 4234 participants of Aichi Workers' Cohort Study who were aged 35-66 years and free of diabetes in 2002 were followed through 2014. Past body weights at the ages of 20, 25, 30, 40 years, and 5 years before baseline as well as measured body weight at baseline were regressed on the ages. Slope and root-mean-square-error of the regression line were obtained and used to represent the weight changes and the weight fluctuation, respectively. The associations of the weight-change slopes and the weight fluctuation with incident T2DM were estimated by Cox proportional hazards models. During the median follow-up of 12.2 years, 400 incident cases of T2DM were documented. After adjustment for baseline overweight and other lifestyle covariates, the weight-change slopes were significantly associated with higher incidence of T2DM (hazard ratio (HR): 1.80, 95% confident interval (CI): 1.17-2.77 for men; and HR: 2.78, 95% CI: 1.07-7.23 for women), while the weight fluctuation was not (HR: 1.08, 95% CI: 1.00-1.18 for men and HR: 1.02, 95% CI: 0.84-1.25 for women). Regardless of the presence of overweight, the long-term weight-change slopes were significantly associated with the increased risk of T2DM; however, the weight fluctuation was not associated with the risk of T2DM in middle-aged Japanese men and women.

The underlying mechanism of proinflammatory NF-κB activation by the mTORC2/Akt/IKKα pathway during skin aging

PubMed Central

Choi, Yeon Ja; Moon, Kyoung Mi; Chung, Ki Wung; Jeong, Ji Won; Park, Daeui; Kim, Dae Hyun; Yu, Byung Pal; Chung, Hae Young

2016-01-01

Mammalian target of rapamycin complex 2 (mTORC2), one of two different enzymatic complexes of mTOR, regulates a diverse set of substrates including Akt. mTOR pathway is one of well-known mediators of aging process, however, its role in skin aging has not been determined. Skin aging can be induced by physical age and ultraviolet (UV) irradiation which are intrinsic and extrinsic factors, respectively. Here, we report increased mTORC2 pathway in intrinsic and photo-induced skin aging, which is implicated in the activation of nuclear factor-κB (NF-κB). UVB-irradiated or aged mice skin revealed that mTORC2 activity and its component, rictor were significantly upregulated which in turn increased Akt activation and Akt-dependent IκB kinase α (IKKα) phosphorylation at Thr23 in vivo. We also confirmed that UVB induced the mTORC2/Akt/IKKα signaling pathway with HaCaT human normal keratinocytes. The increased mTORC2 signaling pathway during skin aging were associated to NF-κB activation. Suppression of mTORC2 activity by the treatment of a mTOR small inhibitor or knockdown of RICTOR partially rescued UVB-induced NF-κB activation through the downregulation of Akt/IKKα activity. Our data demonstrated the upregulation of mTORC2 pathway in intrinsic and photo-induced skin aging and its role in IKKα/NF-κB activation. These data not only expanded the functions of mTOR to skin aging but also revealed the therapeutic potential of inhibiting mTORC2 in ameliorating both intrinsic skin aging and photoaging. PMID:27486771

A dysregulation of glucose metabolism control is associated with carotid atherosclerosis in patients with coronary heart disease (CORDIOPREV-DIAB study).

PubMed

Yubero-Serrano, Elena M; Delgado-Lista, Javier; Alcala-Diaz, Juan F; Garcia-Rios, Antonio; Perez-Caballero, Ana I; Blanco-Rojo, Ruth; Gomez-Delgado, Francisco; Marin, Carmen; Tinahones, Francisco J; Caballero, Javier; Ordovas, Jose M; van Ommen, Ben; Perez-Jimenez, Francisco; Perez-Martinez, Pablo; Lopez-Miranda, Jose

2016-10-01

Patients with coexisting coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM) are at high risk of cardiovascular recurrence, however, it is not well established whether they exhibit an increased intima-media thickness of both common carotid arteries (IMT-CC). Furthermore, whether this relationship is inherent to T2DM or depends on glycemic control has not been tested in large cohorts. Our aim was to determine whether clinical categories and/or analytical markers of glucose metabolism control were associated with IMT-CC in CHD patients. 1002 patients aged 20-75 years, categorized into normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or T2DM, underwent an oral glucose tolerance test (OGTT) and an IMT-CC measurement. IMT-CC was higher in T2DM patients with HbA1c > 6.5% compared to T2DM patients with HbA1c < 6.5% (p = 0.001), patients with IFG or IGT (p < 0.001) and NGT (p < 0.001). When age was considered, IMT-CC was influenced by glucose metabolism control only in e patients with age <61 years (p < 0.01). In a multiple linear regression analysis, glucose concentration at 120 min, but not other OGTT time-points appeared as a significant independent contributor of IMT-CC (p < 0.001). Moreover, a multiple logistic regression and the area under curve (AUC) of the ROC curve analysis showed a predictive power of glucose at 120 min to detect those CHD patients at the highest risk, defined as IMT-CC ≥ 0.7 mm (R 2  = 0.221; AUC = 0.761). Our results highlight the importance of properly controlling glucose metabolism in CHD patients, in younger populations in particular, providing an easy way of categorizing patients with an increased IMT-CC. Moreover, glucose concentration at 120 min could contribute to CVD risk and its determination could be used as a predictive tool to identify those CHD patients at the highest risk. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Breath-hold black-blood T1rho mapping improves liver T1rho quantification in healthy volunteers.

PubMed

Wáng, Yì Xiáng J; Deng, Min; Lo, Gladys G; Liang, Dong; Yuan, Jing; Chen, Weitian

2018-03-01

Background Recent researches suggest that T1rho may be a non-invasive and quantitative technique for detecting and grading liver fibrosis. Purpose To compare a multi-breath-hold bright-blood fast gradient echo (GRE) imaging and a single breath-hold single-shot fast spin echo (FSE) imaging with black-blood effect for liver parenchyma T1rho measurement and to study liver physiological T1rho value in healthy volunteers. Material and Methods The institutional Ethics Committee approved this study. 28 healthy participants (18 men, 10 women; age = 29.6 ± 5.1 years) underwent GRE liver T1rho imaging, and 20 healthy participants (10 men, 10 women; age = 36.9 ± 10.3 years) underwent novel black-blood FSE liver T1rho imaging, both at 3T with spin-lock frequency of 500 Hz. The FSE technique allows simultaneous acquisition of four spin lock times (TSLs; 1 ms, 10 ms, 30 ms, 50msec) in 10 s. Results For FSE technique the intra-scan repeatability intraclass correlation coefficient (ICC) was 0.98; while the inter-scan reproducibility ICC was 0.82 which is better than GRE technique's 0.76. Liver T1rho value in women tended to have a higher value than T1rho values in men (FSE: 42.28 ± 4.06 ms for women and 39.13 ± 2.12 ms for men; GRE: 44.44 ± 1.62 ms for women and 42.36 ± 2.00 ms for men) and FSE technique showed liver T1rho value decreased slightly as age increased. Conclusion Single breath-hold black-blood FSE sequence has better scan-rescan reproducibility than multi-breath-hold bright-blood GRE sequence. Gender and age dependence of liver T1rho in healthy participants is observed, with young women tending to have a higher T1rho measurement.

Long-term influence of physical aging processes in epoxy matrix composites

NASA Technical Reports Server (NTRS)

Kong, E. S. W.

1981-01-01

Selected mechanical properties of (plus or minus 45 degree sub 4s) graphite/epoxy composites were found to be affected by sub T sub g annealing. Postcured specimens of Thornel 300 graphite/Narmco 5208 epoxy were sub T sub G annealed at 413 K (140 C) for ca. 10 to the first through 10 to the fifth powers min., with a prior quenching from above T sub g. The ultimate tensile strength, strain-to-break, and toughness of the composite were found to decrease as a function of sub T sub g annealing time. The time-dependent change in properties can be explained on the basis of physical aging which is related to free volume changes in the non-equilibrium glassy state of network epoxies. The results imply possible changes in composite properties with service time.

The clinical characteristics of patients with mitochondrial tRNA Leu(UUR)m.3243A > G mutation: Compared with type 1 diabetes and early onset type 2 diabetes.

PubMed

Zhu, Jie; Yang, Peng; Liu, Xiang; Yan, Li; Rampersad, Sharvan; Li, Feng; Li, Hong; Sheng, Chunjun; Cheng, Xiaoyun; Zhang, Manna; Qu, Shen

2017-08-01

This study presents nine patients with mitochondrial tRNA Leu (UUR) m.3243A>G mutation and compares the clinical characteristics and diabetes complications with type 1 diabetes (T1DM) or early onset type 2 diabetes (T2DM). The study covers 9 patients with MIDD, 33 patients with T1DM and 86 patients (age of onset ≤35years) with early onset T2DM, matched for sex, age at onset of diabetes, duration of diabetes. All patients with MIDD were confirmed as carrying the m.3243A>G mitochondrial DNA mutation. Serum HbA1c, beta-cell function, retinal and renal complications of diabetes, bone metabolic markers, lumbar spine and femoral neck BMD bone mineral density were compared to characterize the clinical features of all patients. Nine patients were from five unrelated families, and the mean (SD) onset age of those patients was 31.2±7.2year. Two patients required insulin at presentation, and six patients progressed to insulin requirement after a mean of 7.2years. β-Cell function in the MIDD group was intermediate between T1DM and early-onset T2DM. In MIDD, four patients were diagnosed as diabetic retinopathy (4/9) and five patients (5/9) had macroalbuminuria. The number of patients with diabetic retinopathy and macroalbuminuria in the MIDD group was comparable to T1DM or early-onset T2DM. The rate of osteoporosis (BMD T-score<-2.5 SD) in the patient with MIDD was higher than the T1DM or early-onset T2DM group. Our study indicates that of the nine subjects with MIDD, three patients (1-II-1, 1-II-3, 1-II-4) who came from the same family had a history of acute pancreatitis. Compared with T1DM or early-onset T2DM matched for sex, age, duration of diabetes, MIDD patients had the highest rate of osteoporosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Association of telomere length with type 2 diabetes, oxidative stress and UCP2 gene variation.

PubMed

Salpea, Klelia D; Talmud, Philippa J; Cooper, Jackie A; Maubaret, Cecilia G; Stephens, Jeffrey W; Abelak, Kavin; Humphries, Steve E

2010-03-01

High oxidative stress potentially leads to accelerated telomere shortening and consequent premature cell senescence, implicated in type 2 diabetes (T2D) development. Therefore, we studied the association of leukocyte telomere length (LTL) with the presence of T2D, as well as the effect on the patients' LTL of plasma oxidative stress and of variation in UCP2, a gene involved in the mitochondrial production of reactive oxygen species. Mean LTL was determined in 569 Caucasian, 103 South Asian and 70 Afro-Caribbean T2D patients aged from 24 to 92 years, 81 healthy Caucasian male students aged from 18 to 28 years and 367 healthy Caucasian men aged from 40 to 61 years by real-time PCR. Plasma total antioxidant status (TAOS) was measured in the T2D patients by a photometric microassay. The patients were also genotyped for the UCP2 functional variants -866G>A and A55V. Afro-Carribeans had 510bp longer mean length compared to Caucasians (p<0.0001) and 500bp longer than South Asians (p=0.004). T2D subjects displayed shorter age-adjusted LTL compared to controls [6.94(6.8-7.03) vs. 7.72(7.53-7.9), p<0.001] with subjects in the middle and the lowest tertile of LTL having significantly higher odds ratios for T2D compared to those in the highest tertile [1.50(1.08-2.07) and 5.04(3.63-6.99), respectively, p<0.0001]. In the patients, LTL was correlated negatively with age (r=-0.18, p<0.0001) and positively with TAOS measures (r=0.12, p=0.01) after adjusting for age, while carriers of the UCP2 -866A allele had shorter age-adjusted LTL than common homozygotes [6.86(6.76-6.96)kb vs. 7.03(6.91-7.15)kb, p=0.04]. The present data suggest that shorter LTL is associated with the presence of T2D and this could be partially attributed to the high oxidative stress in these patients. The association of the UCP2 functional promoter variant with the LTL implies a link between mitochondrial production of reactive oxygen species and shorter telomere length in T2D.

Ankyrin-B metabolic syndrome combines age-dependent adiposity with pancreatic β cell insufficiency.

PubMed

Lorenzo, Damaris N; Healy, Jane A; Hostettler, Janell; Davis, Jonathan; Yang, Jiayu; Wang, Chao; Hohmeier, Hans Ewald; Zhang, Mingjie; Bennett, Vann

2015-08-03

Rare functional variants of ankyrin-B have been implicated in human disease, including hereditary cardiac arrhythmia and type 2 diabetes (T2D). Here, we developed murine models to evaluate the metabolic consequences of these alterations in vivo. Specifically, we generated knockin mice that express either the human ankyrin-B variant R1788W, which is present in 0.3% of North Americans of mixed European descent and is associated with T2D, or L1622I, which is present in 7.5% of African Americans. Young AnkbR1788W/R1788W mice displayed primary pancreatic β cell insufficiency that was characterized by reduced insulin secretion in response to muscarinic agonists, combined with increased peripheral glucose uptake and concomitantly increased plasma membrane localization of glucose transporter 4 (GLUT4) in skeletal muscle and adipocytes. In contrast, older AnkbR1788W/R1788W and AnkbL1622I/L1622I mice developed increased adiposity, a phenotype that was reproduced in cultured adipocytes, and insulin resistance. GLUT4 trafficking was altered in animals expressing mutant forms of ankyrin-B, and we propose that increased cell surface expression of GLUT4 in skeletal muscle and fatty tissue of AnkbR1788W/R1788W mice leads to the observed age-dependent adiposity. Together, our data suggest that ankyrin-B deficiency results in a metabolic syndrome that combines primary pancreatic β cell insufficiency with peripheral insulin resistance and is directly relevant to the nearly one million North Americans bearing the R1788W ankyrin-B variant.

Time dependent behavior of a graphite/thermoplastic composite and the effects of stress and physical aging

NASA Technical Reports Server (NTRS)

Gates, Thomas S.; Feldman, Mark

1993-01-01

Two complimentary studies were performed to determine the effects of stress and physical aging on the matrix dominated time dependent properties of IM7/8320 composite. The first of these studies, experimental in nature, used isothermal tensile creep/aging test techniques developed for polymers and adapted them for testing of the composite material. From these tests, the time dependent transverse (S22) and shear (S66) compliance's for an orthotropic plate were found from short term creep compliance measurements at constant, sub-T(sub g) temperatures. These compliance terms were shown to be affected by physical aging. Aging time shift factors and shift rates were found to be a function of temperature and applied stress. The second part of the study relied upon isothermal uniaxial tension tests of IM7/8320 to determine the effects of physical aging on the nonlinear material behavior at elevated temperature. An elastic/viscoplastic constitutive model was used to quantify the effects of aging on the rate-independent plastic and rate-dependent viscoplastic response. Sensitivity of the material constants required by the model to aging time were determined for aging times up to 65 hours. Verification of the analytical model indicated that the effects of prior aging on the nonlinear stress/strain/time data of matrix dominated laminates can be predicted.

Adiponectin improves coronary no-reflow injury by protecting the endothelium in rats with type 2 diabetes mellitus.

PubMed

Han, Xue; Wu, Ye; Liu, Xin; Ma, Lu; Lv, Tingting; Sun, Qi; Xu, Wenli; Zhang, Suli; Wang, Ke; Wang, Wen; Ma, Xinliang; Liu, Huirong

2017-08-31

To determine the effect of adiponectin (APN) on the coronary no-reflow (NR) injury in rats with Type 2 diabetes mellitus (T2DM), 80 male Sprague-Dawley rats were fed with a high-sugar-high-fat diet to build a T2DM model. Rats received vehicle or APN in the last week and then were subjected to myocardial ischemia reperfusion (MI/R) injury. Endothelium-dependent vasorelaxation of the thoracic aorta was significantly decreased and serum levels of endothelin-1 (ET-1), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were noticably increased in T2DM rats compared with rats without T2DM. Serum APN was positively correlated with the endothelium-dependent vasorelaxation, but negatively correlated with the serum level of ET-1. Treatment with APN improved T2DM-induced endothelium-dependent vasorelaxation, recovered cardiac function, and decreased both NR size and the levels of ET-1, ICAM-1 and VCAM-1. Hypoadiponectinemia was associated with the aggravation of coronary NR in T2DM rats. APN could alleviate coronary NR injury in T2DM rats by protecting the endothelium and improving microcirculation. © 2017 The Author(s).

Age determination of vessel wall hematoma in spontaneous cervical artery dissection: A multi-sequence 3T Cardiovascular Magnetic resonance study

PubMed Central

2011-01-01

Background Previously proposed classifications for carotid plaque and cerebral parenchymal hemorrhages are used to estimate the age of hematoma according to its signal intensities on T1w and T2w MR images. Using these classifications, we systematically investigated the value of cardiovascular magnetic resonance (CMR) in determining the age of vessel wall hematoma (VWH) in patients with spontaneous cervical artery dissection (sCAD). Methods 35 consecutive patients (mean age 43.6 ± 9.8 years) with sCAD received a cervical multi-sequence 3T CMR with fat-saturated black-blood T1w-, T2w- and TOF images. Age of sCAD was defined as time between onset of symptoms (stroke, TIA or Horner's syndrome) and the CMR scan. VWH were categorized into hyperacute, acute, early subacute, late subacute and chronic based on their signal intensities on T1w- and T2w images. Results The mean age of sCAD was 2.0, 5.8, 15.7 and 58.7 days in patients with acute, early subacute, late subacute and chronic VWH as classified by CMR (p < 0.001 for trend). Agreement was moderate between VWH types in our study and the previously proposed time scheme of signal evolution for cerebral hemorrhage, Cohen's kappa 0.43 (p < 0.001). There was a strong agreement of CMR VWH classification compared to the time scheme which was proposed for carotid intraplaque hematomas with Cohen's kappa of 0.74 (p < 0.001). Conclusions Signal intensities of VWH in sCAD vary over time and multi-sequence CMR can help to determine the age of an arterial dissection. Furthermore, findings of this study suggest that the time course of carotid hematomas differs from that of cerebral hematomas. PMID:22122756

Alcohol-related diseases and alcohol dependence syndrome is associated with increased gout risk: A nationwide population-based cohort study.

PubMed

Tu, Hung-Pin; Tung, Yi-Ching; Tsai, Wen-Chan; Lin, Gau-Tyan; Ko, Ying-Chin; Lee, Su-Shin

2017-03-01

Alcohol intake is strongly associated with hyperuricemia, which may cause gout. This study evaluated the risk of gout in patients with alcohol-related diseases and alcohol dependence syndrome. We used the Taiwan National Health Insurance Research Database (NHIRD) to conduct a nationwide population-based cohort study to assess the risk of gout and gout incidence in patients with alcohol-related diseases and alcohol dependence syndrome (as defined by the International Classification of Diseases, Ninth Revision). In the NHIRD records from 1998 to 2008, we identified 11,675 cases of alcohol-related diseases. The control group comprised 23,350 cases without alcohol-related diseases propensity score-matched (1 case: 2 controls) for age, age group, and sex. The results revealed that alcohol-related diseases were significantly associated with gout risk (adjusted hazard ratio 1.88; P<0.0001). Of the alcohol-related disease cases, 34.1% of the patients had alcohol dependence syndrome (males 34.8%; females 32.4%), and alcohol dependence was independently associated with gout occurrence (relative risk [RR] 2.01; P<0.0001). Severe alcohol-dependent patients (who were also the heavy benzodiazepines users), were associated with an increased risk of gout (RR 1.71 to 4.21, P≤0.0182). Physicians should be aware of the association between alcohol dependence syndrome and gout occurrence, and alcohol use assessment and measures to prevent alcohol dependence should be implemented in the integrative care for patients with gout. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Vitamin E reverses impaired linker for activation of T cells activation in T cells from aged C57BL/6 mice

USDA-ARS?s Scientific Manuscript database

Supplemental vitamin E restores age-related defects in IL-2 production, T cell proliferation, and immune synapse formation. Here, we evaluated the effect of vitamin E on TCR-proximal signaling events. In aged murine CD4+ T cells stimulated via CD3 and CD28, tyrosine 191 of the adaptor protein LAT wa...

Forecasting future prevalence of type 2 diabetes mellitus in Syria

PubMed Central

2013-01-01

Background Type 2 diabetes mellitus (T2DM) is increasingly becoming a major public health problem worldwide. Estimating the future burden of diabetes is instrumental to guide the public health response to the epidemic. This study aims to project the prevalence of T2DM among adults in Syria over the period 2003–2022 by applying a modelling approach to the country’s own data. Methods Future prevalence of T2DM in Syria was estimated among adults aged 25 years and older for the period 2003–2022 using the IMPACT Diabetes Model (a discrete-state Markov model). Results According to our model, the prevalence of T2DM in Syria is projected to double in the period between 2003 and 2022 (from 10% to 21%). The projected increase in T2DM prevalence is higher in men (148%) than in women (93%). The increase in prevalence of T2DM is expected to be most marked in people younger than 55 years especially the 25–34 years age group. Conclusions The future projections of T2DM in Syria put it amongst countries with the highest levels of T2DM worldwide. It is estimated that by 2022 approximately a fifth of the Syrian population aged 25 years and older will have T2DM. PMID:23705638

Immune system development during early childhood in tropical Latin America: evidence for the age-dependent down regulation of the innate immune response.

PubMed

Teran, Rommy; Mitre, Edward; Vaca, Maritza; Erazo, Silvia; Oviedo, Gisela; Hübner, Marc P; Chico, Martha E; Mattapallil, Joseph J; Bickle, Quentin; Rodrigues, Laura C; Cooper, Philip J

2011-03-01

The immune response that develops in early childhood underlies the development of inflammatory diseases such as asthma and there are few data from tropical Latin America (LA). This study investigated the effects of age on the development of immunity during the first 5 years of life by comparing innate and adaptive immune responses in Ecuadorian children aged 6-9 months, 22-26 months, and 48-60 months. Percentages of naïve CD4+ T cells declined with age while those of memory CD4(+) and CD8(+) T cells increased indicating active development of the immune system throughout the first five years. Young infants had greater innate immune responses to TLR agonists compared to older children while regulatory responses including SEB-induced IL-10 and percentages of FoxP3(+) T-regulatory cells decreased with age. Enhanced innate immunity in early life may be important for host defense against pathogens but may increase the risk of immunopathology. Copyright © 2010 Elsevier Inc. All rights reserved.

Temperature dependence of resonant secondary emission in NaNO 2: Spectral behavior

NASA Astrophysics Data System (ADS)

Kato, Riso; Kawaguchi, Yoshizo; Ashida, Masaaki

1990-05-01

Spectral behavior of resonant secondary emission in NaNO 2 has been investigated in the temperature range from 2 to 30 K under the excitation near the v00 line of the lowest singlet absorption. With increasing temperature, luminescence lines separated from multiple-order Raman lines become detectable even under the excitation with the off-resonance energy Δ c ≳ 13 cm -1. The intensity of the luminescence line IL( T) increases with temperature in proportion to the phonon number n( hvp, T) in the temperature range T ≲ Δ c/ k, while it increases more steeply in the range T ≳ Δ c/ k. The temperature dependence of IL( T) is ascribed to the increase in the luminescence from the v00 level after the one-phonon assisted transition to the level induced by the off-resonant incident light. The intensity of the Raman line IR( T) decreases gradually in 2-12 K range and shows rapid drop above 12 K. The temperature dependence of IR( T) is ascribed to the dephasing of the intermediate state due to the two-phonon interaction with the reservoir.

Amino Acid-based Formula in Cow's Milk Allergy: Long-term Effects on Body Growth and Protein Metabolism.

PubMed

Canani, Roberto Berni; Nocerino, Rita; Frediani, Tullio; Lucarelli, Sandra; Di Scala, Carmen; Varin, Elena; Leone, Ludovica; Muraro, Antonella; Agostoni, Carlo

2017-04-01

The long-term effects of amino acid-based formula (AAF) in the treatment of cow's milk allergy (CMA) are largely unexplored. The present study comparatively evaluates body growth and protein metabolism in CMA children treated with AAF or with extensively hydrolyzed whey formula (eHWF), and healthy controls. A 12-month multicenter randomized control trial was conducted in outpatients with CMA (age 5-12 m) randomized in 2 groups, treated with AAF (group 1) and eHWF (group 2), and compared with healthy controls (group 3) fed with follow-on (if age <12 months) or growing-up formula (if age >12 months). At enrolment (T0), after 3 (T3), 6 (T6), and 12 months (T12) a clinical evaluation was performed. At T0 and T3, in subjects with CMA serum levels of albumin, urea, total protein, retinol-binding protein, and insulin-like growth factor 1 were measured. Twenty-one subjects in group 1 (61.9% boys, age 6.5 ± 1.5 months), 19 in group 2 (57.9% boys, age 7 ± 1.7 months) and 25 subjects in group 3 (48% boys, age 5.5 ± 0.5 months) completed the study. At T0, the weight z score was similar in group 1 (-0.74) and 2 (-0.76), with differences compared to group 3 (-0.17, P < 0.05). At T12, the weight z score value was similar between the 3 groups without significant differences. There were no significant changes in protein metabolism in children in groups 1 and 2. Long-term treatment with AAF is safe and allows adequate body growth in children with CMA.

Effective Control of Chronic γ-Herpesvirus Infection by Unconventional MHC Class Ia–Independent CD8 T Cells

PubMed Central

Tibbetts, Scott A; McClellan, Kelly B

2006-01-01

Control of virus infection is mediated in part by major histocompatibility complex (MHC) Class Ia presentation of viral peptides to conventional CD8 T cells. Although important, the absolute requirement for MHC Class Ia–dependent CD8 T cells for control of chronic virus infection has not been formally demonstrated. We show here that mice lacking MHC Class Ia molecules (Kb−/−xDb−/− mice) effectively control chronic γ-herpesvirus 68 (γHV68) infection via a robust expansion of β2-microglobulin (β2-m)-dependent, but CD1d-independent, unconventional CD8 T cells. These unconventional CD8 T cells expressed: (1) CD8αβ and CD3, (2) cell surface molecules associated with conventional effector/memory CD8 T cells, (3) TCRαβ with a significant Vβ4, Vβ3, and Vβ10 bias, and (4) the key effector cytokine interferon-γ (IFNγ). Unconventional CD8 T cells utilized a diverse TCR repertoire, and CDR3 analysis suggests that some of that repertoire may be utilized even in the presence of conventional CD8 T cells. This is the first demonstration to our knowledge that β2-m–dependent, but Class Ia–independent, unconventional CD8 T cells can efficiently control chronic virus infection, implicating a role for β2-n–dependent non-classical MHC molecules in control of chronic viral infection. We speculate that similar unconventional CD8 T cells may be able to control of other chronic viral infections, especially when viruses evade immunity by inhibiting generation of Class Ia–restricted T cells. PMID:16733540

Glucose-lowering effect of whey protein depends upon clinical characteristics of patients with type 2 diabetes.

PubMed

Almario, Rogelio U; Buchan, Wendy M; Rocke, David M; Karakas, Sidika E

2017-01-01

Whey protein (WP) intake has been shown to reduce postprandial glycemia. Majority of WP research in type 2 diabetes (T2DM) involved acute challenge or weight loss studies. It is not known if WP supplementation can provide sustained glucose lowering. Our goal was to investigate the effects of WP on glycemia comprehensively by using continuous glucose monitoring (CGM) while avoiding the confounding effects of variable food intake through controlled feeding. This double-blinded and placebo (PL)-controlled study included 22 patients with T2DM patients (11 male, 11 female; age 57.1±12.6 years) on diet or metformin monotherapy. First, one serving (21 g) of WP was compared with PL in parallel-armed acute challenge studies. Next, in a crossover design, each patient underwent CGM twice, over 2 consecutive weeks, 3.5 days each week. Identical diets were provided by the study during both CGM periods. During the first CGM, one serving of either WP or PL was consumed before breakfast and another before dinner. During the second CGM, participants switched to the alternate supplement. Order of the supplements was randomized. During acute challenge studies, WP stimulated insulin and glucagon-like peptide (GLP)-1 secretion; suppressed ghrelin (all p<0.05), while PL had no effect. During CGM, glucose response to WP varied depending on the baseline characteristics of the patients. When evaluated using linear regression, the most predictive baseline variables were body mass index (BMI) (p=0.0006), triglycerides (p=8.3×10 -5 ) and GLP-1 (p=0.006). Lower BMI, triglyceride and GLP-1 predicted decreased glucose levels on WP. Obesity, hypertriglyceridemia and high fasting GLP-1 concentrations predicted increased glucose levels. Effects of WP supplementation on glycemia in T2DM depend on the baseline characteristics. Lower body weight, normal triglyceride and lower GLP-1 levels predict glucose lowering. In contrast, obesity, hypertriglyceridemia and high baseline GLP-1 predict increased glucose response.

Detection of Natural Toxoplasma gondii Infection in Chicken in Thika Region of Kenya Using Nested Polymerase Chain Reaction

PubMed Central

Karanja, Simon Muturi; Ngotho, Maina; Kamau, David Muchina; Njuguna, Adele Nyambura

2016-01-01

The detection of Toxoplasma gondii in free-range chickens is a good indicator of possible risk to human beings. The aim of this study was to investigate the occurrence of T. gondii in free-range chicken using polymerase chain reaction (PCR). Brain samples from 105 free-range chickens from three administrative areas in Thika region, Kenya, were collected, DNA-extracted, and analyzed using PCR to detect presence of T. gondii. The overall prevalence of T. gondii in all the three areas was 79.0% (95% CI: 70.0–86.4%) and the prevalence across the three areas was not significantly different (P = 0.5088; χ 2 = 1.354). Female chickens had higher (79.4%) prevalence than males (78.6%), although the difference was not significant (P = 0.922, χ 2 = 0.01). However, chickens that were more than 2 years old had significantly (P = 0.003; χ 2 = 11.87) higher prevalence compared to younger ones. The study indicates that there was a high occurrence of T. gondii infection in free-range chickens from Thika region and that the infection rate is age dependent. Further studies should be carried out to determine the possible role of roaming chickens in the epidemiology of the disease among humans in the area. PMID:27981052

Detection of Natural Toxoplasma gondii Infection in Chicken in Thika Region of Kenya Using Nested Polymerase Chain Reaction.

PubMed

Mose, John Mokua; Kagira, John Maina; Karanja, Simon Muturi; Ngotho, Maina; Kamau, David Muchina; Njuguna, Adele Nyambura; Maina, Naomi Wangari

2016-01-01

The detection of Toxoplasma gondii in free-range chickens is a good indicator of possible risk to human beings. The aim of this study was to investigate the occurrence of T. gondii in free-range chicken using polymerase chain reaction (PCR). Brain samples from 105 free-range chickens from three administrative areas in Thika region, Kenya, were collected, DNA-extracted, and analyzed using PCR to detect presence of T. gondii . The overall prevalence of T. gondii in all the three areas was 79.0% (95% CI: 70.0-86.4%) and the prevalence across the three areas was not significantly different ( P = 0.5088; χ 2 = 1.354). Female chickens had higher (79.4%) prevalence than males (78.6%), although the difference was not significant ( P = 0.922, χ 2 = 0.01). However, chickens that were more than 2 years old had significantly ( P = 0.003; χ 2 = 11.87) higher prevalence compared to younger ones. The study indicates that there was a high occurrence of T. gondii infection in free-range chickens from Thika region and that the infection rate is age dependent. Further studies should be carried out to determine the possible role of roaming chickens in the epidemiology of the disease among humans in the area.

Differential effects of bihemispheric and unihemispheric transcranial direct current stimulation in young and elderly adults in verbal learning.

PubMed

Fiori, Valentina; Nitsche, Michael; Iasevoli, Luigi; Cucuzza, Gabriella; Caltagirone, Carlo; Marangolo, Paola

2017-03-15

For the past few years, the potential of transcranial direct current stimulation (tDCS) for the treatment of several pathologies has been investigated. In the language domain, several studies, in healthy and brain-damaged populations, have already shown that tDCS is effective in enhancing naming, repetition and semantic word generation. In those studies, different tDCS electrode configurations have been tested, however, a direct comparison between different montages in verbal learning has never been conducted. In this study, we aimed to explore the impact of bihemispheric and unihemispheric tDCS on verbal learning task performance in two groups (young vs. elderly). Fifteen healthy volunteers participated per group. Each participant received three stimulation conditions: unihemispheric anodal tDCS over the left temporal area, bihemispheric tDCS over the left (anodal) and right (cathodal) temporal areas and a sham condition. During active stimulation, tDCS (20min, 2mA) was applied while each participant learned twenty pseudowords (arbitrarily assigned to corresponding pictures). No significant differences were found between the three conditions for the young group with regard to accuracy and vocal reaction times. In contrast, in the elderly group, real stimulation improved performance compared to sham but bihemispheric tDCS was more efficient than unilateral stimulation. These results suggest that bihemispheric stimulation is more effective in improving language learning but this effect is age-dependent. The hypothesis is advanced that cortical changes in the course of aging might differentially impact on tDCS efficacy on behavioral performance. These data may also have implications for treatment of stroke patients with language impairment. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential regulation and impact of fucosyltransferase VII and core 2 β1,6-N-acetyl-glycosaminyltransferase for generation of E-selectin and P-selectin ligands in murine CD4+ T cells

PubMed Central

Schroeter, Micha F; Ratsch, Boris A; Lehmann, Jeanette; Baumgrass, Ria; Hamann, Alf; Syrbe, Uta

2012-01-01

Ligands for E-selectin and P-selectin (E-lig and P-lig) are induced on CD4+ T cells upon differentiation into effector T cells. Glycosyltransferases, especially α 1,3-fucosyltransferase VII (FucT-VII) and core 2 β1,6-N-acetyl-glycosaminyltransferase I (C2GlcNAcT-I), are critical for their synthesis. We here analysed the signals that control the expression of E-lig, P-lig and mRNA coding for FucT-VII and C2GlcNAcT-I. In line with previous reports, we found that P-lig expression correlates with the regulation of C2GlcNAcT-I, whereas E-lig expression can occur at low levels of C2GlcNAcT-I mRNA but requires high FucT-VII mRNA expression. Interestingly, the two enzymes are regulated by different signals. Activation-induced C2GlcNAcT-I up-regulation under permissive (T helper type 1) conditions was strongly reduced by cyclosporin A (CsA), suggesting the involvement of T-cell receptor-dependent, calcineurin/NFAT-dependent signals in combination with interleukin-12 (IL-12) -mediated signals in the regulation of C2GlcNAcT-I. In contrast, expression of FucT-VII mRNA was not significantly inhibited by CsA. Interleukin-4 inhibited the expression of FucT-VII but IL-2 and IL-7 were found to support induction of FucT-VII and E-lig. E-selectin, P-selectin and their ligands initially appeared to have rather overlapping functions. These findings however, unravel striking differences in the regulation of E-lig and P-lig expression, dictated by the dominance of FucT-VII and C2GlcNAcT-I, respectively, and their dependency on signals from either promiscuous or homeostatic cytokines (FucT-VII) or a strong T-cell receptor signal in combination with inflammatory cytokines in case of C2GlcNAcT-I. PMID:23039181

Anisotropic dependence of the magnetic transition on uniaxial pressure in the Kondo semiconductors Ce T2A l10 (T =Ru and Os)

NASA Astrophysics Data System (ADS)

Hayashi, K.; Umeo, K.; Takeuchi, T.; Kawabata, J.; Muro, Y.; Takabatake, T.

2017-12-01

We have measured the strain, magnetization, and specific heat of the antiferromagnetic (AFM) Kondo semiconductors Ce T2A l10 (T =Ru and Os) under uniaxial pressures applied along the orthorhombic axes. We found a linear dependence of TN on the b -axis parameter for both compounds under uniaxial pressure P ∥b and hydrostatic pressure. This relation indicates that the distance between the Ce-T layers along the b axis is the key structural parameter determining TN. Furthermore, the pressure dependence of the spin-flop transition field indicates that Ce-Ce interchain interactions stabilize the AFM state with the ordered moments pointing to the c axis.

Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

PubMed Central

Daghighi, Mojtaba; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M.; Mahmoudi, Morteza; De Rooij, Felix W. M.; Sijbrands, Eric; Peppelenbosch, Maikel P.; Rezaee, Farhad

2015-01-01

Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs. PMID:26337083

The magnetic resonance imaging spectrum of Pelizaeus-Merzbacher disease: A multicenter study of 19 patients.

PubMed

Sumida, Kaoru; Inoue, Ken; Takanashi, Jun-Ichi; Sasaki, Masayuki; Watanabe, Kenji; Suzuki, Motomasa; Kurahashi, Hirokazu; Omata, Taku; Tanaka, Manabu; Yokochi, Kenji; Iio, Jun; Iyoda, Kuniaki; Kurokawa, Toru; Matsuo, Muneaki; Sato, Tamotu; Iwaki, Akiko; Osaka, Hitoshi; Kurosawa, Kenji; Yamamoto, Toshiyuki; Matsumoto, Naomichi; Maikusa, Norihide; Matsuda, Hiroshi; Sato, Noriko

2016-06-01

We retrospectively evaluated the imaging spectrum of Pelizaeus-Merzbacher disease (PMD) in correlation with the clinical course and genetic abnormality. We collected the magnetic resonance imaging (MRI) findings of 19 genetically proven PMD patients (all males, aged 0-29years old) using our integrated web-based MRI data collection system from 14 hospitals. The patterns of hypomyelination were determined mainly by the signals of the cerebrum, corticospinal tract, and brainstem on T2-weighted images (T2WI). We assessed the degree of myelination age on T1-weighted images (T1WI) and T2WI independently, and we evaluated cerebellar and callosal atrophy. The clinical severity and genetic abnormalities (causal mutations of the proteolipid protein gene PLP1) were analyzed together with the imaging findings. The clinical stage tended to be more severe when the whole brainstem, or corticospinal tract in the internal capsule showed abnormally high intensity on T2WI. Diffuse T2-high signal of brainstem was observed only in the patients with PLP1 point mutation. Myelination age "before birth" on T1WI is a second manifestation correlated with the clinically severe phenotypes. On the other hand, eight patients whose myelination ages were > 4months on T1WI were associated with mild clinical phenotypes. Four of them showed almost complete myelination on T1WI with a discrepancy in myelination age between T1WI and T2WI. A random and patchy pattern of myelination on T2WI was noted in one patient with PLP1 point mutation. Advanced myelination was observed in three of the seven followed-up patients. Four patients had atrophy of the cerebellum, and 17 patients had atrophy of the corpus callosum. Our multicenter study has demonstrated a wide variety of imaging findings of PMD. Signal intensity of brainstem and corticospinal tract of internal capsule would be the points to presume clinical severity in PMD patients. The spectrum of MRI findings should be kept in mind to diagnose PMD and to differentiate from other demyelinating leukodystrophies. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

A physiologically based pharmacokinetic model to predict disposition of CYP2D6 and CYP1A2 metabolized drugs in pregnant women.

PubMed

Ke, Alice Ban; Nallani, Srikanth C; Zhao, Ping; Rostami-Hodjegan, Amin; Isoherranen, Nina; Unadkat, Jashvant D

2013-04-01

Conducting pharmacokinetic (PK) studies in pregnant women is challenging. Therefore, we asked if a physiologically based pharmacokinetic (PBPK) model could be used to evaluate different dosing regimens for pregnant women. We refined and verified our previously published pregnancy PBPK model by incorporating cytochrome P450 CYP1A2 suppression (based on caffeine PK) and CYP2D6 induction (based on metoprolol PK) into the model. This model accounts for gestational age-dependent changes in maternal physiology and hepatic CYP3A activity. For verification, the disposition of CYP1A2-metabolized drug theophylline (THEO) and CYP2D6-metabolized drugs paroxetine (PAR), dextromethorphan (DEX), and clonidine (CLO) during pregnancy was predicted. Our PBPK model successfully predicted THEO disposition during the third trimester (T3). Predicted mean postpartum to third trimester (PP:T3) ratios of THEO area under the curve (AUC), maximum plasma concentration, and minimum plasma concentration were 0.76, 0.95, and 0.66 versus observed values 0.75, 0.89, and 0.72, respectively. The predicted mean PAR steady-state plasma concentration (Css) ratio (PP:T3) was 7.1 versus the observed value 3.7. Predicted mean DEX urinary ratio (UR) (PP:T3) was 2.9 versus the observed value 1.9. Predicted mean CLO AUC ratio (PP:T3) was 2.2 versus the observed value 1.7. Sensitivity analysis suggested that a 100% induction of CYP2D6 during T3 was required to recover the observed PP:T3 ratios of PAR Css, DEX UR, and CLO AUC. Based on these data, it is prudent to conclude that the magnitude of hepatic CYP2D6 induction during T3 ranges from 100 to 200%. Our PBPK model can predict the disposition of CYP1A2, 2D6, and 3A drugs during pregnancy.

Testosterone in advance age: a New Zealand longitudinal cohort study: Life and Living in Advanced Age (Te Puāwaitanga o Ngā Tapuwae Kia Ora Tonu).

PubMed

Connolly, Martin J; Kerse, Ngaire; Wilkinson, Tim; Menzies, Oliver; Rolleston, Anna; Chong, Yih Harng; Broad, Joanna B; Moyes, Simon A; Jatrana, Santosh; Teh, Ruth

2017-11-12

Serum testosterone (T) levels in men decline with age. Low T levels are associated with sarcopenia and frailty in men aged > 80 years. T levels have not previously been directly associated with disability in older men. We explored associations between T levels, frailty and disability in a cohort of octogenarian men. Data from all men from Life and Living in Advanced Age Cohort Study in New Zealand, a longitudinal cohort study in community-dwelling older adults. Community-dwelling ( > 80 years) adult men excluding those receiving T treatment or with prostatic carcinoma. Associations between baseline total testosterone (TT) and calculated free testosterone (fT), frailty (Fried scale) and disability (Nottingham Extended Activities of Daily Living scale (NEADL)) (baseline and 24 months) were examined using multivariate regression and Wald's χ 2 techniques. Subjects with the lowest quartile of baseline TT and fT values were compared with those in the upper three quartiles. Participants: 243 men, mean (SD) age 83.7 (2.0) years. Mean (SD) TT=17.6 (6.8) nmol/L and fT=225.3 (85.4) pmol/L. On multivariate analyses, lower TT levels were associated with frailty: β=0.41, p=0.017, coefficient of determination (R 2 )=0.10 and disability (NEADL) (β=-1.27, p=0.017, R 2 =0.11), low haemoglobin (β=-7.38, p=0.0016, R 2 =0.05), high fasting glucose (β=0.38, p=0.038, R 2 =0.04) and high C reactive protein (CRP) (β=3.57, p=0.01, R 2 =0.06). Low fT levels were associated with frailty (β=0.39, p=0.024, R 2 =0.09) but not baseline NEADL (β=-1.29, p=0.09, R 2 =0.09). Low fT was associated with low haemoglobin (β=-7.83, p=0.0008, R 2 =0.05) and high CRP (β=2.86, p=0.04, R 2 =0.05). Relationships between baseline TT and fT, and 24-month outcomes of disability and frailty were not significant. In men over 80 years, we confirm an association between T levels and baseline frailty scores. The new finding of association between T levels and disability is potentially relevant to debates on T supplementation in older men, though, as associations were not present at 24 months, further work is needed. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Ex vivo T2 relaxation: Associations with age-related neuropathology and cognition

PubMed Central

Dawe, Robert J.; Bennett, David A.; Schneider, Julie A.; Leurgans, Sue E.; Kotrotsou, Aikaterini; Boyle, Patricia A.; Arfanakis, Konstantinos

2014-01-01

The transverse relaxation time constant, T2, is sensitive to brain tissue’s free water content and the presence of paramagnetic materials such as iron. In this study, ex vivo MRI was employed to investigate alterations in T2 related to Alzheimer’s disease (AD) pathology and other types of neuropathology common in old age, as well as the relationship between T2 alterations and cognition. Cerebral hemispheres were obtained from 371 deceased older adults. Using fast spin-echo imaging with multiple echo times, T2 maps were produced and warped to a study-specific template. Hemispheres underwent neuropathologic examination for identification of AD pathology and other common age-related neuropathologies. Voxelwise linear regression was carried out to detect regions of pathology-related T2 alterations and, in separate analyses, regions in which T2 alterations were linked to antemortem cognitive performance. AD pathology was associated with T2 prolongation in white matter of all lobes and T2 shortening in the basal ganglia and insula. Gross infarcts were associated with T2 prolongation in white matter of all lobes, and in the thalamus and basal ganglia. Hippocampal sclerosis was associated with T2 prolongation in the hippocampus and white matter of the temporal lobe. After controlling for neuropathology, T2 prolongation in the frontal lobe white matter was associated with lower performance in the episodic, semantic, and working memory domains. In addition, voxelwise analysis of in vivo and ex vivo T2 values indicated a positive relationship between the two, though further investigation is necessary to accurately translate findings of the current study to the in vivo case. PMID:24582637

Elevated Risk of Type 2 Diabetes for Development of Alzheimer Disease: a Key Role for Oxidative Stress in Brain

PubMed Central

Butterfield, D. Allan; Di Domenico, Fabio; Barone, Eugenio

2014-01-01

Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Epidemiological data show that the incidence of AD increases with age and doubles every 5 years after 65 years of age. From a neuropathological point of view, amyloid-β-peptide (Aβ) leads to senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles and synapse loss, are the principal pathological hallmarks of AD. Aβ is associated with the formation of reactive oxygen (ROS) and nitrogen (RNS) species, and induces calcium-dependent excitotoxicity, impairment of cellular respiration, and alteration of synaptic functions associated with learning and memory. Oxidative stress was found to be associated with type 2 diabetes mellitus (T2DM), which (i) represents another prevalent disease associated with obesity and often aging, and (ii) is considered to be a risk factor for AD development. T2DM is characterized by high blood glucose levels resulting from increased hepatic glucose production, impaired insulin production and peripheral insulin resistance, which close resemble to the brain insulin resistance observed in AD patients. Furthermore, growing evidence suggest that oxidative stress play a pivotal role in the development of insulin resistance and vice versa. This review article provides molecular aspects and the pharmacological approaches from both preclinical and clinical data and interpreted from the point of view of oxidative stress with the aim to highlight progresses in this field. PMID:24949886

Application of an artificial neural network model for diagnosing type 2 diabetes mellitus and determining the relative importance of risk factors.

PubMed

Borzouei, Shiva; Soltanian, Ali Reza

2018-01-01

To identify the most important demographic risk factors for a diagnosis of type 2 diabetes mellitus (T2DM) using a neural network model. This study was conducted on a sample of 234 individuals, in whom T2DM was diagnosed using hemoglobin A1c levels. A multilayer perceptron artificial neural network was used to identify demographic risk factors for T2DM and their importance. The DeLong method was used to compare the models by fitting in sequential steps. Variables found to be significant at a level of p<0.2 in a univariate logistic regression analysis (age, hypertension, waist circumference, body mass index [BMI], sedentary lifestyle, smoking, vegetable consumption, family history of T2DM, stress, walking, fruit consumption, and sex) were entered into the model. After 7 stages of neural network modeling, only waist circumference (100.0%), age (78.5%), BMI (78.2%), hypertension (69.4%), stress (54.2%), smoking (49.3%), and a family history of T2DM (37.2%) were identified as predictors of the diagnosis of T2DM. In this study, waist circumference and age were the most important predictors of T2DM. Due to the sensitivity, specificity, and accuracy of the final model, it is suggested that these variables should be used for T2DM risk assessment in screening tests.

Thermoregulatory effects of caffeine ingestion during rest and exercise in men

NASA Technical Reports Server (NTRS)

Dunagan, Nancy; Greenleaf, John E.; Cisar, Craig J.

1994-01-01

Body temperatures and thermoregulatory responses were measured at rest and during submaximal exercise under normal ambient conditions in 11 aerobically-conditioned men (age = 29.2 +/- 6.2 yr, VO2(max) = 3.73 +/- 0.46 min(sup -1), relative body fat = 12.3 +/- 3.7 percent, mean +/- SD) with (CT) and without (NCT) the ingestion of 10 mg of caffeine per kg of body weight. Oxygen uptake (VO2), heart rate (HR), and rectal (T(sub re)) and mean skin (T-bar(sub sk)) temperatures were recorded for 100 minutes starting one minute after ingestion of caffeine or a placebo. Data were collected throughout 30 minutes of rest (sitting) and the following 70 minutes of sitting leg ergometer exercise using the same constant load (1,088 +/- 153 kgm/min) in both NCT and CT. The load resulted in a mean relative exercise intensity equal to approximately 68 percent of VO2(sub max). Skin heat conductance (H(sub sk)) and sweat rate were calculated. Two-way analysis of covariance revealed no significant (P greater than 0.05) differences between NCT and CT in VO2, HR, T(sub re), T-bar(sub sk), or H(sub sk). A dependent t-test indicated no significant difference between NCT and CT in sweat rate. Thus, a high level of caffeine ingestion has no detrimental effects on body temperatures and thermoregulatory responses during moderately heavy exercise in normal ambient conditions.

Performance of IUCN proxies for generation length.

PubMed

Fung, Han Chi; Waples, Robin S

2017-08-01

One of the criteria used by the International Union for Conservation of Nature (IUCN) to assess threat status is the rate of decline in abundance over 3 generations or 10 years, whichever is longer. The traditional method for calculating generation length (T) uses age-specific survival and fecundity, but these data are rarely available. Consequently, proxies that require less information are often used, which introduces potential biases. The IUCN recommends 2 proxies based on adult mortality rate, T̂d = α + 1/d, and reproductive life span, T̂z = α + z * RL, where α is age at first reproduction, d is adult mortality rate, RL is reproductive life span, and z is a coefficient derived from data for comparable species. We used published life tables for 78 animal and plant populations to evaluate precision and bias of these proxies by comparing T̂d and T̂z with true generation length. Mean error rates in estimating T were 31% for T̂d and 20% for T̂z, but error rates for T̂d were 16% when we subtracted 1 year ( T̂d( adj )=T̂d-1 ), as suggested by theory; T̂d( adj ) also provided largely unbiased estimates regardless of the true generation length. Performance of T̂z depends on compilation of detailed data for comparable species, but our results suggest taxonomy is not a reliable indicator of comparability. All 3 proxies depend heavily on a reliable estimate of age at first reproduction, as we illustrated with 2 test species. The relatively large mean errors for all proxies emphasized the importance of collecting the detailed life-history information necessary to calculate true generation length. Unfortunately, publication of such data is less common than it was decades ago. We identified generic patterns of age-specific change in vital rates that can be used to predict expected patterns of bias from applying T̂d( adj ). Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Manganese scavenging and oxidative stress response mediated by type VI secretion system in Burkholderia thailandensis

PubMed Central

Si, Meiru; Zhao, Chao; Burkinshaw, Brianne; Zhang, Bing; Wei, Dawei; Wang, Yao; Dong, Tao G.; Shen, Xihui

2017-01-01

Type VI secretion system (T6SS) is a versatile protein export machinery widely distributed in Gram-negative bacteria. Known to translocate protein substrates to eukaryotic and prokaryotic target cells to cause cellular damage, the T6SS has been primarily recognized as a contact-dependent bacterial weapon for microbe–host and microbial interspecies competition. Here we report contact-independent functions of the T6SS for metal acquisition, bacteria competition, and resistance to oxidative stress. We demonstrate that the T6SS-4 in Burkholderia thailandensis is critical for survival under oxidative stress and is regulated by OxyR, a conserved oxidative stress regulator. The T6SS-4 is important for intracellular accumulation of manganese (Mn2+) under oxidative stress. Next, we identified a T6SS-4–dependent Mn2+-binding effector TseM, and its interacting partner MnoT, a Mn2+-specific TonB-dependent outer membrane transporter. Similar to the T6SS-4 genes, expression of mnoT is regulated by OxyR and is induced under oxidative stress and low Mn2+ conditions. Both TseM and MnoT are required for efficient uptake of Mn2+ across the outer membrane under Mn2+-limited and -oxidative stress conditions. The TseM–MnoT-mediated active Mn2+ transport system is also involved in contact-independent bacteria–bacteria competition and bacterial virulence. This finding provides a perspective for understanding the mechanisms of metal ion uptake and the roles of T6SS in bacteria–bacteria competition. PMID:28242693

Manganese scavenging and oxidative stress response mediated by type VI secretion system in Burkholderia thailandensis.

PubMed

Si, Meiru; Zhao, Chao; Burkinshaw, Brianne; Zhang, Bing; Wei, Dawei; Wang, Yao; Dong, Tao G; Shen, Xihui

2017-03-14

Type VI secretion system (T6SS) is a versatile protein export machinery widely distributed in Gram-negative bacteria. Known to translocate protein substrates to eukaryotic and prokaryotic target cells to cause cellular damage, the T6SS has been primarily recognized as a contact-dependent bacterial weapon for microbe-host and microbial interspecies competition. Here we report contact-independent functions of the T6SS for metal acquisition, bacteria competition, and resistance to oxidative stress. We demonstrate that the T6SS-4 in Burkholderia thailandensis is critical for survival under oxidative stress and is regulated by OxyR, a conserved oxidative stress regulator. The T6SS-4 is important for intracellular accumulation of manganese (Mn 2+ ) under oxidative stress. Next, we identified a T6SS-4-dependent Mn 2+ -binding effector TseM, and its interacting partner MnoT, a Mn 2+ -specific TonB-dependent outer membrane transporter. Similar to the T6SS-4 genes, expression of mnoT is regulated by OxyR and is induced under oxidative stress and low Mn 2+ conditions. Both TseM and MnoT are required for efficient uptake of Mn 2+ across the outer membrane under Mn 2+ -limited and -oxidative stress conditions. The TseM-MnoT-mediated active Mn 2+ transport system is also involved in contact-independent bacteria-bacteria competition and bacterial virulence. This finding provides a perspective for understanding the mechanisms of metal ion uptake and the roles of T6SS in bacteria-bacteria competition.

Searching for the Kinkeepers: Historian Gender, Age, and Type 2 Diabetes Family History.

PubMed

Giordimaina, Alicia M; Sheldon, Jane P; Kiedrowski, Lesli A; Jayaratne, Toby Epstein

2015-12-01

Kinkeepers facilitate family communication and may be key to family medical history collection and dissemination. Middle-aged women are frequently kinkeepers. Using type 2 diabetes (T2DM) as a model, we explored whether the predicted gender and age effects of kinkeeping can be extended to family medical historians. Through a U.S. telephone survey, nondiabetic Mexican Americans (n = 385), Blacks (n = 387), and Whites (n = 396) reported family histories of T2DM. Negative binomial regressions used age and gender to predict the number of affected relatives reported. Models were examined for the gender gap, parabolic age effect, and gender-by-age interaction predicted by kinkeeping. Results demonstrated support for gender and parabolic age effects but only among Whites. Kinkeeping may have application to the study of White family medical historians, but not Black or Mexican American historians, perhaps because of differences in family structure, salience of T2DM, and/or gender roles. © 2015 Society for Public Health Education.

Newborn HLA-DR,DQ genotype screening: age- and ethnicity-specific type 1 diabetes risk estimates

PubMed Central

Emery, Lisa M; Babu, Sunanda; Bugawan, Teodorica L; Norris, Jill M; Erlich, Henry A; Eisenbarth, George S; Rewers, Marian

2005-01-01

Objective Certain human leukocyte antigen (HLA)-DR,DQ genotypes have been associated with type 1 diabetes mellitus (T1DM) risk, although it is unknown whether the association is due to alleles, haplotypes, genotypes, the formation of heterodimers, or all of the above. To characterize the role of the HLA-DR,DQ genotype and ethnicity on the onset age of T1DM, we analyzed these factors in patients with T1DM and the general population. Methods One thousand three hundred twenty-two well-characterized patients with T1DM were compared with 3339 children from the general population of Denver, Colorado, USA. Because of the extensive available data across age and ethnic groups, this study population is unique. Results The HLA-DR3/4,DQB1*0302, DRX/4,DQB1*0302 (where X = 1, 4, 8, and 9), and HLA-DR3/3 genotypes were associated with T1DM, supporting previous research. Additionally, the DR3/9 genotype showed a positive association with T1DM, which has not previously been described in Caucasian populations. The HLA-DR3/4*0302 genotype was most strongly associated with T1DM in diabetic individuals with the youngest onset age. Genotype frequencies were similar between Hispanics and non-Hispanic whites, except for the DR3/3 genotype, which was more likely to be found in non-Hispanic whites. Conclusions These results indicate that there are multiple alleles and genotypes associated with T1DM and that the risk associated with different genetic markers depends on the age of disease onset, suggesting that some markers may be involved in more rapid disease progression. PMID:16109069

Age-Specific Prostate Specific Antigen Cutoffs for Guiding Biopsy Decision in Chinese Population

PubMed Central

Xu, Jianfeng; Jiang, Haowen; Ding, Qiang

2013-01-01

Background Age-specific prostate specific antigen (PSA) cutoffs for prostate biopsy have been widely used in the USA and European countries. However, the application of age-specific PSA remains poorly understood in China. Methods Between 2003 and 2012, 1,848 men over the age of 40, underwent prostate biopsy for prostate cancer (PCa) at Huashan Hospital, Shanghai, China. Clinical information and blood samples were collected prior to biopsy for each patient. Men were divided into three age groups (≤60, 61 to 80, and >80) for analyses. Digital rectal examination (DRE), transrectal ultrasound (prostate volume and nodule), total PSA (tPSA), and free PSA (fPSA) were also included in the analyses. Logistic regression was used to build the multi-variate model. Results Serum tPSA levels were age-dependent (P = 0.008), while %fPSA (P = 0.051) and PSAD (P = 0.284) were age-independent. At a specificity of 80%, the sensitivities for predicting PCa were 83%, 71% and 68% with tPSA cutoff values of 19.0 ng/mL (age≤60),21.0 ng/mL (age 61–80), and 23.0 ng/mL (age≥81). Also, sensitivities at the same tPSA levels were able to reach relatively high levels (70%–88%) for predicting high-grade PCa. Area (AUC) under the receive operating curves (ROCs) of tPSA, %fPSA, PSAD and multi-variate model were different in age groups. When predicting PCa, the AUC of tPSA, %fPSA, PSAD and multi-variate model were 0.90, 0.57, 0.93 and 0.87 respectively in men ≤60 yr; 0.82, 0.70, 0.88 and 0.86 respectively in men 61–80 yr; 0.79, 0.78, 0.87 and 0.88 respectively in men>80 yr. When predicting Gleason Score ≥7 or 8 PCa, there were no significant differences between AUCs of each variable. Conclusion Age-specific PSA cutoff values for prostate biopsy should be considered in the Chinese population. Indications for prostate biopsies (tPSA, %fPSA and PSAD) should be considered based on age in the Chinese population. PMID:23825670

On a Theory of Rates

DTIC Science & Technology

2005-04-01

be the likelihood of contracting the disease and the jump function one. 51 F. Predator and Prey The Lotka - Volterra equations,[Ball 1985] dx dt = Ax...dt = n0 2t0repro y2 1 t0old age y: Notice that neither set of these rate di¤erential equations look like the Lotka - Volterra equa- tions. We might...218) dy dt = n0 2t0repro y2 1 t0old age y h 1 kpeatx i ktencounter y; 53 which gets us closer to the form of the Lotka - Volterra equations

Vitreous advanced glycation endproducts and α-dicarbonyls in retinal detachment patients with type 2 diabetes mellitus and non-diabetic controls

PubMed Central

Mulder, Douwe J.; Schalkwijk, Casper G.; Scheijen, Jean L.; Smit, Andries J.; Los, Leonoor I.

2017-01-01

Purpose Advanced glycation endproducts (AGEs) and their precursors α-dicarbonyls are implicated in the progression of diabetic retinopathy. The purpose of this study was to assess AGEs and α-dicarbonyls in the vitreous of patients with type 2 diabetes mellitus (T2DM) with early stages or absence of diabetic retinopathy. Methods We examined vitreous samples obtained during vitrectomy from 31 T2DM patients presenting themselves with rhegmatogenous retinal detachment and compared these to 62 non-diabetic rhegmatogenous retinal detachment patients, matched on age, estimated glomerular filtration rate, smoking, intra-ocular lens implantation, and proliferative vitreoretinopathy. AGEs (pentosidine, Nε-(carboxymethyl)lysine, Nε-(carboxyethyl)lysine, and 5-hydro-5-methylimidazolone) and α-dicarbonyls (3-deoxyglucosone, methylglyoxal, and glyoxal) were measured by ultra performance liquid chromatography or high performance liquid chromatography. Skin autofluorescence was measured by the AGE Reader. Results Mean age was 64 ± 7.6 years for T2DM patients and 63 ± 8.1 years for controls. For T2DM patients, median diabetes duration was 2.2 (0.3–7.4) years. Non-proliferative diabetic retinopathy was present in 1 patient and classified as absent or background retinopathy in 30 patients. Vitreous levels of pentosidine (2.20 vs. 1.59 μmol/mol lysine, p = 0.012) and 3-deoxyglucosone (809 vs. 615 nmol/L, p = 0.001) were significantly elevated in T2DM patients compared to controls. Other AGEs and α-dicarbonyls in the vitreous were not significantly different. There was a trend for increased skin autofluorescence in T2DM patients as compared to controls (p = 0.07). Conclusions Pentosidine and 3-deoxyglucosone concentrations were increased in the vitreous of rhegmatogenous retinal detachment patients with a relatively short duration of diabetes compared to non-diabetic rhegmatogenous retinal detachment patients. PMID:28264049

Adolescent oligomenorrhea (age 14-19) tracks into the third decade of life (age 20-28) and predicts increased cardiovascular risk factors and metabolic syndrome.

PubMed

Glueck, Charles J; Woo, Jessica G; Khoury, Philip R; Morrison, John A; Daniels, Stephen R; Wang, Ping

2015-04-01

Assess whether adolescent oligomenorrhea (age 14-19) tracks into young adulthood (age 20-28) and predicts increased cardiometabolic risk factors, metabolic syndrome (MetS), and impaired fasting glucose-type II diabetes mellitus (IFG+T2DM). Prospective study of menstrual cyclicity and its metabolic effects in 865 black and white schoolgirls from age 9 to 19, and 605 of these 865 girls from age 20 to 28. Patterns of menstrual delays (oligomenorrhea) during ages 14-19 and ages 20-28 were closely related (p<.0001). Adolescent menses delay (ages 14-19, p<.0001), mean insulin (ages 20-28, p=.0003), and self-identified polycystic ovary syndrome (PCOS, p=.049) predicted ages 20-28 menses delay. Menses delays during ages 14-19 and 20-28, and, their interaction product were correlated with IFG+T2DM and MetS at ages 20-28. Waist circumference (ages 20-28, p<.0001), mean triglyceride (ages 20-28, p=.005), and the number of average menstrual cycles≥42 days (ages 20-28, p=.04) predicted IFG+T2DM (ages 20-28). MetS (ages 9-19, p<.0001), mean insulin (ages 20-28, p=.0002), the number of ≥42 day gaps between menstrual periods (ages 20-28, p=.02), and cigarette smoking at age 18-19 (p=.04) were significant explanatory variables for MetS at ages 27-28. As MetS status category changed from age 14-19 to 27-28 from best to worst: (no → no), (yes → no), (yes → yes), (no → yes), the number of women with ≥2 menses delays during ages 20-28 rose from 3% to 4% to 15% to 17%, p=.0001. MetS status change from age 9-19 to 27-28 was positively associated with mean insulin (age 20-28, p<.0001), cigarette smoking (age 24-25, p=.01) and the number of menses delays during ages 20-28 (p=.04). Menstrual patterns track from adolescence to young adulthood, and oligomenorrhea predicts MetS and IFG+T2DM. Patterns of menses delays in adolescence should be considered as a significant risk factor for future development of young adult IFG+T2DM, MetS, oligomenorrhea, and polycystic ovary syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

Analysis of Advanced Glycation End Products in the DHS Mind Study

PubMed Central

Adams, Jeremy N.; Martelle, Susan E.; Raffield, Laura M.; Freedman, Barry I.; Langefeld, Carl D.; Hsu, Fang-Chi; Maldjian, Joseph A.; Williamson, Jeff D.; Hugenschmidt, Christina E.; Carr, J. Jeffery; Cox, Amanda J.; Bowden, Donald W.

2016-01-01

Aims Human studies of links between advanced glycation end-products (AGEs) and disease phenotypes are less common than studies of animal and cell models. Here, we examined the association of total AGEs with diabetes risk factors in a predominately type 2 diabetes (T2D) affected cohort. Methods AGEs were measured using an enzyme linked immunosorbant assay in 816 individuals from the DHS Mind Study (n=709 T2D affected), and association analyses were completed. Results Total AGEs were associated with estimated glomerular filtration rate (p= 0.0054; β= −0.1291) and coronary artery calcification (p= 0.0352; β= 1.1489) in the entire cohort. No significant associations were observed when individuals with T2D were analyzed separately. In individuals without T2D, increased circulating AGEs were associated with increased BMI (p= 0.02, β = 0.138), low density lipoproteins (p=0.046, β = 17.07) and triglycerides (p= 0.0004, β = 0.125), and decreased carotid artery calcification (p= 0.0004, β = −1.2632) and estimated glomerular filtration rate (p= 0.0018, β = −0.1405). Strong trends were also observed for an association between AGEs and poorer cognitive performance on the digit symbol substitution test (p=0.046, β = −6.64) and decreased grey matter volume (p=0.037, β = −14.87). Conclusions AGEs may play an important role in a number of phenotypes and diseases, although not necessarily in interindividual variation in people with T2D. Further evaluation of specific AGE molecules may shed more light on these relationships. PMID:26739237

Prenatal exposure to the organophosphate insecticide chlorpyrifos enhances brain oxidative stress and prostaglandin E2 synthesis in a mouse model of idiopathic autism.

PubMed

De Felice, Alessia; Greco, Anita; Calamandrei, Gemma; Minghetti, Luisa

2016-06-14

Autism spectrum disorders (ASD) are emerging as polygenic and multifactorial disorders in which complex interactions between defective genes and early exposure to environmental stressors impact on the correct neurodevelopment and brain processes. Organophosphate insecticides, among which chlorpyrifos (CPF), are widely diffused environmental toxicants associated with neurobehavioral deficits and increased risk of ASD occurrence in children. Oxidative stress and dysregulated immune responses are implicated in both organophosphate neurodevelopmental effects and ASD etiopathogenesis. BTBR T+tf/J mice, a well-studied model of idiopathic autism, show several behavioral and immunological alterations found in ASD children, and we recently showed that CPF gestational exposure strengthened some of these autistic-like traits. In the present study, we aimed at investigating whether the behavioral effects of gestational CPF administration are associated with brain increased oxidative stress and altered lipid mediator profile. Brain levels of F2-isoprostanes (15-F2t-IsoP), as index of in vivo oxidative stress, and prostaglandin E2 (PGE2), a major arachidonic acid metabolite released by immune cells and by specific glutamatergic neuron populations mainly in cortex and hippocampus, were assessed by specific enzyme-immuno assays in brain homogenates from BTBR T+tf/J and C57Bl6/J mice, exposed during gestation to either vehicle or CPF. Measures were performed in mice of both sexes, at different postnatal stages (PNDs 1, 21, and 70). At birth, BTBR T+tf/J mice exhibited higher baseline 15-F2t-IsoP levels as compared to C57Bl6/J mice, suggestive of greater oxidative stress processes. Gestational treatment with CPF-enhanced 15-F2t-IsoP and PGE2 levels in strain- and age-dependent manner, with 15-F2t-IsoP increased in BTBR T+tf/J mice at PNDs 1 and 21, and PGE2 elevated in BTBR T+tf/J mice at PNDs 21 and 70. At PND 21, CPF effects were sex-dependent being the increase of the two metabolites mainly associated with male mice. CPF treatment also induced a reduction of somatic growth, which reached statistical significance at PND 21. These findings indicate that the autistic-like BTBR T+tf/J strain is highly vulnerable to environmental stressors during gestational period. The results further support the hypothesis that oxidative stress might be the link between environmental neurotoxicants such as CPF and ASD. The increased levels of oxidative stress during early postnatal life could result in delayed and long-lasting alterations in specific pathways relevant to ASD, of which PGE2 signaling represents an important one.

Orbitally dependent kinetic exchange in a heterobimetallic pair: Ferromagnetic spin alignment and magnetic anisotropy in the cyano-bridged Cr(III)Fe(II) dimer

NASA Astrophysics Data System (ADS)

Palii, A. V.; Tsukerblat, B. S.; Verdaguer, M.

2002-11-01

The problem of the kinetic exchange interaction in the cyanide-bridged heterobinuclear dimers involving orbitally degenerate transition metal ions is considered. The developed approach is based on the concept of the effective Hamiltonian of the orbitally dependent kinetic exchange. We deduce this many-electron Hamiltonian on the microscopic background so that all relevant biorbital transfer processes are taken into account as well as the properties of the many-electron states. The bioctahedral cyanide-bridged Cr(III)Fe(II) dimer is considered in detail as an example distinctly exhibiting new quantitative and qualitative features of the orbitally dependent exchange and as a structural unit of three-dimensional ferromagnetic crystals {Fe(II)3)Cr(III)(CN62}[middle dot]13H2O. The proposed mechanism of the kinetic exchange involves the electron transfer from the double occupied t2 orbitals of Fe(II) [ground state 5T2(t2)4e2] to the half occupied t2 orbitals of Cr(III) [ground state 4A2(t2)3] resulting in the charge transfer state 3T1(t2)4Cr(II)- 6A1(t2)3e2 Fe(III) and the transfer between the half-occupied t2 orbitals of the metal ions resulting in the charge transfer state 3T1(t2)4Cr(II)- 4T2(t2)3e2 Fe(III). The effective Hamiltonian of the orbitally dependent exchange for the Cr(III)Fe(II) pair deduced within this theoretical framework describes competitive ferro- and antiferromagnetic contributions arising from these two charge transfer states. This Hamiltonian leads to a complex energy pattern, consisting of two interpenetrating Heisenberg-like schemes, one exhibiting ferromagnetic and another one antiferromagnetic splitting. The condition for the ferromagnetic spin alignment in the ground state is deduced. The orbitally dependent terms of the Hamiltonian are shown to give rise to a strong magnetic anisotropy of the system, this result as well as the condition for the spin alignment in the ground term are shown to be out of the scope of the Goodenough-Kanamori rules. Along with the full spin S the energy levels are labeled by the orbital quantum numbers providing thus the direct information about the magnetic anisotropy of the system. Under a reasonable estimation of the excitation energies based on the optical absorption data we conclude that the kinetic exchange in the cyanide-bridged Cr(III)Fe(II) pair leads to the ferromagnetic spin alignment exhibiting at the same time strong axial magnetic anisotropy with C4 easy axis of magnetization.

Weight changes in children in foster care for 1 year.

PubMed

Schneiderman, Janet U; Smith, Caitlin; Arnold-Clark, Janet S; Fuentes, Jorge; Duan, Lei

2013-10-01

The aims of this study of predominately racial/ethnic minority children in foster care (N=360, birth to 19 years old) in Los Angeles, CA were to examine the (1) prevalence of obesity (≥ 95 percentile) and overweight/obese (≥ 85 percentile) upon entrance to foster care (T1) and after 1 year in foster care (T2); (2) comparison of high weight categories to national statistics; (3) relationship of changes in weight status to age, reason for entry into foster care, and placement. Chi-square test and McNemar test comparing paired proportions were used to determine whether there were significant changes in the proportion of high weight categories between T1 and T2. Chi-square test or Fisher's exact test were used to evaluate the association between age, placement, and reason for foster care with the change in weight category. Changes in weight were categorized as (1) decreased in weight, (2) remained at overweight or obese, (3) increased in weight, or (4) remained normal. The proportion of obese and obese/overweight children between ages 2 and 5 were significantly lower at T2 than T1. There were no significant changes in the prevalence of obesity for the total population at T2. Children age 6 or older had a higher prevalence of obesity and overweight/obesity compared to national statistics. Of children at all ages, 64.7% of children of all ages entered foster care with a normal weight and stayed in the normal range during their first year in foster care, 12.2% decreased their weight, 15.4% remained overweight or obese, and 7.7% increased their weight. Age and parental substance use was related to change in weight category from T1 to T2. Children did not become more overweight or obese in foster care; however 28% of the children were obese or overweight upon entry into foster care. Children who are 6 years or older and obese upon entering foster care should be targeted for weight reduction. The pediatric community and child welfare system need to work together by including weight percentiles in the foster care file and training/monitoring child welfare caregivers in weight reduction interventions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gq protein mediates UVB-induced cyclooxygenase-2 expression by stimulating HB-EGF secretion from HaCaT human keratinocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seo, MiRan; Juhnn, Yong-Sung, E-mail: juhnn@snu.ac.kr

Ultraviolet (UV) radiation induces cyclooxygenase-2 expression to produce cellular responses including aging and carcinogenesis in skin. We hypothesised that heterotrimeric G proteins mediate UV-induced COX-2 expression by stimulating secretion of soluble HB-EGF (sHB-EGF). In this study, we aimed to elucidate the role and underlying mechanism of the {alpha} subunit of Gq protein (G{alpha}q) in UVB-induced HB-EGF secretion and COX-2 induction. We found that expression of constitutively active G{alpha}q (G{alpha}qQL) augmented UVB-induced HB-EGF secretion, which was abolished by knockdown of G{alpha}q with shRNA in HaCaT human keratinocytes. G{alpha}q was found to mediate the UVB-induced HB-EGF secretion by sequential activation of phospholipasemore » C (PLC), protein kinase C{delta} (PKC{delta}), and matrix metaloprotease-2 (MMP-2). Moreover, G{alpha}qQL mediated UVB-induced COX-2 expression in an HB-EGF-, EGFR-, and p38-dependent manner. From these results, we concluded that G{alpha}q mediates UV-induced COX-2 expression through activation of EGFR by HB-EGF, of which ectodomain shedding was stimulated through sequential activation of PLC, PKC{delta} and MMP-2 in HaCaT cells.« less

Pressure Dependence of Coherence-Incoherence Crossover Behavior in KFe 2As 2 Observed by Resistivity and 75As-NMR/NQR.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiecki, P.; Taufour, V.; Chung, D. Y.

We present the results of 75As nuclear magnetic resonance (NMR), nuclear quadrupole resonance (NQR), and resistivity measurements in KFe 2As 2 under pressure (p). The temperature dependence of the NMR shift, nuclear spin-lattice relaxation time (T1), and resistivity show a crossover between a high-temperature incoherent, local-moment behavior and a low-temperature coherent behavior at a crossover temperature (T *). T * is found to increase monotonically with pressure, consistent with increasing hybridization between localized 3d orbitalderived bands with the itinerant electron bands. No anomaly in T * is seen at the critical pressure pc = 1.8 GPa where a change ofmore » slope of the superconducting (SC) transition temperature Tc(p) has been observed. In contrast, Tc(p) seems to correlate with antiferromagnetic spin fluctuations in the normal state as measured by the NQR 1/T1 data, although such a correlation cannot be seen in the replacement effects of A in the KFe 2As 2 (A = K, Rb, Cs) family. In the superconducting state, two T1 components are observed at low temperatures, suggesting the existence of two distinct local electronic environments. The temperature dependence of the short T1s indicates a nearly gapless state below Tc. On the other hand, the temperature dependence of the long component 1/T1L implies a large reduction in the density of states at the Fermi level due to the SC gap formation. These results suggest a real-space modulation of the local SC gap structure in KFe 2As 2 under pressure.« less

Adrenocorticotropin-dependent precocious puberty of testicular origin in a boy with X-linked adrenal hypoplasia congenita due to a novel mutation in the DAX1 gene.

PubMed

Domenice, S; Latronico, A C; Brito, V N; Arnhold, I J; Kok, F; Mendonca, B B

2001-09-01

Primary adrenal insufficiency is a rare condition in pediatric age, and its association with precocious sexual development is very uncommon. We report a 2-yr-old Brazilian boy with DAX1 gene mutation whose first clinical manifestation was isosexual gonadotropin-independent precocious puberty. He presented with pubic hair, enlarged penis and testes, and advanced bone age. T levels were elevated, whereas basal and GnRH-stimulated LH levels were compatible with a prepubertal pattern. Chronic GnRH agonist therapy did not reduce T levels, supporting the diagnosis of gonadotropin-independent precocious puberty. Testotoxicosis was ruled out after normal sequencing of exon 11 of the LH receptor gene. At age 3 yr he developed clinical and hormonal features of severe primary adrenal insufficiency. The entire coding region of the DAX1 gene was analyzed through direct sequencing. A nucleotide G insertion between nucleotides 430 and 431 in exon 1, resulting in a novel frameshift mutation and a premature stop codon at position 71 of DAX-1, was identified. Surprisingly, steroid replacement therapy induced a clear decrease in testicular size and T levels to the prepubertal range. These findings suggest that chronic excessive ACTH levels resulting from adrenal insufficiency may stimulate Leydig cells and lead to gonadotropin-independent precocious puberty in some boys with DAX1 gene mutations.

An inherited variable poly-T repeat genotype in TOMM40 in Alzheimer disease.

PubMed

Roses, Allen D

2010-05-01

I coauthored a recently published research article describing a variable length, poly-T polymorphism in the TOMM40 gene, adjacent to apolipoprotein E (APOE) on chromosome 19, that accounts for the age at onset distribution for a complex disease, late-onset Alzheimer disease. These new data explain the mean age at disease onset for patients with the APOE4/4 genotype and differentiate 2 forms of TOMM40 poly-T polymorphisms linked to APOE, with each form associated with a different age at disease onset distribution. When linked to APOE3 (encoding the epsilon3 isoform of APOE), the longer TOMM40 poly-T repeats (19-39 nucleotides) at the rs10524523 (hereafter, 523) locus are associated with earlier age at onset and the shorter TOMM40 523 alleles (11-16 nucleotides) are associated with later age at onset. The data suggest that the poly-T alleles are codominant, with the age at onset phenotype determined by the 2 inherited 523 alleles, but with variable expressivity. Additional data will further refine the relationship between the length of the poly-T alleles and age at disease onset and determine if the relationship is linear.

Electromagnetic field therapy delays cellular senescence and death by enhancement of the heat shock response.

PubMed

Perez, Felipe P; Zhou, Ximing; Morisaki, Jorge; Jurivich, Donald

2008-04-01

Hormesis may result when mild repetitive stress increases cellular defense against diverse injuries. This process may also extend in vitro cellular proliferative life span as well as delay and reverse some of the age-dependent changes in both replicative and non-replicative cells. This study evaluated the potential hormetic effect of non-thermal repetitive electromagnetic field shock (REMFS) and its impact on cellular aging and mortality in primary human T lymphocytes and fibroblast cell lines. Unlike previous reports employing electromagnetic radiation, this study used a long wave length, low energy, and non-thermal REMFS (50MHz/0.5W) for various therapeutic regimens. The primary outcomes examined were age-dependent morphological changes in cells over time, cellular death prevention, and stimulation of the heat shock response. REMFS achieved several biological effects that modified the aging process. REMFS extended the total number of population doublings of mouse fibroblasts and contributed to youthful morphology of cells near their replicative lifespan. REMFS also enhanced cellular defenses of human T cells as reflected in lower cell mortality when compared to non-treated T cells. To determine the mechanism of REMFS-induced effects, analysis of the cellular heat shock response revealed Hsp90 release from the heat shock transcription factor (HSF1). Furthermore, REMFS increased HSF1 phosphorylation, enhanced HSF1-DNA binding, and improved Hsp70 expression relative to non-REMFS-treated cells. These results show that non-thermal REMFS activates an anti-aging hormetic effect as well as reduces cell mortality during lethal stress. Because the REMFS configuration employed in this study can potentially be applied to whole body therapy, prospects for translating these data into clinical interventions for Alzheimer's disease and other degenerative conditions with aging are discussed.

Effects of Sevelamer Carbonate on Advanced Glycation End Products and Antioxidant/Pro-Oxidant Status in Patients with Diabetic Kidney Disease

PubMed Central

Yubero-Serrano, Elena M.; Woodward, Mark; Poretsky, Leonid; Vlassara, Helen

2015-01-01

Background and objectives The primary goals were to re-examine whether sevelamer carbonate (SC) reduces advanced glycation end products (AGEs) (methylglyoxal and carboxymethyllysine [CML]), increases antioxidant defenses, reduces pro-oxidants, and improves hemoglobin A1c (HbA1c) in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Secondary goals examined albuminuria, age, race, sex, and metformin prescription. Design, setting, participants, & measurements This two-center, randomized, intention-to-treat, open-label study evaluated 117 patients with T2DM (HbA1c >6.5%) and stages 2–4 DKD (urinary albumin/creatinine ratio ≥200 mg/g) treated with SC (1600 mg) or calcium carbonate (1200 mg), three times a day, without changing medications or diet. Statistical analyses used linear mixed models adjusted for randomization levels. Preselected subgroup analyses of sex, race, age, and metformin were conducted. Results SC lowered serum methylglyoxal (95% confidence interval [CI], −0.72 to −0.29; P<0.001), serum CML (95% CI, −5.08 to −1.35; P≤0.001), and intracellular CML (95% CI, −1.63 to −0.28; P=0.01). SC increased anti-inflammatory defenses, including nuclear factor like-2 (95% CI, 0.58 to 1.29; P=0.001), AGE receptor 1 (95% CI, 0.23 to 0.96; P=0.001), NAD-dependent deacetylase sirtuin-1 (95% CI, 0.20 to 0.86; P=0.002), and estrogen receptor α (95% CI, 1.38 to 2.73; P ≤0.001). SC also decreased proinflammatory factors such as TNF receptor 1 (95% CI, −1.56 to −0.72; P≤0.001) and the receptor for AGEs (95% CI, −0.58 to 1.53; P≤0.001). There were no differences in HbA1c, GFR, or albuminuria in the overall group. Subanalyses showed that SC lowered HbA1c in women (95% CI, −1.71 to −0.27; P=0.01, interaction P=0.002), and reduced albuminuria in those aged <65 years (95% CI, −1.15 to −0.07; P=0.03, interaction P=0.02) and non-Caucasians (95% CI, −1.11 to −0.22; P=0.003, interaction P≤0.001), whereas albuminuria increased after SC and calcium carbonate in Caucasians. Conclusions SC reduced circulating and cellular AGEs, increased antioxidants, and decreased pro-oxidants, but did not change HbA1c or the albumin/creatinine ratio overall in patients with T2DM and DKD. Because subanalyses revealed that SC may reduce HbA1c and albuminuria in some patients with T2DM with DKD, further studies may be warranted. PMID:25710801

Age Differences in Day-To-Day Speed-Accuracy Tradeoffs: Results from the COGITO Study.

PubMed

Ghisletta, Paolo; Joly-Burra, Emilie; Aichele, Stephen; Lindenberger, Ulman; Schmiedek, Florian

2018-04-23

We examined adult age differences in day-to-day adjustments in speed-accuracy tradeoffs (SAT) on a figural comparison task. Data came from the COGITO study, with over 100 younger and 100 older adults, assessed for over 100 days. Participants were given explicit feedback about their completion time and accuracy each day after task completion. We applied a multivariate vector auto-regressive model of order 1 to the daily mean reaction time (RT) and daily accuracy scores together, within each age group. We expected that participants adjusted their SAT if the two cross-regressive parameters from RT (or accuracy) on day t-1 of accuracy (or RT) on day t were sizable and negative. We found that: (a) the temporal dependencies of both accuracy and RT were quite strong in both age groups; (b) younger adults showed an effect of their accuracy on day t-1 on their RT on day t, a pattern that was in accordance with adjustments of their SAT; (c) older adults did not appear to adjust their SAT; (d) these effects were partly associated with reliable individual differences within each age group. We discuss possible explanations for older adults' reluctance to recalibrate speed and accuracy on a day-to-day basis.

Electron-temperature dependence of the recombination of H3O+(H2O)n ions with electrons

NASA Technical Reports Server (NTRS)

Johnsen, R.

1993-01-01

The T(e) dependence of the recombination of H3O+(H2O)n cluster-ions with electrons has been measured in an afterglow experiment in which the electrons were heated by a radio-frequency electric field. The recombination coefficients were found to vary with T(e) as about T(e) exp -1/2 in better agreement with theoretical expectations than earlier results of microwave-afterglow measurements.

Changes in bone macro- and microstructure in diabetic obese mice revealed by high resolution microfocus X-ray computed tomography

NASA Astrophysics Data System (ADS)

Kerckhofs, G.; Durand, M.; Vangoitsenhoven, R.; Marin, C.; van der Schueren, B.; Carmeliet, G.; Luyten, F. P.; Geris, L.; Vandamme, K.

2016-10-01

High resolution microfocus X-ray computed tomography (HR-microCT) was employed to characterize the structural alterations of the cortical and trabecular bone in a mouse model of obesity-driven type 2 diabetes (T2DM). C57Bl/6J mice were randomly assigned for 14 weeks to either a control diet-fed (CTRL) or a high fat diet (HFD)-fed group developing obesity, hyperglycaemia and insulin resistance. The HFD group showed an increased trabecular thickness and a decreased trabecular number compared to CTRL animals. Midshaft tibia intracortical porosity was assessed at two spatial image resolutions. At 2 μm scale, no change was observed in the intracortical structure. At 1 μm scale, a decrease in the cortical vascular porosity of the HFD bone was evidenced. The study of a group of 8 week old animals corresponding to animals at the start of the diet challenge revealed that the decreased vascular porosity was T2DM-dependant and not related to the ageing process. Our results offer an unprecedented ultra-characterization of the T2DM compromised skeletal micro-architecture and highlight an unrevealed T2DM-related decrease in the cortical vascular porosity, potentially affecting the bone health and fragility. Additionally, it provides some insights into the technical challenge facing the assessment of the rodent bone structure using HR-microCT imaging.

The RNA methyltransferase Dnmt2 is required for efficient Dicer-2-dependent siRNA pathway activity in Drosophila.

PubMed

Durdevic, Zeljko; Mobin, Mehrpouya Balaghy; Hanna, Katharina; Lyko, Frank; Schaefer, Matthias

2013-09-12

Transfer RNA (tRNA) fragmentation in response to stress conditions has been described in many organisms. tRNA fragments have been found in association with small interfering RNA (siRNA) components, but the biological role of these interactions remains unclear. We report here that the tRNA methyltransferase Dnmt2 is essential for efficient Dicer-2 (Dcr-2) function in Drosophila. Using small RNA (sRNA) sequencing, we confirmed that Dnmt2 limits the extent of tRNA fragmentation during the heat-shock response. tRNAs as well as tRNA fragments serve as Dcr-2 substrates, and Dcr-2 degrades tRNA-derived sequences, especially under heat-shock conditions. tRNA-derived RNAs are able to inhibit Dcr-2 activity on long double-stranded RNAs (dsRNAs). Consequently, heat-shocked Dnmt2 mutant animals accumulate dsRNAs, produce fewer siRNAs, and show misregulation of siRNA pathway-dependent genes. These results reveal the impact of tRNA fragmentation on siRNA pathways and implicate tRNA modifications in the regulation of sRNA homeostasis during the heat-shock response. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Quantitative Skeletal Muscle MRI: Part 1, Derived T2 Fat Map in Differentiation Between Boys With Duchenne Muscular Dystrophy and Healthy Boys.

PubMed

Johnston, Jennifer H; Kim, Hee Kyung; Merrow, Arnold C; Laor, Tal; Serai, Suraj; Horn, Paul S; Kim, Dong Hoon; Wong, Brenda L

2015-08-01

The purpose of this study was to validate derived T2 maps as an objective measure of muscular fat for discrimination between boys with Duchenne muscular dystrophy (DMD) and healthy boys. Forty-two boys with DMD (mean age, 9.9 years) and 31 healthy boys (mean age, 11.4 years) were included in the study. Age, body mass index, and clinical function scale grade were evaluated. T1-weighted MR images and T2 maps with and without fat suppression were obtained. Fatty infiltration was graded 0-4 on T1-weighted images, and derived T2 fat values (difference between mean T2 values from T2 maps with and without fat suppression) of the gluteus maximus and vastus lateralis muscles were calculated. Group comparisons were performed. The upper limit of the 95% reference interval of T2 fat values from the control group was applied. There was no significant difference in age or body mass index between groups. All healthy boys and 19 boys (45.2%) with DMD had a normal clinical function scale grade. Grade 1 fatty infiltration was seen in 90.3% (gluteus maximus) and 71.0% (vastus lateralis) of healthy boys versus 33.3% (gluteus maximus) and 52.4% (vastus lateralis) of boys with DMD. T2 fat values of boys with DMD were significantly longer than in the control group (p < 0.001). Using a 95% reference interval for healthy boys for the gluteus maximus (28.3 milliseconds) allowed complete separation from boys with DMD (100% sensitivity, 100% specificity), whereas the values for the vastus lateralis (7.28 milliseconds) resulted in 83.3% sensitivity and 100% specificity. Measurement of muscular fat with T2 maps is accurate for differentiating boys with DMD from healthy boys.

Mixed pinning landscape in nanoparticle-introduced YGdBa2Cu3Oy films grown by metal organic deposition

NASA Astrophysics Data System (ADS)

Miura, M.; Maiorov, B.; Baily, S. A.; Haberkorn, N.; Willis, J. O.; Marken, K.; Izumi, T.; Shiohara, Y.; Civale, L.

2011-05-01

We study the field (H) and temperature (T) dependence of the critical current density (Jc) and irreversibility field (Hirr) at different field orientations in Y0.77Gd0.23Ba2Cu3Oy with randomly distributed BaZrO3 nanoparticles (YGdBCO+BZO) and YBa2Cu3Oy (YBCO) films. Both MOD films have large RE2Cu2O5 (225) nanoparticles (˜80 nm in diameter) and a high density of twin boundaries (TB). In addition, YGdBCO+BZO films have a high density of BZO nanoparticles (˜25 nm in diameter). At high temperatures (T > 40 K), the superconducting properties, such as Jc, Hirr, and flux creep rates, are greatly affected by the BZO nanoparticles, while at low temperatures the superconducting properties of both the YBCO and YGdBCO+BZO films show similar field and temperature dependencies. In particular, while the Jc of YBCO films follow a power-law dependence (∝H-α) at all measured T, this dependence is only followed at low T for YGdBCO+BZO films. As a function of T, the YGdBCO+BZO film shows Jc(T,0.01T)~[1-(T/Tc)2]n with n ˜ 1.24 ± 0.05, which points to “δTc pinning.” We analyze the role of different types of defects in the different temperature regimes and find that the strong pinning of the BZO nanoparticles yields a higher Hirr and improved Jc along the c axis and at intermediate orientations at high T. The mixed pinning landscapes due to the presence of disorder of various dimensionalities have an important role in the improvement of in-field properties.

Effectiveness and safety of citicoline in mild vascular cognitive impairment: the IDEALE study.

PubMed

Cotroneo, Antonino Maria; Castagna, Alberto; Putignano, Salvatore; Lacava, Roberto; Fantò, Fausto; Monteleone, Francesco; Rocca, Filomena; Malara, Alba; Gareri, Pietro

2013-01-01

The studio di intervento nel decadimento vascolare lieve (IDEALE study) was an open multicenter Italian study, the aim of which was to assess the effectiveness and safety of oral citicoline in elderly people with mild vascular cognitive impairment. The study was performed in 349 patients. The active or citicoline group was composed of 265 patients and included 122 men and 143 women of mean age 79.9 ± 7.8 years selected from six Italian regions. Inclusion criteria were age ≥ 65 years, Mini-Mental State Examination (MMSE) score ≥ 21, subjective memory complaints but no evidence of deficits on MMSE, and evidence of vascular lesions on neuroradiology. Those with probable Alzheimer's disease were excluded. The control group consisted of 84 patients, including 36 men and 48 women of mean age 78.9 ± 7.01 (range 67-90) years. Patients included in the study underwent brain computed tomography or magnetic resonance imaging, and plasma dosage of vitamin B12, folate, and thyroid hormones. Functional dependence was investigated by scores on the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales, mood was assessed by the Geriatric Depression Scale (GDS), and behavioral disorders using the Neuropsychiatric Inventory scale. Comorbidity was assessed using the Cumulative Illness Rating Scale. An assessment was made at baseline (T0), after 3 months (T1), and after 9 months (T2, ie, 6 months after T1). The main outcomes were an improvement in MMSE, ADL, and IADL scores in the study group compared with the control group. Side effects were also investigated. The study group was administered oral citicoline 500 mg twice a day throughout the study. MMSE scores remained unchanged over time (22.4 ± 4 at T0; 22.7 ± 4 at T1; 22.9 ± 4 at T2), whereas a significant difference was found between the study and control groups, both in T1 and in T2. No differences were found in ADL and IADL scores between the two groups. A slight but not statistically significant difference was found in GDS score between the study and control groups (P = 0.06). No adverse events were recorded. In this study, citicoline was effective and well tolerated in patients with mild vascular cognitive impairment. Citicoline activates biosynthesis of phospholipids in neuronal membranes, increases brain metabolism as well as norepinephrine and dopamine levels in the central nervous system, and has neuroprotective effects during hypoxia and ischemia. Therefore, citicoline may be recommended for patients with mild vascular cognitive impairment.

Actigraphic motor activity during sleep from infancy to adulthood.

PubMed

Tonetti, Lorenzo; Scher, Anat; Atun-Einy, Osnat; Samuel, Moran; Boreggiani, Michele; Natale, Vincenzo

2017-01-01

A secondary analysis of longitudinal and cohort studies was carried out to quantitatively investigate the motor activity pattern, recorded through actigraphy, during the first six hours of nocturnal sleep. The first study was of longitudinal nature. Ten healthy participants (four females) were monitored three times, at baseline (T1) when they were infants (mean age 7.10 ± 0.32 months), at the first follow-up examination (T2) around 4 months later (mean age 11.20 ± 0.63 months) and at the second follow-up (T3) around three years later, when they were preschoolers (mean age 4.68 ± 0.14 years). At T1, T2 and T3 each participant wore the actigraph Basic Mini-Motionlogger (Ambulatory Monitoring, Inc., Ardsley, NY, USA) over at least two consecutive nycthemeral cycles, with the aim to measure the mean hourly motor activity count. Seven- and 11-month-old infants had a higher level of motor activity over the night compared to preschoolers. Furthermore, motor activity increased as the night progressed, with a pronounced increment at both T1 and T2, while at T3 such an increase was less marked. The second study was cross-sectional and aimed to explore the motor activity pattern, using actigraphy, during the first six hours of nocturnal sleep in multiple-age healthy groups, from infancy to adulthood. We assigned participants to eight groups according to age: 20 (five females) aged around 10 months old (mean age 10.65 ± 0.67 months); 13 (nine females) aged around 4 years (mean age 4.38 ± 0.51 years); 21 (10 females) aged around 10 years (mean age 9.67 ± 0.91 years); 21 (nine females) aged around 20 years (mean age 19.33 ± 2.44 years); 20 (10 females) aged around 30 years (mean age 29.80 ± 1.99 years); 20 (15 females) aged around 40 years (mean age 40.70 ± 1.26 years); 20 (11 females) aged around 50 years (mean age 50.15 ± 2.80 years) and 20 (nine females) aged around 60 years (mean age 59.25 ± 3.23 years). The participants aged between 10 and 60 years wore the actigraph Basic Mini-Motionlogger over seven consecutive nycthemeral cycles (infants and preschoolers wore the actigraph over at least two consecutive nycthemeral cycles), with the aim to measure the mean hourly motor activity count. The results indicated a significantly higher motor activity count in 10-month-old infants compared to all the remaining age groups. Moreover, the pattern of motor activity of 10-month-old infants was different from that of all other groups, with the highest motor activity counts from the second to the sixth hour of sleep. Considered as a whole, the results of both studies converge regarding the high motor activity detected among infants, which could be explained by the presence of a maturational process that has not yet been fully completed at this stage of life. In both studies, only the motor activity of infants was above the cutoff level established for normal adults, highlighting the need to establish a specific cutoff value for infants.

Seroepidemiology of Toxoplasma gondii infection in Tepehuanos in Durango, Mexico.

PubMed

Alvarado-Esquivel, Cosme; Estrada-Martínez, Sergio; García-López, Claudia Rosalba; Rojas-Rivera, Amparo; Sifuentes-Álvarez, Antonio; Liesenfeld, Oliver

2012-02-01

The epidemiology of Toxoplasma gondii infection is known to depend on a number of behavioral factors, including contact with animals and eating habits. The epidemiology in specific populations (i.e., in indigenous ethnic groups) is not well studied. We therefore investigated the presence of anti-Toxoplasma IgG and IgM antibodies in 156 Tepehuanos, an indigenous ethnic group in Durango State in northern Mexico, using ELISAs. Of the 156 Tepehuanos (mean age 31.03±16.71 years), 35 (22.4%) had anti-Toxoplasma IgG antibodies. IgG levels of 14-99, 100-150, and >150 IU/mL were found in 15 (42.9%), 1 (2.8%), and 19 (54.3%) anti-Toxoplasma IgG-positive Tepehuanos, respectively. Also, 15 (9.6%) subjects had anti-Toxoplasma IgM antibodies. Male Tepehuanos aged 31-50 years showed a significantly higher frequency of exposure to T. gondii than female Tepehuanos of the same age. Seroprevalence of anti-T. gondii IgM antibodies was significantly higher in Tepehuanos without education than those with 7-12 years of education. Tepehuanos suffering from frequent headaches had significantly higher seroprevalences of anti-T. gondii IgG and IgM antibodies than those without this clinical feature. In addition, Tepehuanos suffering from hearing impairment had significantly higher seroprevalence of anti-T. gondii IgM antibodies than those without this clinical feature. Logistic regression analysis did not show an association of T. gondii exposure with any behavioral characteristics, including contact with cats or eating habits. The seroprevalence of T. gondii exposure in Tepehuanos is comparable to that reported in other populations in North America; however, seroprevalence in the largely rural Tepehuanos is higher than that reported in a nearby urban center. Toxoplasma may be impacting the health of Tepehuanos. This is the first report of T. gondii infection in Tepehuanos, and the results should prove useful for the design of preventive measures.

Anodal Transcranial Direct Current Stimulation Shows Minimal, Measure-Specific Effects on Dynamic Postural Control in Young and Older Adults: A Double Blind, Sham-Controlled Study

PubMed Central

Doumas, Michail

2017-01-01

We investigated whether stimulating the cerebellum and primary motor cortex (M1) using transcranial direct current stimulation (tDCS) could affect postural control in young and older adults. tDCS was employed using a double-blind, sham-controlled design, in which young (aged 18–35) and older adults (aged 65+) were assessed over three sessions, one for each stimulatory condition–M1, cerebellar and sham. The effect of tDCS on postural control was assessed using a sway-referencing paradigm, which induced platform rotations in proportion to the participant’s body sway, thus assessing sensory reweighting processes. Task difficulty was manipulated so that young adults experienced a support surface that was twice as compliant as that of older adults, in order to minimise baseline age differences in postural sway. Effects of tDCS on postural control were assessed during, immediately after and 30 minutes after tDCS. Additionally, the effect of tDCS on corticospinal excitability was measured by evaluating motor evoked potentials using transcranial magnetic stimulation immediately after and 30 minutes after tDCS. Minimal effects of tDCS on postural control were found in the eyes open condition only, and this was dependent on the measure assessed and age group. For young adults, stimulation had only offline effects, as cerebellar stimulation showed higher mean power frequency (MPF) of sway 30 minutes after stimulation. For older adults, both stimulation conditions delayed the increase in sway amplitude witnessed between blocks one and two until stimulation was no longer active. In conclusion, despite tDCS’ growing popularity, we would caution researchers to consider carefully the type of measures assessed and the groups targeted in tDCS studies of postural control. PMID:28099522

Anodal Transcranial Direct Current Stimulation Shows Minimal, Measure-Specific Effects on Dynamic Postural Control in Young and Older Adults: A Double Blind, Sham-Controlled Study.

PubMed

Craig, Chesney E; Doumas, Michail

2017-01-01

We investigated whether stimulating the cerebellum and primary motor cortex (M1) using transcranial direct current stimulation (tDCS) could affect postural control in young and older adults. tDCS was employed using a double-blind, sham-controlled design, in which young (aged 18-35) and older adults (aged 65+) were assessed over three sessions, one for each stimulatory condition-M1, cerebellar and sham. The effect of tDCS on postural control was assessed using a sway-referencing paradigm, which induced platform rotations in proportion to the participant's body sway, thus assessing sensory reweighting processes. Task difficulty was manipulated so that young adults experienced a support surface that was twice as compliant as that of older adults, in order to minimise baseline age differences in postural sway. Effects of tDCS on postural control were assessed during, immediately after and 30 minutes after tDCS. Additionally, the effect of tDCS on corticospinal excitability was measured by evaluating motor evoked potentials using transcranial magnetic stimulation immediately after and 30 minutes after tDCS. Minimal effects of tDCS on postural control were found in the eyes open condition only, and this was dependent on the measure assessed and age group. For young adults, stimulation had only offline effects, as cerebellar stimulation showed higher mean power frequency (MPF) of sway 30 minutes after stimulation. For older adults, both stimulation conditions delayed the increase in sway amplitude witnessed between blocks one and two until stimulation was no longer active. In conclusion, despite tDCS' growing popularity, we would caution researchers to consider carefully the type of measures assessed and the groups targeted in tDCS studies of postural control.

Diabetes incidence and projections from prevalence surveys in Fiji.

PubMed

Morrell, Stephen; Lin, Sophia; Tukana, Isimeli; Linhart, Christine; Taylor, Richard; Vatucawaqa, Penina; Magliano, Dianna J; Zimmet, Paul

2016-11-25

Type 2 diabetes mellitus (T2DM) incidence is traditionally derived from cohort studies that are not always feasible, representative, or available. The present study estimates T2DM incidence in Fijian adults from T2DM prevalence estimates assembled from surveys of 25-64 year old adults conducted over 30 years (n = 14,288). T2DM prevalence by five-year age group from five population-based risk factor surveys conducted over 1980-2011 were variously adjusted for urban-rural residency, ethnicity, and sex to previous censuses (1976, 1986, 1996, 2009) to improve representativeness. Prevalence estimates were then used to calculate T2DM incidence based on birth cohorts from the age-period (Lexis) matrix following the Styblo technique, first used to estimate annual risk of tuberculosis infection (incidence) from sequential Mantoux population surveys. Poisson regression of year, age, sex, and ethnicity strata (n = 160) was used to develop projections of T2DM prevalence and incidence to 2020 based on various scenarios of population weight measured by body mass index (BMI) change. T2DM prevalence and annual incidence increased in Fiji over 1980-2011. Prevalence was higher in Indians and men than i-Taukei and women. Incidence was higher in Indians and women. From regression analyses, absolute reductions of 2.6 to 5.1% in T2DM prevalence (13-26% lower), and 0.5-0.9 per 1000 person-years in incidence (8-14% lower), could be expected in 2020 in adults if mean population weight could be reduced by 1-4 kg, compared to the current period trend in weight gain. This is the first application of the Styblo technique to calculate T2DM incidence from population-based prevalence surveys over time. Reductions in population BMI are predicted to reduce T2DM incidence and prevalence in Fiji among adults aged 25-64 years.

The relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus.

PubMed

Noh, Jin-Won; Jung, Jin Hee; Park, Jeong Eun; Lee, Jung Hwa; Sim, Kang Hee; Park, Jumin; Kim, Min Hee; Yoo, Ki-Bong

2018-02-01

[Purpose] The purpose of the present study was to assess the relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus (T2D). [Subjects and Methods] Subjects with T2D patients who received outpatient care for blood sugar control were randomly sampled at 13 general hospitals and 969 subjects were included. Cox proportional hazard models were used to confirm associations between age of onset and risk factors including family history and life style in Korean population with T2D. [Results] Parent history of T2D was significantly associated with age of onset. Compared to none of family members with T2D, those whose both father and mother had a history showed the highest the risk of early-onset (HR=2.36; 95% CI=1.45-3.85). Mother and father's history of T2D (HR=1.73; 95% CI=1.46-2.05; HR=1.83; 95% CI=1.40-2.37) were associated with the risk of early-onset. Moreover, exercise (HR=1.23, CI=1.08-1.40) smoking status (HR=1.62, CI=1.32-1.99), and drinking (HR=1.32, CI=1.13-1.54) were associated with a higher risk for the early-onset. [Conclusion] Family history as well as life style including exercise, smoking, and drinking are the risk factors for early-onset factor in Korean population with T2D.

The relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus

PubMed Central

Noh, Jin-Won; Jung, Jin Hee; Park, Jeong Eun; Lee, Jung Hwa; Sim, Kang Hee; Park, Jumin; Kim, Min Hee; Yoo, Ki-Bong

2018-01-01

[Purpose] The purpose of the present study was to assess the relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus (T2D). [Subjects and Methods] Subjects with T2D patients who received outpatient care for blood sugar control were randomly sampled at 13 general hospitals and 969 subjects were included. Cox proportional hazard models were used to confirm associations between age of onset and risk factors including family history and life style in Korean population with T2D. [Results] Parent history of T2D was significantly associated with age of onset. Compared to none of family members with T2D, those whose both father and mother had a history showed the highest the risk of early-onset (HR=2.36; 95% CI=1.45–3.85). Mother and father’s history of T2D (HR=1.73; 95% CI=1.46–2.05; HR=1.83; 95% CI=1.40–2.37) were associated with the risk of early-onset. Moreover, exercise (HR=1.23, CI=1.08–1.40) smoking status (HR=1.62, CI=1.32–1.99), and drinking (HR=1.32, CI=1.13–1.54) were associated with a higher risk for the early-onset. [Conclusion] Family history as well as life style including exercise, smoking, and drinking are the risk factors for early-onset factor in Korean population with T2D. PMID:29545678

Vav1-phospholipase C-γ1 (Vav1-PLC-γ1) pathway initiated by T cell antigen receptor (TCRγδ) activation is required to overcome inhibition by ubiquitin ligase Cbl-b during γδT cell cytotoxicity.

PubMed

Yin, Shanshan; Zhang, Jianmin; Mao, Yujia; Hu, Yu; Cui, Lianxian; Kang, Ning; He, Wei

2013-09-13

T cell antigen receptor γδ (TCRγδ) and natural killer group 2, member D (NKG2D) are two crucial receptors for γδT cell cytotoxicity. Compelling evidences suggest that γδT cell cytotoxicity is TCRγδ-dependent and can be co-stimulated by NKG2D. However, the molecular mechanism of underlying TCRγδ-dependent activation of γδT cells remains unclear. In this study we demonstrated that TCRγδ but not NKG2D engagement induced lytic granule polarization and promoted γδT cell cytotoxicity. TCRγδ activation alone was sufficient to trigger Vav1-dependent phospholipase C-γ1 signaling, resulting in lytic granule polarization and effective killing, whereas NKG2D engagement alone failed to trigger cytotoxicity-related signaling to overcome the inhibitory effect of Cbl-b; therefore, NKG2D engagement alone could not induce effective killing. However, NKG2D ligation augmented the activation of γδT cell cytotoxicity through the Vav1-phospholipase C-γ1 pathway. Vav1 overexpression or Cbl-b knockdown not only enhanced TCRγδ activation-initiated killing but also enabled NKG2D activation alone to induce γδT cell cytotoxicity. Taken together, our results suggest that the activation of γδT cell cytotoxicity requires a strong activation signal to overcome the inhibitory effect of Cbl-b. Our finding provides new insights into the molecular mechanisms underlying the initiation of γδT cell cytotoxicity and likely implications for optimizing γδT cell-based cancer immunotherapy.

Physical Functioning in Older Patients With Breast Cancer: A Prospective Cohort Study in the TEAM Trial.

PubMed

Derks, Marloes G M; de Glas, Nienke A; Bastiaannet, Esther; de Craen, Anton J M; Portielje, Johanneke E A; van de Velde, Cornelis J H; van Leeuwen, Floor E; Liefers, Gerrit-Jan

2016-08-01

Previous retrospective studies have shown that physical functioning in older cancer survivors is affected after treatment, yet prospective data are lacking. The aim of this study was to assess change in physical functioning in different age groups of patients with hormone receptor-positive breast cancer who were enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) phase III trial. Two physical parameters were assessed. Physical functioning was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire 1 year (T1) and 2 years (T2) after diagnosis. Physical activity was measured in metabolic equivalent of task (MET) hours/week at T1 and T2. Physical activity before diagnosis (T0) was assessed retrospectively at the T1 questionnaire. Patients were divided into three age groups: <60, 60-69, and ≥70 years. Decline in physical functioning was assessed using linear regression analysis. Differences in mean values of physical activity levels were calculated using repeated-measures one-way analysis of variance. A total of 431 patients were included for analysis. In all age groups, physical activity levels at T1 and T2 were significantly lower than prediagnostic physical activity levels (T0) (p < .001 for all age groups). Age ≥70 years was independently associated with decline in physical functioning between T1 and T2 (β = -4.62, 95% confidence interval -8.73 to -0.51, p = .028). Patients aged 70 years or older treated with breast surgery and adjuvant hormonal therapy did not improve between years 1 and 2 after diagnosis to the same extent as did younger patients. Although older patients constitute a large share of the breast cancer population, little is known about the effect and consequences of treatment of breast cancer in this specific age group. This study revealed that, unlike younger patients, older patients do not regain their physical abilities after surgical and adjuvant treatment for breast cancer. In older adults, the effect of treatment on physical functioning and independency could be more relevant than survival outcomes. Clinicians and older patients should be aware of the impact of treatment on physical functioning and prevent older patients from experiencing physical decline, which could lead to institutionalization and loss of independence. There is a need for age-specific guidelines that take into account the heterogeneity of the older population and for evidence-based treatment that focuses not only on cancer-specific outcomes but also on the consequences of treatment for physical and cognitive functioning and quality of life. ©AlphaMed Press.

Assessment of long-term outcomes associated with urinary prostate cancer antigen 3 and TMPRSS2:ERG gene fusion at repeat biopsy.

PubMed

Merdan, Selin; Tomlins, Scott A; Barnett, Christine L; Morgan, Todd M; Montie, James E; Wei, John T; Denton, Brian T

2015-11-15

In men with clinically localized prostate cancer who have undergone at least 1 previous negative biopsy and have elevated serum prostate-specific antigen (PSA) levels, long-term health outcomes associated with the assessment of urinary prostate cancer antigen 3 (PCA3) and the transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene fusion (T2:ERG) have not been investigated previously in relation to the decision to recommend a repeat biopsy. The authors performed a decision analysis using a decision tree for men with elevated PSA levels. The probability of cancer was estimated using the Prostate Cancer Prevention Trial Risk Calculator (version 2.0). The use of PSA alone was compared with the use of PCA3 and T2:ERG scores, with each evaluated independently, in combination with PSA to trigger a repeat biopsy. When PCA3 and T2:ERG score evaluations were used, predefined thresholds were established to determine whether the patient should undergo a repeat biopsy. Biopsy outcomes were defined as either positive (with a Gleason score of <7, 7, or >7) or negative. Probabilities and estimates of 10-year overall survival and 15-year cancer-specific survival were derived from previous studies and a literature review. Outcomes were defined as age-dependent and Gleason score-dependent 10-year overall and 15-year cancer-specific survival rates and the percentage of biopsies avoided. Incorporating the PCA3 score (biopsy threshold, 25; generated based on the urine PCA3 level normalized to the amount of PSA messenger RNA) or the T2:ERG score (biopsy threshold, 10; based on the urine T2:ERG level normalized to the amount of PSA messenger RNA) into the decision to recommend repeat biopsy would have avoided 55.4% or 64.7% of repeat biopsies for the base-case patient, respectively, and changes in the 10-year survival rate were only 0.93% or 1.41%, respectively. Multi-way sensitivity analyses suggested that these results were robust with respect to the model parameters. The use of PCA3 or T2:ERG testing for repeat biopsy decisions can substantially reduce the number of biopsies without significantly affecting 10-year survival. © 2015 American Cancer Society.

Phenotypic and Functional Characterization of Peripheral Blood Lymphocytes from Various Age- and Sex-Specific Groups of Owl Monkeys (Aotus nancymaae).

PubMed

Nehete, Pramod N; Nehete, Bharti P; Chitta, Sriram; Williams, Lawrence E; Abee, Christian R

2017-02-01

Owl monkeys (Aotus nancymaae) are New World NHP that serve an important role in vaccine development and as a model for human disease conditions such as malaria. Despite the past contributions of this animal model, limited information is available about the phenotype and functional properties of peripheral blood lymphocytes in reference to sex and age. Using a panel of human antibodies and a set of standardized human immune assays, we identified and characterized various peripheral blood lymphocyte subsets, evaluated the immune functions of T cells, and analyzed cytokines relative to sex and age in healthy owl monkeys. We noted age- and sex-dependent changes in CD28+ (an essential T cell costimulatory molecule) and CD95+ (an apoptotic surface marker) T cells and various levels of cytokines in the plasma. In immune assays of freshly isolated peripheral blood mononuclear cells, IFNγ and perforin responses were significantly higher in female than in male monkeys and in young adults than in juvenile and geriatric groups, despite similar lymphocyte (particularly T cell) populations in these groups. Our current findings may be useful in exploring Aotus monkeys as a model system for the study of aging, susceptibility to infectious diseases, and age-associated differences in vaccine efficacy, and other challenges particular to pediatric and geriatric patients.

Energy dependence of π±, p and pbar transverse momentum spectra for Au + Au collisions at √{sNN} = 62.4 and 200 GeV

NASA Astrophysics Data System (ADS)

Abelev, B. I.; Aggarwal, M. M.; Ahammed, Z.; Anderson, B. D.; Arkhipkin, D.; Averichev, G. S.; Bai, Y.; Balewski, J.; Barannikova, O.; Barnby, L. S.; Baumgart, S.; Belaga, V. V.; Bellingeri-Laurikainen, A.; Bellwied, R.; Benedosso, F.; Betts, R. R.; Bharadwaj, S.; Bhasin, A.; Bhati, A. K.; Bichsel, H.; Bielcik, J.; Bielcikova, J.; Billmeier, A.; Bland, L. C.; Blyth, S.-L.; Bombara, M.; Bonner, B. E.; Botje, M.; Bouchet, J.; Brandin, A. V.; Bravar, A.; Burton, T. P.; Bystersky, M.; Cadman, R. V.; Cai, X. Z.; Caines, H.; Calderón de la Barca Sánchez, M.; Callner, J.; Catu, O.; Cebra, D.; Chajecki, Z.; Chaloupka, P.; Chattopadhyay, S.; Chen, H. F.; Chen, J. H.; Chen, J. Y.; Cheng, J.; Cherney, M.; Chikanian, A.; Choi, H. A.; Christie, W.; Chung, S. U.; Coffin, J. P.; Cormier, T. M.; Cosentino, M. R.; Cramer, J. G.; Crawford, H. J.; Das, D.; Dash, S.; Daugherity, M.; de Moura, M. M.; Dedovich, T. G.; DePhillips, M.; Derevschikov, A. A.; Didenko, L.; Dietel, T.; Djawotho, P.; Dogra, S. M.; Dong, X.; Drachenberg, J. L.; Draper, J. E.; Du, F.; Dunin, V. B.; Dunlop, J. C.; Dutta Mazumdar, M. R.; Eckardt, V.; Edwards, W. R.; Efimov, L. G.; Emelianov, V.; Engelage, J.; Eppley, G.; Erazmus, B.; Estienne, M.; Fachini, P.; Fatemi, R.; Fedorisin, J.; Feng, A.; Filip, P.; Finch, E.; Fine, V.; Fisyak, Y.; Fornazier, K. S. F.; Fu, J.; Gagliardi, C. A.; Gaillard, L.; Ganti, M. S.; Garcia-Solis, E.; Ghazikhanian, V.; Ghosh, P.; Gorbunov, Y. G.; Gos, H.; Grebenyuk, O.; Grosnick, D.; Guertin, S. M.; Guimaraes, K. S. F. F.; Gupta, N.; Haag, B.; Hallman, T. J.; Hamed, A.; Harris, J. W.; He, W.; Heinz, M.; Henry, T. W.; Hepplemann, S.; Hippolyte, B.; Hirsch, A.; Hjort, E.; Hoffman, A. M.; Hoffmann, G. W.; Hofman, D.; Hollis, R.; Horner, M. J.; Huang, H. Z.; Hughes, E. W.; Humanic, T. J.; Igo, G.; Iordanova, A.; Jacobs, P.; Jacobs, W. W.; Jakl, P.; Jia, F.; Jiang, H.; Jones, P. G.; Judd, E. G.; Kabana, S.; Kang, K.; Kapitan, J.; Kaplan, M.; Keane, D.; Kechechyan, A.; Kettler, D.; Khodyrev, V. Yu.; Kim, B. C.; Kiryluk, J.; Kisiel, A.; Kislov, E. M.; Klein, S. R.; Knospe, A. G.; Kocoloski, A.; Koetke, D. D.; Kollegger, T.; Kopytine, M.; Kotchenda, L.; Kouchpil, V.; Kowalik, K. L.; Kramer, M.; Kravtsov, P.; Kravtsov, V. I.; Krueger, K.; Kuhn, C.; Kulikov, A. I.; Kumar, A.; Kurnadi, P.; Kuznetsov, A. A.; Lamont, M. A. C.; Landgraf, J. M.; Lange, S.; LaPointe, S.; Laue, F.; Lauret, J.; Lebedev, A.; Lednicky, R.; Lee, C.-H.; Lehocka, S.; LeVine, M. J.; Li, C.; Li, Q.; Li, Y.; Lin, G.; Lin, X.; Lindenbaum, S. J.; Lisa, M. A.; Liu, F.; Liu, H.; Liu, J.; Liu, L.; Ljubicic, T.; Llope, W. J.; Long, H.; Longacre, R. S.; Lopez-Noriega, M.; Love, W. A.; Lu, Y.; Ludlam, T.; Lynn, D.; Ma, G. L.; Ma, J. G.; Ma, Y. G.; Mahapatra, D. P.; Majka, R.; Mangotra, L. K.; Manweiler, R.; Margetis, S.; Markert, C.; Martin, L.; Matis, H. S.; Matulenko, Yu. A.; McClain, C. J.; McShane, T. S.; Melnick, Yu.; Meschanin, A.; Millane, J.; Miller, M. L.; Minaev, N. G.; Mioduszewski, S.; Mironov, C.; Mischke, A.; Mitchell, J.; Mohanty, B.; Molnar, L.; Morozov, D. A.; Munhoz, M. G.; Nandi, B. K.; Nattrass, C.; Nayak, T. K.; Nelson, J. M.; Nepali, C.; Netrakanti, P. K.; Nikitin, V. A.; Nogach, L. V.; Nurushev, S. B.; Odyniec, G.; Ogawa, A.; Okorokov, V.; Oldenburg, M.; Olson, D.; Pachr, M.; Pal, S. K.; Panebratsev, Y.; Panitkin, S. Y.; Pavlinov, A. I.; Pawlak, T.; Peitzmann, T.; Perevoztchikov, V.; Perkins, C.; Peryt, W.; Phatak, S. C.; Planinic, M.; Pluta, J.; Poljak, N.; Porile, N.; Poskanzer, A. M.; Potekhin, M.; Potrebenikova, E.; Potukuchi, B. V. K. S.; Prindle, D.; Pruneau, C.; Putschke, J.; Qattan, I. A.; Raniwala, R.; Raniwala, S.; Ray, R. L.; Razin, S. V.; Reinnarth, J.; Relyea, D.; Ridiger, A.; Ritter, H. G.; Roberts, J. B.; Rogachevskiy, O. V.; Romero, J. L.; Rose, A.; Roy, C.; Ruan, L.; Russcher, M. J.; Sahoo, R.; Sakrejda, I.; Sakuma, T.; Salur, S.; Sandweiss, J.; Sarsour, M.; Savin, I.; Sazhin, P. S.; Schambach, J.; Scharenberg, R. P.; Schmitz, N.; Seger, J.; Selyuzhenkov, I.; Seyboth, P.; Shabetai, A.; Shahaliev, E.; Shao, M.; Sharma, M.; Shen, W. Q.; Shimanskiy, S. S.; Sichtermann, E.; Simon, F.; Singaraju, R. N.; Smirnov, N.; Snellings, R.; Sorensen, P.; Sowinski, J.; Speltz, J.; Spinka, H. M.; Srivastava, B.; Stadnik, A.; Stanislaus, T. D. S.; Stock, R.; Strikhanov, M.; Stringfellow, B.; Suaide, A. A. P.; Suarez, M. C.; Subba, N. L.; Sumbera, M.; Sun, X. M.; Sun, Z.; Surrow, B.; Symons, T. J. M.; Szanto de Toledo, A.; Takahashi, J.; Tang, A. H.; Tarnowsky, T.; Thomas, J. H.; Timmins, A. R.; Timoshenko, S.; Tokarev, M.; Trainor, T. A.; Trentalange, S.; Tribble, R. E.; Tsai, O. D.; Ulery, J.; Ullrich, T.; Underwood, D. G.; Van Buren, G.; van der Kolk, N.; van Leeuwen, M.; Vander Molen, A. M.; Varma, R.; Vasilevski, I. M.; Vasiliev, A. N.; Vernet, R.; Vigdor, S. E.; Viyogi, Y. P.; Vokal, S.; Voloshin, S. A.; Waggoner, W. T.; Wang, F.; Wang, G.; Wang, J. S.; Wang, X. L.; Wang, Y.; Watson, J. W.; Webb, J. C.; Westfall, G. D.; Wetzler, A.; Whitten, C., Jr.; Wieman, H.; Wissink, S. W.; Witt, R.; Wu, J.; Wu, J.; Xu, N.; Xu, Q. H.; Xu, Z.; Yepes, P.; Yoo, I.-K.; Yue, Q.; Yurevich, V. I.; Zhan, W.; Zhang, H.; Zhang, W. M.; Zhang, Y.; Zhang, Z. P.; Zhao, Y.; Zhong, C.; Zoulkarneev, R.; Zoulkarneeva, Y.; Zubarev, A. N.; Zuo, J. X.; STAR Collaboration

2007-11-01

We study the energy dependence of the transverse momentum (pT) spectra for charged pions, protons and anti-protons for Au + Au collisions at √{sNN} = 62.4 and 200 GeV. Data are presented at mid-rapidity (| y | < 0.5) for 0.2 7GeV / c) the modification is similar for both energies. The p /π+ and pbar /π- ratios for central collisions at √{sNN} = 62.4GeV peak at pT ≃ 2GeV / c. In the pT range where recombination is expected to dominate, the p /π+ ratios at 62.4 GeV are larger than at 200 GeV, while the pbar /π- ratios are smaller. For pT > 2GeV / c, the pbar /π- ratios at the two beam energies are independent of pT and centrality indicating that the dependence of the pbar /π- ratio on pT does not change between 62.4 and 200 GeV. These findings challenge various models incorporating jet quenching and/or constituent quark coalescence.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakai, H.; Ronning, F.; Hattori, T.

Here, we have used nuclear quadrupole resonance (NQR) to probe microscopically the response of a prototypical quantum critical metal CeCoIn 5 to substitutions of small amounts of Cd for In. Approximately half of the Cd substituents induce local Ce moments in their close proximity, as observed by site-dependent longitudinal nuclear spin relaxation rates 1/T 1. In order to reaffirm that localized f moments are induced around the Cd substituents, we find a Gaussian spin-echo decay rate 1/T 2G of transverse nuclear spin relaxation. Furthermore,more » $${T}_{1}T/{T}_{2\\text{G}}^{2}$$ for the NQR subpeak is found to be proportional to temperatures, again indicating local moments fluctuations around the Cd substituents, while that for the NQR main peak shows a T 0.7-dependence. The latter temperature dependence is close to 0.75 in pure CeCoIn 5 and indicates that the bulk electronic state is located close to a two dimensional quantum critical instability.« less

Clinical features of celiac disease: a prospective birth cohort.

PubMed

Agardh, Daniel; Lee, Hye-Seung; Kurppa, Kalle; Simell, Ville; Aronsson, Carin Andrén; Jörneus, Ola; Hummel, Michael; Liu, Edwin; Koletzko, Sibylle

2015-04-01

To investigate clinical features of celiac disease (CD) and their association with risk factors for CD in a genetic risk birth cohort. Children from 6 clinical centers in 4 countries positive for HLA-DR3-DQ2 or DR4-DQ8 were annually screened for tissue transglutaminase antibodies (tTGA) and assessed for symptoms by questionnaires. Associations of symptoms with anthropometrics, known risk factors for CD, tTGA levels, and mucosal lesions in those biopsied were examined. Of 6706 screened children, 914 developed persistent positive tTGA, 406 underwent biopsies, and 340 had CD. Compared with age-matched tTGA-negative children, those with persistent tTGA were more likely to have symptoms at 2 (34% vs 19%, P < .001) and 3 years of age (28% vs 19%, P = .009) but not at 4 years (27% vs 21%, NS). Z-scores for height, weight, and BMI did not differ between groups. In children with persistent tTGA, having ≥ 1 symptom was associated with family history of CD (odds ratio = 2.59, 95% confidence interval, 1.21-5.57) but not with age, gender, or HLA-DR3-DQ2 homozygosity. At seroconversion, tTGA levels were higher in symptomatic than asymptomatic children (P < .001), in those from CD families (P < .001), and in US participants (P < .001) but not associated with age, gender, or HLA genotype. tTGA levels correlated with severity of mucosal lesions both in symptomatic (r = 0.53, P < .001) and asymptomatic children (r = 0.22, P = .01). A majority of children detected with persistent tTGA in screenings are asymptomatic and have normal growth by age 4 years. tTGA levels correlate more strongly with severity of mucosal lesions in symptomatic as compared with asymptomatic children. Copyright © 2015 by the American Academy of Pediatrics.

Sex-dependent Association of a Common Low Density Lipoprotein Receptor Polymorphism with RNA Splicing Efficiency in the Brain and Alzheimers Disease

PubMed Central

Zou, Fanggeng; Gopalraj, Rangaraj K.; Lok, Johann; Zhu, Haiyan; Ling, I-Fang; Simpson, James F.; Tucker, H. Michael; Kelly, Jeremiah F.; Younkin, Samuel G.; Dickson, Dennis W.; Petersen, Ronald C; Graff-Radford, Neill R.; Bennett, David A.; Crook, Julia E.; G.Younkin, Steven; Estus, Steven

2008-01-01

Since apoE allele status is the predominant Alzheimers disease (AD) genetic risk factor, functional single nucleotide polymorphisms (SNP)s in brain apoE receptors represent excellent candidates for association with AD. Recently, we identified a SNP, rs688, as modulating the splicing efficiency of low-density lipoprotein receptor (LDLR) exon 12 in the female human liver and in minigene transfected HepG2 cells. Moreover, the rs688T minor allele associated with significantly higher LDL and total cholesterol in women in the Framingham Offspring Study. Since LDLR is a major apoE receptor in the brain, we hypothesized that rs688 modulates LDLR splicing in neural tissues and associates with AD. To evaluate this hypothesis, we first transfected LDLR minigenes into SH-SY5Y neuroblastoma cells and found that rs688T reduces exon 12 inclusion in this neural model. We then evaluated rs688 association with exon 12 splicing efficiency in vivo by quantifying LDLR splicing in human anterior cingulate tissue obtained at autopsy; the rs688T allele associated with decreased LDLR exon 12 splicing efficiency in aged men but not women. Lastly, we evaluated whether rs688 associates with AD by genotyping DNA from 1,457 men and 2,055 women drawn from three case-control series. The rs688T/T genotype was associated with increased AD odds in males (recessive model, odds ratio (OR) of 1.49, 95% confidence interval (CI) of 1.13−1.97, uncorrected p=0.005), but not in females. In summary, these studies identify a functional apoE receptor SNP that is associated with AD in a sex-dependent fashion. PMID:18065781

Comparison of Silent and Conventional MR Imaging for the Evaluation of Myelination in Children

PubMed Central

Matsuo-Hagiyama, Chisato; Watanabe, Yoshiyuki; Tanaka, Hisashi; Takahashi, Hiroto; Arisawa, Atsuko; Yoshioka, Eri; Nabatame, Shin; Nakano, Sayaka; Tomiyama, Noriyuki

2017-01-01

Purpose: Silent magnetic resonance imaging (MRI) scans produce reduced acoustic noise and are considered more gentle for sedated children. The aim of this study was to compare the validity of T1- (T1W) and T2-weighted (T2W) silent sequences for myelination assessment in children with conventional spin-echo sequences. Materials and Methods: A total of 30 children (21 boys, 9 girls; age range: 1–83 months, mean age: 35.5 months, median age: 28.5 months) were examined using both silent and spin-echo sequences. Acoustic noise levels were analyzed and compared. The degree of myelination was qualitatively assessed via consensus, and T1W and T2W signal intensities were quantitatively measured by percent contrast. Results: Acoustic noise levels were significantly lower during silent sequences than during conventional sequences (P < 0.0001 for both T1W and T2W). Inter-method comparison indicated overall good to excellent agreement (T1W and T2W images, κ = 0.76 and 0.80, respectively); however, agreement was poor for cerebellar myelination on T1W images (κ = 0.14). The percent contrast of silent and conventional MRI sequences had a strong correlation (T1W, correlation coefficient [CC] = 0.76; T1W excluding the middle cerebellar peduncle, CC = 0.82; T2W, CC = 0.91). Conclusions: For brain MRI, silent sequences significantly reduced acoustic noise and provided diagnostic image quality for myelination evaluations; however, the two methods differed with respect to cerebellar delineation on T1W sequences. PMID:27795484

Finite-size effects in the short-time height distribution of the Kardar-Parisi-Zhang equation

NASA Astrophysics Data System (ADS)

Smith, Naftali R.; Meerson, Baruch; Sasorov, Pavel

2018-02-01

We use the optimal fluctuation method to evaluate the short-time probability distribution P(H, L, t) of height at a single point, H=h(x=0, t) , of the evolving Kardar-Parisi-Zhang (KPZ) interface h(x, t) on a ring of length 2L. The process starts from a flat interface. At short times typical (small) height fluctuations are unaffected by the KPZ nonlinearity and belong to the Edwards-Wilkinson universality class. The nonlinearity, however, strongly affects the (asymmetric) tails of P(H) . At large L/\\sqrt{t} the faster-decaying tail has a double structure: it is L-independent, -\\lnP˜≤ft\\vert H\\right\\vert 5/2/t1/2 , at intermediately large \\vert H\\vert , and L-dependent, -\\lnP˜ ≤ft\\vert H\\right\\vert 2L/t , at very large \\vert H\\vert . The transition between these two regimes is sharp and, in the large L/\\sqrt{t} limit, behaves as a fractional-order phase transition. The transition point H=Hc+ depends on L/\\sqrt{t} . At small L/\\sqrt{t} , the double structure of the faster tail disappears, and only the very large-H tail, -\\lnP˜ ≤ft\\vert H\\right\\vert 2L/t , is observed. The slower-decaying tail does not show any L-dependence at large L/\\sqrt{t} , where it coincides with the slower tail of the GOE Tracy-Widom distribution. At small L/\\sqrt{t} this tail also has a double structure. The transition between the two regimes occurs at a value of height H=Hc- which depends on L/\\sqrt{t} . At L/\\sqrt{t} \\to 0 the transition behaves as a mean-field-like second-order phase transition. At \\vert H\\vert <\\vert H_c-\\vert the slower tail behaves as -\\lnP˜ ≤ft\\vert H\\right\\vert 2L/t , whereas at \\vert H\\vert >\\vert H_c-\\vert it coincides with the slower tail of the GOE Tracy-Widom distribution.

Age, sex, and nutritional status modify the CD4+ T-cell recovery rate in HIV-tuberculosis co-infected patients on combination antiretroviral therapy.

PubMed

Ezeamama, Amara E; Mupere, Ezekiel; Oloya, James; Martinez, Leonardo; Kakaire, Robert; Yin, Xiaoping; Sekandi, Juliet N; Whalen, Christopher C

2015-06-01

Baseline age and combination antiretroviral therapy (cART) were examined as determinants of CD4+ T-cell recovery during 6 months of tuberculosis (TB) therapy with/without cART. It was determined whether this association was modified by patient sex and nutritional status. This longitudinal analysis included 208 immune-competent, non-pregnant, ART-naive HIV-positive patients from Uganda with a first episode of pulmonary TB. CD4+ T-cell counts were measured using flow cytometry. Age was defined as ≤24, 25-29, 30-34, and 35-39 vs. ≥40 years. Nutritional status was defined as normal (>18.5kg/m(2)) vs. underweight (≤18.5kg/m(2)) using the body mass index (BMI). Multivariate random effects linear mixed models were fitted to estimate differences in CD4+ T-cell recovery in relation to specified determinants. cART was associated with a monthly rise of 15.7 cells/μl (p<0.001). Overall, age was not associated with CD4+ T-cell recovery during TB therapy (p = 0.655). However, among patients on cART, the age-associated CD4+ T-cell recovery rate varied by sex and nutritional status, such that age <40 vs. ≥40 years predicted superior absolute CD4+ T-cell recovery among females (p=0.006) and among patients with a BMI ≥18.5kg/m(2) (p<0.001). TB-infected HIV-positive patients aged ≥40 years have a slower rate of immune restoration given cART, particularly if BMI is >18.5kg/m(2) or they are female. These patients may benefit from increased monitoring and nutritional support during cART. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Fundamental Research on Infrared Detection

DTIC Science & Technology

2006-10-15

2. Antimony-based type-II superlattice (T2-SL) photodetectors – We explored the temperature dependent and noise current characteristics of interband...their CZT substrates. Task 2. Antimony-based type-II superlattice (T2-SL) photodetectors – We explored the temperature dependent and noise ...structures, leading to potentially high device performance in photovoltaic mode with low noise and normal incidence detection. The ICDs have a

Depression of T lymphocyte function in chimpanzees receiving thymectomy and irradiation. [X Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilbertsen, R.B.; Metzgar, R.S.

1978-03-01

In studies analogous to those in which the thymus dependency of immune functions in murine systems was determined, three chimpanzees were thymectomized, splenectomized, exposed to lethal doses of whole body x-irradiation with limited bone marrow shielding, and subsequently evaluated for lymphocyte markers and functions over a period of years. In the oldest animal studied (Irena, 7.2 years at surgery), the percentage of peripheral blood T cells decreased to about 60% of control values and remained at that level for approximately 1/sup 1///sub 2/ years before returning to normal. In the two youngest chimpanzees T cell rosette values dropped to 15more » to 40% of control values after irradiation. T cell percentages in one of these young chimpanzees returned to about 75% of the controls 2/sup 1///sub 2/ years after x-irradiation. Phytohemagglutinin and concanavalin A mitogen responses were less affected in the oldest chimpanzee. However, even in the oldest animal, the responses to phytohemagglutinin and concanavalin A began to show a gradual and consistent decline 1/sup 1///sub 2/ years after irradiation. Mixed leukocyte culture responsiveness was most affected by the experimental procedures, being greatly reduced in all three chimpanzees during varying time intervals. In general, the effects of the experimental procedures used to produce T cell deficiencies varied with the age of the chimpanzee at surgery, the time after irradiation when the animal was tested, and the lymphocyte marker or function studied.« less

The Association of Type 2 Diabetes Mellitus with Cerebral Gray Matter Volume Is Independent of Retinal Vascular Architecture and Retinopathy.

PubMed

Moran, C; Tapp, R J; Hughes, A D; Magnussen, C G; Blizzard, L; Phan, T G; Beare, R; Witt, N; Venn, A; Münch, G; Amaratunge, B C; Srikanth, V

2016-01-01

It is uncertain whether small vessel disease underlies the relationship between Type 2 Diabetes Mellitus (T2DM) and brain atrophy. We aimed to study whether retinal vascular architecture, as a proxy for cerebral small vessel disease, may modify or mediate the associations of T2DM with brain volumes. In this cross-sectional study using Magnetic Resonance Imaging (MRI) scans and retinal photographs in 451 people with and without T2DM, we measured brain volumes, geometric measures of retinal vascular architecture, clinical retinopathy, and MRI cerebrovascular lesions. There were 270 people with (mean age 67.3 years) and 181 without T2DM (mean age 72.9 years). T2DM was associated with lower gray matter volume (p = 0.008). T2DM was associated with greater arteriolar diameter (p = 0.03) and optimality ratio (p = 0.04), but these associations were attenuated by adjustments for age and sex. Only optimality ratio was associated with lower gray matter volume (p = 0.03). The inclusion of retinal measures in regression models did not attenuate the association of T2DM with gray matter volume. The association of T2DM with lower gray matter volume was independent of retinal vascular architecture and clinical retinopathy. Retinal vascular measures or retinopathy may not be sufficiently sensitive to confirm a microvascular basis for T2DM-related brain atrophy.

Hyper telomere recombination accelerates replicative senescence and may promote premature aging

PubMed Central

Hagelstrom, R. Tanner; Blagoev, Krastan B.; Niedernhofer, Laura J.; Goodwin, Edwin H.; Bailey, Susan M.

2010-01-01

Werner syndrome and Bloom syndrome result from defects in the RecQ helicases Werner (WRN) and Bloom (BLM), respectively, and display premature aging phenotypes. Similarly, XFE progeroid syndrome results from defects in the ERCC1-XPF DNA repair endonuclease. To gain insight into the origin of cellular senescence and human aging, we analyzed the dependence of sister chromatid exchange (SCE) frequencies on location [i.e., genomic (G-SCE) vs. telomeric (T-SCE) DNA] in primary human fibroblasts deficient in WRN, BLM, or ERCC1-XPF. Consistent with our other studies, we found evidence of elevated T-SCE in telomerase-negative but not telomerase-positive backgrounds. In telomerase-negative WRN-deficient cells, T-SCE—but not G-SCE—frequencies were significantly increased compared with controls. In contrast, SCE frequencies were significantly elevated in BLM-deficient cells irrespective of genome location. In ERCC1-XPF-deficient cells, neither T- nor G-SCE frequencies differed from controls. A theoretical model was developed that allowed an in silico investigation into the cellular consequences of increased T-SCE frequency. The model predicts that in cells with increased T-SCE, the onset of replicative senescence is dramatically accelerated even though the average rate of telomere loss has not changed. Premature cellular senescence may act as a powerful tumor-suppressor mechanism in telomerase-deficient cells with mutations that cause T-SCE levels to rise. Furthermore, T-SCE-driven premature cellular senescence may be a factor contributing to accelerated aging in Werner and Bloom syndromes, but not XFE progeroid syndrome. PMID:20798040

Glomerular filtration rate as measured by serum cystatin C is an important determinant of plasma homocysteine and serum methylmalonic acid in the elderly.

PubMed

Lewerin, C; Ljungman, S; Nilsson-Ehle, H

2007-01-01

To explore the dependence of glomerular filtration rate (GFR) on plasma total homocysteine (tHcy) and serum methylmalonic acid (MMA), as well as the consequences for the diagnosis of cobalamin and/or folic acid deficiency in an elderly community-dwelling population. Population-based study of 209 community-dwelling subjects, mean age 76 years. Four months' treatment study with oral vitamin B(12), folic acid and B(6) or placebo. Determinants of tHcy and MMA: cystatin C as a marker of GFR and serum/plasma concentrations of vitamin B(12) and folate, age and sex. Elevated cystatin C (>1.55 mg L(-1)) was found in 31.3% (men) and 13.0% (women). Elevated tHcy (> or = 16 micromol L(-1)) occurred in 53% and elevated MMA (> or = 0.34 micromol L(-1)) in 11% of all subjects. When GFR was taken into consideration, the proportion of elevated tHcy was reduced to 10% (20/209), whilst the proportion of elevated MMA was unchanged. Cystatin C was correlated with tHcy (r = 0.45, P < 0.001) and with MMA (r =0.28, P < 0.001), independently of vitamin B(12)- and folate status. According to multiple regression, independent predictors for tHcy were plasma folate (15%), cystatin C (11%) and vitamin B(12) (4%), and for MMA, cystatin C (8%) and vitamin B(12) (2%). The prevalence of elevated tHcy may be overestimated in elderly populations unless GFR is taken into account. Nomograms for evaluation of tHcy and MMA in relation to both cystatin C and serum creatinine are presented.

Grip strength is not associated with incident type 2 diabetes mellitus in healthy adults: The CoLaus study.

PubMed

Marques-Vidal, Pedro; Vollenweider, Peter; Waeber, Gérard; Jornayvaz, François R

2017-10-01

We examined the association of grip strength with incident type 2 diabetes mellitus (T2DM) in healthy subjects initially aged 50 to 75years after a follow-up of 5.5years and 10.7years. This was a prospective, population-based study derived from the CoLaus (Cohorte Lausannoise) study including 2318 participants (aged 60.2y; 1354 women) free from T2DM at baseline. Grip strength was assessed using a handheld dynamometer. The effect of grip strength on the incidence of T2DM was analyzed by logistic regression. After a follow-up of 5.5years, 190 (8.2%) T2DM cases were identified. In bivariate analysis, participants who developed T2DM had a higher absolute grip strength (35.3±10.6 versus 33.2±10.7kg, P=0.013). Analysis between grip strength expressed in 5kg increment and incident TD2M showed a negative association when adjusted for age and sex [ORs (95% CI): 0.88 (0.79, 0.98)], or for age, sex and body mass index (BMI) [ORs (95% CI): 0.87 (0.78, 097)]. After a follow-up of 10.7years, 131 supplemental (7.3%) T2DM cases were identified, but there was no association between grip strength and incident T2DM in bivariate and multivariable analysis, potentially due to a lack of statistical power. In non elderly healthy adults, the risk of incident T2DM is overall not associated with grip strength over a maximum follow-up of 10.7years. Future studies are warranted to better assess the association between grip strength and incident T2DM in bigger and even younger cohorts. Copyright © 2017 Elsevier B.V. All rights reserved.

Hyperinsulinemia and metabolic syndrome at mean age of 10 years in black and white schoolgirls and development of impaired fasting glucose and type 2 diabetes mellitus by mean age of 24 years.

PubMed

Morrison, John A; Glueck, Charles J; Umar, Muhammad; Daniels, Stephen; Dolan, Lawrence M; Wang, Ping

2011-01-01

The objective of the study was to evaluate preteen insulin and metabolic syndrome (MS) as independent predictors of impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM) in black and white females by mean age of 24 years. This was a prospective cohort study. There were 8 measures of fasting glucose and insulin from mean age of 10 years through mean age of 24 years, and insulin also at mean age of 25 years. Childhood MS was defined by at least 3 abnormal values among waist circumference, triglyceride, high-density lipoprotein cholesterol, blood pressure, and glucose. Hyperinsulinemia was defined by insulin greater than or equal to race-specific 75th percentile. Patients with type 1 diabetes mellitus were excluded. The study was held in schools and in an outpatient clinical center. Participants were schoolgirls (260 white, 296 black). There was no intervention. The outcome measures were IFG (fasting glucose of at least 100 to 125 mg/dL) and T2DM (fasting glucose of at least 126 mg/dL). By the age of 24 years, there were 11 cases of T2DM (2%) and 108 cases of IFG (19%). By the age of 24 years, IFG + T2DM was present in 18% of women (73/412) who had normal insulin-no MS at the age of 10 years vs 28% (34/122) of those with high insulin-no MS at the age of 10 years (P = .014) and 67% (10/15) of those with high insulin + MS at the age of 10 years (P < .0001). By stepwise logistic regression, significant, independent, positive predictors of IFG + T2DM were first insulin measure in childhood, age at last sampling, childhood MS, change in body mass index over 15 years, and, separately, initial glucose of at least 100 mg/dL and average of all insulin quartile ranks over 15 years. The correlation between childhood insulin z score and insulin z score 15 years later was r = .30, P < .0001. Insulin and MS at a mean age of 10 years plus change in body mass index over 15 years, and 15-year average insulin rank independently predict IFG + T2DM by mean age of 24 years, suggesting avenues for primary prevention. Copyright © 2011 Elsevier Inc. All rights reserved.

Ankylosing spondylitis and other inflammatory spondyloarthritis increase the risk of developing type 2 diabetes in an Asian population.

PubMed

Chen, Hsin-Hung; Yeh, Su-Yin; Chen, Hue-Yong; Lin, Cheng-Li; Sung, Fung-Chang; Kao, Chia-Hung

2014-02-01

This study evaluated whether people with ankylosing spondylitis (AS) and spondyloarthritis are at higher risk of type 2 diabetes mellitus (T2DM). We used a sub-dataset of the National Health Insurance Research Database from 1996 to 2010 to established a AS cohort consisting new patients with AS or spondyloarthritis (N = 7,778) and a non-AS cohort without the diseases (N = 31,112). Incidences of T2DM in the two cohorts, hazard ratios (HRs) of risk of T2DM in association with AS, and cumulative probability of having T2DM were estimated by the end of 2010. The incidence of T2DM was 1.17-fold higher in the AS cohort than in the non-AS cohort (13.5 vs. 11.5, per 1,000 person-years), with an adjusted HR of 1.16 (95 % CI = 1.05-1.29). The T2DM incidence was higher for women than for men; while the Cox model measured sex-specific adjusted HR of T2DM was higher for men than for women. The incidence rate of T2DM increased with age in both cohorts, while the age-specific measures showed that the adjusted HR of T2DM was higher in young AS patients (≤50 years of age) than older ones, compared to their peers of non-AS group. The plot of Kaplan-Meier analysis showed that the overall probability of having T2DM was 2 % higher in the AS cohort than in the non-AS cohort (log-rank test: p < 0.0001). Patients with AS and spondyloarthritis have an increased risk of developing T2DM.

Humanized in vivo Model for Autoimmune Diabetes

DTIC Science & Technology

2009-02-01

Manuscripts Gebe JA, Yue BB, Unrath KA, Falk BA, and Nepom GT. Restricted autoantigen recognition associated with deletional and adaptive regulatory...Unrath KA, Falk BA, Ito K, Wen L, Daniels TL, Lernmark A, Nepom GT. Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid...Miyake T, Falk BA, Nepom GT. Autoreactive human T-cell receptor initiates insulitis and impaired glucose tolerance in HLA DR4 transgenic mice. J

Postmaximal contraction blood volume responses are blunted in obese and type 2 diabetic subjects in a muscle-specific manner

PubMed Central

Sanchez, Otto A.; Copenhaver, Elizabeth A.; Chance, Marti A.; Fowler, Michael J.; Towse, Theodore F.; Kent-Braun, Jane A.

2011-01-01

The purpose of this study was to determine whether there are differences in postisometric contraction blood volume and oxygenation responses among groups of type 2 diabetes mellitus (T2DM), obese, and lean individuals detectable using MRI. Eight T2DM patients were individually matched by age, sex, and race to non-T2DM individuals with similar body mass index (obese) and lean subjects. Functional MRI was performed using a dual-gradient-recalled echo, echo-planar imaging sequence with a repetition time of 1 s and at two echo times (TE = 6 and 46 ms). Data were acquired before, during, and after 10-s isometric dorsiflexion contractions performed at 50 and 100% of maximal voluntary contraction (MVC) force. MRI signal intensity (SI) changes from the tibialis anterior and extensor digitorum longus muscles were plotted as functions of time for each TE. From each time course, the difference between the minimum and the maximum postcontraction SI (ΔSI) were determined for TE = 6 ms (ΔSI6) and TE = 46 ms (ΔSI46), reflecting variations in blood volume and oxyhemoglobin saturation, respectively. Following 50% MVC contractions, the mean postcontraction ΔSI6 values were similar in the three groups. Following MVC only, and in the EDL muscle only, T2DM and obese participants had ∼56% lower ΔSI6 than the lean individuals. Also following MVC only, the ΔSI46 response in the EDL was lower in T2DM subjects than in lean individuals. These data suggest that skeletal muscle small vessel impairment occurs in T2DM and body mass index-matched subjects, in muscle-specific and contraction intensity-dependent manners. PMID:21572006

S175. AMOTIVATION IS ASSOCIATED WITH SMALLER VENTRAL STRIATUM VOLUMES IN OLDER PATIENTS WITH SCHIZOPHRENIA

PubMed Central

Caravaggio, Fernando; Fervaha, Gagan; Iwata, Yusuke; Plitman, Eric; Chung, Jun Ku; Nakajima, Shinichiro; Mar, Wanna; Gerretsen, Philip; Kim, Julia; Chakravarty, Mallar; Mulsant, Benoit; Pollock, Bruce; Mamo, David; Remington, Gary; Graff-Guerrero, Ariel

2018-01-01

Abstract Background Motivational deficits are prevalent in patients with schizophrenia, persist despite antipsychotic treatment, and predict long‐term outcomes. Evidence suggests that patients with greater amotivation have smaller ventral striatum (VS) volumes. We wished to replicate this finding in a sample of older, chronically medicated patients with schizophrenia. Using structural imaging and positron emission tomography, we examined whether amotivation uniquely predicted VS volumes beyond the effects of striatal dopamine D2/3 receptor (D2/3R) blockade by antipsychotics. Methods Data from 41 older schizophrenia patients (mean age: 60.2 ± 6.7; 11 female) were reanalysed from previously published imaging data. We constructed multivariate linear stepwise regression models with VS volumes as the dependent variable and various sociodemographic and clinical variables as the initial predictors: age, gender, total brain volume, and antipsychotic striatal D2/3R occupancy. Amotivation was included as a subsequent step to determine any unique relationships with VS volumes beyond the contribution of the covariates. In a reduced sample (n = 36), general cognition was also included as a covariate. Results Amotivation uniquely explained 8% and 6% of the variance in right and left VS volumes, respectively (right: β = -.38, t = -2.48, P = .01; left: β = -.31, t = -2.17, P = .03). Considering cognition, amotivation levels uniquely explained 9% of the variance in right VS volumes (β = -.43, t = -0.26, P = .03). Discussion We replicate and extend the finding of reduced VS volumes with greater amotivation. We demonstrate this relationship uniquely beyond the potential contributions of striatal D2/3R blockade by antipsychotics. Elucidating the structural correlates of amotivation in schizophrenia may help develop treatments for this presently irremediable deficit.

Oxidative Stress, Obesity, and Breast Cancer Risk: Results From the Shanghai Women's Health Study

PubMed Central

Dai, Qi; Gao, Yu-Tang; Shu, Xiao-Ou; Yang, Gong; Milne, Ginger; Cai, Qiuyin; Wen, Wanqing; Rothman, Nathaniel; Cai, Hui; Li, Honglan; Xiang, Yongbing; Chow, Wong-Ho; Zheng, Wei

2009-01-01

Purpose Increased reactive oxygen species may exhaust the antioxidant capability of human defense systems, leading to oxidative stress and cancer development. Urinary F2-isoprostanes, secondary end products of lipid peroxidation, are more accurate markers of oxidative stress than other available biomarkers. No prospective study has investigated whether levels of 15-F2t-isoprostane (15-F2t-IsoP) and its metabolite 2,3-dinor-5,6-dihydro-15-F2t-IsoP (15-F2t-IsoPM) are related to breast cancer risk. Patients and Methods We conducted a nested case-control study within the Shanghai Women's Health Study, a population-based cohort study of 74,942 Chinese women between 40 and 70 years of age. Prediagnostic urinary 15-F2t-IsoP and 15-F2t-IsoPM were measured by gas chromatography mass spectrometry for 436 breast cancer cases and 852 individually matched controls. Results Urinary excretion of isoprostanes was not significantly different between cases and controls. However, among overweight women, levels of isoprostanes were positively associated with breast cancer risk, which became stronger with increasing body mass index (BMI). Among women with a BMI ≥ 29, the odds ratio (OR) increased to 10.27 (95% CI, 2.41 to 43.80) for the highest compared with the lowest tertile of 15-F2t-IsoPM (P for trend = .003; P for interaction = .0004). In contrast, 15-F2t-IsoP and 15-F2t-IsoPM were inversely associated with breast cancer risk among nonoverweight women. Among women with a BMI ≤ 23, breast cancer risk was reduced with increasing 15-F2t-IsoP levels in a dose-response manner (P for trend = .006), with an OR of 0.46 (95% CI, 0.26 to 0.80) for the highest tertile versus the lowest (P for interaction = .006). Conclusion Our results suggest that the role of oxidative stress in breast cancer development may depend on adiposity. PMID:19380446

Age-related T cell responses to allergens in childhood.

PubMed

Smart, J M; Suphioglu, C; Kemp, A S

2003-03-01

T cell priming, as determined by allergen-induced proliferative responses, is believed to occur principally in early childhood in both atopic and non-atopic infants under the influence of multiple factors including environmental allergen exposure. It is considered that T cell priming with expansion of Th2 cells is a crucial factor in the development of atopic disease. To examine T cell priming to commonly encountered allergens in childhood in relation to age. In a cross-sectional study T cell proliferation in relation to age was examined for three common allergens, ovalbumin (OVA), house dust mite (HDM) and rye grass pollen (RYE), in atopic and non-atopic children. The effect of age on Th1 (IFN-gamma) and Th2 (IL-5 and IL-13) cytokine production in response to these allergens was investigated to examine the possibility of immune deviation with time. A significant increase in T cell proliferation with age was observed with RYE among atopic children only. However, the same was not observed with the two other allergens studied (i.e. OVA and HDM). In addition, RYE-induced (but not HDM or OVA) cytokine production showed an increased Th2 deviation with age as reflected in the increasing IL-5/IFN-gamma and IL-13/IFN-gamma ratios only among the atopic subjects with rye grass pollen sensitivity. These findings suggest that grass pollen sensitivity in childhood is accompanied by a progressive accumulation of allergen-primed T cells and progressive deviation of the allergen-induced cytokine response towards a Th2 response in atopic subjects throughout childhood.

Age-dependent changes of the antioxidant system in rat livers are accompanied by altered MAPK activation and a decline in motor signaling

PubMed Central

Yang, Wei; Burkhardt, Britta; Fischer, Luise; Beirow, Maja; Bork, Nadja; Wönne, Eva C.; Wagner, Cornelia; Husen, Bettina; Zeilinger, Katrin; Liu, Liegang; Nussler, Andreas K.

2015-01-01

Aging is characterized by a progressive decrease of cellular functions, because cells gradually lose their capacity to respond to injury. Increased oxidative stress is considered to be one of the major contributors to age-related changes in all organs including the liver. Our study has focused on elucidating whether important antioxidative enzymes, the mTOR pathway, and MAPKs exhibit age-dependent changes in the liver of rats during aging. We found an age-dependent increase of GSH in the cytosol and mitochondria. The aged liver showed an increased SOD enzyme activity, while the CAT enzyme activity decreased. HO-1 and NOS-2 gene expression was lower in adult rats, but up-regulated in aged rats. Western blot analysis revealed that SOD1, SOD2, GPx, GR, γ-GCL, and GSS were age-dependent up-regulated, while CAT remained constant. We also demonstrated that the phosphorylation of Akt, JNK, p38, and TSC2Ser1254 decreased while ERK1/2 and TSC2Thr1462 increased age-dependently. Furthermore, our data show that the mTOR pathway seems to be activated in livers of aged rats, and hence stimulating cell proliferation/regeneration, as confirmed by an age-dependent increase of PCNA and p-eIF4ESer209 protein expression. Our data may help to explain the fact that liver cells only proliferate in cases of necessity, like injury and damage. In summary, we have demonstrated that, age-dependent changes of the antioxidant system and stress-related signaling pathways occur in the livers of rats, which may help to better understand organ aging. PMID:27004051

Regulation of Ca(2+)-dependent protein turnover in skeletal muscle by thyroxine

NASA Technical Reports Server (NTRS)

Zeman, Richard J.; Bernstein, Paul L.; Ludemann, Robert; Etlinger, Joseph D.

1986-01-01

Dantrolene, an agent that inhibits Ca(2+) mobilization, improved protein balance in skeletal muscle, as thyroid status was increased, by altering rates of protein synthesis and degradation. Thyroxine (T4) caused increases in protein degradation that were blocked by leupeptin, a proteinase inhibitor previously shown to inhibit Ca(2+)-dependent nonlysosomal proteolysis in these muscles. In addition, T4 abolished sensitivity to the lysosomotropic agent methylamine and the autophagy inhibitor 3-methyladenine, suggesting that T4 inhibits autophagic/lysosomal proteolysis.

Risk of Type 2 Diabetes Mellitus Development in the Native Population of Low- and High-Altitude Regions of Kyrgyzstan: Finnish Diabetes Risc Score Questionnaire Results.

PubMed

Moldobaeva, Marina S; Vinogradova, Anastasiya V; Esenamanova, Marina K

2017-12-01

Moldobaeva, Marina S., Anastasiya V. Vinogradova, and Marina K. Esenamanova. Risk of type 2 diabetes mellitus development in the native population of low- and high-altitude regions of Kyrgyzstan: Finnish Diabetes Risc Score questionnaire results. High Alt Med Biol. 18:428-435, 2017. The number of patients with diabetes is steadily growing, but likely only half of all cases are ever identified. The Kyrgyz, native inhabitants of Central Asia, live in the mountainous area and have a particular lifestyle and nutrition. However, the risk of type 2 diabetes mellitus (T2DM) in our population is not well defined. Therefore, we aimed at determining the risk of T2DM development in the Kyrgyz population residing in low- and high-altitude (HAlt) regions by using the Finnish Diabetes Risc Score (FINDRISC) questionnaire. We included in the study 3190 randomly selected participants, including 1780 low-altitude (LAlt) residents (Chu region, 500-1200 m) and 1410 HAlt residents (Naryn region, 2000-4500 m), among whom there were 1207 men and 1983 women. Assessment of T2DM development was conducted by using the FINDRISC questionnaire and risk stratification was performed by region of residency, gender, and age. An irregular intake of vegetables and fruits, increased waist circumference (WC), and increased body mass index (BMI) were identified as leading risk factors of T2DM development in native residents of Chu and Naryn regions of Kyrgyzstan. The 10-year risk stratification of T2DM development revealed the absence of a very high-risk group; high-risk status was more frequently identified among residents of the LAlt Chu district (4.7% of women and 2.1% of men), as compared with the HAlt population (1.9% of women and 1% of men) (p = 0.0018 for women and p = 0.09 for men). In the Kyrgyz population, a 10-year high risk of T2DM development is greater among residents of LAlts as compared with HAlts, irrespective of gender. No very high-risk group was detected in residents of low or HAlts. The leading composites of FINDRISC score are increased WC and BMI, possibly due to irregular intake of vegetables and fruits that are dependent on the altitude of residence and age.

Quantitative MRI reveals the elderly ischemic brain is susceptible to increased early blood–brain barrier permeability following tissue plasminogen activator related to claudin 5 and occludin disassembly

PubMed Central

Kaur, Jaspreet; Tuor, Ursula I; Zhao, Zonghang; Barber, Philip A

2011-01-01

Great uncertainty exists as to whether aging enhances the detrimental effects of tissue plasminogen activator (tPA) on vascular integrity of the ischemic brain. We hypothesized that tPA treatment would augment ischemic injury by causing increased blood–brain barrier (BBB) breakdown as determined by quantitative serial T1 and T2 magnetic resonance imaging (MRI), and the transfer constant for gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) from blood to brain in aged (18 to 20 months) compared with young (3 to 4 months) Wistar rats after middle cerebral artery occlusion, mediated through the acute disassembly of claudin 5 and occludin. Increased T2 values over the first hour of postreperfusion were independently augmented following treatment with tPA (P<0.001) and aging (P<0.01), supporting a synergistic effect of tPA on the aged ischemic brain. Blood–brain barrier permeability for Gd-DTPA (KGd) was substantial following reperfusion in all animal groups and was exacerbated by tPA treatment in the elderly rat (P<0.001). The frequency of hematoma formation was proportionately increased in the elderly ischemic brain (P<0.05). Both tPA and age independently increased claudin 5 and occludin phosphorylation during ischemia. Early BBB permeability detected by quantitative MRI following ischemic stroke is enhanced by increased age and tPA and is related to claudin 5 and occludin phosphorylation. PMID:21610723

Effects of whole-body exposure to 915 MHz RFID on secretory functions of the thyroid system in rats.

PubMed

Kim, Hye Sun; Paik, Man-Jeong; Kim, Yeon Ju; Lee, Gwang; Lee, Yun-Sil; Choi, Hyung-Do; Kim, Byung Chan; Pack, Jeong-Ki; Kim, Nam; Ahn, Young Hwan

2013-10-01

As a part of an investigation on the potential risks of radiofrequency identification (RFID) on human health, we studied whether exposure to 915 MHz RFID in rats significantly affected the secretory function of the thyroid system. A reverberation chamber was used as a whole-body exposure system. Male Sprague-Dawley rats were exposed for 8 h per day, 5 days per week, for a duration of 2, 4, 8, or 16 weeks. The estimated whole-body average specific absorption rate (SAR) varied from 3.2 to 4.6 W/kg depending on the age/mass of the animals for the field of the 915 MHz RFID reader. Plasma levels of triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) were evaluated via enzyme-linked immunosorbent assay. Morphological changes in the thyroid gland were then analyzed. No changes in T3, T4, or TSH were observed over time between the sham- and RFID-exposed groups. We suggest that subchronic exposure to 915 MHz RFID at a SAR of 4 W/kg does not cause significant effects on thyroid secretory function. © 2013 Wiley Periodicals, Inc.

Fetal intracranial hemorrhage. Imaging by ultrasound and magnetic resonance imaging.

PubMed

Kirkinen, P; Partanen, K; Ryynänen, M; Ordén, M R

1997-08-01

To describe the magnetic resonance imaging (MRI) findings associated with fetal intracranial hemorrhage and to compare them with ultrasound findings. In four pregnancies complicated by fetal intracranial hemorrhage, fetal imaging was carried out using T2-weighted fast spin echo sequences and T1-weighted fast low angle shot imaging sequences and by transabdominal ultrasonography. An antepartum diagnosis of hemorrhage was made by ultrasound in one case and by MRI in two. Retrospectively, the hemorrhagic area could be identified from the MRI images in an additional two cases and from the ultrasound images in one case. In the cases of intraventricular hemorrhage, the MRI signal intensity in the T1-weighted images was increased in the hemorrhagic area as compared to the contralateral ventricle and brain parenchyma. In a case with subdural hemorrhage, T2-weighted MRI signals from the hemorrhagic area changed from low-to high-intensity signals during four weeks of follow-up. Better imaging of the intracranial anatomy was possible by MRI than by transabdominal ultrasonography. MRI can be used for imaging and dating fetal intracranial hemorrhages. Variable ultrasound and MRI findings are associated with this complication, depending on the age and location of the hemorrhage.

Nonequilibrium material effects on the behavior of polymeric composite matrices and their related composites

NASA Technical Reports Server (NTRS)

Wilkes, G. L.

1982-01-01

The effects of physical aging on the material properties of some linear and network macromolecular glasses are discussed. The free volume concept is used to describe this behavior. The effect of physical aging on properties of some uniaxial graphite/fiber epoxy resin composites is investigated using stress relaxation in both tensile and flexural modes. The matrix polymers used were resins both of which are based on a 4,4-methylenedianiline derivative of epichlorohydrin with diamino diphenyl sulfone (DDS) as the curing agent. The matrix resin, as used in the practical application in composites, not fully cured and the glass transition of the network was dependent on the curing schedule. The physical aging of the bulk crosslinked epoxy was found to depend on the annealing temperature, and the T sub g of the resin. The physical aging of the composite, monitored by the stress relaxation method, was found to be dependent on the testing direction.

A generalised age- and phase-structured model of human tumour cell populations both unperturbed and exposed to a range of cancer therapies.

PubMed

Basse, Britta; Ubezio, Paolo

2007-07-01

We develop a general mathematical model for a population of cells differentiated by their position within the cell division cycle. A system of partial differential equations governs the kinetics of cell densities in certain phases of the cell division cycle dependent on time t (hours) and an age-like variable tau (hours) describing the time since arrival in a particular phase of the cell division cycle. Transition rate functions control the transfer of cells between phases. We first obtain a theoretical solution on the infinite domain -infinity < t < infinity. We then assume that age distributions at time t=0 are known and write our solution in terms of these age distributions on t=0. In practice, of course, these age distributions are unknown. All is not lost, however, because a cell line before treatment usually lies in a state of asynchronous balanced growth where the proportion of cells in each phase of the cell cycle remain constant. We assume that an unperturbed cell line has four distinct phases and that the rate of transition between phases is constant within a short period of observation ('short' relative to the whole history of the tumour growth) and we show that under certain conditions, this is equivalent to exponential growth or decline. We can then gain expressions for the age distributions. So, in short, our approach is to assume that we have an unperturbed cell line on t

Distinct DC subsets regulate adaptive Th1 and 2 responses during Trichuris muris infection.

PubMed

Demiri, M; Müller-Luda, K; Agace, W W; Svensson-Frej, M

2017-10-01

Low- and high-dose infections with the murine large intestinal nematode Trichuris muris are associated with induction of adaptive Th1 and Th2 responses, respectively, in mesenteric lymph nodes (MLN). Classical dendritic cells (cDC) accumulate in the large intestinal mucosa and MLN upon T. muris infection, yet their role in driving adaptive responses to infection remains largely unknown. We performed low- and high-dose T. muris infections of mice deficient in defined cDC subsets to investigate their role in induction of adaptive immune responses. Mice lacking IRF4-dependent cDC failed to clear a high-dose infection and displayed impaired Th2 responses. Conversely, mice lacking IRF8-dependent cDC cleared a low-dose infection and displayed an impaired Th1 response while increased production of Th2 cytokines. Finally, mice lacking both IRF4- and IRF8-dependent cDC were able to generate a Th2 response and clear a low-dose infection. Collectively, these results suggest that IRF4- and IRF8-dependent cDC act antagonistically during T. muris infection, and demonstrate that intestinal Th2 responses can be generated towards T. muris in the absence of IRF4-dependent cDC. © 2017 John Wiley & Sons Ltd.

Pinning in the flux-line-cutting regime of Bi 2Sr 2Ca 1Cu 2O 8 single crystals at high field

NASA Astrophysics Data System (ADS)

D'Anna, G.; André, M.-O.; Indenbom, M. V.; Benoit, W.

1994-09-01

Using a low-frequency torsion pendulum we show that in a Bi 2Sr 2Ca 1Cu 2O 8 single crystal the irreversibility line Birr( T) is frequency dependent down to 10 -5 Hz in the high-field regime. The activation energy has a logarithmic field dependence, U0( B)= U∗ 1n( B∗/ B). A microscopic model for flux-line-cutting and pancake collision yields quantitative expressions for U0 and for Birr( T)= B∗ exp(- T/T∗), which reproduce the experimental data very well.

230Th/U dating of a late Pleistocene alluvial fan along the southern San Andreas fault

USGS Publications Warehouse

Fletcher, Kathryn E.K.; Sharp, Warren D.; Kendrick, Katherine J.; Behr, Whitney M.; Hudnut, Kenneth W.; Hanks, Thomas C.

2010-01-01

U-series dating of pedogenic carbonate-clast coatings provides a reliable, precise minimum age of 45.1 ± 0.6 ka (2σ) for the T2 geomorphic surface of the Biskra Palms alluvial fan, Coachella Valley, California. Concordant ages for multiple subsamples from individual carbonate coatings provide evidence that the 238U-234U-230Th system has remained closed since carbonate formation. The U-series minimum age is used to assess previously published 10Be exposure ages of cobbles and boulders. All but one cobble age and some boulder 10Be ages are younger than the U-series minimum age, indicating that surface cobbles and some boulders were partially shielded after deposition of the fan and have been subsequently exhumed by erosion of fine-grained matrix to expose them on the present fan surface. A comparison of U-series and 10Be ages indicates that the interval between final alluvial deposition on the T2 fan surface and accumulation of dateable carbonate is not well resolved at Biskra Palms; however, the “time lag” inherent to dating via U-series on pedogenic carbonate can be no larger than ∼10 k.y., the uncertainty of the 10Be-derived age of the T2 fan surface. Dating of the T2 fan surface via U-series on pedogenic carbonate (minimum age, 45.1 ± 0.6 ka) and 10Be on boulder-top samples using forward modeling (preferred age, 50 ± 5 ka) provides broadly consistent constraints on the age of the fan surface and helps to elucidate its postdepositional development.

230Th/U dating of a late pleistocene alluvial fan along the southern san andreas fault

USGS Publications Warehouse

Fletcher, K.E.K.; Sharp, W.D.; Kendrick, K.J.; Behr, W.M.; Hudnut, K.W.; Hanks, T.C.

2010-01-01

U-series dating of pedogenic carbonate-clast coatings provides a reliable, precise minimum age of 45.1 ?? 0.6 ka (2??) for the T2 geomorphic surface of the Biskra Palms alluvial fan, Coachella Valley, California. Concordant ages for multiple subsamples from individual carbonate coatings provide evidence that the 238U-234U-230Th system has remained closed since carbonate formation. The U-series minimum age is used to assess previously published 10Be exposure ages of cobbles and boulders. All but one cobble age and some boulder 10Be ages are younger than the U-series minimum age, indicating that surface cobbles and some boulders were partially shielded after deposition of the fan and have been subsequently exhumed by erosion of fine-grained matrix to expose them on the present fan surface. A comparison of U-series and 10Be ages indicates that the interval between final alluvial deposition on the T2 fan surface and accumulation of dateable carbonate is not well resolved at Biskra Palms; however, the "time lag" inherent to dating via U-series on pedogenic carbonate can be no larger than ~10 k.y., the uncertainty of the 10Be-derived age of the T2 fan surface. Dating of the T2 fan surface via U-series on pedogenic carbonate (minimum age, 45.1 ?? 0.6 ka) and 10Be on boulder-top samples using forward modeling (preferred age, 50 ?? 5 ka) provides broadly consistent constraints on the age of the fan surface and helps to elucidate its postdepositional development. ?? 2010 Geological Society of America.

Clinical and Sociodemographic Predictors of the Quality of Life among Patients with Type 2 Diabetes Mellitus on the East Coast of Peninsular Malaysia.

PubMed

Jusoh, Zaleha; Tohid, Hizlinda; Omar, Khairani; Muhammad, Noor Azimah; Ahmad, Saharuddin

2018-02-01

The quality of life (QoL) describes the multidimensional self-perceived well-being of a person, which is an important diabetes outcome. This study aimed to measure the QoL scores among patients with type 2 diabetes mellitus (T2DM), as well as their clinical and sociodemographic predictors. This cross-sectional study involved 180 randomly sampled patients at a primary care clinic on the East Coast of Peninsular Malaysia. A self-administered questionnaire containing the Audit of Diabetes Dependent Quality of Life-18 (ADDQoL-18) was used. Most of the respondents (96.7%) were Malay, with a median (interquartile range, IQR) age of 54.0 (14.0) years old. The majority of them were females (60.0%), married (81.1%) and from low-income families (63.3%), who attained a secondary education or lower (75.6%). Only 49.4% of them were employed. The mean (standard deviation, SD) ADDQoL-18 average weighted impact score was -4.58 (2.21) and all 18 domains were negatively affected, particularly the living condition, family life and working life. The multiple linear regression analysis showed that the age (adjusted B = 0.05, P = 0.004) and insulin use (adjusted B = -0.84, P = 0.011) were QoL predictors. T2DM negatively impacts the patient's QoL in all aspects of their life. The QoL improvement with age suggests that the older patients had accepted and adapted to their illness. The need to improve the QoL among insulin users was also highlighted.

Wiedemann-Franz law and nonvanishing temperature scale across the field-tuned quantum critical point of YbRh2Si2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reid, J.-Ph.; Tanatar, Makariy; Daou, R.

2014-01-23

The in-plane thermal conductivity kappa and electrical resistivity rho of the heavy-fermion metal YbRh2Si2 were measured down to 50 mK for magnetic fields H parallel and perpendicular to the tetragonal c axis, through the field-tuned quantum critical point H-c, at which antiferromagnetic order ends. The thermal and electrical resistivities, w L0T/kappa and rho, show a linear temperature dependence below 1 K, typical of the non-Fermi-liquid behavior found near antiferromagnetic quantum critical points, but this dependence does not persist down to T = 0. Below a characteristic temperature T-star similar or equal to 0.35 K, which depends weakly on H, w(T)more » and rho(T) both deviate downward and converge as T -> 0. We propose that T-star marks the onset of short-range magnetic correlations, persisting beyond H-c. By comparing samples of different purity, we conclude that the Wiedemann-Franz law holds in YbRh2Si2, even at H-c, implying that no fundamental breakdown of quasiparticle behavior occurs in this material. The overall phenomenology of heat and charge transport in YbRh2Si2 is similar to that observed in the heavy-fermion metal CeCoIn5, near its own field-tuned quantum critical point.« less

Nrf2-Dependent and -Independent Effects of tert-Butylhydroquinone, CDDO-Im, and H2O2 in Human Jurkat T Cells as Determined by CRISPR/Cas9 Gene Editing.

PubMed

Zagorski, Joseph W; Maser, Tyler P; Liby, Karen T; Rockwell, Cheryl E

2017-05-01

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a stress-activated transcription factor activated by stimuli such as electrophilic compounds and other reactive xenobiotics. Previously, we have shown that the commonly used food additive and Nrf2 activator tert -butylhydroquinone (tBHQ) suppresses interleukin-2 (IL-2) production, CD25 expression, and NF κ B activity in human Jurkat T cells. The purpose of the current studies was to determine whether these effects were dependent upon Nrf2 by developing a human Nrf2-null T cell model using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 technology. The current studies show that suppression of CD25 expression by tBHQ is partially dependent on Nrf2, whereas inhibition of IL-2 secretion is largely Nrf2-independent. Interestingly, tBHQ inhibited NF κ B activation in an Nrf2-independent manner. This was an unexpected finding since Nrf2 inhibits NF κ B activation in other models. These results led us to investigate another more potent Nrf2 activator, the synthetic triterpenoid 1[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im). Treatment of wild-type and Nrf2-null Jurkat T cells with CDDO-Im resulted in an Nrf2-dependent suppression of IL-2. Furthermore, susceptibility to reactive oxygen species was significantly enhanced in the Nrf2-null clones as determined by decreased mitochondrial membrane potential and cell viability. Importantly, this study is the first to describe the generation of a human Nrf2-null model, which is likely to have multiple applications in immunology and cancer biology. Collectively, this study demonstrates a role for Nrf2 in the effects of CDDO-Im on CD25 and IL-2 expression, whereas the effect of tBHQ on these parameters is complex and likely involves modulation of multiple stress-activated transcription factors, including NF κ B and Nrf2. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Applying ethnic-specific bone mineral density T-scores to Chinese women in the USA.

PubMed

Lo, J C; Kim, S; Chandra, M; Ettinger, B

2016-12-01

Caucasian reference data are used to classify bone mineral density in US women of all races. However, use of Chinese American reference data yields lower osteoporosis prevalence in Chinese women. The reduction in osteoporosis labeling may be relevant for younger Chinese women at low fracture risk. Caucasian reference data are used for osteoporosis classification in US postmenopausal women regardless of race, including Asians who tend to have lower bone mineral density (BMD) than women of white race. This study examines BMD classification by ethnic T-scores for Chinese women. Using BMD data in a Northern California healthcare population, Chinese women aged 50-79 years were compared to age-matched white women (1:5 ratio), with femoral neck (FN), total hip (TH), and lumbar spine (LS) T-scores calculated using Caucasian versus Chinese American reference data. Comparing 4039 Chinese and 20,195 white women (44.8 % age 50-59 years, 37.5 % age 60-69 years, 17.7 % age 70-79 years), Chinese women had lower BMD T-scores at the FN, TH, and LS (median T-score 0.29-0.72 units lower across age groups, p < 0.001) using Caucasian reference data. Using Chinese American BMD reference data resulted in an average +0.47, +0.36, and +0.48 units higher FN, TH, and LS T-scores, respectively, reducing the prevalence of osteoporosis (T-score ≤ -2.5) in Chinese women at the FN (16.7 to 6.6 %), TH (9.8 to 3.2 %), and LS (23.2 to 8.9 %); osteoporosis prevalence at any one of three sites fell from 29.6 to 12.6 % (22.4 to 8.1 % for age 50-64 years and 43.2 to 21.0 % for age 65-79 years). Use of Chinese American BMD reference data yields higher (ethnic) T-scores by 0.4-0.5 units, with a large proportion of Chinese women reclassified from osteoporosis to osteopenia. The reduction in osteoporosis labeling with ethnic T-scores may be relevant for younger Chinese women at low fracture risk.

[Clinical and genetic characteristics of children with Leigh syndrome].

PubMed

Fang, F; Shen, Y; Shen, D M; Liu, Z M; Ding, C H; Zhang, W C; Sun, S Z; Lyu, J L; Han, T L; Wang, X H; Zhang, W H; Yang, X Y; Li, J W; Wu, H S

2017-03-02

Objective: To investigate the clinically and genetic characteristics of children with Leigh syndrome. Method: Patients with clinically diagnosed Leigh syndrome(LS)in the department of Neurology, Beijing Children's Hospital from January 2013 to February 2016 underwent the mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) detecting with next generation sequencing (NGS) technology. The clinical data of gene confirmed cases were retrospectively collected and analyzed. The differences in the onset age, clinical manifestations, lactic acid level and MRI results between the mtDNA variation and nDNA variation were compared and analyzed. t test, Chi-square test and Fisher's exact test were used for statistical analysis. Result: Thirty-five cases were diagnosed by gene detection, including 20 males and 15 females. The median onset age was 1 year (ranging from the neonatal period to 4.4 years old). The age of onset within 2 years accounted for 74%(26 cases). The onset age of initial symptoms, including developmental delay, developmental regression, and seizures, were 6 (4, 12) months, 12 (8, 14) months, and 6 (1, 23) months respectively. The onset age of ptosis, extrapyramidal symptoms and ataxia were 26 (18, 44) months, 28 (23, 40) months and 28 (19, 35) months, respectively. There were significant differences in the onset age between the three groups ( H =21.919, P =0.01). Within the 35 cases, 29 were manifested with developmental delay (83%), 26 with dystonia (74%), 18 with growth retardation, 15 with myasthenia, 13 with developmental regression, 11 with dysphagia, 10 with feeding difficulties, 4 with skeletal dysplasia, and 2 with digestive tract symptoms; nystagmus and respiratory abnormalities were observed in 9 cases respectively; extrapyramidal symptoms, peripheral nerve injury, ptosis, seizures were observed in 8 cases respectively; and ataxia, ophthalmoplegia and hypertrichiasis were found in 5 cases respectively.The blood lactic acid was measured in 32 LS patients, within which 23 cases (72%) had increased results; 8 out of 11 cases who underwent were cerebrospinal fluid lactic acid test had increased results. The results of neuroimaging revealed that all the patients were involved in the brainstem and (or) basal ganglia, of whom 27 (77%) had brainstem involvement, 24 (69%) had basal ganglia involvement. Thirteen out of 14 patients who had medulla oblongata involvement had nDNA variation; while 7 out of 8 patients with cerebellar involvement had nDNA variation. Genetic etiology was confirmed in all patients, among whom there were 17 cases (49%) with mtDNA mutation, including 8993T>C/G ( n =5), 14487T>C ( n =4), 13513G>A ( n =2), 9176T>C, 10158T>C, 3697G>A, 10191T>C, 14459A>G and 11777C>A ( n =1) respectively. Remaining 18 cases(51%) had nDNA mutation, including SURF1 gene( n =10), PDHA1 gene( n =3) and one case each of NDUFV1, NDUFAF6, NDUFAF5, NDUFS1 and COQ7 genes. In this study, 27 types of mutations were founded, 15 of which had not been previously reported. Respiratory chain gene mutations have been found in 31 cases(89%); 3 cases had PDHc gene mutations, and 1 case had other mutation. Conclusion: LS usually occurs in infants. The most common primary symptoms are age-dependent abnormal movements, ocular symptoms, and seizures. Respiratory chain defects is the most common causes of LS.SURF1 is the most common variation, followed by 8993T>C/G, 14487 T>C and 13513G>A mutation.

A Quantitative MR Imaging Assessment of Leukoencephalopathy in Children Treated for Acute Lymphoblastic Leukemia without Irradiation

PubMed Central

Reddick, Wilburn E.; Glass, John O.; Helton, Kathleen J.; Langston, James W.; Li, Chin-Shang; Pui, Ching-Hon

2008-01-01

PURPOSE Intravenous methotrexate (IV-MTX), an effective treatment for acute lymphoblastic leukemia (ALL), has a significant toxic effect on the central nervous system, with leukoencephalopathy (LE) being the most common form. The purpose of this study was to use objective quantitative MR imaging to prospectively assess the temporal evolution of LE extent and intensity. METHODS Forty-five children (low-risk, 10 mol/L/12F; mean age, 5.0 years at diagnosis; standard/high-risk, 11 mol/L/12F; mean age, 9.2 years at diagnosis) treated for ALL on a single institutional protocol were evaluated longitudinally to assess the extent of LE (proportion of white matter impacted) through tissue segmentation and the relative intensity of LE through relative elevations in T1 and T2 relaxation rates. One-sided Wilcoxon-Mann-Whitney tests were used to assess differences in quantitative measures at 4 different points in therapy both within and between risk arms. RESULTS The proportion of white matter affected in both patient groups increased significantly with additional courses of IV-MTX, whereas the intensity of LE also increased steadily; however, both the intensity and extent of LE declined significantly ∼1.5 years after completion of IV-MTX. Increases in the T1 and T2 relaxation rates above normal-appearing white matter were significantly correlated with each other and were dependent on the proportion of white matter affected. CONCLUSION Higher doses and more courses of IV-MTX were associated with increased intensity and extent of LE. There was a significant reduction in both the intensity and extent of LE after completion of therapy. The impact of these changes on neurocognitive functioning and quality of life in survivors remains to be determined. PMID:16219848

Identification of Cerebral Metal Ion Imbalance in the Brain of Aging Octodon degus

PubMed Central

Braidy, Nady; Poljak, Anne; Marjo, Chris; Rutlidge, Helen; Rich, Anne; Jugder, Bat-Erdene; Jayasena, Tharusha; Inestrosa, Nibaldo C.; Sachdev, Perminder S.

2017-01-01

The accumulation of redox-active transition metals in the brain and metal dyshomeostasis are thought to be associated with the etiology and pathogenesis of several neurodegenerative diseases, and Alzheimer’s disease (AD) in particular. As well, distinct biometal imaging and role of metal uptake transporters are central to understanding AD pathogenesis and aging but remain elusive, due inappropriate detection methods. We therefore hypothesized that Octodon degus develop neuropathological abnormalities in the distribution of redox active biometals, and this effect may be due to alterations in the expression of lysosomal protein, major Fe/Cu transporters, and selected Zn transporters (ZnTs and ZIPs). Herein, we report the distribution profile of biometals in the aged brain of the endemic Chilean rodent O. degus—a natural model to investigate the role of metals on the onset and progression of AD. Using laser ablation inductively coupled plasma mass spectrometry, our quantitative images of biometals (Fe, Ca, Zn, Cu, and Al) appear significantly elevated in the aged O. degus and show an age-dependent rise. The metals Fe, Ca, Zn, and Cu were specifically enriched in the cortex and hippocampus, which are the regions where amyloid plaques, tau phosphorylation and glial alterations are most commonly reported, whilst Al was enriched in the hippocampus alone. Using whole brain extracts, age-related deregulation of metal trafficking pathways was also observed in O. degus. More specifically, we observed impaired lysosomal function, demonstrated by increased cathepsin D protein expression. An age-related reduction in the expression of subunit B2 of V-ATPase, and significant increases in amyloid beta peptide 42 (Aβ42), and the metal transporter ATP13a2 were also observed. Although the protein expression levels of the zinc transporters, ZnT (1,3,4,6, and 7), and ZIP7,8 and ZIP14 increased in the brain of aged O. degus, ZnT10, decreased. Although no significant age-related change was observed for the major iron/copper regulator IRP2, we did find a significant increase in the expression of DMT1, a major transporter of divalent metal species, 5′-aminolevulinate synthase 2 (ALAS2), and the proto-oncogene, FOS. Collectively, our data indicate that transition metals may be enriched with age in the brains of O. degus, and metal dyshomeostasis in specific brain regions is age-related. PMID:28405187

Effects of red wine, tannic acid, or ethanol on glucose tolerance in non-insulin-dependent diabetic patients and on starch digestibility in vitro.

PubMed

Gin, H; Rigalleau, V; Caubet, O; Masquelier, J; Aubertin, J

1999-09-01

This study examines the effect of moderate intake of red wine, tannic acid, or ethanol during a meal in type 2 diabetic patients and the influence of tannic acid on the digestibility of starch by alpha-amylase. Thirty non-insulin-dependent diabetes mellitus (NIDDM) patients aged 53 +/- 6 years were studied (in vivo study) 10 of whom received red wine (200 mL), 10 tannic acid (150 mg), and 10 ethanol (16 g) with their midday meal (600 calories, 65 g carbohydrate, 20 g lipid, and 34 g protein). All patients were tested on two occasions (water or placebo v wine, alcohol, or tannic acid). The influence of tannic acid (0.25, 0.5, and 1 mg) on the digestibility of starch (100 mg) by alpha-amylase (100 U) was tested in vitro by sequential incubation at 37 degrees C (in vitro study). The maximum glucose excursion after lunch was 2.6 +/- 0.8 mmol/L at 90 minutes (T90) for water and 1.8 +/- 0.9 mmol/L at T90 for red wine taken with the meal. The values at T60 and T90 were significant (P < .01). Comparable results were obtained with tannic acid alone (nonalcoholic component of wine): the maximum glucose excursion after lunch was 2.76 +/- 0.9 mmol/L at T120 for placebo and 1.97 +/- 0.9 mmol/L at T90 for tannic acid (P < .01); no difference in glucose and insulin excursion was observed between water and ethanol. No interaction between tannic acid and starch was observed in the in vitro experiments, although after preincubation of alpha-amylase with tannic acid, digestion was slowed in a dose-dependent manner (6.1 +/- 1.1 minutes for 0.25 mg tannic acid and 13.1 +/- 1.59 minutes for 1 mg tannic acid). Drinking red wine with a meal did not increase blood glucose in NIDDM patients, and led to a slight decrease in some instances. The effect appeared to be mediated by the nonalcoholic compounds in wine such as tannic acid. Ethanol itself had no effect on plasma glucose or insulin levels.

Genetic polymorphisms in CYP2A6 are associated with a risk of cigarette smoking and predispose to smoking at younger ages.

PubMed

Pérez-Rubio, Gloria; López-Flores, Luis Alberto; Ramírez-Venegas, Alejandra; Noé-Díaz, Valeri; García-Gómez, Leonor; Ambrocio-Ortiz, Enrique; Sánchez-Romero, Candelaria; Hernández-Zenteno, Rafael De Jesús; Sansores, Raúl Humberto; Falfán-Valencia, Ramcés

2017-09-10

Nicotine is the main component of cigarettes that causes addiction, which is considered a complex disease, and genetic factors have been proposed to be involved in the development of addiction. The CYP2A6 gene encodes the main enzyme responsible for nicotine metabolism. Depending on the study population, different genetic variants of CYP2A6 associated with cigarette smoking have been described. Therefore, we evaluated the possible association between SNPs in CYP2A6 with cigarette smoking and nicotine addiction-related variables in Mexican mestizo smokers. We performed a genetic association study comparing light smokers (LS, n=349), heavy smokers (HS, n=351) and never-smokers (NS, n=394). SNPs rs1137115, rs4105144, rs1801272 and rs28399433 were genotyped in the CYP2A6 gene. We found that the A allele of rs1137115 (OR=1.41) in exon 1 of CYP2A6 and the T allele of rs4105144 (OR=1.32) in the 5' UTR of the gene are associated with the risk of cigarette smoking (p<0.05); rs1137115 affects the level of alternative splicing, resulting in a CYP2A6 isoform with low enzymatic activity, whereas rs4105144 is likely to be in a binding site for the transcription factor for glucocorticoids receptor (GR) and regulates the expression of CYP2A6. In addition, having a greater number of risk alleles (rs1137115 (A), rs4105144 (T) and rs28399433 (G)) is associated with a younger age at onset. The present study shows that in Mexican mestizos, the analyzed SNPs confer greater risk in terms of consumption and age of onset. Copyright © 2017. Published by Elsevier B.V.

Suppression of electron correlations in the collapsed tetragonal phase of CaFe2As2 under ambient pressure demonstrated by As75 NMR/NQR measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furukawa, Yuji; Roy, Beas; Ran, Sheng

2014-03-20

The static and the dynamic spin correlations in the low-temperature collapsed tetragonal and the high-temperature tetragonal phase in CaFe2As2 have been investigated by As75 nuclear magnetic resonance (NMR) and nuclear quadrupole resonance (NQR) measurements. Through the temperature (T) dependence of the nuclear spin lattice relaxation rates (1/T1) and the Knight shifts, although stripe-type antiferromagnetic (AFM) spin correlations are realized in the high-temperature tetragonal phase, no trace of the AFM spin correlations can be found in the nonsuperconducting, low-temperature, collapsed tetragonal (cT) phase. Given that there is no magnetic broadening in As75 NMR spectra, together with the T-independent behavior of magneticmore » susceptibility χ and the T dependence of 1/T1Tχ, we conclude that Fe spin correlations are completely quenched statically and dynamically in the nonsuperconducting cT phase in CaFe2As2.« less

Advanced Glycation Endproducts and Bone Material Properties in Type 1 Diabetic Mice

PubMed Central

Rubin, Mishaela R.; Paschalis, Eleftherios P.; Poundarik, Atharva; Sroga, Gyna E.; McMahon, Donald J.; Gamsjaeger, Sonja; Klaushofer, Klaus; Vashishth, Deepak

2016-01-01

Fractures, particularly at the lower extremities and hip, are a complication of diabetes. In both type 1 (T1D) and type 2 diabetes (T2D), fracture risk is disproportionately worse than that predicted from the measurement of bone mineral density. Although an explanation for this discrepancy is the presence of organic matrix abnormalities, it has not been fully elucidated how advanced glycation endproducts (AGEs) relate to bone deterioration at both the macroscopic and microscopic levels. We hypothesized that there would be a relationship between skeletal AGE levels (determined by Raman microspectroscopy at specific anatomical locations) and bone macroscopic and microscopic properties, as demonstrated by the biomechanical measures of crack growth and microindentation respectively. We found that in OVE26 mice, a transgenic model of severe early onset T1D, AGEs were increased by Raman (carboxymethyl-lysine [CML] wildtype (WT): 0.0143 ±0.0005 vs T1D: 0.0175 ±0.0002, p = 0.003) at the periosteal surface. These differences were associated with less tough bone in T1D by fracture mechanics (propagation toughness WT: 4.73 ± 0.32 vs T1D: 3.39 ± 0.24 NM/m1/2, p = 0.010) and by reference point indentation (indentation distance increase WT: 6.85 ± 0.44 vs T1D: 9.04 ± 0.77 μm; p = 0.043). Within T1D, higher AGEs by Raman correlated inversely with macroscopic bone toughness. These data add to the existing body of knowledge regarding AGEs and the relationship between skeletal AGEs with biomechanical indices. PMID:27140650

Kinetic phenomena in zero-gap semiconductors CuFeS2 and CuFeTe2: Effect of pressure and heat treatment

NASA Astrophysics Data System (ADS)

Popov, V. V.; Konstantinov, P. P.; Rud', Yu. V.

2011-10-01

Electrical resistivity ρ and Hal coefficient R are measured as a function of the temperature ( T = 1.7-310 K) and the magnetic field (up to H = 28 kOe) in zero-gap semiconductor CuFeS2 samples subjected to hydrostatic compression and under various heat-treatment conditions. At low temperatures, anomalies are observed in the kinetic effects related to the presence of ferromagnetic clusters: the magnetoresistance at T = 4.2 K and T = 20.4 K acquires a hysteretic character and thermopower α changes its sign at T < 15 K. The temperature dependence of conduction-electron concentration n in CuFeS2 has a power form in the temperature range T = 14-300 K, which is characteristic of the intrinsic conductivity in zero-gap semiconductors. In CuFeS2, we have n( T) ∝ T 1.2; in isoelectron compound Cu1.13Fe1.22Te2, we have n( T) ∝ T 1.93. Heat treatment is found to affect the intrinsic conductivity of CuFeS2, as the action of hydrostatic compression (carrier concentration changes); that is, the carrier concentration changes. However, a power form of the n( T) and ρ( T) dependences is retained.

Long-term weight-change slope, weight fluctuation and risk of type 2 diabetes mellitus in middle-aged Japanese men and women: findings of Aichi Workers' Cohort Study

PubMed Central

Zhang, Y; Yatsuya, H; Li, Y; Chiang, C; Hirakawa, Y; Kawazoe, N; Tamakoshi, K; Toyoshima, H; Aoyama, A

2017-01-01

Objective: This study aims to investigate the association of long-term weight-change slopes, weight fluctuation and the risk of type 2 diabetes mellitus (T2DM) in middle-aged Japanese men and women. Methods: A total of 4234 participants of Aichi Workers' Cohort Study who were aged 35–66 years and free of diabetes in 2002 were followed through 2014. Past body weights at the ages of 20, 25, 30, 40 years, and 5 years before baseline as well as measured body weight at baseline were regressed on the ages. Slope and root-mean-square-error of the regression line were obtained and used to represent the weight changes and the weight fluctuation, respectively. The associations of the weight-change slopes and the weight fluctuation with incident T2DM were estimated by Cox proportional hazards models. Results: During the median follow-up of 12.2 years, 400 incident cases of T2DM were documented. After adjustment for baseline overweight and other lifestyle covariates, the weight-change slopes were significantly associated with higher incidence of T2DM (hazard ratio (HR): 1.80, 95% confident interval (CI): 1.17–2.77 for men; and HR: 2.78, 95% CI: 1.07–7.23 for women), while the weight fluctuation was not (HR: 1.08, 95% CI: 1.00–1.18 for men and HR: 1.02, 95% CI: 0.84–1.25 for women). Conclusions: Regardless of the presence of overweight, the long-term weight-change slopes were significantly associated with the increased risk of T2DM; however, the weight fluctuation was not associated with the risk of T2DM in middle-aged Japanese men and women. PMID:28319107

Leptin but not adiponectin is related to type 2 diabetes mellitus in obese adolescents.

PubMed

Reinehr, Thomas; Woelfle, Joachim; Wiegand, Susanna; Karges, Beate; Meissner, Thomas; Nagl, Katrin; Holl, Reinhard W

2016-06-01

Adipokines have been suggested to be involved in the development of type 2 diabetes mellitus (T2DM). However, studies in humans are controversial and analyzes at the onset of disease are scarce. We compared adiponectin and leptin levels between 74 predominately Caucasian adolescents with T2DM and 74 body mass index (BMI)-, age-, and gender-matched controls without T2DM. Adiponectin and leptin were correlated to age, BMI, hemoglobin A1c (HbA1c), blood pressure, and lipids. Adolescents with T2DM showed significant lower leptin levels as compared with controls (18 ± 12 vs. 37 ± 23 ng/mL, p < 0.001), whereas the adiponectin levels did not differ between the adolescents with and without T2DM (5.0 ± 2.5 vs. 4.9 ± 2.5 µg/mL, p = 0.833). The associations between adiponectin and high-density lipoprotein (HDL) cholesterol (r = 0.42), systolic (r = -0.15), and diastolic blood pressure (r = -0.20) were stronger as the associations of leptin to these parameters (all r < 0.07). In multiple linear regression analysis, leptin was significantly and positively associated with BMI [β-coefficient: 1.3 (95% confidence interval (95% CI): ±0.5), p < 0.001] and female sex [β-coefficient: 9.7 (95% CI: ±6.7), p = 0.005], and negatively with age [β-coefficient: -2.3 (95% CI: ±2.1), p < 0.001] and HbA1c [β-coefficient -3.1 (95% CI: ±2.1), p = 0.011]. Adiponectin was not significantly associated with BMI, HbA1c, age, or gender in multiple linear regression analysis. Because adiponectin levels did not differ between obese adolescents with and without T2DM, hypoadiponectinemia as observed in obesity seems not to be involved in the genesis of T2DM. The relative hypoleptinemia in obese adolescents with T2DM as compared with obese adolescents without T2DM may contribute to the development of T2DM. Future longitudinal studies in humans are necessary to prove this hypothesis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Age Dependence of Immunity Induced by a Candidate Universal Influenza Vaccine in Mice

PubMed Central

García, Mayra; Misplon, Julia A.; Price, Graeme E.; Lo, Chia-Yun; Epstein, Suzanne L.

2016-01-01

Influenza has a major impact on the elderly due to increased susceptibility to infection with age and poor response to current vaccines. We have studied universal influenza vaccine candidates based on influenza A nucleoprotein and matrix 2 (A/NP+M2). Long-lasting protection against influenza virus strains of divergent subtypes is induced, especially with mucosal immunization. Here, we tested universal vaccination in BALB/c mice of different ages. Vaccination used intramuscular DNA priming to A/NP+M2 followed by intranasal (i.n.) boosting with recombinant adenoviruses (rAd) expressing the same antigens, or only A/NP+M2-rAd given i.n. Antigen-specific systemic antibody responses were induced in young, middle-aged, and elderly mice (2, 11–17, and 20 months old, respectively), but decreased with age. Antibody responses in bronchoalveolar lavage (BAL) were detected only in young mice. Antigen-specific T cell responses were seen in young and middle-aged but not elderly mice. A/NP+M2 vaccination by the two regimens above protected against stringent challenge in young and middle-aged mice, but not in elderly mice. However, mice vaccinated with A/NP-rAd or A/M2-rAd during their youth were partially protected against challenge 16 months later when they were elderly. In addition, a regimen of two doses of A/NP+M2-rAd given i.n. one month apart beginning in old age protected elderly mice against stringent challenge. This study highlights the potential benefit of cross-protective vaccines through middle age, and suggests that their performance might be enhanced in elderly individuals who had been exposed to influenza antigens early in life, as most humans have been, or by a two-dose rAd regimen given later in life. PMID:27055234

Age Dependence of Immunity Induced by a Candidate Universal Influenza Vaccine in Mice.

PubMed

García, Mayra; Misplon, Julia A; Price, Graeme E; Lo, Chia-Yun; Epstein, Suzanne L

2016-01-01

Influenza has a major impact on the elderly due to increased susceptibility to infection with age and poor response to current vaccines. We have studied universal influenza vaccine candidates based on influenza A nucleoprotein and matrix 2 (A/NP+M2). Long-lasting protection against influenza virus strains of divergent subtypes is induced, especially with mucosal immunization. Here, we tested universal vaccination in BALB/c mice of different ages. Vaccination used intramuscular DNA priming to A/NP+M2 followed by intranasal (i.n.) boosting with recombinant adenoviruses (rAd) expressing the same antigens, or only A/NP+M2-rAd given i.n. Antigen-specific systemic antibody responses were induced in young, middle-aged, and elderly mice (2, 11-17, and 20 months old, respectively), but decreased with age. Antibody responses in bronchoalveolar lavage (BAL) were detected only in young mice. Antigen-specific T cell responses were seen in young and middle-aged but not elderly mice. A/NP+M2 vaccination by the two regimens above protected against stringent challenge in young and middle-aged mice, but not in elderly mice. However, mice vaccinated with A/NP-rAd or A/M2-rAd during their youth were partially protected against challenge 16 months later when they were elderly. In addition, a regimen of two doses of A/NP+M2-rAd given i.n. one month apart beginning in old age protected elderly mice against stringent challenge. This study highlights the potential benefit of cross-protective vaccines through middle age, and suggests that their performance might be enhanced in elderly individuals who had been exposed to influenza antigens early in life, as most humans have been, or by a two-dose rAd regimen given later in life.

Prevalence of type 2 diabetes mellitus (T2DM) in the adult Russian population (NATION study).

PubMed

Dedov, Ivan; Shestakova, Marina; Benedetti, Massimo Massi; Simon, Dominique; Pakhomov, Iakov; Galstyan, Gagik

2016-05-01

To estimate type 2 diabetes mellitus (T2DM) prevalence in Russian adults. NATION is a national, epidemiological, cross-sectional study, conducted in Russia. In adults (aged 20-79 years), recruitment was stratified by age, sex, geographic region and settlement type to obtain a representative sample. Recruitment was in public areas with high numbers of people. T2DM was diagnosed by glycated haemoglobin A1c (HbA1c) levels (diabetes: HbA1c ≥6.5% [≥48mmol/mol]; pre-diabetes: HbA1c ≥5.7 to <6.5% [≥39 to <48mmol/mol]). Socio-demographic and anthropometric data were collected. Blood samples from 26,620 subjects were available. Overall, 5.4% were diagnosed with T2DM (previously diagnosed: 2.5%; previously undiagnosed: 2.9%); 19.3% were pre-diabetic. T2DM prevalence increased with age (up to 70 years) and was higher among females than males (6.1% vs. 4.7%, p<0.001). The estimated proportion of subjects with pre-diabetes and T2DM tended to increase with increasing body mass index. T2DM prevalence was higher in rural versus urban populations (6.7% vs. 5.0%, p<0.001). In the Russian adult population, 19.3% had pre-diabetes, T2DM prevalence was 5.4%, and 54% of subjects with diabetes were previously undiagnosed. These results may help to develop a new T2DM predictive, preventative and management programme in Russia. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Pulmonary CCR2+CD4+ T cells are immune regulatory and attenuate lung fibrosis development.

PubMed

Milger, Katrin; Yu, Yingyan; Brudy, Eva; Irmler, Martin; Skapenko, Alla; Mayinger, Michael; Lehmann, Mareike; Beckers, Johannes; Reichenberger, Frank; Behr, Jürgen; Eickelberg, Oliver; Königshoff, Melanie; Krauss-Etschmann, Susanne

2017-11-01

Animal models have suggested that CCR2-dependent signalling contributes to the pathogenesis of pulmonary fibrosis, but global blockade of CCL2 failed to improve the clinical course of patients with lung fibrosis. However, as levels of CCR2 + CD4 + T cells in paediatric lung fibrosis had previously been found to be increased, correlating with clinical symptoms, we hypothesised that distinct CCR2 + cell populations might either increase or decrease disease pathogenesis depending on their subtype. To investigate the role of CCR2 + CD4 + T cells in experimental lung fibrosis and in patients with idiopathic pulmonary fibrosis and other fibrosis. Pulmonary CCR2 + CD4 + T cells were analysed using flow cytometry and mRNA profiling, followed by in silico pathway analysis, in vitro assays and adoptive transfer experiments. Frequencies of CCR2 + CD4 + T cells were increased in experimental fibrosis-specifically the CD62L - CD44 + effector memory T cell phenotype, displaying a distinct chemokine receptor profile. mRNA profiling of isolated CCR2 + CD4 + T cells from fibrotic lungs suggested immune regulatory functions, a finding that was confirmed in vitro using suppressor assays. Importantly, adoptive transfer of CCR2 + CD4 + T cells attenuated fibrosis development. The results were partly corroborated in patients with lung fibrosis, by showing higher percentages of Foxp3 + CD25 + cells within bronchoalveolar lavage fluid CCR2 + CD4 + T cells as compared with CCR2 - CD4 + T cells. Pulmonary CCR2 + CD4 + T cells are immunosuppressive, and could attenuate lung inflammation and fibrosis. Therapeutic strategies completely abrogating CCR2-dependent signalling will therefore also eliminate cell populations with protective roles in fibrotic lung disease. This emphasises the need for a detailed understanding of the functions of immune cell subsets in fibrotic lung disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

In vivo quantification of T2* anisotropy in white matter fibers in marmoset monkeys

PubMed Central

Sati, P.; Silva, A. C.; van Gelderen, P.; Gaitan, M. I.; Wohler, J. E.; Jacobson, S.; Duyn, J. H.; Reich, D. S.

2011-01-01

T2*-weighted MRI at high field is a promising approach for studying noninvasively the tissue structure and composition of the brain. However, the biophysical origin of T2* contrast, especially in white matter, remains poorly understood. Recent work has shown that R2* (=1/T2*) may depend on the tissue’s orientation relative to the static magnetic field (B0) and suggested that this dependence could be attributed to local anisotropy in the magnetic properties of brain tissue. In the present work, we analyzed high-resolution, multi-gradient-echo images of in vivo marmoset brains at 7T, and compared them with ex vivo diffusion tensor images, to show that R2* relaxation in white matter is highly sensitive to the fiber orientation relative to the main field. We directly demonstrate this orientation dependence by performing in vivo multi-gradient-echo acquisitions in two orthogonal brain positions, uncovering a nearly 50% change in the R2*relaxation rate constant of the optic radiations. We attribute this substantial R2* anisotropy to local subvoxel susceptibility effects arising from the highly ordered and anisotropic structure of the myelin sheath. PMID:21906687

Potential Antiferromagnetic Fluctuations in Hole-Doped Iron-Pnictide Superconductor Ba1-xKxFe2As2 Studied by 75As Nuclear Magnetic Resonance Measurement0.1143/JPSJ.81.054704

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirano, Masanori; Yamada, Yuji; Saito, Taku

2012-04-12

We have performed 75As nuclear magnetic resonance (NMR) and nuclear quadrupole resonance (NQR) measurements on single-crystalline Ba1-xKxFe2As2 for x = 0.27–1. 75As nuclear quadruple resonance frequency (νQ) increases linearly with increasing x. The Knight shift K in the normal state shows Pauli paramagnetic behavior with a weak temperature T dependence. K increases gradually with increasing x. By contrast, the nuclear spin–lattice relaxation rate 1/T1 in the normal state has a strong T dependence, which indicates the existence of large antiferomagnetic (AF) spin fluctuations for all x's. The T dependence of 1/T1 shows a gaplike behavior below approximately 100 K formore » 0.6 < x < 0.9. This behaviors is well explained by the change in the band structure with the expansion of hole Fermi surfaces and the shrinkage and disappearance of electron Fermi surfaces at the Brillouin zone (BZ) with increasing x. The anisotropy of 1/T1, represented by the ratio of 1/T1ab to 1/T1c, is always larger than 1 for all x's, which indicates that stripe-type AF fluctuations are dominant in this system. The K in the superconducting (SC) state decreases, which corresponds to the appearance of spin-singlet superconductivity. The T dependence of 1/T1 in the SC state indicates a multiple-SC-gap feature. A simple two-gap model analysis shows that the larger superconducting gap gradually decreases with increasing x from 0.27 to 1 and a smaller gap decreases rapidly and nearly vanishes for x > 0.6 where electron pockets in BZ disappear.« less

Speech intelligibility after glossectomy and speech rehabilitation.

PubMed

Furia, C L; Kowalski, L P; Latorre, M R; Angelis, E C; Martins, N M; Barros, A P; Ribeiro, K C

2001-07-01

Oral tumor resections cause articulation deficiencies, depending on the site, extent of resection, type of reconstruction, and tongue stump mobility. To evaluate the speech intelligibility of patients undergoing total, subtotal, or partial glossectomy, before and after speech therapy. Twenty-seven patients (24 men and 3 women), aged 34 to 77 years (mean age, 56.5 years), underwent glossectomy. Tumor stages were T1 in 3 patients, T2 in 4, T3 in 8, T4 in 11, and TX in 1; node stages, N0 in 15 patients, N1 in 5, N2a-c in 6, and N3 in 1. No patient had metastases (M0). Patients were divided into 3 groups by extent of tongue resection, ie, total (group 1; n = 6), subtotal (group 2; n = 9), and partial (group 3; n = 12). Different phonological tasks were recorded and analyzed by 3 experienced judges, including sustained 7 oral vowels, vowel in a syllable, and the sequence vowel-consonant-vowel (VCV). The intelligibility of spontaneous speech (sequence story) was scored from 1 to 4 in consensus. All patients underwent a therapeutic program to activate articulatory adaptations, compensations, and maximization of the remaining structures for 3 to 6 months. The tasks were recorded after speech therapy. To compare mean changes, analyses of variance and Wilcoxon tests were used. Patients of groups 1 and 2 significantly improved their speech intelligibility (P<.05). Group 1 improved vowels, VCV, and spontaneous speech; group 2, syllable, VCV, and spontaneous speech. Group 3 demonstrated better intelligibility in the pretherapy phase, but the improvement after therapy was not significant. Speech therapy was effective in improving speech intelligibility of patients undergoing glossectomy, even after major resection. Different pretherapy ability between groups was seen, with improvement of speech intelligibility in groups 1 and 2. The improvement of speech intelligibility in group 3 was not statistically significant, possibly because of the small and heterogeneous sample.

Risk factors associated with higher body fat in US Army female soldiers.

PubMed

Anderson, Morgan K; Grier, Tyson; Canham-Chervak, Michelle; Bushman, Timothy T; Jones, Bruce H

2014-01-01

Increased body fat among US Soldiers is a continuing challenge that contributes to increased health risks and decreased combat readiness. Factors contributing to higher body fat among US Army female Soldiers have been minimally investigated. To investigate the risk factors associated with exceeding US Army body fat standards among active duty women in a light infantry brigade. Investigated risk factors include personal characteristics, physical training, physical fitness, and injury history. Data were obtained by survey from women in 3 US Army infantry brigades. Body fat percentage was calculated, and the women were categorized as either meeting or exceeding the maximum Army body fat standard of 30% for ages 17-20, 32% for ages 21-27, 34% for ages 28-39, and 36% for age 40 years or more. Army Physical Fitness Test (APFT) results were converted into tertiles (T), where T1=lowest 1/3 of performance and T3=highest 1/3 of performance. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from a multivariate analysis assessing risk associated with exceeding the Army body fat standards. Among the women surveyed (n=629), 22% exceeded Army body fat standards. Higher risk of being above the Army standard was associated with older age (≥29 years / ≤23 years) (OR=47, 95% CI, 1.24-4.92), and poor aerobic fitness (APFT 2-mile run) (T1/T3) OR=6.11, 95% CI, 2.62-14.24), (T1/T2) OR=2.66, 95% CI, 1.12-6.33). A marginal association was found for poor muscular strength (APFT sit-ups) (T1/T3). The results suggest that women who are older, and/or have poor aerobic fitness are more likely to exceed the maximum Army body fat standards.

Application of an integrated outbreak management plan for the control of leptospirosis in dairy cattle herds.

PubMed

Mughini-Gras, L; Bonfanti, L; Natale, A; Comin, A; Ferronato, A; La Greca, E; Patregnani, T; Lucchese, L; Marangon, S

2014-06-01

Two outbreaks of Leptospira borgpetersenii serovar Hardjo infection in dairy cattle herds were managed through the application of enhanced biosecurity measures, whole-herd antibiotic treatment and vaccination. Micro-agglutination test antibody titres were determined in paired serum samples at 3 weeks (T1: n = 125, 97% seropositivity, median 800, range 100-12 800) and 24 weeks (T2: n = 110, 88% seropositivity, median 200, range 100-6400) after vaccination and studied in relation to cows' age, herd of origin and sampling time. From T1 to T2, vaccine-elicited antibody titres decreased by 84·7% (95% CI 76·2-90·1). Consistent with increasing immunocompetence in calves (aged <12 months) and immunosenescence in adult cows (aged >36 months) associated with ageing, antibody titres correlated positively with calves' age and negatively with adult cows' age. No cow had cultivable, (histo)pathologically detectable and/or PCR-detectable leptospires in urine or kidney samples after treatment and vaccination. Vaccination together with proper biosecurity measures and chemoprophylaxis are an affordable insurance to control bovine leptospirosis.

CD4+ T-Cell- and Gamma Interferon-Dependent Protection against Murine Malaria by Immunization with Linear Synthetic Peptides from a Plasmodium yoelii 17-Kilodalton Hepatocyte Erythrocyte Protein

PubMed Central

Charoenvit, Yupin; Majam, Victoria Fallarme; Corradin, Giampietro; Sacci, John B.; Wang, Ruobing; Doolan, Denise L.; Jones, Trevor R.; Abot, Esteban; Patarroyo, Manuel E.; Guzman, Fanny; Hoffman, Stephen L.

1999-01-01

Most work on protective immunity against the pre-erythrocytic stages of malaria has focused on induction of antibodies that prevent sporozoite invasion of hepatocytes, and CD8+ T-cell responses that eliminate infected hepatocytes. We recently reported that immunization of A/J mice with an 18-amino-acid synthetic linear peptide from Plasmodium yoelii sporozoite surface protein 2 (SSP2) in TiterMax adjuvant induces sterile protection that is dependent on CD4+ T cells and gamma interferon (IFN-γ). We now report that immunization of inbred A/J mice and outbred CD1 mice with each of two linear synthetic peptides from the 17-kDa P. yoelii hepatocyte erythrocyte protein (HEP17) in the same adjuvant also induces protection against sporozoite challenge that is dependent on CD4+ T cells and IFN-γ. The SSP2 peptide and the two HEP17 peptides are recognized by B cells as well as T cells, and the protection induced by these peptides appears to be directed against the infected hepatocytes. In contrast to the peptide-induced protection, immunization of eight different strains of mice with radiation-attenuated sporozoites induces protection that is absolutely dependent on CD8+ T cells. Data represented here demonstrate that CD4+ T-cell-dependent protection can be induced by immunization with linear synthetic peptides. These studies therefore provide the foundation for an approach to pre-erythrocytic-stage malaria vaccine development, based on the induction of protective CD4+ T-cell responses, which will complement efforts to induce protective antibody and CD8+ T-cell responses. PMID:10531206

Neural space and biomechanical integrity of the developing cervical spine in compression.

PubMed

Nuckley, David J; Van Nausdle, Joseph A; Eck, Michael P; Ching, Randal P

2007-03-15

A factorial study design was used to examine the biomechanical and neuroprotective integrity of the cervical spine throughout maturation using a postmortem baboon model. To investigate changes with spinal development that affect the neuroprotective ability of the cervical spine in compressive loading. Child spinal cord injuries claim and debilitate thousands of children in the United States each year. Many of these injuries are diagnostically and mechanistically difficult to classify, treat, and prevent. Biomechanical studies on maturing spinal tissues have identified decreased stiffness and tolerance characteristics for children compared with adults. Unfortunately, while neurologic deficit typically dictates functional outcome, no previous studies have examined the neuroprotective role of the pediatric cervical spine. Twenty-two postmortem baboon cervical spines across the developmental age spectrum were tested. Two functional spinal unit segments (Oc-C2, C3-C5, and C6-T1) were instrumented with transducers to measure dynamic changes in the spinal canal. These tissues were compressed to 70% strain dynamically, and the resultant mechanics and spinal canal occlusions were recorded. Classic injury patterns were observed in all of the specimens tested. The compressive mechanics exhibited a significant age relationship (P < 0.0001). Furthermore, while the peak-percent spinal canal occlusion was not age dependent, the percent occlusion just before failure did demonstrate a significant decrease with advancing age (P = 0.0001). The neuroprotective ability of the cervical spine preceding failure appears to be age dependent, where the young spine can produce greater spinal canal occlusions without failure than its adult counterpart. The overall percent of the spinal canal occluded during a compression injury was not age dependent; however, these data reveal the neuroprotective ability of the child spine to be more sensitive as an injury predictor than the biomechanical fracture data.

Influence of high glucose and advanced glycation end-products (ages) levels in human osteoblast-like cells gene expression.

PubMed

Miranda, Cristina; Giner, Mercè; Montoya, M José; Vázquez, M Angeles; Miranda, M José; Pérez-Cano, Ramón

2016-08-31

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporotic fracture. Several factors have been identified as being potentially responsible for this risk, such as alterations in bone remodelling that may have been induced by changes in circulating glucose or/and by the presence of non-oxidative end products of glycosylation (AGEs). The aim of this study is to assess whether such variations generate a change in the gene expression related to the differentiation and osteoblast activity (OPG, RANKL, RUNX2, OSTERIX, and AGE receptor) in primary cultures of human osteoblast-like cells (hOB). We recruited 32 patients; 10 patients had osteoporotic hip fractures (OP group), 12 patients had osteoporotic hip fractures with T2DM (T2DM group), and 10 patients had hip osteoarthritis (OA group) with no osteoporotic fractures and no T2DM. The gene expression was analyzed in hOB cultures treated with physiological glucose concentration (4.5 mM) as control, high glucose (25 mM), and high glucose plus AGEs (2 μg/ml) for 24 h. The hOB cultures from patients with hip fractures presented slower proliferation. Additionally, the hOB cultures from the T2DM group were the most negatively affected with respect to RUNX2 and OSX gene expression when treated solely with high glucose or with high glucose plus AGEs. Moreover, high levels of glucose induced a major decrease in the RANKL/OPG ratio when comparing the OP and the T2DM groups to the OA group. Our data indicates an altered bone remodelling rate in the T2DM group, which may, at least partially, explain the reduced bone strength and increased incidence of non-traumatic fractures in diabetic patients.

Effects of RF profile on precision of quantitative T2 mapping using dual-echo steady-state acquisition.

PubMed

Wu, Pei-Hsin; Cheng, Cheng-Chieh; Wu, Ming-Long; Chao, Tzu-Cheng; Chung, Hsiao-Wen; Huang, Teng-Yi

2014-01-01

The dual echo steady-state (DESS) sequence has been shown successful in achieving fast T2 mapping with good precision. Under-estimation of T2, however, becomes increasingly prominent as the flip angle decreases. In 3D DESS imaging, therefore, the derived T2 values would become a function of the slice location in the presence of non-ideal slice profile of the excitation RF pulse. Furthermore, the pattern of slice-dependent variation in T2 estimates is dependent on the RF pulse waveform. Multi-slice 2D DESS imaging provides better inter-slice consistency, but the signal intensity is subject to integrated effects of within-slice distribution of the actual flip angle. Consequently, T2 measured using 2D DESS is prone to inaccuracy even at the designated flip angle of 90°. In this study, both phantom and human experiments demonstrate the above phenomena in good agreement with model prediction. © 2013.

Advanced Glycation End Products and Oxidative Stress in Type 2 Diabetes Mellitus

PubMed Central

Nowotny, Kerstin; Jung, Tobias; Höhn, Annika; Weber, Daniela; Grune, Tilman

2015-01-01

Type 2 diabetes mellitus (T2DM) is a very complex and multifactorial metabolic disease characterized by insulin resistance and β cell failure leading to elevated blood glucose levels. Hyperglycemia is suggested to be the main cause of diabetic complications, which not only decrease life quality and expectancy, but are also becoming a problem regarding the financial burden for health care systems. Therefore, and to counteract the continually increasing prevalence of diabetes, understanding the pathogenesis, the main risk factors, and the underlying molecular mechanisms may establish a basis for prevention and therapy. In this regard, research was performed revealing further evidence that oxidative stress has an important role in hyperglycemia-induced tissue injury as well as in early events relevant for the development of T2DM. The formation of advanced glycation end products (AGEs), a group of modified proteins and/or lipids with damaging potential, is one contributing factor. On the one hand it has been reported that AGEs increase reactive oxygen species formation and impair antioxidant systems, on the other hand the formation of some AGEs is induced per se under oxidative conditions. Thus, AGEs contribute at least partly to chronic stress conditions in diabetes. As AGEs are not only formed endogenously, but also derive from exogenous sources, i.e., food, they have been assumed as risk factors for T2DM. However, the role of AGEs in the pathogenesis of T2DM and diabetic complications—if they are causal or simply an effect—is only partly understood. This review will highlight the involvement of AGEs in the development and progression of T2DM and their role in diabetic complications. PMID:25786107

Does Tinnitus Distress Depend on Age of Onset?

PubMed Central

Schlee, Winfried; Kleinjung, Tobias; Hiller, Wolfgang; Goebel, Gerhard; Kolassa, Iris-Tatjana; Langguth, Berthold

2011-01-01

Objectives Tinnitus is the perception of a sound in the absence of any physical source of it. About 5–15% of the population report hearing such a tinnitus and about 1–2% suffer from their tinnitus leading to anxiety, sleep disorders or depression. It is currently not completely understood why some people feel distressed by their tinnitus, while others don't. Several studies indicate that the amount of tinnitus distress is associated with many factors including comorbid anxiety, comorbid depression, personality, the psychosocial situation, the amount of the related hearing loss and the loudness of the tinnitus. Furthermore, theoretical considerations suggest an impact of the age at tinnitus onset influencing tinnitus distress. Methods Based on a sample of 755 normal hearing tinnitus patients we tested this assumption. All participants answered a questionnaire on the amount of tinnitus distress together with a large variety of clinical and demographic data. Results Patients with an earlier onset of tinnitus suffer significantly less than patients with an onset later in life. Furthermore, patients with a later onset of tinnitus describe their course of tinnitus distress as more abrupt and distressing right from the beginning. Conclusion We argue that a decline of compensatory brain plasticity in older age accounts for this age-dependent tinnitus decompensation. PMID:22125612

Physical activity and hippocampal volume in middle-aged patients with type 1 diabetes.

PubMed

Nunley, Karen A; Leckie, Regina L; Orchard, Trevor J; Costacou, Tina; Aizenstein, Howard J; Jennings, J Richard; Erickson, Kirk I; Rosano, Caterina

2017-04-18

To examine the cross-sectional association between physical activity (PA) and hippocampal volume in middle-aged adults with childhood-onset type 1 diabetes (T1D), and whether hyperglycemia and insulin sensitivity contribute to this relationship. We analyzed neuroimaging and self-reported PA data from 79 adults with T1D from the Pittsburgh Epidemiology of Diabetes Complications Study (mean age 50 years, mean duration 41 years) and 122 similarly aged adults without T1D (mean age 48 years). Linear regression models, controlling for intracranial volume, sex, education, and age, tested associations between PA and gray matter volumes of hippocampi and total brain in the 2 groups. For the T1D group, models further controlled for hyperglycemia and glucose disposal rate, a measure of insulin sensitivity. PA was significantly lower in the T1D than in the non-T1D group (median [interquartile range] 952 kcal [420-2,044] vs 1,614 kcal [588-3,091], respectively). Higher PA was significantly associated with larger hippocampi for T1D, but not for non-T1D (standardized β [ p values] from regression models adjusted for intracranial volume, sex, age, and education: 0.270 [ p < 0.001] and 0.098 [ p = 0.12], respectively). Neither hyperglycemia nor glucose disposal rate substantially modified this association. Relationships between PA and total brain gray matter volume were similar. A cross-sectional association between higher PA and larger hippocampi is already detectable by middle age for these patients with T1D, and it appears robust to chronic hyperglycemia and insulin sensitivity. Proof-of-concept studies should investigate whether increasing PA preserves hippocampal volume and the mechanisms underlying the effects of PA on hippocampal volume. © 2017 American Academy of Neurology.

Decreasing incidence of type 2 diabetes mellitus in the United States, 2007-2012: Epidemiologic findings from a large US claims database.

PubMed

Weng, Wayne; Liang, Yuanjie; Kimball, Edward S; Hobbs, Todd; Kong, Sheldon X; Sakurada, Brian; Bouchard, Jonathan

2016-07-01

To explore epidemiological trends in type 2 diabetes mellitus (T2D) in the US between 2007 and 2012 using a large US claims database, with a particular focus on demographics, prevalence, newly-diagnosed cases, and comorbidities. Truven Health MarketScan® Databases were used to identify patients with claims evidence of T2D in the years 2007 and 2012. Newly-diagnosed T2D was characterized by an absence of any T2D claims or related drug claims for 6months preceding the index claim. Demographic and comorbidity characteristics of the prevalent and new-onset T2D groups were compared and analyzed descriptively for trends over time. The overall prevalence of T2D remained stable from 2007 (1.24 million cases/15.07 million enrolled; 8.2%) to 2012 (2.04 million cases/24.52 million enrolled; 8.3%), while the percentage of newly-diagnosed cases fell dramatically from 2007 (152,252 cases; 1.1%) to 2012 (147,011 cases; 0.65%). The mean age of patients with prevalent T2D was similar in 2007 (60.6y) and 2012 (60.0y), while the mean age of newly-diagnosed T2D patients decreased by 3years from 2007 (57.7y) to 2012 (54.8y). Hypertension and hyperlipidemia were the most common comorbidities, evident in 50-75% of T2D patients, and increased markedly from 2007 to 2012 in both prevalent and new-onset T2D populations. Cardiovascular disease decreased slightly in prevalent (-0.9%) and new-onset (-2.8%) cases. This large US health claims database analysis suggests stabilization in prevalence and declining incidence of T2D over a recent 5-year period, a downward shift in age at T2D diagnosis, but increases in several comorbidities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prevalence and risk factors for type 2 diabetes mellitus with Prader-Willi syndrome: a single center experience.

PubMed

Yang, Aram; Kim, Jinsup; Cho, Sung Yoon; Jin, Dong-Kyu

2017-08-30

Prader-Willi syndrome (PWS) is often related to severe obesity and type-2 diabetes mellitus (T2DM). However, few studies, and none in Korea, have examined prevalence of T2DM and other variables in PWS. The aim of this study was to identify the prevalence and associated risk factors for T2DM in Korean patients with PWS. We performed a retrospective cohort study of the 84 PWS patients aged 10 or over (10.3-35.8 years of age) diagnosed with PWS at Samsung Medical Center from 1994 to 2016. We estimated occurrence of T2DM according to age (10-18 years versus >18 years), body mass index (BMI), genotype, history of growth hormone therapy, homeostasis model of assessment-insulin resistance (HOMA-IR), and the presence of dyslipidemia, hypogonadism, or central precocious puberty. Additionally, we investigated cutoff values of risk factors for development of T2DM. Twenty-nine of a total 211 patients, diagnosed with PWS over the study period, were diagnosed as having T2DM (13.7%, mean age 15.9 ± 3.6 years). In the >18 years group, obesity, HOMA-IR, and presence of dyslipidemia, hypogonadism, or central precocious puberty were associated with the occurrence of T2DM in univariate analysis. In multivariate logistic regression analysis, only obesity (p = 0.001) and HOMA-IR (p < 0.001) were significant predictive factors for T2DM. Based on the receiver operating a characteristic curve analysis, the cutoff values of HOMA-IR and BMI for predicting T2DM were >2.7 and >28.49 kg/m 2 , respectively. Of the 29 patients, seven had ≥1 microvascular complication, with non-proliferative diabetic retinopathy in 6 of 7 cases. Advanced age and HOMA-IR were positively correlated with diabetic microvascular complications (p < 0.05, Spearman correlation coefficient 0.393 and 0.434, respectively). The prevalence of diabetes in Korean PWS was similar to that in previous results. BMI and HOMA-IR were strong predictive factors for the development of T2DM in PWS. We specifically suggest the regular monitoring of glucose homeostasis parameters through a detailed settlement of ethnically specific cutoff values for BMI and HOMA-IR in PWS to prevent progression of T2DM and diabetic microvascular complications.

A Point System for Predicting 10-Year Risk of Developing Type 2 Diabetes Mellitus in Japanese Men: Aichi Workers' Cohort Study.

PubMed

Yatsuya, Hiroshi; Li, Yuanying; Hirakawa, Yoshihisa; Ota, Atsuhiko; Matsunaga, Masaaki; Haregot, Hilawe Esayas; Chiang, Chifa; Zhang, Yan; Tamakoshi, Koji; Toyoshima, Hideaki; Aoyama, Atsuko

2018-03-17

Relatively little evidence exists for type 2 diabetes mellitus (T2DM) prediction models from long-term follow-up studies in East Asians. This study aims to develop a point-based prediction model for 10-year risk of developing T2DM in middle-aged Japanese men. We followed 3,540 male participants of Aichi Workers' Cohort Study, who were aged 35-64 years and were free of diabetes in 2002, until March 31, 2015. Baseline age, body mass index (BMI), smoking status, alcohol consumption, regular exercise, medication for dyslipidemia, diabetes family history, and blood levels of triglycerides (TG), high density lipoprotein cholesterol (HDLC) and fasting blood glucose (FBG) were examined using Cox proportional hazard model. Variables significantly associated with T2DM in univariable models were simultaneously entered in a multivariable model for determination of the final model using backward variable selection. Performance of an existing T2DM model when applied to the current dataset was compared to that obtained in the present study's model. During the median follow-up of 12.2 years, 342 incident T2DM cases were documented. The prediction system using points assigned to age, BMI, smoking status, diabetes family history, and TG and FBG showed reasonable discrimination (c-index: 0.77) and goodness-of-fit (Hosmer-Lemeshow test, P = 0.22). The present model outperformed the previous one in the present subjects. The point system, once validated in the other populations, could be applied to middle-aged Japanese male workers to identify those at high risk of developing T2DM. In addition, further investigation is also required to examine whether the use of this system will reduce incidence.

Obesity is a determinant of arterial stiffness independent of traditional risk factors in Asians with young-onset type 2 diabetes.

PubMed

Liu, Jian-Jun; Sum, Chee Fang; Tavintharan, Subramaniam; Yeoh, Lee Ying; Ng, Xiao Wei; Moh, Angela Mei Chung; Lee, Simon; Tang, Wern Ee; Lim, Su Chi

2014-10-01

Type 2 diabetes (T2DM) among the young population has become a serious concern globally, presumably due to the rising trend of obesity. Compared to other forms of diabetes, young-onset T2DM experiences more cardiovascular events and other vascular complications although the underlying mechanisms remain largely unknown. Increased arterial stiffness is a hallmark of vasculopathy. We aim to study the clinical and metabolic determinants of arterial stiffness in a cohort of multi-ethnic Asians with young-onset T2DM. 179 subjects with T2DM onset age below 30 years old were selected in this cross sectional study. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV). PWV was correlated with age, duration of diabetes, systolic blood pressure, alanine aminotransferase, urinary albumin-to-creatinine ratio (ACR) and eGFR in bivariate correlation analysis. However, PWV was only significantly correlated with body mass index (BMI), waist circumference, urinary ACR and eGFR after adjustment for age. Overweight individuals with young-onset T2DM had significantly higher PWV levels compared to their lean counterparts (7.3 ± 2.4 m/s vs 6.4 ± 2.3 m/s, p = 0.072 and p < 0.0001 without and with adjustment for age, respectively). Multivariable regression models revealed that age, BMI, eGFR and usage of insulin were independently associated with PWV. These 4 variables explained 35.5% variance in PWV levels. Age, BMI, renal function and insulin usage are the main determinants of PWV levels in Asians with young-onset T2DM. Notably, obesity is a modifiable determinant of arterial stiffness independent of high blood pressure, dyslipidemia and hyperglycemia in this population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

24-Hour Kinetics of Cardiac Troponin-T Using a "High-Sensitivity" Assay in Thoroughbred Chuckwagon Racing Geldings after Race and Associated Clinical Sampling Guidelines.

PubMed

Shields, E; Seiden-Long, I; Massie, S; Leguillette, R

2018-01-01

A "high-sensitivity" cardiac troponin-T (hscTnT) assay recently has been validated for use in horses and is a specific biomarker of myocardial damage. Postexercise release kinetics of cTnT utilizing the hscTnT assay have yet to be established in horses. To determine: (1) cTnT release kinetics in racing Thoroughbreds after a high-intensity 5/8th mile Chuckwagon race; (2) the effects of age on pre- and postrace cTnT concentrations; and (3) sampling guidelines for clinicians evaluating horses presenting after exercise. Samples were obtained from 38 Thoroughbred geldings aged 5-16 years before racing and immediately, 2, 3, 4, 6, 12, and 24 hour postrace. Prospective, observational study with convenience sampling. A fifth-generation hscTnT assay was used for plasma sample analysis, and concentrations were compared at all time-points. Correlations were determined between cTnT concentrations and age. Biochemistry analysis was performed to assess rhabdomyolysis, renal failure, and exercise-induced dehydration. All horses with measureable cTnT concentrations had significant postexercise increases in cTnT with a median peak (8.0 ng/L) at 3-hour postrace. All horses had peak postexercise cTnT concentrations 2- to 6-hour postrace ≤ the 99th percentile upper reference limit of 23.2 ng/L, after which all cTnT concentrations decreased until returning to baseline by 12-24 hours. There was no correlation over time between cTnT concentrations and age. In racing Thoroughbreds completing short-duration, high-intensity Chuckwagon races, cTnT concentrations are expected to be increased 2- to 6-hour postrace and to decrease by 12-24 hours while remaining ≤23.2 ng/L throughout. This study contributes to establishing guidelines for clinical use of the hscTnT assay in exercising horses. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Halogen Occultation Experiment (HALOE) optical filter characterization

NASA Technical Reports Server (NTRS)

Harvey, Gale A.

1989-01-01

The Halogen Occultation Experiment (HALOE) is a solar occultation experiment that will fly on the Upper Atmosphere Research Satellite to measure mixing ratio profiles of O3, H2O, NO2, NO, CH4, HCl, and HF. The inversion of the HALOE data will be critically dependent on a detailed knowledge of eight optical filters. A filter characterization program was undertaken to measure in-band transmissions, out-of-band transmissions, in-band transmission shifts with temperature, reflectivities, and age stability. Fourier Transform Infrared Spectrometers were used to perform measurements over the spectral interval 400/cm to 6300/cm (25 micrometers to 1.6 micrometers). Very high precision (0.1 percent T) in-band measurements and very high resolution (0.0001 percent T) out-of-band measurements have been made. The measurements revealed several conventional leaks at 0.01 percent transmission and greatly enhanced (1,000) leaks to the 2-element filters when placed in a Fabry-Perot cavity. Filter throughput changes by 5 percent for a 25 C change in filter temperature.

[Application and usefulness of flowcytometry in the haematology laboratory].

PubMed

Kubota, K; Makino, M

1991-02-01

Recent technological advances, in both hardware and software, and availability of various monoclonal antibodies (MoAb) for membrane antigens of blood cells have expanded the application of flow cytometry (FCM) in medicine. In the haematology laboratory, FCM has been used mainly for assessment of leukemia and lymphoma and for determination of lymphocyte subsets. In acute leukemia, FCM is useful to classify ALL accurately, particularly for bi phenotypic or mixed lineage leukemia. In lymphocyte subset determination, we found that the use of magnetic beads to remove contaminating monocytes and some granulocytes to purify the lymphocyte-population is helpful in clarify the subsets. We present data describing the age dependent variation in lymphocyte subsets in the pediatric population. In early life (up to 2 years old), CD4 (+) 2H4 (+) lymphocyte overwhelmed CD4 (+) 2H4 (-) cells, implying predominance of suppressor-inducer activity. We also presented some cases of markedly increased double negative T cells (gamma/delta TCR) and a rare case of double positive (CD4+, CD8+) T cells.