[Association of cognitive impairments with carbohydrate and lipid metabolic parameters in type 2 diabetes mellitus patients undergoing coronary bypass surgery].

PubMed

Trubnikova, О А; Mamontova, A S; Tarasova, I V; Maleva, O V; Kuzmina, A A; Barbarash, O L

2015-01-01

AIM. To comparatively analyze neuropsychological parameters in patients with coronary artery disease (CAD) depending on the presence of type 2 diabetes mellitus (DM) and to evaluate their relationship to carbohydrate and lipid metabolic parameters. Fifty-two male patients with type 2 DM (mean age 58.0 ± 5.7 years) and 46 male patients without this condition (mean age 57.1 ± 6.2 years) were examined. Besides standard clinical examination, neurophysiological testing and determinations of glycated hemoglobin (HbA(1c),) and insulin concentrations, QUICKI index, and blood lipid profile were made. The patients with DM differed from those without DM in the lower speeds of sensorimotor reactions during neurodynamic testing and in worse attention values. In the patients with type 2 DM, the worse neuropsychological status was associated with the higher plasma concentrations of glucose, insulin, HbA(1c), total cholesterol, low-density lipoproteins, and triglycerides and with the lower levels of high-density lipoproteins. These relationships were not observed in the patients without DM. The patients with CAD concurrent with DM had a worse neurophysiological status than those without DM. Only the DM group demonstrated a relationship between cognitive impairments and carbohydrate metabolic markers. Carbohydrate and lipid metabolic disturbances may be assumed to make a negative contribution to the development of cognitive impairments in patients with CAD concurrent with type 2 DM.

Dietary tartary buckwheat intake attenuates insulin resistance and improves lipid profiles in patients with type 2 diabetes: a randomized controlled trial.

PubMed

Qiu, Ju; Liu, Yanping; Yue, Yanfen; Qin, Yuchang; Li, Zaigui

2016-12-01

Tartary buckwheat (TB) is rich in protein, dietary fiber, and flavonoids and has been reported to affect type 2 diabetes mellitus (T2DM) in animal experiments, but limited information on the benefit of TB as a whole food in T2DM patients is available. Thus, we tested the hypothesis that a daily replacement of a portion of the staple food with TB will improve risk factors of T2DM, including fasting glucose, insulin resistance, and lipid profile. In a parallel, randomized, open-label, controlled trial, 165 T2DM patients were randomly assigned to a control diet group (DC group; systematic diet plans and intensive nutritional education) or a TB intervention group (TB group; daily replacement of a portion of staple food with TB food). Blood samples and diet information were collected at baseline and after 4 weeks of intervention. The TB group decreased fasting insulin (2.46-2.39 Ln mU/L), total cholesterol (5.08-4.79 mmol/L), and low-density lipoprotein cholesterol (3.00-2.80 mmol/L) compared with the DC group at 4 weeks (P<.05). No significant differences in blood glucose or glycated hemoglobin levels were noted between the TB and DC groups. In addition, subgroup analyses based on daily TB intake dose showed a reduction in insulin, total cholesterol, and low-density lipoprotein cholesterol, but also insulin resistance was observed when TB intake dose was greater than 110 g/d. These results support the hypothesis that TB may improve insulin resistance and lipid profile in T2DM patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Beneficial Effects of Vildagliptin on Metabolic Parameters in Patients with Type 2 Diabetes.

PubMed

Shimodaira, Masanori; Niwa, Tomohiro; Nakajima, Koji; Kobayashi, Mutsuhiro

2015-01-01

Blood pressure and lipid profile are important determinants of cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). To identify the pleiotropic effects of vildagliptin other than blood glucose lowering effect, a retrospective study was conducted in 128 patients with T2DM treated with vildagliptin 50 mg twice daily. The patients were separated into two groups: patients who were initiated with vildagliptin as monotherapy or add-on therapy (add-on group, n = 66) and patients who were switched from sitagliptin 100 mg once daily to vildagliptin (switching group, n = 62). Hemoglobin A1c (HbA1c), body mass index (BMI), systolic/diastolic blood pressure, lipid profiles, and uric acid (UA) at 3, 6, and 12 months of vildagliptin therapy were compared with those at baseline in each group. At baseline, there were no significant differences in HbA1c, BMI, blood pressures, lipid profiles, and UA levels between the two groups. After vildagliptin initiation, HbA1c decreased significantly but BMI and blood pressure did not change in both groups. Only in the add-on group, total cholesterol and low density lipoprotein cholesterol decreased significantly from baseline to 3, 6, and 12 months. On the other hand, triglyceride and high-density lipoprotein cholesterol did not change in both groups. Serum UA levels decreased only in the switching group from baseline to 3, 6, and 12 months. These results indicate that vildagliptin add-on treatment may have beneficial effects on lipid profiles, and switching from sitagliptin to vildagliptin reduces UA in patients with T2DM; these are important findings linked to the beneficial effects of vildagliptin on lipid and UA metabolisms in the treatment of T2DM.

The Distribution and Annihilation of Dark Matter Around Black Holes

NASA Technical Reports Server (NTRS)

Schnittman, Jeremy D.

2015-01-01

We use a Monte Carlo code to calculate the geodesic orbits of test particles around Kerr black holes, generating a distribution function of both bound and unbound populations of dark matter (DM) particles. From this distribution function, we calculate annihilation rates and observable gamma-ray spectra for a few simple DM models. The features of these spectra are sensitive to the black hole spin, observer inclination, and detailed properties of the DM annihilation cross-section and density profile. Confirming earlier analytic work, we find that for rapidly spinning black holes, the collisional Penrose process can reach efficiencies exceeding 600%, leading to a high-energy tail in the annihilation spectrum. The high particle density and large proper volume of the region immediately surrounding the horizon ensures that the observed flux from these extreme events is non-negligible.

Finite Temperature Density Profile in SFDM

NASA Astrophysics Data System (ADS)

Robles, Victor H.; Matos, T.

Recent high-quality observations of low surface brightness (LSB) galaxies have shown that their dark matter (DM) halos prefer flat central density profiles. On the other hand the standard cold dark matter model simulations predict a more cuspy behavior. Feedback from star formation has been widely used to reconcile simulations with observations, this might be successful in field dwarf galaxies but its success in high mass LSB galaxies remains unclear. Additionally, including too much feedback in the simulations is a double-edged sword, in order to obtain a cored DM distribution from an initially cuspy one, feedback recipes require to remove a large quantity of baryons from the center of galaxies, however, other feedback recipes produce twice more satellite galaxies of a given luminosity and with much smaller mass to light ratios from those that are observed. Therefore, one DM profile that produces cores naturally and that does not require large amounts of feedback would be preferable. We find both requirements to be satisfied in the scalar field dark matter model. Here, we consider that the dark matter is an auto-interacting real scalar field in a thermal bath of temperature T with an initial Z 2 symmetric potential, as the universe expands the temperature drops so that the Z 2 symmetry is spontaneously broken and the field rolls down to a new minimum. We give an exact analytic solution to the Newtonian limit of this system and show both, that it satisfies the two desired requirements and that the rotation curve profile is not longer universal.

Effectiveness of chamomile tea on glycemic control and serum lipid profile in patients with type 2 diabetes.

PubMed

Rafraf, M; Zemestani, M; Asghari-Jafarabadi, M

2015-02-01

This study aimed at assessing the effects of chamomile tea consumption on glycemic control and serum lipid profile in patients with type 2 diabetes mellitus (T2DM). This single-blind randomized controlled clinical trial was conducted on 64 individuals with T2DM (males and females) aged between 30 and 60 years. The intervention group (n = 32) consumed chamomile tea (3 g/150 mL hot water) three times per day immediately after meals for 8 weeks. The control group (n = 32) followed a water regimen for the same intervention period. Fasting blood samples, anthropometric measurements, and 3-day, 24-h dietary recalls were collected at the baseline and at the end of the trial. Data were analyzed by independent t test, paired t test, Pearson correlation test, and analysis of covariance. Chamomile tea significantly decreased concentration of HbA1C (p = 0.03), serum insulin levels (p < 0.001), homeostatic model assessment for insulin resistance (p < 0.001), total cholesterol (p = 0.001), triglyceride (p < 0.001), and low-density lipoprotein cholesterol (p = 0.05) compared with control group. No significant changes were shown in serum high-density lipoprotein cholesterol levels in both groups. Chamomile tea has some beneficial effects on glycemic control and serum lipid profile in T2DM patients.

Self-Heating Dark Matter via Semiannihilation

NASA Astrophysics Data System (ADS)

Kamada, Ayuki; Kim, Hee Jung; Kim, Hyungjin; Sekiguchi, Toyokazu

2018-03-01

The freeze-out of dark matter (DM) depends on the evolution of the DM temperature. The DM temperature does not have to follow the standard model one, when the elastic scattering is not sufficient to maintain the kinetic equilibrium. We study the temperature evolution of the semiannihilating DM, where a pair of the DM particles annihilate into one DM particle and another particle coupled to the standard model sector. We find that the kinetic equilibrium is maintained solely via semiannihilation until the last stage of the freeze-out. After the freeze-out, semiannihilation converts the mass deficit to the kinetic energy of DM, which leads to nontrivial evolution of the DM temperature. We argue that the DM temperature redshifts like radiation as long as the DM self-interaction is efficient. We dub this novel temperature evolution as self-heating. Notably, the structure formation is suppressed at subgalactic scales like keV-scale warm DM but with GeV-scale self-heating DM if the self-heating lasts roughly until the matter-radiation equality. The long duration of the self-heating requires the large self-scattering cross section, which in turn flattens the DM density profile in inner halos. Consequently, self-heating DM can be a unified solution to apparent failures of cold DM to reproduce the observed subgalactic scale structure of the Universe.

Effect of inulin-type fructans on blood lipid profile and glucose level: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Liu, F; Prabhakar, M; Ju, J; Long, H; Zhou, H-W

2017-01-01

This systematic review and meta-analysis was performed to assess the effects of inulin-type fructans (ITF) on human blood lipids and glucose homeostasis associated with metabolic abnormalities, including dyslipidemia, overweight or obesity, and type-2 diabetes mellitus (T2DM). The MEDLINE, EMBASE and Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) before January 2016. Human trials that investigated the effects of ITF supplementation on the lipid profile, fasting glucose and insulin were included using Review Manager 5.3. Twenty RCTs with 607 adult participants were included in this systematic review and meta-analysis. In the overall analysis, the supplementation of ITF reduced only the low density lipoprotein-cholesterol (LDL-c) (mean difference (MD): -0.15; 95% confidence interval (CI): -0.29, -0.02; P=0.03) without affecting the other endpoints. Within the T2DM subgroup analysis, ITF supplementation was positively associated with a decreased fasting insulin concentration (MD: -4.01; 95% CI: -5.92, -2.09; P<0.0001) and increased high density lipoprotein-cholesterol (HDL-c) (MD: 0.07; 95% CI: 0, 0.14; P=0.05). Moreover, a reduced fasting glucose tendency was identified only in the T2DM subgroup (MD: -0.42; 95% CI: -0.90, 0.06; P=0.09). There was a potential publication bias, and few trials were available for the T2DM subgroup analysis. In summary, the use of ITF may have benefits for LDL-c reduction across all study populations, whereas HDL-c improvement and glucose control were demonstrated only in the T2DM subgroup. Thus, additional, well-powered, long-term, randomized clinical trials are required for a definitive conclusion. Overall, ITF supplementation may provide a novel direction for improving the lipid profile and glucose metabolism.

Associated liver enzymes with hyperlipidemic profile in type 2 diabetes patients.

PubMed

Al-Jameil, Noura; Khan, Farah A; Arjumand, Sadia; Khan, Mohammad F; Tabassum, Hajera

2014-01-01

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and is associated with dyslipidemia and disturbed liver function. Aim of the present work is to assess the liver enzymes and to find its association with hyperlipidemic profile in T2DM. Total of 157 subjects were studied and divided into two groups; diabetes (n=81) and non-diabetes (n=76). Various biochemical parameters like fasting glucose, post prandial glucose, HbA1c, total cholesterol (TC), triglycerides (Tg), high density lipoprotein cholesterol (HDL-C), alanine amino transferase (ALT), aspartate amino transferase (AST) and gamma-glutamyl transferase (GGT) were analyzed by ROCHE module Cobas 6000 (C501 & C601) analyzer, kits were procured by ROCHE diagnostics. Low density lipoprotein cholesterol (LDL-C) was estimated by Freidwald's formula. Statistical analysis was performed by applying student t test and Pearson's correlation coefficient, at 0.0001 and 0.05 level of significance, respectively. All the glycemic control parameters, lipid profile parameters except HDL-C and liver enzymes were found increased in diabetes group and significantly differ from non-diabetes group (p>0.0001). ALT showed significant positive correlation with fasting glucose, post prandial glucose, HbA1c, TC, Tg, LDL-C and GGT at p>0.05. AST showed very weak relation with all parameters while GGT was positively associated with fasting glucose, post prandial glucose, HbA1c, TC, Tg, LDL-C and ALT at p>0.05. In conclusion, T2DM incline to elevate liver enzymes, especially ALT and GGT were of significance. Routine screening of ALT and GGT in T2DM patients may assists early detection of liver abnormalities and to arrest the progress of disease.

Assessment of gender-related differences in vitamin D levels and cardiovascular risk factors in Saudi patients with type 2 diabetes mellitus.

PubMed

Abudawood, Manal; Tabassum, Hajera; Ansar, Sabah; Almosa, Khalid; Sobki, Samia; Ali, Mir Naiman; Aljohi, Ali

2018-01-01

Diabetes is a major risk factor for cardiovascular disease (CVD) including stroke, coronary heart disease, and peripheral artery disease. It remains a leading cause of mortality throughout the world, affecting both women and men. This investigation was aimed to study gender based differences in cardiovascular risk factors of adult population with type-2 diabetes mellitus (T2DM) and to check the correlation between serum HbA1C, lipid profile and serum vitamin D levels, in T2DM patients of Riyadh, Saudi Arabia. This hospital-based cross-sectional study involving subjects was divided into two gender based groups; normal male (800), diabetic male (800) and normal female (800) and T2DM females (800). Blood samples were analyzed for fasting glucose (FBG), HbA1c, total cholesterol (TC), triglycerides (Tg), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and serum levels of 25(OH)-vitamin D in all groups. All the glycemic control parameters and lipid profile parameters were found to be significantly different in diabetic vs non-diabetic group (p < 0.001) in both genders. The results also show that vitamin D concentration decreased significantly (p < 0.001) in diabetic patients than the healthy individuals in both the genders. Vitamin-D and HbA1C were negatively correlated in both males and females in T2DM patients and significant at P < 0.05. Our study reveals that dyslipidemia remains one of the major risk factors of CVD in T2DM. In addition to dyslipidemia, decreased levels of vitamin-D associated with increased HbA1C alarms the early diagnosis of Type 2 Diabetes.

Elevated 1-hour postload plasma glucose levels identify subjects with normal glucose tolerance but impaired β-cell function, insulin resistance, and worse cardiovascular risk profile: the GENFIEV study.

PubMed

Bianchi, Cristina; Miccoli, Roberto; Trombetta, Maddalena; Giorgino, Francesco; Frontoni, Simona; Faloia, Emanuela; Marchesini, Giulio; Dolci, Maria A; Cavalot, Franco; Cavallo, Gisella; Leonetti, Frida; Bonadonna, Riccardo C; Del Prato, Stefano

2013-05-01

In subjects with normal glucose tolerance (NGT) 1-hour postload plasma glucose (1-h oral glucose tolerance test [OGTT]) of >155 mg/dL predicts type 2 diabetes (T2DM) and is associated with subclinical atherosclerosis. The purpose of this study was to evaluate β-cell function, insulin resistance, and cardiovascular risk profile in subjects with NGT with a 1-h OGTT glucose of >155 mg/dL. The GENFIEV (Genetics, PHYsiopathology, and Evolution of Type 2 diabetes) study is a multicenter study recruiting individuals at high risk of T2DM. A total of 926 subjects underwent a 75-g OGTT for assessment of plasma glucose and C-peptide for mathematical modeling of β-cell function (derivative and proportional control). Fasting insulin, lipid profile, and clinical parameters were determined as well. A 1-hour OGTT glucose of >155 mg/dL was found in 39% of subjects with NGT, 76% with impaired fasting glucose (IFG), 90% with impaired glucose tolerance (IGT), and 99% and 98% with IFG + IGT or newly diagnosed T2DM, respectively. Among subjects with NGT (n = 474), those with 1-hour OGTT glucose of >155 mg/dL were more insulin-resistant and had worse β-cell function than those with 1-hour OGTT glucose of ≤155 mg/dL. Moreover, glycosylated hemoglobin, blood pressure, low-density lipoprotein cholesterol, and triglycerides were higher in subjects with NGT with 1-hour OGTT glucose of >155 mg/dL, whereas high-density lipoprotein cholesterol was lower compared with that in subjects with NGT with 1-hour OGTT glucose of ≤155 mg/dL. Compared with subjects with IGT, those with NGT with 1-hour OGTT glucose of >155 mg/dL had comparable cardiovascular risk profile and insulin resistance but slightly better β-cell function. Among subjects with NGT, those with 1-hour OGTT glucose of >155 mg/dL showed lower insulin sensitivity, impaired β-cell function, and worse cardiovascular risk profile and therefore are at greater risk of developing T2DM and cardiovascular disease.

Correlation of Lipid Profile and Risk of Developing Type 2 Diabetes Mellitus in 10-14 Year Old Children.

PubMed

Habiba, Nusrath M; Fulda, Kimberly G; Basha, Riyaz; Shah, Deep; Fernando, Shane; Nguyen, Bao; Xiong, Yi; Franks, Susan F; Matches, Sarah J; Magie, Richard D; Bowman, W Paul

2016-01-01

The role of lipid profile in predicting the risk of Type 2 diabetes mellitus (T2DM) in children is not clearly established. Our aim is to screen non-diabetic children aged 10-14 years for risk of developing T2DM and evaluate the association of abnormal lipids and socioeconomic status (SES). Data on race/ethnicity, family history, body mass index percentile, blood pressure and presence of neck pigmentation (acanthosis nigricans) were collected from 149 non-diabetic children. Using these factors, children were classified into low risk (<3 risk factors) and high risk (>3 risk factors) groups. Logistic regression model and chi-square tests were used to evaluate the association of blood lipid profile and demographic variables. Independent t-test was used to compare the ratio of Total Cholesterol (TC) and High Density Lipids (HDL) with T2DM risk. 60% of children were at high risk for developing T2DM. HDL (p<0.001), triglycerides (p=0.02) and TC/HDL ratio (p<.001) were significantly abnormal in high risk group. Low SES showed a marginal association with high risk group. There were no gender or age differences between high and low risk groups. The significant determinants associated with high risk group were modifiable factors providing an opportunity for early intervention and prevention. © 2016 The Author(s) Published by S. Karger AG, Basel.

Phalangeal quantitative ultrasound and metabolic control in pre-menopausal women with type 1 diabetes mellitus.

PubMed

Catalano, A; Morabito, N; Di Vieste, G; Pintaudi, B; Cucinotta, D; Lasco, A; Di Benedetto, A

2013-05-01

Several studies have reported increased fracture risk in Type 1 diabetes mellitus (T1DM). Quantitative Ultrasound (QUS) provides information on the structure and elastic properties of bone, which are important determinants of fracture risk, along with bone mineral density. To study phalangeal sites by QUS, examine bone turnover markers and analyze association between these factors with metabolic control in a population of pre-menopausal women with T1DM. Thirty-five T1DM pre-menopausal women (mean age 34.5 ± 6.8 yr) attending the Diabetic Outpatients Clinic in the Department of Internal Medicine, University of Messina, were consecutively enrolled and divided into two groups, taking into account the mean value of glycated hemoglobin in the last three years. Twenty healthy age-matched women served as controls. Phalangeal ultrasound measurements [Amplitude Dependent Speed of Sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), TScore, Z-Score] were performed using a DBM Sonic Bone Profiler. Osteocalcin and deoxypyridinoline served as markers of bone formation and bone resorption, respectively. T1DM women with poor metabolic control showed lower phalangeal QUS values compared to healthy controls (p<0.01) and T1DM women with good metabolic control (p<0.05). No significant differences in QUS measurements were detected between T1DM women with good metabolic control and healthy controls. Lower bone formation and increased bone resorption, although not statistically significant, were observed in patients with poor metabolic control in comparison to patients with good metabolic control. Poor metabolic control may worsen the quality of bone in T1DM. Phalangeal QUS could be considered as a tool to screen T1DM women for osteoporosis in pre-menopausal age.

Dark matter annihilation in the circumgalactic medium at high redshifts

NASA Astrophysics Data System (ADS)

Schön, S.; Mack, K. J.; Wyithe, J. S. B.

2018-03-01

Annihilating dark matter (DM) models offer promising avenues for future DM detection, in particular via modification of astrophysical signals. However, when modelling such potential signals at high redshift, the emergence of both DM and baryonic structure, as well as the complexities of the energy transfer process, needs to be taken into account. In the following paper, we present a detailed energy deposition code and use this to examine the energy transfer efficiency of annihilating DM at high redshift, including the effects on baryonic structure. We employ the PYTHIA code to model neutralino-like DM candidates and their subsequent annihilation products for a range of masses and annihilation channels. We also compare different density profiles and mass-concentration relations for 105-107 M⊙ haloes at redshifts 20 and 40. For these DM halo and particle models, we show radially dependent ionization and heating curves and compare the deposited energy to the haloes' gravitational binding energy. We use the `filtered' annihilation spectra escaping the halo to calculate the heating of the circumgalactic medium and show that the mass of the minimal star-forming object is increased by a factor of 2-3 at redshift 20 and 4-5 at redshift 40 for some DM models.

Mate tea (Ilex paraguariensis) improves glycemic and lipid profiles of type 2 diabetes and pre-diabetes individuals: a pilot study.

PubMed

Klein, Graziela A; Stefanuto, Aliny; Boaventura, Brunna C B; de Morais, Elayne C; Cavalcante, Luciana da S; de Andrade, Fernanda; Wazlawik, Elisabeth; Di Pietro, Patrícia F; Maraschin, Marcelo; da Silva, Edson L

2011-10-01

Yerba mate (Ilex paraguariensis) infusions have been shown to reduce plasma glucose in animals and serum lipids in humans. The aim of this study was to evaluate the effects of roasted mate tea consumption, with or without dietary counseling, on the glycemic and lipid profiles of individuals with type 2 diabetes mellitus (T2DM) or pre-diabetes. Twenty-nine T2DM and 29 pre-diabetes subjects were divided into 3 groups: mate tea, dietary intervention, and mate tea and dietary intervention. Individuals drank 330 mL of roasted mate tea 3 times a day and/or received nutritional counseling over 60 days. Blood samples were collected and food intake was assessed at baseline and after 20, 40, and 60 days of treatments. Mate tea consumption decreased significantly the levels of fasting glucose (25.0 mg/dL), glycated hemoglobin A(1c) (HbA(1c)) (0.85%), and low-density lipoprotein cholesterol (LDL-c) (13.5 mg/dL) of T2DM subjects (p < 0.05); however, it did not change the intake of total energy, protein, carbohydrate, cholesterol, and fiber. In pre-diabetes individuals, mate tea consumption combined with nutritional counseling diminished significantly the levels of LDL-c (11 mg/dL), non-high-density lipoprotein cholesterol (HDL-c) (21.5 mg/dL), and triglycerides (53.0 mg/dL) (p < 0.05). Individuals of this group decreased significantly their consumption of total fat (14%), cholesterol (28%), and saturated (23.8%) and monounsaturated (28.0%) fatty acids, and increased their fiber intake by 35% (p < 0.05). Mate tea consumption improved the glycemic control and lipid profile of T2DM subjects, and mate tea consumption combined with nutritional intervention was highly effective in decreasing serum lipid parameters of pre-diabetes individuals, which may reduce their risk of developing coronary disease.

Favorable cardiovascular risk factor profile is associated with lower healthcare expenditure and resource utilization among adults with diabetes mellitus free of established cardiovascular disease: 2012 Medical Expenditure Panel Survey (MEPS).

PubMed

Feldman, David I; Valero-Elizondo, Javier; Salami, Joseph A; Rana, Jamal S; Ogunmoroti, Oluseye; Osondu, Chukwuemeka U; Spatz, Erica S; Virani, Salim S; Blankstein, Ron; Blaha, Michael J; Veledar, Emir; Nasir, Khurram

2017-03-01

Given the prevalence and economic burden of diabetes mellitus (DM), we studied the impact of a favorable cardiovascular risk factor (CRF) profile on healthcare expenditures and resource utilization among individuals without cardiovascular disease (CVD), by DM status. 25,317 participants were categorized into 3 mutually-exclusive strata: "Poor", "Average" and "Optimal" CRF profiles (≥4, 2-3, 0-1 CRF, respectively). Two-part econometric models were utilized to study cost data. Mean age was 45 (48% male), with 54% having optimal, 39% average, and 7% poor CRF profiles. Individuals with DM were more likely to have poor CRF profile vs. those without DM (OR 7.7, 95% CI 6.4, 9.2). Individuals with DM/poor CRF profile had a mean annual expenditure of $9,006, compared to $6,461 among those with DM/optimal CRF profile (p < 0.001). A favorable CRF profile is associated with significantly lower healthcare expenditures and utilization in CVD-free individuals across DM status, suggesting that these individuals require aggressive individualized prescriptions targeting lifestyle modifications and therapeutic treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

Association between glycemic control and antidiabetic drugs in type 2 diabetes mellitus patients with cardiovascular complications

PubMed Central

Huri, Hasniza Zaman; Ling, Doris Yew Hui; Ahmad, Wan Azman Wan

2015-01-01

Purpose Cardiovascular disease (CVD) is a macrovascular complication in patients with type 2 diabetes mellitus (T2DM). To date, glycemic control profiles of antidiabetic drugs in cardiovascular (CV) complications have not been clearly elucidated. Therefore, this study was conducted retrospectively to assess the association of antidiabetic drugs and glycemic control with CV profiles in T2DM patients. The association of concurrent medications and comorbidities with glycemic control was also investigated. Methods A total of 220 T2DM patients from the University of Malaya Medical Centre, Malaysia, who had at least one CV complication and who had been taking at least one antidiabetic drug for at least 3 months, were included. The associations of antidiabetics, cardiovascular diseases, laboratory parameters, concurrent medications, comorbidities, demographics, and clinical characteristics with glycemic control were investigated. Results Sulfonylureas in combination (P=0.002) and sulfonylurea monotherapy (P<0.001) were found to be associated with good glycemic control, whereas insulin in combination (P=0.051), and combination biguanides and insulin therapy (P=0.012) were found to be associated with poor glycemic control. Stroke (P=0.044) was the only type of CVD that seemed to be significantly associated with good glycemic control. Other factors such as benign prostatic hyperplasia (P=0.026), elderly patients (P=0.018), low-density lipoprotein cholesterol levels (P=0.021), and fasting plasma glucose (P<0.001) were found to be significantly correlated with good glycemic control. Conclusion Individualized treatment in T2DM patients with CVDs can be supported through a better understanding of the association between glycemic control and CV profiles in T2DM patients. PMID:26316711

Postprandial Effect of a High-Fat Meal on Endotoxemia in Arab Women with and without Insulin-Resistance-Related Diseases

PubMed Central

Al-Disi, Dara A.; Al-Daghri, Nasser M.; Khan, Nasiruddin; Alfadda, Assim A.; Sallam, Reem M.; Alsaif, Mohammed; Sabico, Shaun; Tripathi, Gyanendra; McTernan, Philip G.

2015-01-01

This study determined the effects of a high-fat meal on circulating endotoxin and cardiometabolic indices in adult Arab women. The cohort consisted of 92 consenting Saudi women (18 non-diabetic (ND)) control subjects; Age 24.4 ± 7.9 year; body mass index (BMI) 22.2 ± 2.2 Kg/m2), 24 overweight/obese (referred to as overweight-plus (overweight+)) subjects (Age 32.0 ± 7.8 year; BMI 28.5 ± 1.5 Kg/m2) and 50 type 2 diabetes mellitus (T2DM) patients (Age 41.5 ± 6.2 year; BMI 35.2 ± 7.7 Kg/m2). All were given a high-fat meal (standardized meal: 75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast of 12–14 h. Anthropometrics were obtained and fasting blood glucose, lipids, and endotoxin were serially measured for four consecutive postprandial hours. Endotoxin levels were significantly elevated prior to a high-fat meal in the overweight+ and T2DM than the controls (p < 0.05). Furthermore, the postprandial cardiometabolic changes led to a more detrimental risk profile in T2DM subjects than other groups, with serial changes most notable in glucose, triglycerides, high density lipoprotein-cholesterol (HDL-cholesterol), and insulin levels (p-values < 0.05). The same single meal given to subjects with different metabolic states had varying impacts on cardiometabolic health. Endotoxemia is exacerbated by a high-fat meal in Arab subjects with T2DM, accompanied by a parallel increase in cardiometabolic risk profile, suggesting disparity in disease pathogenesis of those with or without T2DM through the altered cardiometabolic risk profile rather than variance in metabolic endotoxinaemia with a high-fat meal. PMID:26247966

Postprandial Effect of a High-Fat Meal on Endotoxemia in Arab Women with and without Insulin-Resistance-Related Diseases.

PubMed

Al-Disi, Dara A; Al-Daghri, Nasser M; Khan, Nasiruddin; Alfadda, Assim A; Sallam, Reem M; Alsaif, Mohammed; Sabico, Shaun; Tripathi, Gyanendra; McTernan, Philip G

2015-08-04

This study determined the effects of a high-fat meal on circulating endotoxin and cardiometabolic indices in adult Arab women. The cohort consisted of 92 consenting Saudi women (18 non-diabetic (ND)) control subjects; Age 24.4 ± 7.9 year; body mass index (BMI) 22.2 ± 2.2 Kg/m2), 24 overweight/obese (referred to as overweight-plus (overweight+)) subjects (Age 32.0 ± 7.8 year; BMI 28.5 ± 1.5 Kg/m2) and 50 type 2 diabetes mellitus (T2DM) patients (Age 41.5 ± 6.2 year; BMI 35.2 ± 7.7 Kg/m2). All were given a high-fat meal (standardized meal: 75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast of 12-14 h. Anthropometrics were obtained and fasting blood glucose, lipids, and endotoxin were serially measured for four consecutive postprandial hours. Endotoxin levels were significantly elevated prior to a high-fat meal in the overweight+ and T2DM than the controls (p < 0.05). Furthermore, the postprandial cardiometabolic changes led to a more detrimental risk profile in T2DM subjects than other groups, with serial changes most notable in glucose, triglycerides, high density lipoprotein-cholesterol (HDL-cholesterol), and insulin levels (p-values < 0.05). The same single meal given to subjects with different metabolic states had varying impacts on cardiometabolic health. Endotoxemia is exacerbated by a high-fat meal in Arab subjects with T2DM, accompanied by a parallel increase in cardiometabolic risk profile, suggesting disparity in disease pathogenesis of those with or without T2DM through the altered cardiometabolic risk profile rather than variance in metabolic endotoxinaemia with a high-fat meal.

[Estimated glucose disposal rate in patients under 18 years of age with type 1 diabetes mellitus and overweight or obesity].

PubMed

Palomo Atance, Enrique; Ballester Herrera, M José; Giralt Muiña, Patricio; Ruiz Cano, Rafael; León Martín, Alberto; Giralt Muiña, Juan

2013-01-01

To assess the estimated glucose disposal rate (eGDR), insulin dose, and lipoprotein profile in children with type 1 diabetes mellitus (T1DM) and overweight or obesity as compared to children with T1DM and normal weight. A total of 115 patients (aged 5-16 years) with T1DM on intensive insulin therapy were recruited. The following parameters were measured: weight, height, body mass index, waist and hip circumference, insulin dose, eGDR, glycosylated hemoglobin, blood pressure, and lipoprotein profile. Results were stratified by sex and age. No significant differences were found in eGDR between children with normal weight, overweight, and obesity. However, obese children older than 11 years had lower eGDR values (9.3±1.3 vs 10.1±0.8 mg kg(-1)min(-1); p<0.01). Insulin dose was higher in overweight and obese children, especially in IU/m2/day (37.7 vs 36.1 vs. 29.4 respectively; p<0.01). Obese children had higher low-density lipoprotein cholesterol levels than children with overweight and normal weight (106.5 vs 91.7 vs 91.5mg/dL respectively; p<0.01). No correlation was found between waist circumference and the different markers of insulin resistance. Values of eGDR values were lower in obese children with T1DM older than 11 years, and this may therefore be considered a marker of insulin resistance. Insulin dose was higher in diabetic patients with overweight or obesity, specially in IU/m2/day. Obese children with T1DM had a lipoprotein profile of cardiovascular risk. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Under the sword of Damocles: plausible regeneration of dark matter cusps at the smallest galactic scales

NASA Astrophysics Data System (ADS)

Laporte, Chervin F. P.; Peñarrubia, Jorge

2015-04-01

We study the evolution of the dark matter (DM) halo profiles of dwarf galaxies driven by the accretion of DM substructures through controlled N-body experiments. Our initial conditions assume that early supernova feedback erases the primordial DM cusps of haloes with z = 0 masses of 109 - 1010 M⊙. The orbits and masses of the infalling substructures are borrowed from the Aquarius cosmological simulations. Our experiments show that a fraction of haloes that undergo 1:3 down to 1:30 mergers are susceptible to reform a DM cusp by z ≈ 0. Cusp regrowth is driven by the accretion of DM substructures that are dense enough to reach the central regions of the main halo before being tidally disrupted. The infall of substructures on the mean of the reported mass-concentration relation and a mass ratio above 1:6 systematically leads to cusp regrowth. Substructures with 1:6-1:8, and 1:8-1:30 only reform DM cusps if their densities are 1σ and 2σ above the mean, respectively. The merging time-scales of these dense, low-mass substructures is relatively long (5 - 11 Gyr), which may pose a time-scale problem for the longevity of DM cores in dwarfs galaxies and possibly explain the existence of dense dwarfs-like Draco. These results suggest that within cold dark matter a non-negligible level of scatter in the mass profiles of galactic haloes acted on by feedback is to be expected given the stochastic mass accretion histories of low-mass haloes and the diverse star formation histories observed in the Local Group dwarfs.

Effects of a regular exercise program on biochemical parameters of type 2 diabetes mellitus patients.

PubMed

Dinçer, Şensu; Altan, Mehmet; Terzioğlu, Duygu; Uslu, Ezel; Karşidağ, Kubilay; Batu, Şule; Metin, Gökhan

2016-11-01

We aimed to investigate the effects of a regular exercise program on exercise capacity, blood biochemical profiles, certain antioxidant and oxidative stress parameters of type 2 Diabetes mellitus (DM) patients. Thirty one type 2 DM patients (ages ranging from 42-65 years) who have hemoglobin A1c (HbA1c) levels ≥7.5% and ≤9.5% were included to study and performed two cardiopulmonary exercise tests (CPET) before and after the exercise program. Subjects performed aerobic exercise training for 90 minutes a day; 3 days a week during 12 weeks. Blood samples were collected to analyze certain oxidant and antioxidant parameters (advanced oxidation protein products [AOPP], ferric reducing ability of plasma [FRAP], malondialdehyde [MDA], and sialic acid [SA]), blood lipid profile, fasting blood glucose (FBG) and HbA1c. At the end of the program HbA1c and FBG, triglyceride (TG) and very-low-density lipoprotein (VLDL) levels decreased and high-density lipoprotein (HDL) increased significantly (P=0.000, P=0.001, P=0.008, P=0,001 and P=0.02, respectively). AOPP, FRAP, SA levels of the patients increased significantly following first CPET (P=0.000, P=0.049, P=0.014 respectively). At the end of the exercise program AOPP level increased significantly following last CPET. Baseline SA level increased significantly following exercise program (P=0.002). We suggest that poor glycemic control which plays the major role in the pathogenesis of DM and its complications would be improved by 12 weeks of a regular exercise program. Whereas the acute exercise induces protein oxidation, regularly aerobic training may enhance the antioxidant status of type 2 DM patients.

CLUMPY: A code for γ-ray signals from dark matter structures

NASA Astrophysics Data System (ADS)

Charbonnier, Aldée; Combet, Céline; Maurin, David

2012-03-01

We present the first public code for semi-analytical calculation of the γ-ray flux astrophysical J-factor from dark matter annihilation/decay in the Galaxy, including dark matter substructures. The core of the code is the calculation of the line of sight integral of the dark matter density squared (for annihilations) or density (for decaying dark matter). The code can be used in three modes: i) to draw skymaps from the Galactic smooth component and/or the substructure contributions, ii) to calculate the flux from a specific halo (that is not the Galactic halo, e.g. dwarf spheroidal galaxies) or iii) to perform simple statistical operations from a list of allowed DM profiles for a given object. Extragalactic contributions and other tracers of DM annihilation (e.g. positrons, anti-protons) will be included in a second release.

Cognitive dysfunctions in middle-aged type 2 diabetic patients and neuroimaging correlations: a cross-sectional study.

PubMed

García-Casares, Natalia; Jorge, Ricardo E; García-Arnés, Juan A; Acion, Laura; Berthier, Marcelo L; Gonzalez-Alegre, Pedro; Nabrozidis, Alejandro; Gutiérrez, Antonio; Ariza, María José; Rioja, Jose; González-Santos, Pedro

2014-01-01

The aim was to assess the neuropsychological performance of a group of middle-aged patients with well-controlled type 2 diabetes mellitus (T2DM) and to examine whether the neuropsychological deficits correlate with structural and functional brain alterations. We compared 25 subjects with T2DM aged 45-65 years with 25 control participants matched for age, gender, and educational level. The neuropsychological battery was designed to examine executive functions, attention, information processing speed, and verbal memory. Severity of depression was assessed using the Hamilton Depression Rating Scale and cardiovascular risk factors were assessed using the Framingham Cardiovascular Risk Profile Score. The presence of at least one APOEε4 allele was determined. Reduced gray matter density was analyzed using voxel-based morphometry and brain glucose metabolic changes were assessed by 18FDG-PET. T2DM subjects had significantly lower scores than subjects without T2DM in the Trail-making Test B (p < 0.004), Color-Word Stroop test (p < 0.005), Semantic Fluency (p < 0.006), Digit-Symbol modalities test (p < 0.02), Text Recall from the Wechsler Memory Scale (p < 0.0001), Rey-Osterrieth Complex Figure-copy (p < 0.004), and delayed reproduction (p < 0.03). Worse executive functions and memory functioning correlated predominantly with less gray matter density and reduced glucose metabolism in the orbital and prefrontal cortex, temporal (middle gyrus, parahippocampus and uncus), and cerebellum regions (p < 0.001). T2DM subjects presented cognitive dysfunctions compared with controls. Clinical-neuroimaging correlations corresponded to brain changes (reduced gray matter density and glucose metabolism) mainly in fronto-temporal areas.

High-Intensity Interval Training as a Tool for Counteracting Dyslipidemia in Women.

PubMed

Alvarez, Cristian; Ramirez-Campillo, Rodrigo; Martinez-Salazar, Cristian; Castillo, Angélica; Gallardo, Francisco; Ciolac, Emmanuel Gomes

2018-05-01

Sedentary overweight or obese adult (age<60 years) women, allocated in type 2 diabetes mellitus (T2DM, n =13), dyslipidemia alone (DYS, n =12), dyslipidemia associated with hyperglycaemia (DYSHG, N=12), or healthy control (CON, n =10) groups, had their lipid, glucose, blood pressure, endurance performance, and anthropometry variables assessed before and after 16 weeks of a thrice-weekly high-intensity interval training (HIIT) program. Triglycerides reduced significantly ( P <0.05) in all groups, and high-density lipoprotein increased ( P <0.01) in T2DM, DYS and DYSHG; however, low-density lipoprotein reduced ( P <0.05) only in DYSHG, and total cholesterol reduced ( P <0.01) only in DYS and DYSHG. Fasting glucose reduced ( P <0.05) significantly in T2DM, DYS and DYSHG, but with higher decreases in T2DM and DYSHG. Blood pressure, endurance performance and body composition improved ( P <0.05) in all groups. The HIIT program was effective for restoring lipid profile of DYS and DYSHG, and fasting glucose of DYSHG to levels similar to those of CON, with a weekly time commitment 25% to 56% lower than the minimum recommended in current exercise guidelines. These findings suggest that HIIT may be a time-efficient intervention for counteracting dyslipidemia. © Georg Thieme Verlag KG Stuttgart · New York.

Influences of the current density on the performances of the chrome-plated layer in deterministic electroplating repair

NASA Astrophysics Data System (ADS)

Xia, H.; Shen, X. M.; Yang, X. C.; Xiong, Y.; Jiang, G. L.

2018-01-01

Deterministic electroplating repair is a novel method for rapidly repairing the attrited parts. By the qualitative contrast and quantitative comparison, influences of the current density on performances of the chrome-plated layer were concluded in this study. The chrome-plated layers were fabricated under different current densities when the other parameters were kept constant. Hardnesses, thicknesses and components, surface morphologies and roughnesses, and wearability of the chrome-plated layers were detected by the Vickers hardness tester, scanning electron microscope / energy dispersive X-ray detector, digital microscope in the 3D imaging mode, and the ball-milling instrument with profilograph, respectively. In order to scientifically evaluate each factor, the experimental data was normalized. A comprehensive evaluation model was founded to quantitative analyse influence of the current density based on analytic hierarchy process method and the weighted evaluation method. The calculated comprehensive evaluation indexes corresponding to current density of 40A/dm2, 45A/dm2, 50A/dm2, 55A/dm2, 60A/dm2, and 65A/dm2 were 0.2246, 0.4850, 0.4799, 0.4922, 0.8672, and 0.1381, respectively. Experimental results indicate that final optimal option was 60A/dm2, and the priority orders were 60A/dm2, 55A/dm2, 45A/dm2, 50A/dm2, 40A/dm2, and 65A/dm2.

Probing dark matter with star clusters: a dark matter core in the ultra-faint dwarf Eridanus II

NASA Astrophysics Data System (ADS)

Contenta, Filippo; Balbinot, Eduardo; Petts, James A.; Read, Justin I.; Gieles, Mark; Collins, Michelle L. M.; Peñarrubia, Jorge; Delorme, Maxime; Gualandris, Alessia

2018-05-01

We present a new technique to probe the central dark matter (DM) density profile of galaxies that harnesses both the survival and observed properties of star clusters. As a first application, we apply our method to the `ultra-faint' dwarf Eridanus II (Eri II) that has a lone star cluster ˜45 pc from its centre. Using a grid of collisional N-body simulations, incorporating the effects of stellar evolution, external tides and dynamical friction, we show that a DM core for Eri II naturally reproduces the size and the projected position of its star cluster. By contrast, a dense cusped galaxy requires the cluster to lie implausibly far from the centre of Eri II (>1 kpc), with a high inclination orbit that must be observed at a particular orbital phase. Our results, therefore, favour a DM core. This implies that either a cold DM cusp was `heated up' at the centre of Eri II by bursty star formation or we are seeing an evidence for physics beyond cold DM.

[HDL-C/apoA-I]: A multivessel cardiometabolic risk marker in women with T2DM.

PubMed

Hermans, Michel P; Valensi, Paul; Ahn, Sylvie A; Rousseau, Michel F

2018-01-01

Although women have higher high-density lipoprotein cholesterol (HDL-C) than have men, their HDL particles are also prone to become small, dense, and dysfunctional in case of type 2 diabetes mellitus (T2DM). To assess the vascular risk related to HDLs of different sizes/densities without direct measurement, we adjusted HDL-C to its main apolipoprotein (apoA-I) as [HDL-C/apoA-I]. This ratio estimates HDL sizes and provides indices as to their number, cholesterol load, and density. We stratified 280 Caucasian T2DM women according to [HDL-C/apoA-I] quartiles (Q) to determine how they are segregated according to cardiometabolic risk, β-cell function, glycaemic control, and vascular complications. Five parameters were derived from combined determination of HDL-C and apoA-I: HDL size, HDL number, cholesterol load per particle (pP), apoA-I pP, and HDL density. An adverse cardiometabolic profile characterized QI and QII patients whose HDLs were denser and depleted in apoA-I, whereas QIII patients had HDLs with characteristics closer to those of controls. QIV patients had HDLs of supernormal size/composition and a more favourable phenotype in terms of fat distribution; insulin sensitivity (64% vs 41%), metabolic syndrome, and β-cell function (32% vs 23%); exogenous insulin (44 vs 89 U·d -1 ); and glycaemic control (glycated haemoglobin, 56 vs 61 mmol·mol -1 ), associated with lower prevalence of microvascular/macrovascular complications: all-cause microangiopathy 47% vs 61%; retinopathy 22% vs 34%; all-cause macroangiopathy 19% vs 31%; and coronary artery disease 6% vs 24% (P < .05). [HDL-C/apoA-I] can stratify T2DM women according to metabolic phenotype, macrovascular and coronary damage, β-cell function, microangiopathic risk, and retinopathy. This ratio is a versatile and readily available marker of cardiometabolic status and vascular complications in T2DM women. Copyright © 2017 John Wiley & Sons, Ltd.

Effects of an aquatic-based exercise program to improve cardiometabolic profile, quality of life, and physical activity levels in men with type 2 diabetes mellitus.

PubMed

Cugusi, Lucia; Cadeddu, Christian; Nocco, Silvio; Orrù, Fabio; Bandino, Stefano; Deidda, Martino; Caria, Alessandra; Bassareo, Pier Paolo; Piras, Alessandra; Cabras, Sergio; Mercuro, Giuseppe

2015-02-01

The role of structured exercise in improving cardiometabolic profile and quality of life in patients with type 2 diabetes mellitus (2DM) has been widely demonstrated. Little is known about the effects of an aquatic-based exercise program in patients with 2DM. To evaluate the effects of a supervised aquatic-based exercise program on cardiometabolic profile, quality of life, and physical activity levels in patients with 2DM. Observational study, community pre-post aquatic-based exercise program, primary care intervention. Eighteen men diagnosed with 2DM (52.2 ± 9.3 years). and Cardiometabolic profile, quality of life, and physical activity levels were assessed before and after 12 weeks of an aquatic-based exercise program. The results show a significant improvement of cardiometabolic assessments (maximum oxygen consumption: 24.1 versus 21.1 mL/kg/min, P < .05; blood pressure: 125.4/77 versus 130.7/82.5 mm Hg, P < .05; fasting blood glucose: 119.6 versus 132.5 mg/dL, P < .05; body mass index: 29.9 versus 31.1 kg/m², P < .005; low-density lipoprotein cholesterol: 95.2 versus 104.9 mg/dL, P < .05; and diastolic function: E/E' 9.1 versus 10.1, P < .005) and an increase in quality of life and physical activity levels (Medical Outcome Study 36-item Short Form Health Survey mental component summary: 72.3 versus 67, P < .05; Problems Area About Diabetes: 20.1 versus 33.2, P < .005) and energy expenditure in general physical activity (physical activity: 3888.7 versus 1239.5 kcal/wk, P < .05). These findings demonstrate that an aquatic-based exercise program produces benefits for the cardiovascular system and metabolic profile and appears to be safe and effective in improving quality of life and increasing physical activity levels in patients with 2DM. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Evaluation of serum lipid profile, body mass index, and waistline in Chinese patients with type 2 diabetes mellitus.

PubMed

Cui, Rongtao; Qi, Zhiming; Zhou, Lin; Li, Zuohong; Li, Qing; Zhang, Junyong

2016-01-01

People with type 2 diabetes are at an increased risk of hypertension, arteriosclerosis, heart disease, and stroke. Glucose intolerance (insulin resistance) is the main feature of type 2 diabetes. Obesity leads to insulin resistance, dyslipidemia, etc. The aim of this study was to assess the biochemical parameters and measures of obesity in type 2 diabetes mellitus (T2DM). A total of 2,273 males and 6,547 females previously healthy volunteers (aged 41-95 years old) were recruited by open invitation. The basic information, including age, sex, height, weight, body mass index (BMI), waistline, hipline, menstrual cycle, and medical history, was collected by questionnaire survey and physical examination. Serum lipid profile, liver transaminase, blood glucose, postprandial blood glucose, and hemoglobin A1c were obtained after 12 hours of fasting. According to our results, diabetic patients presented serum lipid abnormality. Elevated triglyceride (TG) levels (≥1.7 mmol/L) were noted in 19.69% of males and 20.40% of females, and reduced high-density lipoprotein cholesterol (HDL-C) levels (≤1.15 mmol/L) were noted in 21.96% of males and 15.74% of females. The combination of elevated TG and reduced HDL-C was the most prevalent of the combined lipid abnormalities. In contrast, no differences were observed in the levels of low-density lipoprotein cholesterol and total cholesterol. Moreover, there were statistically significant differences in the levels of BMI and waistline between T2DM and non-T2DM participants. After adjustment for BMI, logistic regression analysis revealed that the subjects with BMI ≤20 kg/m(2) and >30 kg/m(2) had a significantly elevated hazard ratio of T2DM compared with participants having a BMI range of 20-30 kg/m(2) in both males and females. However, there was a significant difference between T2DM patients and non-T2DM patients in waistline (χ (2)=8.57, P<0.001) than in BMI parameter (χ (2)=6.29, P<0.001). The present study shows for the first time that low levels of HDL-C, high levels of TG, and abnormal levels in BMI and waistline increase the risk of type 2 T2DM in Chinese people.

MASS ACCRETION AND ITS EFFECTS ON THE SELF-SIMILARITY OF GAS PROFILES IN THE OUTSKIRTS OF GALAXY CLUSTERS

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

Lau, Erwin T.; Nagai, Daisuke; Avestruz, Camille

2015-06-10

Galaxy clusters exhibit remarkable self-similar behavior which allows us to establish simple scaling relationships between observable quantities and cluster masses, making galaxy clusters useful cosmological probes. Recent X-ray observations suggested that self-similarity may be broken in the outskirts of galaxy clusters. In this work, we analyze a mass-limited sample of massive galaxy clusters from the Omega500 cosmological hydrodynamic simulation to investigate the self-similarity of the diffuse X-ray emitting intracluster medium (ICM) in the outskirts of galaxy clusters. We find that the self-similarity of the outer ICM profiles is better preserved if they are normalized with respect to the mean densitymore » of the universe, while the inner profiles are more self-similar when normalized using the critical density. However, the outer ICM profiles as well as the location of accretion shock around clusters are sensitive to their mass accretion rate, which causes the apparent breaking of self-similarity in cluster outskirts. We also find that the collisional gas does not follow the distribution of collisionless dark matter (DM) perfectly in the infall regions of galaxy clusters, leading to 10% departures in the gas-to-DM density ratio from the cosmic mean value. Our results have a number implications for interpreting observations of galaxy clusters in X-ray and through the Sunyaev–Zel’dovich effect, and their applications to cosmology.« less

Exact Solution to Finite Temperature SFDM: Natural Cores without Feedback

NASA Astrophysics Data System (ADS)

Robles, Victor H.; Matos, T.

2013-01-01

Recent high-quality observations of low surface brightness (LSB) galaxies have shown that their dark matter (DM) halos prefer flat central density profiles. However, the standard cold dark matter model simulations predict a more cuspy behavior. One mechanism used to reconcile the simulations with the observed data is the feedback from star formation. While this mechanism may be successful in isolated dwarf galaxies, its success in LSB galaxies remains unclear. Additionally, the inclusion of too much feedback in the simulations is a double-edged sword—in order to obtain a cored DM distribution from an initially cuspy one, the feedback recipes usually require one to remove a large quantity of baryons from the center of the galaxies; however, some feedback recipes produce twice the number of satellite galaxies of a given luminosity and with much smaller mass-to-light ratios from those that are observed. Therefore, one DM profile that produces cores naturally and that does not require large amounts of feedback would be preferable. We find both requirements to be satisfied in the scalar field dark matter model. Here, we consider that DM is an auto-interacting real scalar field in a thermal bath at temperature T with an initial Z 2 symmetric potential. As the universe expands, the temperature drops so that the Z 2 symmetry is spontaneously broken and the field rolls down to a new minimum. We give an exact analytic solution to the Newtonian limit of this system, showing that it can satisfy the two desired requirements and that the rotation curve profile is no longer universal.

Targeted lipidomics analysis identified altered serum lipid profiles in patients with polymyositis and dermatomyositis.

PubMed

Raouf, Joan; Idborg, Helena; Englund, Petter; Alexanderson, Helene; Dastmalchi, Maryam; Jakobsson, Per-Johan; Lundberg, Ingrid E; Korotkova, Marina

2018-05-02

Polymyositis (PM) and dermatomyositis (DM) are severe chronic autoimmune diseases, characterized by muscle fatigue and low muscle endurance. Conventional treatment includes high doses of glucocorticoids and immunosuppressive drugs; however, few patients recover full muscle function. One explanation of the persistent muscle weakness could be altered lipid metabolism in PM/DM muscle tissue as we previously reported. Using a targeted lipidomic approach we aimed to characterize serum lipid profiles in patients with PM/DM compared to healthy individuals (HI) in a cross-sectional study. Also, in the longitudinal study we compared serum lipid profiles in patients newly diagnosed with PM/DM before and after immunosuppressive treatment. Lipidomic profiles were analyzed in serum samples from 13 patients with PM/DM, 12 HI and 8 patients newly diagnosed with PM/DM before and after conventional immunosuppressive treatment using liquid chromatography tandem mass spectrometry (LC-MS/MS) and a gas-chromatography flame ionization detector (GC-FID). Functional Index (FI), as a test of muscle performance and serum levels of creatine kinase (s-CK) as a proxy for disease activity were analyzed. The fatty acid (FA) composition of total serum lipids was altered in patients with PM/DM compared to HI; the levels of palmitic (16:0) acid were significantly higher while the levels of arachidonic (20:4, n-6) acid were significantly lower in patients with PM/DM. The profiles of serum phosphatidylcholine and triacylglycerol species were changed in patients with PM/DM compared to HI, suggesting disproportionate levels of saturated and polyunsaturated FAs that might have negative effects on muscle performance. After immunosuppressive treatment the total serum lipid levels of eicosadienoic (20:2, n-6) and eicosapentaenoic (20:5, n-3) acids were increased and serum phospholipid profiles were altered in patients with PM/DM. The correlation between FI or s-CK and levels of several lipid species indicate the important role of lipid changes in muscle performance and inflammation. Serum lipids profiles are significantly altered in patients with PM/DM compared to HI. Moreover, immunosuppressive treatment in patients newly diagnosed with PM/DM significantly affected serum lipid profiles. These findings provide new evidence of the dysregulated lipid metabolism in patients with PM/DM that could possibly contribute to low muscle performance.

Volumetric versus area-based density assessment: comparisons using automated quantitative measurements from a large screening cohort

NASA Astrophysics Data System (ADS)

Gastounioti, Aimilia; Hsieh, Meng-Kang; Pantalone, Lauren; Conant, Emily F.; Kontos, Despina

2018-03-01

Mammographic density is an established risk factor for breast cancer. However, area-based density (ABD) measured in 2D mammograms consider the projection, rather than the actual volume of dense tissue which may be an important limitation. With the increasing utilization of digital breast tomosynthesis (DBT) in screening, there's an opportunity to routinely estimate volumetric breast density (VBD). In this study, we investigate associations between DBT-VBD and ABD extracted from standard-dose mammography (DM) and synthetic 2D digital mammography (sDM) increasingly replacing DM. We retrospectively analyzed bilateral imaging data from a random sample of 1000 women, acquired over a transitional period at our institution when all women had DBT, sDM and DM acquired as part of their routine breast screening. For each exam, ABD was measured in DM and sDM images with the publicly available "LIBRA" software, while DBT-VBD was measured using a previously validated, fully-automated computer algorithm. Spearman correlation (r) was used to compare VBD to ABD measurements. For each density measure, we also estimated the within woman intraclass correlation (ICC) and finally, to compare to clinical assessments, we performed analysis of variance (ANOVA) to evaluate the variation to the assigned clinical BI-RADS breast density category for each woman. DBT-VBD was moderately correlated to ABD from DM (r=0.70) and sDM (r=0.66). All density measures had strong bilateral symmetry (ICC = [0.85, 0.95]), but were significantly different across BI-RADS density categories (ANOVA, p<0.001). Our results contribute to further elaborating the clinical implications of breast density measures estimated with DBT which may better capture the volumetric amount of dense tissue within the breast than area-based measures and visual assessment.

Density profile of dark matter haloes and galaxies in the HORIZON-AGN simulation: the impact of AGN feedback

NASA Astrophysics Data System (ADS)

Peirani, Sébastien; Dubois, Yohan; Volonteri, Marta; Devriendt, Julien; Bundy, Kevin; Silk, Joe; Pichon, Christophe; Kaviraj, Sugata; Gavazzi, Raphaël; Habouzit, Mélanie

2017-12-01

Using a suite of three large cosmological hydrodynamical simulations, HORIZON-AGN, HORIZON–NOAGN (no AGN feedback) and HORIZON-DM (no baryons), we investigate how a typical sub-grid model for AGN feedback affects the evolution of the inner density profiles of massive dark matter haloes and galaxies. Based on direct object-to-object comparisons, we find that the integrated inner mass and density slope differences between objects formed in these three simulations (hereafter, HAGN, HnoAGN and HDM) significantly evolve with time. More specifically, at high redshift (z ∼ 5), the mean central density profiles of HAGN and HnoAGN dark matter haloes tend to be much steeper than their HDM counterparts owing to the rapidly growing baryonic component and ensuing adiabatic contraction. By z ∼ 1.5, these mean halo density profiles in HAGN have flattened, pummelled by powerful AGN activity ('quasar mode'): the integrated inner mass difference gaps with HnoAGN haloes have widened, and those with HDM haloes have narrowed. Fast forward 9.5 billion years, down to z = 0, and the trend reverses: HAGN halo mean density profiles drift back to a more cusped shape as AGN feedback efficiency dwindles ('radio mode'), and the gaps in integrated central mass difference with HnoAGN and HDM close and broaden, respectively. On the galaxy side, the story differs noticeably. Averaged stellar profile central densities and inner slopes are monotonically reduced by AGN activity as a function of cosmic time, resulting in better agreement with local observations.

Serum phospholipid omega-3 polyunsaturated fatty acids and insulin resistance in type 2 diabetes mellitus and non-alcoholic fatty liver disease.

PubMed

Lou, Da-Jun; Zhu, Qi-Qian; Si, Xu-Wei; Guan, Li-Li; You, Qiao-Ying; Yu, Zhong-Ming; Zhang, Ai-Zhen

2014-01-01

To investigate the relationship between serum phospholipid omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). 51 patients with T2DM and NAFLD (T2DM+NAFLD group), 50 with T2DM alone (T2DM group), 45 with NAFLD alone (NAFLD group), and 42 healthy control subjects (NC group) were studied. Serum ω-3 PUFA profiles were analyzed by gas chromatography, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and serum lipid concentrations were measured. Insulin resistance was assessed by the homeostasis model assessment method (HOMA-IR). HOMA-IR levels were higher in the T2DM+NAFLD group than in the T2DM, NAFLD and NC groups (p<0.05), as were ALT, AST, GGT, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) concentrations (p<0.05). Conversely, serum ω-3 PUFA levels were significantly lower in the T2DM+NAFLD group than in the other groups (p<0.05). The ω-3 PUFA level was negatively correlated with HOMA-IR, TC, LDL-C and TG. Serum phospholipid ω-3 PUFA levels were significantly decreased in patients with T2DM and NAFLD, and were negatively related with insulin resistance. Thus, reduced ω-3 PUFAs may play an important role in the development of T2DM and NAFLD. Copyright © 2014 Elsevier Inc. All rights reserved.

Safety and metabolic impact of Ramadan fasting in children and adolescents with type 1 diabetes.

PubMed

El-Hawary, Amany; Salem, Nanees; Elsharkawy, Ashraf; Metwali, Abdelhameed; Wafa, Alaa; Chalaby, Nehad; El-Gilany, Abelhady; Abo-Elmagd, Megahed; El-Ziny, Magdy

2016-05-01

Annually, many children and adolescents with type 1 diabetes mellitus (T1DM) insist on fasting for Ramadan despite being exempted and despite knowing all the risks. We aimed to assess the safety and metabolic impact of Ramadan fasting in children with T1DM using different insulin regimens. Children with T1DM who choose to fast during Ramadan 1434/2013 (29 days) were recruited 3 months before Ramadan. They received pre-Ramadan intensive education. Three insulin regimens were included; Regimen-I (regular insulin/NPH); Regimen-II (regular insulin/insulin glargine) and Regimen-III (premixed insulin). Changes in weight, insulin dose, HbA1c, fructosamine and lipid profile were evaluated. Out of total 53 patients (24 male), 28 patients (52.8%) completed Ramadan fasting (fasting group). The remaining 25 patients were included in (broke-fasting group). Positive correlation between fructosamine changes and number of days fasted during Ramadan. Significant decrease in post-Ramadan fructosamine (<0.001) and increase in post-Ramadan total cholesterol and low density lipoprotein (LDL) levels were detected within fasting, broke-fasting and insulin regimen groups. Significant higher blood glucose at three time points, pre-Iftar, pre-Sohur and midday in Regimen-I compared to Regimen-II and Regimen-III (p=0.004). Fasting during Ramadan is feasible and is associated with significant improvement in fructosamine level in children with T1DM using different insulin regimens. Mandatory consideration to the quality and quantity of food offered to patients with T1DM during Ramadan to guard against adverse changes in lipid profile.

Constraint on the velocity dependent dark matter annihilation cross section from gamma-ray and kinematic observations of ultrafaint dwarf galaxies

NASA Astrophysics Data System (ADS)

Zhao, Yi; Bi, Xiao-Jun; Yin, Peng-Fei; Zhang, Xinmin

2018-03-01

Searching for γ rays from dwarf spheroidal galaxies (dSphs) is a promising approach to detect dark matter (DM) due to the high DM densities and low baryon components in dSphs. The Fermi-LAT observations from dSphs have set stringent constraints on the velocity independent annihilation cross section. However, the constraints from dSphs may change in velocity dependent annihilation scenarios because of the different velocity dispersions in galaxies. In this work, we study how to set constraints on the velocity dependent annihilation cross section from the combined Fermi-LAT observations of dSphs with the kinematic data. In order to calculate the γ ray flux from the dSph, the correlation between the DM density profile and velocity dispersion at each position should be taken into account. We study such correlation and the relevant uncertainty from kinematic observations by performing a Jeans analysis. Using the observational results of three ultrafaint dSphs with large J-factors, including Willman 1, Reticulum II, and Triangulum II, we set constraints on the p-wave annihilation cross section in the Galaxy as an example.

Microbiological, lipid and immunological profiles in children with gingivitis and type 1 diabetes mellitus.

PubMed

Duque, Cristiane; João, Mariana Ferreira Dib; Camargo, Gabriela Alessandra da Cruz Galhardo; Teixeira, Gláucia Schuindt; Machado, Thamiris Santana; Azevedo, Rebeca de Souza; Mariano, Flávia Sammartino; Colombo, Natália Helena; Vizoto, Natália Leal; Mattos-Graner, Renata de Oliveira

2017-01-01

The aim of this study was to compare the prevalence of periodontal pathogens, systemic inflammatory mediators and lipid profiles in type 1 diabetes children (DM) with those observed in children without diabetes (NDM), both with gingivitis. Twenty-four DM children and twenty-seven NDM controls were evaluated. The periodontal status, glycemic and lipid profiles were determined for both groups. Subgingival samples of periodontal sites were collected to determine the prevalence of periodontal microorganisms by PCR. Blood samples were collected for IL-1-β, TNF-α and IL-6 analysis using ELISA kits. Periodontal conditions of DM and NDM patients were similar, without statistical differences in periodontal indices. When considering patients with gingivitis, all lipid parameters evaluated were highest in the DM group; Capnocytophaga sputigena and Capnocytophaga ochracea were more prevalent in the periodontal sites of DM children. "Red complex" bacteria were detected in few sites of DM and NDM groups. Fusobacterium nucleatum and Campylobacter rectus were frequently found in both groups. Similar levels of IL-1-β, TNF-α and IL-6 were detected in DM and NDM children. Clinical and immunological profiles are similar between DM and NDM children. The presence of Capnocytophaga sputigena and Capnocytophaga ochracea were associated with gingivitis in DM children.

Microbiological, lipid and immunological profiles in children with gingivitis and type 1 diabetes mellitus

PubMed Central

DUQUE, Cristiane; JOÃO, Mariana Ferreira Dib; CAMARGO, Gabriela Alessandra da Cruz Galhardo; TEIXEIRA, Gláucia Schuindt; MACHADO, Thamiris Santana; AZEVEDO, Rebeca de Souza; MARIANO, Flávia Sammartino; COLOMBO, Natália Helena; VIZOTO, Natália Leal; MATTOS-GRANER, Renata de Oliveira

2017-01-01

Abstract Objective The aim of this study was to compare the prevalence of periodontal pathogens, systemic inflammatory mediators and lipid profiles in type 1 diabetes children (DM) with those observed in children without diabetes (NDM), both with gingivitis. Material and methods Twenty-four DM children and twenty-seven NDM controls were evaluated. The periodontal status, glycemic and lipid profiles were determined for both groups. Subgingival samples of periodontal sites were collected to determine the prevalence of periodontal microorganisms by PCR. Blood samples were collected for IL-1-β, TNF-α and IL-6 analysis using ELISA kits. Results Periodontal conditions of DM and NDM patients were similar, without statistical differences in periodontal indices. When considering patients with gingivitis, all lipid parameters evaluated were highest in the DM group; Capnocytophaga sputigena and Capnocytophaga ochracea were more prevalent in the periodontal sites of DM children. “Red complex” bacteria were detected in few sites of DM and NDM groups. Fusobacterium nucleatum and Campylobacter rectus were frequently found in both groups. Similar levels of IL-1-β, TNF-α and IL-6 were detected in DM and NDM children. Conclusion Clinical and immunological profiles are similar between DM and NDM children. The presence of Capnocytophaga sputigena and Capnocytophaga ochracea were associated with gingivitis in DM children. PMID:28403363

Photosynthate partitioning in basal zones of tall fescue leaf blades. [Festuca arundinacea Schreb

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

Allard, G.; Nelson, C.J.

Elongating grass leaves have successive zones of cell division, cell elongation, and cell maturation in the basal portion of the blade and are a strong sink for photosynthate. Our objective was to determine dry matter (DM) deposition and partitioning in basal zones of elongating tall fescue (Festuca arundinacea Schreb.) leaf blades. Vegetative tall fescue plants were grown in continuous light (350 micromoles per square meter per second photosynthetic photon flux density) to obtain a constant spatial distribution of elongation growth with time. Content and net deposition rates of water-soluble carbohydrates (WSC) and DM along elongating leaf blades were determined. Thesemore » data were compared with accumulation of {sup 14}C in the basal zones following leaf-labeling with {sup 14}CO{sub 2}. Net deposition of DM was highest in the active cell elongation zone, due mainly to deposition of WSC. The maturation zone, just distal to the elongation zone, accounted for 22% of total net deposition of DM in elongating leaves. However, the spatial profile of {sup 14}C accumulation suggested that the elongation zone and the maturation zone were sinks of equal strength. WSC-free DM accounted for 55% of the total net DM deposition in elongating leaf blades, but only 10% of incoming {sup 14}C-photosynthate accumulated in the water-insoluble fraction (WIF {approximately} WSC-free DM) after 2 hours. In the maturation zone, more WSC was used for synthesis of WSC-free DM than was imported as recent photosynthate.« less

Associations of dietary intake patterns identified using reduced rank regression with markers of arterial stiffness among youth with type 1 diabetes.

PubMed

Lamichhane, A P; Liese, A D; Urbina, E M; Crandell, J L; Jaacks, L M; Dabelea, D; Black, M H; Merchant, A T; Mayer-Davis, E J

2014-12-01

Youth with type 1 diabetes (T1DM) are at substantially increased risk for adverse vascular outcomes, but little is known about the influence of dietary behavior on cardiovascular disease (CVD) risk profile. We aimed to identify dietary intake patterns associated with CVD risk factors and evaluate their impact on arterial stiffness (AS) measures collected thereafter in a cohort of youth with T1DM. Baseline diet data from a food frequency questionnaire and CVD risk factors (triglycerides, low density lipoprotein-cholesterol, systolic blood pressure, hemoglobin A1c, C-reactive protein and waist circumference) were available for 1153 youth aged ⩾10 years with T1DM from the SEARCH for Diabetes in Youth Study. A dietary intake pattern was identified using 33 food groups as predictors and six CVD risk factors as responses in reduced rank regression (RRR) analysis. Associations of this RRR-derived dietary pattern with AS measures (augmentation index (AIx75), n=229; pulse wave velocity, n=237; and brachial distensibility, n=228) were then assessed using linear regression. The RRR-derived pattern was characterized by high intakes of sugar-sweetened beverages (SSB) and diet soda, eggs, potatoes and high-fat meats and low intakes of sweets/desserts and low-fat dairy; major contributors were SSB and diet soda. This pattern captured the largest variability in adverse CVD risk profile and was subsequently associated with AIx75 (β=0.47; P<0.01). The mean difference in AIx75 concentration between the highest and the lowest dietary pattern quartiles was 4.3% in fully adjusted model. Intervention strategies to reduce consumption of unhealthy foods and beverages among youth with T1DM may significantly improve CVD risk profile and ultimately reduce the risk for AS.

Search for γ -Ray Line Signals from Dark Matter Annihilations in the Inner Galactic Halo from 10 Years of Observations with H.E.S.S.

NASA Astrophysics Data System (ADS)

Abdallah, H.; Abramowski, A.; Aharonian, F.; Ait Benkhali, F.; Angüner, E. O.; Arakawa, M.; Arrieta, M.; Aubert, P.; Backes, M.; Balzer, A.; Barnard, M.; Becherini, Y.; Becker Tjus, J.; Berge, D.; Bernhard, S.; Bernlöhr, K.; Blackwell, R.; Böttcher, M.; Boisson, C.; Bolmont, J.; Bonnefoy, S.; Bordas, P.; Bregeon, J.; Brun, F.; Brun, P.; Bryan, M.; Büchele, M.; Bulik, T.; Capasso, M.; Caroff, S.; Carosi, A.; Carr, J.; Casanova, S.; Cerruti, M.; Chakraborty, N.; Chaves, R. C. G.; Chen, A.; Chevalier, J.; Colafrancesco, S.; Condon, B.; Conrad, J.; Davids, I. D.; Decock, J.; Deil, C.; Devin, J.; deWilt, P.; Dirson, L.; Djannati-Ataï, A.; Domainko, W.; Donath, A.; Drury, L. O'C.; Dutson, K.; Dyks, J.; Edwards, T.; Egberts, K.; Eger, P.; Emery, G.; Ernenwein, J.-P.; Eschbach, S.; Farnier, C.; Fegan, S.; Fernandes, M. V.; Fiasson, A.; Fontaine, G.; Förster, A.; Funk, S.; Füßling, M.; Gabici, S.; Gallant, Y. A.; Garrigoux, T.; Gaté, F.; Giavitto, G.; Giebels, B.; Glawion, D.; Glicenstein, J. F.; Gottschall, D.; Grondin, M.-H.; Hahn, J.; Haupt, M.; Hawkes, J.; Heinzelmann, G.; Henri, G.; Hermann, G.; Hinton, J. A.; Hofmann, W.; Hoischen, C.; Holch, T. L.; Holler, M.; Horns, D.; Ivascenko, A.; Iwasaki, H.; Jacholkowska, A.; Jamrozy, M.; Janiak, M.; Jankowsky, D.; Jankowsky, F.; Jingo, M.; Jouvin, L.; Jung-Richardt, I.; Kastendieck, M. A.; Katarzyński, K.; Katsuragawa, M.; Katz, U.; Kerszberg, D.; Khangulyan, D.; Khélifi, B.; King, J.; Klepser, S.; Klochkov, D.; Kluźniak, W.; Komin, Nu.; Kosack, K.; Krakau, S.; Kraus, M.; Krüger, P. P.; Laffon, H.; Lamanna, G.; Lau, J.; Lees, J.-P.; Lefaucheur, J.; Lemière, A.; Lemoine-Goumard, M.; Lenain, J.-P.; Leser, E.; Liu, R.; Lohse, T.; Lorentz, M.; López-Coto, R.; Lypova, I.; Malyshev, D.; Marandon, V.; Marcowith, A.; Mariaud, C.; Marx, R.; Maurin, G.; Maxted, N.; Mayer, M.; Meintjes, P. J.; Meyer, M.; Mitchell, A. M. W.; Moderski, R.; Mohamed, M.; Mohrmann, L.; Morâ, K.; Moulin, E.; Murach, T.; Nakashima, S.; de Naurois, M.; Ndiyavala, H.; Niederwanger, F.; Niemiec, J.; Oakes, L.; O'Brien, P.; Odaka, H.; Ohm, S.; Ostrowski, M.; Oya, I.; Padovani, M.; Panter, M.; Parsons, R. D.; Pekeur, N. W.; Pelletier, G.; Perennes, C.; Petrucci, P.-O.; Peyaud, B.; Piel, Q.; Pita, S.; Poireau, V.; Poon, H.; Prokhorov, D.; Prokoph, H.; Pühlhofer, G.; Punch, M.; Quirrenbach, A.; Raab, S.; Rauth, R.; Reimer, A.; Reimer, O.; Renaud, M.; de los Reyes, R.; Rieger, F.; Rinchiuso, L.; Romoli, C.; Rowell, G.; Rudak, B.; Rulten, C. B.; Sahakian, V.; Saito, S.; Sanchez, D. A.; Santangelo, A.; Sasaki, M.; Schandri, M.; Schlickeiser, R.; Schüssler, F.; Schulz, A.; Schwanke, U.; Schwemmer, S.; Seglar-Arroyo, M.; Settimo, M.; Seyffert, A. S.; Shafi, N.; Shilon, I.; Shiningayamwe, K.; Simoni, R.; Sol, H.; Spanier, F.; Spir-Jacob, M.; Stawarz, Ł.; Steenkamp, R.; Stegmann, C.; Steppa, C.; Sushch, I.; Takahashi, T.; Tavernet, J.-P.; Tavernier, T.; Taylor, A. M.; Terrier, R.; Tibaldo, L.; Tiziani, D.; Tluczykont, M.; Trichard, C.; Tsirou, M.; Tsuji, N.; Tuffs, R.; Uchiyama, Y.; van der Walt, J.; van Eldik, C.; van Rensburg, C.; van Soelen, B.; Vasileiadis, G.; Veh, J.; Venter, C.; Viana, A.; Vincent, P.; Vink, J.; Voisin, F.; Völk, H. J.; Vuillaume, T.; Wadiasingh, Z.; Wagner, S. J.; Wagner, P.; Wagner, R. M.; White, R.; Wierzcholska, A.; Willmann, P.; Wörnlein, A.; Wouters, D.; Yang, R.; Zaborov, D.; Zacharias, M.; Zanin, R.; Zdziarski, A. A.; Zech, A.; Zefi, F.; Ziegler, A.; Zorn, J.; Żywucka, N.; H. E. S. S. Collaboration

2018-05-01

Spectral lines are among the most powerful signatures for dark matter (DM) annihilation searches in very-high-energy γ rays. The central region of the Milky Way halo is one of the most promising targets given its large amount of DM and proximity to Earth. We report on a search for a monoenergetic spectral line from self-annihilations of DM particles in the energy range from 300 GeV to 70 TeV using a two-dimensional maximum likelihood method taking advantage of both the spectral and spatial features of the signal versus background. The analysis makes use of Galactic center observations accumulated over ten years (2004-2014) with the H.E.S.S. array of ground-based Cherenkov telescopes. No significant γ -ray excess above the background is found. We derive upper limits on the annihilation cross section ⟨σ v ⟩ for monoenergetic DM lines at the level of 4 ×10-28 cm3 s-1 at 1 TeV, assuming an Einasto DM profile for the Milky Way halo. For a DM mass of 1 TeV, they improve over the previous ones by a factor of 6. The present constraints are the strongest obtained so far for DM particles in the mass range 300 GeV-70 TeV. Ground-based γ -ray observations have reached sufficient sensitivity to explore relevant velocity-averaged cross sections for DM annihilation into two γ -ray photons at the level expected from the thermal relic density for TeV DM particles.

What sets the central structure of dark matter haloes?

NASA Astrophysics Data System (ADS)

Ogiya, Go; Hahn, Oliver

2018-02-01

Dark matter (DM) haloes forming near the thermal cut-off scale of the density perturbations are unique, since they are the smallest objects and form through monolithic gravitational collapse, while larger haloes contrastingly have experienced mergers. While standard cold dark matter (CDM) simulations readily produce haloes that follow the universal Navarro-Frenk-White (NFW) density profile with an inner slope, ρ ∝ r-α, with α = 1, recent simulations have found that when the free-streaming cut-off expected for the CDM model is resolved, the resulting haloes follow nearly power-law density profiles of α ∼ 1.5. In this paper, we study the formation of density cusps in haloes using idealized N-body simulations of the collapse of proto-haloes. When the proto-halo profile is initially cored due to particle free-streaming at high redshift, we universally find ∼r-1.5 profiles irrespective of the proto-halo profile slope outside the core and large-scale non-spherical perturbations. Quite in contrast, when the proto-halo has a power-law profile, then we obtain profiles compatible with the NFW shape when the density slope of the proto-halo patch is shallower than a critical value, αini ∼ 0.3, while the final slope can be steeper for αini ≳ 0.3. We further demonstrate that the r-1.5 profiles are sensitive to small-scale noise, which gradually drives them towards an inner slope of -1, where they become resilient to such perturbations. We demonstrate that the r-1.5 solutions are in hydrostatic equilibrium, largely consistent with a simple analytic model, and provide arguments that angular momentum appears to determine the inner slope.

Identification of novel autoantibodies in type 1 diabetic patients using a high-density protein microarray.

PubMed

Koo, Bo Kyung; Chae, Sehyun; Kim, Kristine M; Kang, Min Jueng; Kim, Eunhee G; Kwak, Soo Heon; Jung, Hye Seung; Cho, Young Min; Choi, Sung Hee; Park, Young Joo; Shin, Choong Ho; Jang, Hak C; Shin, Chan Soo; Hwang, Daehee; Yi, Eugene C; Park, Kyong Soo

2014-09-01

Autoantibodies can facilitate diagnostic and therapeutic means for type 1 diabetes (T1DM). We profiled autoantibodies from serum samples of 16 T1DM patients, 16 type 2 diabetic (T2DM) patients, and 27 healthy control subjects with normal glucose tolerance (NGT) by using protein microarrays containing 9,480 proteins. Two novel autoantibodies, anti-EEF1A1 and anti-UBE2L3, were selected from microarrays followed by immunofluorescence staining of pancreas. We then tested the validity of the candidates by ELISA in two independent test cohorts: 1) 95 adults with T1DM, 49 with T2DM, 11 with latent autoimmune diabetes in adults (LADA), 20 with Graves disease, and 66 with NGT and 2) 33 children with T1DM and 34 healthy children. Concentrations of these autoantibodies were significantly higher in T1DM patients than in NGT and T2DM subjects (P < 0.01), which was also confirmed in the test cohort of children (P < 0.05). Prevalence of anti-EEF1A1 and anti-UBE2L3 antibodies was 29.5% and 35.8% in T1DM, respectively. Of note, 40.9% of T1DM patients who lack anti-GAD antibodies (GADA) had anti-EEF1A1 and/or anti-UBE2L3 antibodies. These were also detected in patients with fulminant T1DM but not LADA. Our approach identified autoantibodies that can provide a new dimension of information indicative of T1DM independent of GADA and new insights into diagnosis and classification of T1DM. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

NIHAO - XIV. Reproducing the observed diversity of dwarf galaxy rotation curve shapes in ΛCDM

NASA Astrophysics Data System (ADS)

Santos-Santos, Isabel M.; Di Cintio, Arianna; Brook, Chris B.; Macciò, Andrea; Dutton, Aaron; Domínguez-Tenreiro, Rosa

2018-02-01

The significant diversity of rotation curve (RC) shapes in dwarf galaxies has recently emerged as a challenge to Λ cold dark matter (ΛCDM): in dark matter (DM) only simulations, DM haloes have a universal cuspy density profile that results in self-similar RC shapes. We compare RC shapes of simulated galaxies from the NIHAO (Numerical Investigation of a Hundred Astrophysical Objects) project with observed galaxies from the homogeneous SPARC data set. The DM haloes of the NIHAO galaxies can expand to form cores, with the degree of expansion depending on their stellar-to-halo mass ratio. By means of the V2kpc-VRlast relation (where VRlast is the outermost measured rotation velocity), we show that both the average trend and the scatter in RC shapes of NIHAO galaxies are in reasonable agreement with SPARC: this represents a significant improvement compared to simulations that do not result in DM core formation, suggesting that halo expansion is a key process in matching the diversity of dwarf galaxy RCs. Note that NIHAO galaxies can reproduce even the extremely slowly rising RCs of IC 2574 and UGC 5750. Revealingly, the range where observed galaxies show the highest diversity corresponds to the range where core formation is most efficient in NIHAO simulations, 50 < VRlast/km s-1 < 100. A few observed galaxies in this range cannot be matched by any NIHAO RC nor by simulations that predict a universal halo profile. Interestingly, the majority of these are starbursts or emission-line galaxies, with steep RCs and small effective radii. Such galaxies represent an interesting observational target providing new clues to the process/viability of cusp-core transformation, the relationship between starburst and inner potential well, and the nature of DM.

Pronounced weight gain in insulin-treated patients with type 2 diabetes mellitus is associated with an unfavourable cardiometabolic risk profile.

PubMed

Jansen, H J; Vervoort, G; van der Graaf, M; Tack, C J

2010-11-01

Pronounced weight gain after start of insulin therapy in patients with type 2 diabetes mellitus (T2DM) may offset beneficial effects conferred by the improvement of glycaemic control. This hypothesis was tested by comparing the cardiometabolic risk profile of a group of type 2 diabetes patients with a marked increase in body weight ('gainers) after the start of insulin treatment and a similar group without any or only minimal weight gain ('non-gainers'). In a cross-sectional study, we compared two predefined groups of patients with T2DM who had been on insulin therapy for a mean of 4.0 years: 'gainers' vs 'non-gainers'. Cardiometabolic risk was assessed by measuring fat content and distribution (physical examination, bioelectrical impedance analysis, dual energy X-ray absorption, and magnetic resonance imaging), liver fat content (magnetic resonance spectroscopy), physical activity levels (Sensewear® armband) and plasma markers. Each subgroup consisted of 14 patients. Gainers had significantly more total body and trunk fat (especially subcutaneous fat) compared with no-gainers. Gainers had similar liver fat content, and slightly higher levels of fat hormones. Furthermore, gainers performed significantly less physical activity. Lastly, gainers had higher total cholesterol, low-density lipoprotein cholesterol, and alanine aminotransferase levels with similar cholesterol-lowering treatment. Patients with T2DM who show pronounced weight gain during insulin therapy have a less favourable cardiometabolic risk profile compared with patients who show no or minimal weight gain.

Association of apolipoprotein E polymorphism with type 2 diabetes mellitus in a Saudi population.

PubMed

Alharbi, Khalid Khalaf; Khan, Imran Ali; Syed, Rabbani

2014-09-01

Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disorder characterized by persistent hyperglycemia. It is considered to be a major risk factor for obesity and cardiovascular diseases. The cause of T2DM is likely due to a complex interaction between genetic and environmental factors. Apolipoprotein E (ApoE) gene plays a key role in lipid metabolism. The aim of this contemporary study was to investigate the ApoE polymorphism in a Saudi population with T2DM subjects. Two common single-nucleotide polymorphisms, that is, rs429358 and rs7412, in the ApoE gene were genotyped by TaqMan assay in T2DM patients (n=438) and controls (n=460). The results of the present study indicate that ApoE polymorphism was significantly associated with T2DM in a Saudi population with the ɛ2 and ɛ4 alleles (p=0.0001). We found statistically significant difference in the genotype distribution between T2DM patients and controls [for E4/E4: OR, 4.39 (95% CI: 2.16-8.92); p=0.0001]. A significant difference was observed in the lipid profile parameters, like triglycerides, low-density lipoprotein, and ApoE alleles (p=0.0001). Further studies are carried out in a Saudi population with different diseases to confirm the risk allele. In conclusion, our study results suggest that ApoE variants constitute risk markers of T2DM in a Saudi population.

Semi-empirical catalog of early-type galaxy-halo systems: dark matter density profiles, halo contraction and dark matter annihilation strength

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

Chae, Kyu-Hyun; Kravtsov, Andrey V.; Frieman, Joshua A.

With Sloan Digital Sky Survey galaxy data and halo data from up-to-date N-body simulations within the ΛCDM framework we construct a semi-empirical catalog (SEC) of early-type galaxy-halo systems by making a self-consistent bivariate statistical match of stellar mass (M{sub *}) and velocity dispersion (σ) with halo virial mass (M{sub vir}) as demonstrated here for the first time. We then assign stellar mass profile and velocity dispersion profile parameters to each system in the SEC using their observed correlations with M{sub *} and σ. Simultaneously, we solve for dark matter density profile of each halo using the spherical Jeans equation. Themore » resulting dark matter density profiles deviate in general from the dissipationless profile of Navarro-Frenk-White or Einasto and their mean inner density slope and concentration vary systematically with M{sub vir}. Statistical tests of the distribution of profiles at fixed M{sub vir} rule out the null hypothesis that it follows the distribution predicted by dissipationless N-body simulations for M{sub vir}∼<10{sup 13.5} {sup –} {sup 14.5} M{sub s}un. These dark matter profiles imply that dark matter density is, on average, enhanced significantly in the inner region of halos with M{sub vir}∼<10{sup 13.5} {sup –} {sup 14.5} M{sub s}un supporting halo contraction. The main characteristics of halo contraction are: (1) the mean dark matter density within the effective radius has increased by a factor varying systematically up to ≈ 3–4 at M{sub vir} = 10{sup 12} M{sub s}un, and (2) the inner density slope has a mean of (α) ≈ 1.3 with ρ{sub dm}(r)∝r{sup −α} and a halo-to-halo rms scatter of rms(α) ∼ 0.4–0.5 for 10{sup 12} M{sub s}un∼« less

A comparative study of volumetric breast density estimation in digital mammography and magnetic resonance imaging: results from a high-risk population

NASA Astrophysics Data System (ADS)

Kontos, Despina; Xing, Ye; Bakic, Predrag R.; Conant, Emily F.; Maidment, Andrew D. A.

2010-03-01

We performed a study to compare methods for volumetric breast density estimation in digital mammography (DM) and magnetic resonance imaging (MRI) for a high-risk population of women. DM and MRI images of the unaffected breast from 32 women with recently detected abnormalities and/or previously diagnosed breast cancer (age range 31-78 yrs, mean 50.3 yrs) were retrospectively analyzed. DM images were analyzed using QuantraTM (Hologic Inc). The MRI images were analyzed using a fuzzy-C-means segmentation algorithm on the T1 map. Both methods were compared to Cumulus (Univ. Toronto). Volumetric breast density estimates from DM and MRI are highly correlated (r=0.90, p<=0.001). The correlation between the volumetric and the area-based density measures is lower and depends on the training background of the Cumulus software user (r=0.73-84, p<=0.001). In terms of absolute values, MRI provides the lowest volumetric estimates (mean=14.63%), followed by the DM volumetric (mean=22.72%) and area-based measures (mean=29.35%). The MRI estimates of the fibroglandular volume are statistically significantly lower than the DM estimates for women with very low-density breasts (p<=0.001). We attribute these differences to potential partial volume effects in MRI and differences in the computational aspects of the image analysis methods in MRI and DM. The good correlation between the volumetric and the area-based measures, shown to correlate with breast cancer risk, suggests that both DM and MRI volumetric breast density measures can aid in breast cancer risk assessment. Further work is underway to fully-investigate the association between volumetric breast density measures and breast cancer risk.

Search for γ-Ray Line Signals from Dark Matter Annihilations in the Inner Galactic Halo from 10 Years of Observations with H.E.S.S.

PubMed

Abdallah, H; Abramowski, A; Aharonian, F; Ait Benkhali, F; Angüner, E O; Arakawa, M; Arrieta, M; Aubert, P; Backes, M; Balzer, A; Barnard, M; Becherini, Y; Becker Tjus, J; Berge, D; Bernhard, S; Bernlöhr, K; Blackwell, R; Böttcher, M; Boisson, C; Bolmont, J; Bonnefoy, S; Bordas, P; Bregeon, J; Brun, F; Brun, P; Bryan, M; Büchele, M; Bulik, T; Capasso, M; Caroff, S; Carosi, A; Carr, J; Casanova, S; Cerruti, M; Chakraborty, N; Chaves, R C G; Chen, A; Chevalier, J; Colafrancesco, S; Condon, B; Conrad, J; Davids, I D; Decock, J; Deil, C; Devin, J; deWilt, P; Dirson, L; Djannati-Ataï, A; Domainko, W; Donath, A; Drury, L O'C; Dutson, K; Dyks, J; Edwards, T; Egberts, K; Eger, P; Emery, G; Ernenwein, J-P; Eschbach, S; Farnier, C; Fegan, S; Fernandes, M V; Fiasson, A; Fontaine, G; Förster, A; Funk, S; Füßling, M; Gabici, S; Gallant, Y A; Garrigoux, T; Gaté, F; Giavitto, G; Giebels, B; Glawion, D; Glicenstein, J F; Gottschall, D; Grondin, M-H; Hahn, J; Haupt, M; Hawkes, J; Heinzelmann, G; Henri, G; Hermann, G; Hinton, J A; Hofmann, W; Hoischen, C; Holch, T L; Holler, M; Horns, D; Ivascenko, A; Iwasaki, H; Jacholkowska, A; Jamrozy, M; Janiak, M; Jankowsky, D; Jankowsky, F; Jingo, M; Jouvin, L; Jung-Richardt, I; Kastendieck, M A; Katarzyński, K; Katsuragawa, M; Katz, U; Kerszberg, D; Khangulyan, D; Khélifi, B; King, J; Klepser, S; Klochkov, D; Kluźniak, W; Komin, Nu; Kosack, K; Krakau, S; Kraus, M; Krüger, P P; Laffon, H; Lamanna, G; Lau, J; Lees, J-P; Lefaucheur, J; Lemière, A; Lemoine-Goumard, M; Lenain, J-P; Leser, E; Liu, R; Lohse, T; Lorentz, M; López-Coto, R; Lypova, I; Malyshev, D; Marandon, V; Marcowith, A; Mariaud, C; Marx, R; Maurin, G; Maxted, N; Mayer, M; Meintjes, P J; Meyer, M; Mitchell, A M W; Moderski, R; Mohamed, M; Mohrmann, L; Morå, K; Moulin, E; Murach, T; Nakashima, S; de Naurois, M; Ndiyavala, H; Niederwanger, F; Niemiec, J; Oakes, L; O'Brien, P; Odaka, H; Ohm, S; Ostrowski, M; Oya, I; Padovani, M; Panter, M; Parsons, R D; Pekeur, N W; Pelletier, G; Perennes, C; Petrucci, P-O; Peyaud, B; Piel, Q; Pita, S; Poireau, V; Poon, H; Prokhorov, D; Prokoph, H; Pühlhofer, G; Punch, M; Quirrenbach, A; Raab, S; Rauth, R; Reimer, A; Reimer, O; Renaud, M; de Los Reyes, R; Rieger, F; Rinchiuso, L; Romoli, C; Rowell, G; Rudak, B; Rulten, C B; Sahakian, V; Saito, S; Sanchez, D A; Santangelo, A; Sasaki, M; Schandri, M; Schlickeiser, R; Schüssler, F; Schulz, A; Schwanke, U; Schwemmer, S; Seglar-Arroyo, M; Settimo, M; Seyffert, A S; Shafi, N; Shilon, I; Shiningayamwe, K; Simoni, R; Sol, H; Spanier, F; Spir-Jacob, M; Stawarz, Ł; Steenkamp, R; Stegmann, C; Steppa, C; Sushch, I; Takahashi, T; Tavernet, J-P; Tavernier, T; Taylor, A M; Terrier, R; Tibaldo, L; Tiziani, D; Tluczykont, M; Trichard, C; Tsirou, M; Tsuji, N; Tuffs, R; Uchiyama, Y; van der Walt, J; van Eldik, C; van Rensburg, C; van Soelen, B; Vasileiadis, G; Veh, J; Venter, C; Viana, A; Vincent, P; Vink, J; Voisin, F; Völk, H J; Vuillaume, T; Wadiasingh, Z; Wagner, S J; Wagner, P; Wagner, R M; White, R; Wierzcholska, A; Willmann, P; Wörnlein, A; Wouters, D; Yang, R; Zaborov, D; Zacharias, M; Zanin, R; Zdziarski, A A; Zech, A; Zefi, F; Ziegler, A; Zorn, J; Żywucka, N

2018-05-18

Spectral lines are among the most powerful signatures for dark matter (DM) annihilation searches in very-high-energy γ rays. The central region of the Milky Way halo is one of the most promising targets given its large amount of DM and proximity to Earth. We report on a search for a monoenergetic spectral line from self-annihilations of DM particles in the energy range from 300 GeV to 70 TeV using a two-dimensional maximum likelihood method taking advantage of both the spectral and spatial features of the signal versus background. The analysis makes use of Galactic center observations accumulated over ten years (2004-2014) with the H.E.S.S. array of ground-based Cherenkov telescopes. No significant γ-ray excess above the background is found. We derive upper limits on the annihilation cross section ⟨σv⟩ for monoenergetic DM lines at the level of 4×10^{-28}  cm^{3} s^{-1} at 1 TeV, assuming an Einasto DM profile for the Milky Way halo. For a DM mass of 1 TeV, they improve over the previous ones by a factor of 6. The present constraints are the strongest obtained so far for DM particles in the mass range 300 GeV-70 TeV. Ground-based γ-ray observations have reached sufficient sensitivity to explore relevant velocity-averaged cross sections for DM annihilation into two γ-ray photons at the level expected from the thermal relic density for TeV DM particles.

Association of trace elements with lipid profiles and glycaemic control in patients with type 1 diabetes mellitus in northern Sardinia, Italy: An observational study.

PubMed

Peruzzu, Angela; Solinas, Giuliana; Asara, Yolande; Forte, Giovanni; Bocca, Beatrice; Tolu, Francesco; Malaguarnera, Lucia; Montella, Andrea; Madeddu, Roberto

2015-08-01

Sardinia is an Italian region with a high incidence of type 1 diabetes mellitus. This study aimed to determine the associations of trace elements with lipid profiles and glycaemic control in patients with T1DM. A total of 192 patients with T1DM who attended the Unit of Diabetology and Metabolic Diseases in Sassari, Italy, were enrolled. Trace elements zinc, copper, selenium, chromium, and iron were measured in whole blood by sector field inductively coupled plasma mass spectrometry. The correlations between metabolic variables and the levels of trace elements were determined. Zinc was positively correlated with total cholesterol (P=0.023), low-density lipoprotein (P=0.0015), and triglycerides (P=0.027). Iron as significantly correlated with TC (P=0.0189), LDL (P=0.0121), and high-density lipoprotein (HDL) (P=0.0466). In males, Cr was positively correlated with HDL (P=0.0079) and Se, in females was correlated with TG (P=0.0113). The mean fasting plasma glucose was166.2mgdL(-1). Chromium was correlated with fasting plasma glucose (P=0.0149), particularly in males (P=0.0038). Overall, 63.5% of the patients had moderate HbA1c (7-9%). Copper was significantly correlated with HbA1c% in males (P=0.0155). In conclusion, the results of this study indicate that trace elements show different associations with lipid levels and glycaemic control in T1DM. Zinc, Fe, and Se were associated with lipid levels whereas Cu and Cr were associated with HbA1c%. Copyright © 2015 Elsevier Ltd. All rights reserved.

THE TEMPERATURE OF HOT GAS IN GALAXIES AND CLUSTERS: BARYONS DANCING TO THE TUNE OF DARK MATTER

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

Hansen, Steen H.; Maccio, Andrea V.; Romano-Diaz, Emilio

2011-06-10

The temperature profile of hot gas in galaxies and galaxy clusters is largely determined by the depth of the total gravitational potential and thereby by the dark matter (DM) distribution. We use high-resolution hydrodynamical simulations of galaxy formation to derive a surprisingly simple relation between the gas temperature and DM properties. We show that this relation holds not just for galaxy clusters but also for equilibrated and relaxed galaxies at radii beyond the central stellar-dominated region of typically a few kpc. It is then clarified how a measurement of the temperature and density of the hot gas component can leadmore » to an indirect measurement of the DM velocity anisotropy in galaxies. We also study the temperature relation for galaxy clusters in the presence of self-regulated, recurrent active galactic nuclei (AGNs), and demonstrate that this temperature relation even holds outside the inner region of {approx}30 kpc in clusters with an active AGN.« less

Body mass index and glycemic control influence lipoproteins in children with type 1 diabetes.

PubMed

Vaid, Shalini; Hanks, Lynae; Griffin, Russell; Ashraf, Ambika P

2016-01-01

Patients with type 1 diabetes mellitus (T1DM) have an extremely high risk of cardiovascular disease (CVD) morbidity and mortality. It is well known that dyslipidemia is a subclinical manifestation of atherosclerosis. To analyze presence and predicting factors of lipoprotein abnormalities prevalent in children with T1DM and whether race-specific differences exist between non-Hispanic white (NHW) and non-Hispanic black (NHB) in the lipoprotein characteristics. A retrospective electronic chart review including 600 (123 NHB and 477 NHW) T1DM patients aged 7.85 ± 3.75 years who underwent lipoprotein analysis. Relative to NHW counterparts, NHB T1DM subjects had a higher HbA1c, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), apoB 100, lipoprotein (a), and high-density lipoprotein cholesterol (HDL-c), HDL-2, and HDL-3. Body mass index (BMI) was positively associated with TC, LDL-c, apoB 100, and non-HDL-c and inversely associated with HDL, HDL-2, and HDL-3. HbA1c was positively associated with TC, LDL-c, apoB 100, non-HDL-c, and HDL-3. Multilinear regression analysis demonstrated that HbA1c was positively associated with apoB 100 in both NHB and NHW, and BMI was a positive determinant of apoB 100 in NHW only. Poor glycemic control and high BMI may contribute to abnormal lipoprotein profiles. Glycemic control (in NHB and NHW) and weight management (in NHW) may have significant implications in T1DM. ApoB 100 concentrations in subjects with T1DM were determined by modifiable risk factors, BMI, HbA1C, and blood pressure, indicating the importance of adequate weight, glycemic, and blood pressure control for better diabetes care and likely lower CVD risk. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Galaxy clusters in the context of superfluid dark matter

NASA Astrophysics Data System (ADS)

Hodson, Alistair O.; Zhao, Hongsheng; Khoury, Justin; Famaey, Benoit

2017-11-01

Context. The mass discrepancy in the Universe has not been solved by the cold dark matter (CDM) or the modified Newtonian dynamics (MOND) paradigms so far. The problems and solutions of either scenario are mutually exclusive on large and small scales. It has recently been proposed, by assuming that dark matter is a superfluid, that MOND-like effects can be achieved on small scales whilst preserving the success of ΛCDM on large scales. Detailed models within this "superfluid dark matter" (SfDM) paradigm are yet to be constructed. Aims: Here, we aim to provide the first set of spherical models of galaxy clusters in the context of SfDM. We aim to determine whether the superfluid formulation is indeed sufficient to explain the mass discrepancy in galaxy clusters. Methods: The SfDM model is defined by two parameters. Λ can be thought of as a mass scale in the Lagrangian of the scalar field that effectively describes the phonons, and it acts as a coupling constant between the phonons and baryons. m is the mass of the DM particles. Based on these parameters, we outline the theoretical structure of the superfluid core and the surrounding "normal-phase" dark halo of quasi-particles. The latter are thought to encompass the largest part of galaxy clusters. Here, we set the SfDM transition at the radius where the density and pressure of the superfluid and normal phase coincide, neglecting the effect of phonons in the superfluid core. We then apply the formalism to a sample of galaxy clusters, and directly compare the SfDM predicted mass profiles to data. Results: We find that the superfluid formulation can reproduce the X-ray dynamical mass profile of clusters reasonably well, but with a slight under-prediction of the gravity in the central regions. This might be partly related to our neglecting of the effect of phonons in these regions. Two normal-phase halo profiles are tested, and it is found that clusters are better defined by a normal-phase halo resembling an Navarro-Frenk-White-like structure than an isothermal profile. Conclusions: In this first exploratory work on the topic, we conclude that depending on the amount of baryons present in the central galaxy and on the actual effect of phonons in the inner regions, this superfluid formulation could be successful in describing galaxy clusters. In the future, our model could be made more realistic by exploring non-sphericity and a more realistic SfDM to normal phase transition. The main result of this study is an estimate of the order of magnitude of the theory parameters for the superfluid formalism to be reasonably consistent with clusters. These values will have to be compared to the true values needed in galaxies.

Effects of supplemental copper on the serum lipid profile, meat quality, and carcass composition of goat kids.

PubMed

Huang, Yanling; Wang, Yong; Lin, Xi; Guo, Chunhua

2014-06-01

To evaluate the effects of copper (Cu) supplementation on the serum lipid profile, meat quality, and carcass composition of goat kids, thirty-five 3-4-month-old Jian Yang big-eared goat kids (BW 20.3±0.6 kg) were randomly assigned to one of seven dietary Cu treatments (n=5/treatment). The dietary Cu concentrations were: (1) control (no supplemental Cu), (2) 20 mg, (3) 40 mg, (4) 80 mg, (5) 160 mg, (6) 320 mg, and (7) 640 mg of supplemental Cu/kg dry matter (DM). Copper was supplemented as CuSO4.5H2O (25.2 % Cu). The goats were fed a high-concentrate basal diet with the different concentrations of supplemental Cu/kg DM for 96 days. The serum lipid profile was determined on day 51 and day 96. Meat quality and carcass composition of longissimus dorsi muscle were measured after the goats were slaughtered at 96 days. Serum total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C) were not affected by treatment (P>0.18). No differences were observed in drip loss, cooking loss, a* (redness/greenness) and b* (yellowness/blueness) values (P>0.17); however, the 24-h pH value (linear; P=0.0009) and L* (brightness) value (linear; P=0.0128) decreased, and shear force increased (linear; P=0.0005) as Cu supplementation increased. The intramuscular fat (%) increased (linear; P=0.001) as supplemental Cu increased. No differences (P>0.21) in the moisture, crude protein, and ash (%) were observed. Results of this study indicate that supplemental Cu does not modify the serum lipid profile; however, it can impact intramuscular fat content and the meat quality of goat kids.

Cone Photoreceptor Irregularity on Adaptive Optics Scanning Laser Ophthalmoscopy Correlates With Severity of Diabetic Retinopathy and Macular Edema

PubMed Central

Lammer, Jan; Prager, Sonja G.; Cheney, Michael C.; Ahmed, Amel; Radwan, Salma H.; Burns, Stephen A.; Silva, Paolo S.; Sun, Jennifer K.

2016-01-01

Purpose To determine whether cone density, spacing, or regularity in eyes with and without diabetes (DM) as assessed by high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) correlates with presence of diabetes, diabetic retinopathy (DR) severity, or presence of diabetic macular edema (DME). Methods Participants with type 1 or 2 DM and healthy controls underwent AOSLO imaging of four macular regions. Cone assessment was performed by independent graders for cone density, packing factor (PF), nearest neighbor distance (NND), and Voronoi tile area (VTA). Regularity indices (mean/SD) of NND (RI-NND) and VTA (RI-VTA) were calculated. Results Fifty-three eyes (53 subjects) were assessed. Mean ± SD age was 44 ± 12 years; 81% had DM (duration: 22 ± 13 years; glycated hemoglobin [HbA1c]: 8.0 ± 1.7%; DM type 1: 72%). No significant relationship was found between DM, HbA1c, or DR severity and cone density or spacing parameters. However, decreased regularity of cone arrangement in the macular quadrants was correlated with presence of DM (RI-NND: P = 0.04; RI-VTA: P = 0.04), increasing DR severity (RI-NND: P = 0.04), and presence of DME (RI-VTA: P = 0.04). Eyes with DME were associated with decreased density (P = 0.04), PF (P = 0.03), and RI-VTA (0.04). Conclusions Although absolute cone density and spacing don't appear to change substantially in DM, decreased regularity of the cone arrangement is consistently associated with the presence of DM, increasing DR severity, and DME. Future AOSLO evaluation of cone regularity is warranted to determine whether these changes are correlated with, or predict, anatomic or functional deficits in patients with DM. PMID:27926754

Cone Photoreceptor Irregularity on Adaptive Optics Scanning Laser Ophthalmoscopy Correlates With Severity of Diabetic Retinopathy and Macular Edema.

PubMed

Lammer, Jan; Prager, Sonja G; Cheney, Michael C; Ahmed, Amel; Radwan, Salma H; Burns, Stephen A; Silva, Paolo S; Sun, Jennifer K

2016-12-01

To determine whether cone density, spacing, or regularity in eyes with and without diabetes (DM) as assessed by high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) correlates with presence of diabetes, diabetic retinopathy (DR) severity, or presence of diabetic macular edema (DME). Participants with type 1 or 2 DM and healthy controls underwent AOSLO imaging of four macular regions. Cone assessment was performed by independent graders for cone density, packing factor (PF), nearest neighbor distance (NND), and Voronoi tile area (VTA). Regularity indices (mean/SD) of NND (RI-NND) and VTA (RI-VTA) were calculated. Fifty-three eyes (53 subjects) were assessed. Mean ± SD age was 44 ± 12 years; 81% had DM (duration: 22 ± 13 years; glycated hemoglobin [HbA1c]: 8.0 ± 1.7%; DM type 1: 72%). No significant relationship was found between DM, HbA1c, or DR severity and cone density or spacing parameters. However, decreased regularity of cone arrangement in the macular quadrants was correlated with presence of DM (RI-NND: P = 0.04; RI-VTA: P = 0.04), increasing DR severity (RI-NND: P = 0.04), and presence of DME (RI-VTA: P = 0.04). Eyes with DME were associated with decreased density (P = 0.04), PF (P = 0.03), and RI-VTA (0.04). Although absolute cone density and spacing don't appear to change substantially in DM, decreased regularity of the cone arrangement is consistently associated with the presence of DM, increasing DR severity, and DME. Future AOSLO evaluation of cone regularity is warranted to determine whether these changes are correlated with, or predict, anatomic or functional deficits in patients with DM.

Double Muscling in Cattle: Genes, Husbandry, Carcasses and Meat

PubMed Central

Fiems, Leo O.

2012-01-01

Simple Summary Selection for an increased meatiness in beef cattle has resulted in double-muscled (DM) animals, owing to the inactivation of the myostatin gene. These animals are characterized by an excellent conformation and an extremely high carcass yield, coinciding with a reduced organ mass. As a consequence, voluntary feed intake is reduced, but feed efficiency is considerably improved, although maintenance requirements are not clearly reduced. DM animals are more susceptible to respiratory disease, stress and dystocia, requiring extra attention for accommodation and welfare. Carcasses of DM animals are very lean, and intramuscular fat content is low. The fatty acid profile is different when compared with non-DM animals, containing less saturated fatty acids. Collagen content of the meat is lower, so that meat from double-muscled animals is mostly more tender. However, meat tenderness, color and juiciness are not always improved. A different metabolism as a consequence of faster glycolytic myofibers can be partly responsible for this phenomenon. DM animals are interesting for the producer and butcher, and beneficial for the consumer, if an appropriate nutrition and accommodation, and adequate slaughter conditions are taken into account. Abstract Molecular biology has enabled the identification of the mechanisms whereby inactive myostatin increases skeletal muscle growth in double-muscled (DM) animals. Myostatin is a secreted growth differentiation factor belonging to the transforming growth factor-β superfamily. Mutations make the myostatin gene inactive, resulting in muscle hypertrophy. The relationship between the different characteristics of DM cattle are defined with possible consequences for livestock husbandry. The extremely high carcass yield of DM animals coincides with a reduction in the size of most vital organs. As a consequence, DM animals may be more susceptible to respiratory disease, urolithiasis, lameness, nutritional stress, heat stress and dystocia, resulting in a lower robustness. Their feed intake capacity is reduced, necessitating a diet with a greater nutrient density. The modified myofiber type is responsible for a lower capillary density, and it induces a more glycolytic metabolism. There are associated changes for the living animal and post-mortem metabolism alterations, requiring appropriate slaughter conditions to maintain a high meat quality. Intramuscular fat content is low, and it is characterized by more unsaturated fatty acids, providing healthier meat for the consumer. It may not always be easy to find a balance between the different disciplines underlying the livestock husbandry of DM animals to realize a good performance and health and meat quality. PMID:26487034

How do stars affect ψDM halos?

NASA Astrophysics Data System (ADS)

Chan, James H. H.; Schive, Hsi-Yu; Woo, Tak-Pong; Chiueh, Tzihong

2018-04-01

Wave dark matter (ψDM) predicts a compact soliton core and a granular halo in every galaxy. This work presents the first simulation study of an elliptical galaxy by including both stars and ψDM, focusing on the systematic changes of the central soliton and halo granules. With the addition of stars in the inner halo, we find the soliton core consistently becomes more prominent by absorbing mass from the host halo than that without stars, and the halo granules become "non-isothermal", "hotter" in the inner halo and "cooler" in the outer halo, as opposed to the isothermal halo in pure ψDM cosmological simulations. Moreover, the composite (star+ψDM) mass density is found to follow a r-2 isothermal profile near the half-light radius in most cases. Most striking is the velocity dispersion of halo stars that increases rapidly toward the galactic center by a factor of at least 2 inside the half-light radius caused by the deepened soliton gravitational potential, a result that compares favorably with observations of elliptical galaxies and bulges in spiral galaxies. However in some rare situations we find a phase segregation turning a compact distribution of stars into two distinct populations with high and very low velocity dispersions; while the high-velocity component mostly resides in the halo, the very low-velocity component is bound to the interior of the soliton core, resembling stars in faint dwarf spheroidal galaxies.

MiniSODAR(TradeMark) Evaluation

NASA Technical Reports Server (NTRS)

Short, David A.; Wheeler, Mark M.

2003-01-01

This report describes results of the AMU's Instrumentation and Measurement task for evaluation of the Doppler miniSODAR(TradeMark) System (DmSS). The DmSS is an acoustic wind profiler providing high resolution data to a height of approx. 410 ft. The Boeing Company installed a DmSS near Space Launch Complex 37 in mid-2002 as a substitute for a tall wind tower and plans to use DmSS data for the analysis and forecasting of winds during ground and launch operations. Peak wind speed data are of particular importance to Launch Weather Officers of the 45th Weather Squadron for evaluating user Launch Commit Criteria. The AMU performed a comparative analysis of wind data between the DmSS and nearby wind towers from August 2002 to July 2003. The DmSS vertical profile of average wind speed showed good agreement with the wind towers. However, the DMSS peak wind speeds were higher, on average, than the wind tower peak wind speeds by about 25%. A statistical model of an idealized Doppler profiler was developed and it predicted that average wind speeds would be well determined but peak wind speeds would be over-estimated due to an under-specification of vertical velocity variations in the atmosphere over the Profiler.

Preclinical safety profile of trastuzumab emtansine (T-DM1): Mechanism of action of its cytotoxic component retained with improved tolerability

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

Poon, Kirsten Achilles, E-mail: achilles.kirsten@gene.com; Flagella, Kelly; Beyer, Joseph

2013-12-01

Trastuzumab emtansine (T-DM1) is the first antibody-drug conjugate (ADC) approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The therapeutic premise of ADCs is based on the hypothesis that targeted delivery of potent cytotoxic drugs to tumors will provide better tolerability and efficacy compared with non-targeted delivery, where poor tolerability can limit efficacious doses. Here, we present results from preclinical studies characterizing the toxicity profile of T-DM1, including limited assessment of unconjugated DM1. T-DM1 binds primate ErbB2 and human HER2 but not the rodent homolog c-neu. Therefore, antigen-dependent and non-antigen-dependent toxicity was evaluated in monkeysmore » and rats, respectively, in both single- and repeat-dose studies; toxicity of DM1 was assessed in rats only. T-DM1 was well tolerated at doses up to 40 mg/kg (∼ 4400 μg DM1/m{sup 2}) and 30 mg/kg (∼ 6000 μg DM1/m{sup 2}) in rats and monkeys, respectively. In contrast, DM1 was only tolerated up to 0.2 mg/kg (1600 μg DM1/m{sup 2}). This suggests that at least two-fold higher doses of the cytotoxic agent are tolerated in T-DM1, supporting the premise of ADCs to improve the therapeutic index. In addition, T-DM1 and DM1 safety profiles were similar and consistent with the mechanism of action of DM1 (i.e., microtubule disruption). Findings included hepatic, bone marrow/hematologic (primarily platelet), lymphoid organ, and neuronal toxicities, and increased numbers of cells of epithelial and phagocytic origin in metaphase arrest. These adverse effects did not worsen with chronic dosing in monkeys and are consistent with those reported in T-DM1-treated patients to date. - Highlights: • T-DM1 was well tolerated in preclinical studies in rats and cynomolgus monkeys. • T-DM1 is associated with bone marrow/hematologic, hepatic, and neuronal toxicities. • T-DM1 toxicities are related to DM1 mechanisms of action and pharmacologic activity. • When conjugated in T-DM1, higher doses of DM1 can be tolerated. • Antibody-drug conjugates may improve the therapeutic window for cytotoxic agents.« less

Dapagliflozin in patients with type II diabetes mellitus, with and without elevated triglyceride and reduced high-density lipoprotein cholesterol levels.

PubMed

Bays, Harold E; Sartipy, Peter; Xu, John; Sjöström, Carl David; Underberg, James A

Dapagliflozin is a selective sodium-glucose cotransporter 2 inhibitor that improves glycemic control in patients with type II diabetes mellitus (T2DM) by reducing renal glucose reabsorption. The aim was to evaluate the lipid effects of dapagliflozin 10 mg or placebo in patients with T2DM with/without baseline elevated triglyceride and reduced high-density lipoprotein (HDL) cholesterol levels. This was a post hoc analysis of 10 phase 3, placebo-controlled studies of dapagliflozin 10 mg (N = 2237) or placebo (N = 2164) administered for 24 weeks in patients with T2DM. Patients with elevated triglyceride (≥150 mg/dL [1.69 mmol/L]) and reduced HDL cholesterol levels (<40 mg/dL [1.04 mmol/L] in men; <50 mg/dL [1.29 mmol/L] in women) were included (group A). The reference group (group B) included patients who did not meet the defined lipid criteria. The effects of dapagliflozin on fasting lipid profiles were generally similar in the 2 lipid groups (ie, groups A and B) and, compared with placebo, were associated with minor increases in non-HDL cholesterol, low-density lipoprotein, and HDL cholesterol levels. The effects on triglyceride levels were inconsistent. The incidence of adverse events (AEs)/serious AEs, and AEs of genital infection, urinary tract infection, volume reduction, renal function, and hypoglycemia were similar in the 2 lipid groups. Patients with T2DM treated with dapagliflozin experienced minor changes in lipid levels; the changes were generally similar in the 2 lipid groups. The clinical significance of these changes in lipids is unclear, especially in view of the positive effects of dapagliflozin on other cardiovascular disease risk factors. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Altered sphingoid base profiles in type 1 compared to type 2 diabetes.

PubMed

Wei, Nancy; Pan, Jessica; Pop-Busui, Rodica; Othman, Alaa; Alecu, Irina; Hornemann, Thorsten; Eichler, Florian S

2014-10-11

Sphingolipids are increasingly recognized to play a role in insulin resistance and diabetes. Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). It is unknown whether 1-deoxySL in patients with diabetes type 1 (T1DM) are similarly elevated. We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 1-deoxySLs were significantly higher in the groups with T2DM but not different between T1DM and controls. In contrast to patients with T2DM, 1-deoxSL levels are not elevated in T1DM. Our study indicates that the 1-deoxySL formation is not per-se caused by hyperglycemia but rather specifically associated with metabolic changes in T2DM, such as elevated triglyceride levels.

Halo-independence with quantified maximum entropy at DAMA/LIBRA

NASA Astrophysics Data System (ADS)

Fowlie, Andrew

2017-10-01

Using the DAMA/LIBRA anomaly as an example, we formalise the notion of halo-independence in the context of Bayesian statistics and quantified maximum entropy. We consider an infinite set of possible profiles, weighted by an entropic prior and constrained by a likelihood describing noisy measurements of modulated moments by DAMA/LIBRA. Assuming an isotropic dark matter (DM) profile in the galactic rest frame, we find the most plausible DM profiles and predictions for unmodulated signal rates at DAMA/LIBRA. The entropic prior contains an a priori unknown regularisation factor, β, that describes the strength of our conviction that the profile is approximately Maxwellian. By varying β, we smoothly interpolate between a halo-independent and a halo-dependent analysis, thus exploring the impact of prior information about the DM profile.

An integrated multiple-analyte pharmacokinetic model to characterize trastuzumab emtansine (T-DM1) clearance pathways and to evaluate reduced pharmacokinetic sampling in patients with HER2-positive metastatic breast cancer.

PubMed

Lu, Dan; Joshi, Amita; Wang, Bei; Olsen, Steve; Yi, Joo-Hee; Krop, Ian E; Burris, Howard A; Girish, Sandhya

2013-08-01

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate recently approved by the US Food and Drug Administration for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer previously treated with trastuzumab and taxane chemotherapy. It comprises the microtubule inhibitory cytotoxic agent DM1 conjugated to the HER2-targeted humanized monoclonal antibody trastuzumab via a stable linker. To characterize the pharmacokinetics of T-DM1 in patients with metastatic breast cancer, concentrations of multiple analytes were quantified, including serum concentrations of T-DM1 conjugate and total trastuzumab (the sum of conjugated and unconjugated trastuzumab), as well as plasma concentrations of DM1. The clearance of T-DM1 conjugate is approximately 2 to 3 times faster than its parent antibody, trastuzumab. However, the clearance pathways accounting for this faster clearance rate are unclear. An integrated population pharmacokinetic model that simultaneously fits the pharmacokinetics of T-DM1 conjugate and total trastuzumab can help to elucidate the clearance pathways of T-DM1. The model can also be used to predict total trastuzumab pharmacokinetic profiles based on T-DM1 conjugate pharmacokinetic data and sparse total trastuzumab pharmacokinetic data, thereby reducing the frequency of pharmacokinetic sampling. T-DM1 conjugate and total trastuzumab serum concentration data, including baseline trastuzumab concentrations prior to T-DM1 treatment, from phase I and II studies were used to develop this integrated population pharmacokinetic model. Based on a hypothetical T-DM1 catabolism scheme, two-compartment models for T-DM1 conjugate and trastuzumab were integrated by assuming a one-step deconjugation clearance from T-DM1 conjugate to trastuzumab. The ability of the model to predict the total trastuzumab pharmacokinetic profile based on T-DM1 conjugate pharmacokinetics and various sampling schemes of total trastuzumab pharmacokinetics was assessed to evaluate total trastuzumab sampling schemes. The final model reflects a simplified catabolism scheme of T-DM1, suggesting that T-DM1 clearance pathways include both deconjugation and proteolytic degradation. The model fits T-DM1 conjugate and total trastuzumab pharmacokinetic data simultaneously. The deconjugation clearance of T-DM1 was estimated to be ~0.4 L/day. Proteolytic degradation clearances for T-DM1 and trastuzumab were similar (~0.3 L/day). This model accurately predicts total trastuzumab pharmacokinetic profiles based on T-DM1 conjugate pharmacokinetic data and sparse total trastuzumab pharmacokinetic data sampled at preinfusion and end of infusion in cycle 1, and in one additional steady state cycle. This semi-mechanistic integrated model links T-DM1 conjugate and total trastuzumab pharmacokinetic data, and supports the inclusion of both proteolytic degradation and deconjugation as clearance pathways in the hypothetical T-DM1 catabolism scheme. The model attributes a faster T-DM1 conjugate clearance versus that of trastuzumab to the presence of a deconjugation process and suggests a similar proteolytic clearance of T-DM1 and trastuzumab. Based on the model and T-DM1 conjugate pharmacokinetic data, a sparse pharmacokinetic sampling scheme for total trastuzumab provides an entire pharmacokinetic profile with similar predictive accuracy to that of a dense pharmacokinetic sampling scheme.

SUPERMODEL ANALYSIS OF GALAXY CLUSTERS

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

Fusco-Femiano, R.; Cavaliere, A.; Lapi, A.

2009-11-01

We present the analysis of the X-ray brightness and temperature profiles for six clusters belonging to both the Cool Core (CC) and Non Cool Core (NCC) classes, in terms of the Supermodel (SM) developed by Cavaliere et al. Based on the gravitational wells set by the dark matter (DM) halos, the SM straightforwardly expresses the equilibrium of the intracluster plasma (ICP) modulated by the entropy deposited at the boundary by standing shocks from gravitational accretion, and injected at the center by outgoing blast waves from mergers or from outbursts of active galactic nuclei. The cluster set analyzed here highlights notmore » only how simply the SM represents the main dichotomy CC versus NCC clusters in terms of a few ICP parameters governing the radial entropy run, but also how accurately it fits even complex brightness and temperature profiles. For CC clusters like A2199 and A2597, the SM with a low level of central entropy straightforwardly yields the characteristic peaked profile of the temperature marked by a decline toward the center, without requiring currently strong radiative cooling and high mass deposition rates. NCC clusters like A1656 require instead a central entropy floor of a substantial level, and some like A2256 and even more A644 feature structured temperature profiles that also call for a definite floor extension; in such conditions the SM accurately fits the observations, and suggests that in these clusters the ICP has been just remolded by a merger event, in the way of a remnant cool core. The SM also predicts that DM halos with high concentration should correlate with flatter entropy profiles and steeper brightness in the outskirts; this is indeed the case with A1689, for which from X-rays we find concentration values c approx 10, the hallmark of an early halo formation. Thus, we show the SM to constitute a fast tool not only to provide wide libraries of accurate fits to X-ray temperature and density profiles, but also to retrieve from the ICP archives specific information concerning the physical histories of DM and baryons in the inner and the outer cluster regions.« less

THE FORMATION AND EVOLUTION OF YOUNG LOW-MASS STARS WITHIN HALOS WITH HIGH CONCENTRATION OF DARK MATTER PARTICLES

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

Casanellas, Jordi; Lopes, IlIDio, E-mail: jordicasanellas@ist.utl.p, E-mail: ilidio.lopes@ist.utl.p

2009-11-01

The formation and evolution of low-mass stars within dense halos of dark matter (DM) leads to evolution scenarios quite different from the classical stellar evolution. As a result of our detailed numerical work, we describe these new scenarios for a range of DM densities on the host halo, for a range of scattering cross sections of the DM particles considered, and for stellar masses from 0.7 to 3 M {sub sun}. For the first time, we also computed the evolution of young low-mass stars in their Hayashi track in the pre-main-sequence phase and found that, for high DM densities, thesemore » stars stop their gravitational collapse before reaching the main sequence, in agreement with similar studies on first stars. Such stars remain indefinitely in an equilibrium state with lower effective temperatures (|DELTAT{sub eff}|>10{sup 3} K for a star of one solar mass), the annihilation of captured DM particles in their core being the only source of energy. In the case of lower DM densities, these protostars continue their collapse and progress through the main-sequence burning hydrogen at a lower rate. A star of 1 M{sub sun} will spend a time period greater than the current age of the universe consuming all the hydrogen in its core if it evolves in a halo with DM density rho{sub c}hi = 10{sup 9} GeV cm{sup -3}. We also show the strong dependence of the effective temperature and luminosity of these stars on the characteristics of the DM particles and how this can be used as an alternative method for DM research.« less

Circulating C5L2 gene polymorphism is associated with type 2 diabetes mellitus in Saudi population.

PubMed

Alharbi, Khalid K; Khan, Imran Ali; Syed, Rabbani

2013-11-01

The aim of the present study was to examine the relationship between the novel single nucleotide polymorphism, 698C>T that causes an amino acid change from proline to leucine at codon 233 and type 2 diabetes mellitus (T2DM) in the Saudi population. From the general population in the Saudi Arabia a total of 551 samples were collected and categorized them as T2DM (n = 376) and healthy controls (n = 175). Five ml of the blood sample was collected and used for the Biochemical and Molecular analysis. With the help of serum sample lipid profile: Fasting blood sugar (FBS), Total Cholesterol (TC), Triglycerides (TG), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) and VLDL were performed. PCR–RFLP was performed after separating the genomic DNA from the EDTA blood. The genotype distribution of C698T polymorphism was performed by the Chi square test with SPSS version 16.0 software for comparing T2DM subjects and healthy controls. In our study, genotypic distributions of C5L2 C698T polymorphism and allele frequency of patients and controls were found to be significant difference in the allele and the genotypic distribution. [For T Vs C; p = 0.01; Odds ratio = 3.594 (95 % CI; 1.256–10.28); and CT+TT Vs CC; p = 0.009; Odds ratio = 3.707 (95 % CI; 1.285–10.69)]. TT genotype was completely absent in both the cases and the controls. In conclusion, our study indicates that 698C>T polymorphism of C5L2 gene is associated with the T2DM in individuals of Saudi population which was found to be similar with other studies.

Effects of tea or tea extract on metabolic profiles in patients with type 2 diabetes mellitus: a meta-analysis of ten randomized controlled trials.

PubMed

Li, Yanchuan; Wang, Cheng; Huai, Qingjie; Guo, Fuchuan; Liu, Liyan; Feng, Rennan; Sun, Changhao

2016-01-01

As consumption of tea has been confirmed as a protective factor for type 2 diabetes mellitus (T2DM), it would be interesting to know if T2DM patients could benefit from tea. Because of small sample sizes and inconsistent results of previous studies, we performed this meta-analysis to reevaluate the effects of tea or tea extract on all available outcomes in patients with T2DM. We systematically searched electronic databases of PubMed, Cochrane Library and EMBASE to identify randomized controlled trials of tea in T2DM patients up to January 2015. Weight mean differences for the changes in all outcomes were pooled by Review Manager 5.2 (Cochrane Collaboration, Oxford, England). A total of ten trials including 608 subjects were identified. The meta-analysis found that tea could alleviate the decrease of fasting blood insulin [1.30 U/L, 95% CI (0.36, 2.24)], and reduced waist circumference only in more than 8-week intervention [-2.70 cm, 95% CI (-4.72, -0.69)], whereas there were no statistically significant differences with regard to homeostasis model of insulin resistance 0.38 (-0.18, 0.95), fasting blood glucose -0.05 mmol/L (-0.51, 0.40), low density lipoprotein-cholesterol 0.07 mmol/L (-0.15, 0.29), high density lipoprotein-cholesterol 0.01 mmol/L (-0.08, 0.09), body mass index -0.15 kg/m(2) (-0.50, 0.21), SBP 0.35 mmHg (-3.54, 4.24), DBP -1.02 mmHg (-3.53, 1.48), triglycerides -0.11 mmol/L (-0.28, 0.05) and fasting cholesterol -0.05 mmol/L (-0.20, 0.11) in patients with T2DM, and leptin, ADPN, CRE and UA were also non-significant. The intervention of tea or tea extraction could maintain a stable fasting blood insulin and reduce waist circumference in the T2DM patients; however, the effects on other outcomes were not significant. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Halo-independence with quantified maximum entropy at DAMA/LIBRA

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

Fowlie, Andrew, E-mail: andrew.j.fowlie@googlemail.com

2017-10-01

Using the DAMA/LIBRA anomaly as an example, we formalise the notion of halo-independence in the context of Bayesian statistics and quantified maximum entropy. We consider an infinite set of possible profiles, weighted by an entropic prior and constrained by a likelihood describing noisy measurements of modulated moments by DAMA/LIBRA. Assuming an isotropic dark matter (DM) profile in the galactic rest frame, we find the most plausible DM profiles and predictions for unmodulated signal rates at DAMA/LIBRA. The entropic prior contains an a priori unknown regularisation factor, β, that describes the strength of our conviction that the profile is approximately Maxwellian.more » By varying β, we smoothly interpolate between a halo-independent and a halo-dependent analysis, thus exploring the impact of prior information about the DM profile.« less

Increased Skin Inflammation and Blood Vessel Density in Human and Experimental Diabetes

PubMed Central

Tellechea, Ana; Kafanas, Antonios; Leal, Ermelindo C; Tecilazich, Francesco; Kuchibhotla, Sarada; Auster, Michael E; Kontoes, Iraklis; Paolino, Jacqueline; Carvalho, Eugenia; Nabzdyk, Leena Pradhan; Veves, Aristidis

2013-01-01

Systemic inflammation is associated with impaired wound healing in diabetic patients. Using immunohistochemistry techniques, the authors investigated changes in skin inflammation and skin blood vessels in human and experimental diabetes. Comparing to the non-DM human subjects, the total number of inflammatory cells per biopsy and the number of inflammatory cells around blood vessels, a strong indication of inflammation, were higher in DM subjects irrespective of their risk for developing diabetic foot ulcer. Inflammatory cell infiltration was robustly increased in all diabetic animal models compared to their non-diabetic controls. The number and density of blood vessels and CD31 positive proliferating endothelial cells around pre-existing skin vessels was also higher in the DM patients. However, there were no differences in the skin blood flow between the non-DM and DM subjects. The number of skin blood vessels was also increased in the DM animals; however, these differences were less obvious than the ones observed for inflammatory cells. We conclude that skin inflammation and skin blood vessel density is increased in diabetic human subjects and in rodent and rabbit models of diabetes. PMID:23446362

Prevalence of thyroid disorders in North Indian Type 2 diabetic subjects: A cross sectional study.

PubMed

Ozair, Maaz; Noor, Saba; Raghav, Alok; Siddiqi, Sheelu Shafiq; Chugtai, Anjum Mirza; Ahmad, Jamal

2018-05-01

Type 2 diabetes mellitus (T2DM) is a major health burden worldwide with many patients encountering thyroid dysfunction later in their life. Various studies have found that diabetes and thyroid disorders mutually influence each other and both disorders tend to coexists. However, the prevalence of thyroid dysfunction and associated clinical variables in these patients has not been investigated. The study aimed at determining the incidence and prevalence of thyroid dysfunction in patients with T2DM in relation to age, sex, metabolic syndrome and other co-morbid conditions. In this cross-sectional study, 250 Type 2 DM patients were enrolled aged between 40 and 75 years. All the patients were evaluated for thyroid dysfunction by testing thyroid profile (T3, T4 and TSH. These subjects were also investigated for fasting blood sugar (FBS), post prandial glucose (PPG) glycosylated hemoglobin (HbA1c), serum cholesterol, serum triglycerides, high density lipoprotein (HDL), low density lipoprotein(LDL), very low density lipoprotein(VLDL), blood urea, serum creatinine and presence of other co-morbid conditions. The observations and interpretations were recorded and results obtained were statistically analyzed. A high prevalence of thyroid dysfunction (28%) was observed in type 2 diabetic patients with subclinical hypothyroidism (18.8%) as the commonest thyroid disorder. Thyroid dysfunction was more prevalent in females, with presence of dyslipidemia, retinopathy, poor glycemic state (HbA1c ≥7) and longer duration of diabetes as significant contributing factors associated. In addition to glycemic status, screening of thyroid disorder should be routinely done in type 2 diabetic subjects along with other comorbid conditions. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Dietary supplementation with d-tagatose in subjects with type 2 diabetes leads to weight loss and raises high-density lipoprotein cholesterol.

PubMed

Donner, Thomas W; Magder, Laurence S; Zarbalian, Kiarash

2010-12-01

Oral d-tagatose (d-tag) attenuates the rise in plasma glucose during an oral glucose tolerance test in subjects with type 2 diabetes mellitus (DM) and reduces food intake in healthy human subjects. A reduction in food consumption and less weight gain occur in rats fed tagatose. This pilot study explored the metabolic effects of d-tag given daily to 8 human subjects with type 2 DM for 1 year. We hypothesized that this treatment period would lead to weight loss and improvements in glycated hemoglobin and the lipid profile. A 2-month run-in period was followed by a 12-month treatment period when 15 g of oral d-tag was taken 3 times daily with food. No serious adverse effects were seen during the 12-month treatment period. Ten of the initially 12 recruited subjects experienced gastrointestinal side effects that tended to be mild and transient. When 3 subjects were excluded who had oral diabetes, medications added and/or dosages increased during the study and mean (SD) body weight declined from 108.4 (9.0) to 103.3 (7.3) kg (P = .001). Glycated hemoglobin fell nonsignificantly from 10.6% ± 1.9% to 9.6% ± 2.3% (P = .08). High-density lipoprotein cholesterol progressively rose from a baseline level of 30.5 ± 15.8 to 41.7 ± 12.1 mg/dL at month 12 in the 6 subjects who did not have lipid-modifying medications added during the study (P < .001). Significant improvements in body weight and high-density lipoprotein cholesterol in this pilot study suggest that d-tag may be a potentially useful adjunct in the management of patients with type 2 DM. Copyright © 2010 Elsevier Inc. All rights reserved.

Management of Dyslipidemia in Type 2 Diabetes: Recent Advances in Nonstatin Treatment.

PubMed

Sugiyama, Kazutoshi; Saisho, Yoshifumi

2018-05-24

Dyslipidemia is a major risk factor for cardiovascular disease (CVD), which is the leading cause of morbidity and mortality in type 2 diabetes (T2DM). Statins have played a crucial role in its management, but residual risk remains since many patients cannot achieve their desired low-density lipoprotein cholesterol (LDL-C) level and up to 20% of patients are statin-intolerant, experiencing adverse events perceived to be caused by statins, most commonly muscle symptoms. Recently, great advances have been made in nonstatin treatment with ezetimibe, a cholesterol absorption inhibitor, and proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs), all showing a proven benefit with an excellent safety profile in cardiovascular outcome trials. This review summarizes the key aspects and the evolving role of these agents in the management of dyslipidemia in patients with T2DM, along with a brief introduction of novel drugs currently in development.

Average glandular dose in paired digital mammography and digital breast tomosynthesis acquisitions in a population based screening program: effects of measuring breast density, air kerma and beam quality

NASA Astrophysics Data System (ADS)

Helge Østerås, Bjørn; Skaane, Per; Gullien, Randi; Catrine Trægde Martinsen, Anne

2018-02-01

The main purpose was to compare average glandular dose (AGD) for same-compression digital mammography (DM) and digital breast tomosynthesis (DBT) acquisitions in a population based screening program, with and without breast density stratification, as determined by automatically calculated breast density (Quantra™). Secondary, to compare AGD estimates based on measured breast density, air kerma and half value layer (HVL) to DICOM metadata based estimates. AGD was estimated for 3819 women participating in the screening trial. All received craniocaudal and mediolateral oblique views of each breasts with paired DM and DBT acquisitions. Exposure parameters were extracted from DICOM metadata. Air kerma and HVL were measured for all beam qualities used to acquire the mammograms. Volumetric breast density was estimated using Quantra™. AGD was estimated using the Dance model. AGD reported directly from the DICOM metadata was also assessed. Mean AGD was 1.74 and 2.10 mGy for DM and DBT, respectively. Mean DBT/DM AGD ratio was 1.24. For fatty breasts: mean AGD was 1.74 and 2.27 mGy for DM and DBT, respectively. For dense breasts: mean AGD was 1.73 and 1.79 mGy, for DM and DBT, respectively. For breasts of similar thickness, dense breasts had higher AGD for DM and similar AGD for DBT. The DBT/DM dose ratio was substantially lower for dense compared to fatty breasts (1.08 versus 1.33). The average c-factor was 1.16. Using previously published polynomials to estimate glandularity from thickness underestimated the c-factor by 5.9% on average. Mean AGD error between estimates based on measurements (air kerma and HVL) versus DICOM header data was 3.8%, but for one mammography unit as high as 7.9%. Mean error of using the AGD value reported in the DICOM header was 10.7 and 13.3%, respectively. Thus, measurement of breast density, radiation dose and beam quality can substantially affect AGD estimates.

Average glandular dose in paired digital mammography and digital breast tomosynthesis acquisitions in a population based screening program: effects of measuring breast density, air kerma and beam quality.

PubMed

Østerås, Bjørn Helge; Skaane, Per; Gullien, Randi; Martinsen, Anne Catrine Trægde

2018-01-25

The main purpose was to compare average glandular dose (AGD) for same-compression digital mammography (DM) and digital breast tomosynthesis (DBT) acquisitions in a population based screening program, with and without breast density stratification, as determined by automatically calculated breast density (Quantra ™ ). Secondary, to compare AGD estimates based on measured breast density, air kerma and half value layer (HVL) to DICOM metadata based estimates. AGD was estimated for 3819 women participating in the screening trial. All received craniocaudal and mediolateral oblique views of each breasts with paired DM and DBT acquisitions. Exposure parameters were extracted from DICOM metadata. Air kerma and HVL were measured for all beam qualities used to acquire the mammograms. Volumetric breast density was estimated using Quantra ™ . AGD was estimated using the Dance model. AGD reported directly from the DICOM metadata was also assessed. Mean AGD was 1.74 and 2.10 mGy for DM and DBT, respectively. Mean DBT/DM AGD ratio was 1.24. For fatty breasts: mean AGD was 1.74 and 2.27 mGy for DM and DBT, respectively. For dense breasts: mean AGD was 1.73 and 1.79 mGy, for DM and DBT, respectively. For breasts of similar thickness, dense breasts had higher AGD for DM and similar AGD for DBT. The DBT/DM dose ratio was substantially lower for dense compared to fatty breasts (1.08 versus 1.33). The average c-factor was 1.16. Using previously published polynomials to estimate glandularity from thickness underestimated the c-factor by 5.9% on average. Mean AGD error between estimates based on measurements (air kerma and HVL) versus DICOM header data was 3.8%, but for one mammography unit as high as 7.9%. Mean error of using the AGD value reported in the DICOM header was 10.7 and 13.3%, respectively. Thus, measurement of breast density, radiation dose and beam quality can substantially affect AGD estimates.

High prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus despite different hormonal profiles.

PubMed

Samara-Boustani, Dinane; Colmenares, Ana; Elie, Caroline; Dabbas, Myriam; Beltrand, Jacques; Caron, Virgile; Ricour, Claude; Jacquin, Paul; Tubiana-Rufi, Nadia; Levy-Marchal, Claire; Delcroix, Christine; Martin, Delphine; Benadjaoud, Lila; Jacqz Aigrain, Evelyne; Trivin, Christine; Laborde, Kathleen; Thibaud, Elisabeth; Robert, Jean-Jacques; Polak, Michel

2012-02-01

To compare the pubertal development, the hormonal profiles and the prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus (T1DM). Data were collected from 96 obese adolescent girls and 78 adolescent girls with T1DM at Tanner stage IV or V, whose ages ranged between 11.9 and 17.9 years. High prevalence of hirsutism and menstrual disorder was found in the obese adolescent girls (36.5 and 42% respectively) and the adolescent girls with T1DM (21 and 44% respectively). The obese girls were significantly younger at pubarche, thelarche and menarche than the girls with T1DM. Hirsutism in the obese girls and those with T1DM was associated with hyperandrogenaemia and a raised free androgen index (FAI). When the cause of the raised FAI was investigated in both the groups of girls with hirsutism, the raised FAI in the obese girls was due to low serum sex hormone-binding globulin (SHBG) levels. In contrast, the raised FAI of the girls with T1DM and hirsutism was due to hyperandrogenaemia. Menstrual disorders in the T1DM girls were associated also with hyperandrogenaemia unlike obese girls. Hirsutism and menstrual disorders are common in obese adolescent girls and adolescent girls with T1DM. Although hyperandrogenaemia is present in both groups of girls, the androgenic profiles of the two groups differ. The hyperandrogenaemia in the obese girls is primarily due to their decreased serum SHBG levels, whereas the hyperandrogenaemia in the girls with T1DM is due to their increased androgen production.

Altered Expression of Diabetes-Related Genes in Alzheimer's Disease Brains: The Hisayama Study

PubMed Central

Hokama, Masaaki; Oka, Sugako; Leon, Julio; Ninomiya, Toshiharu; Honda, Hiroyuki; Sasaki, Kensuke; Iwaki, Toru; Ohara, Tomoyuki; Sasaki, Tomio; LaFerla, Frank M.; Kiyohara, Yutaka; Nakabeppu, Yusaku

2014-01-01

Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM. PMID:23595620

Dark matter searches with Cherenkov telescopes: nearby dwarf galaxies or local galaxy clusters?

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

Sánchez-Conde, Miguel A.; Cannoni, Mirco; Gómez, Mario E.

2011-12-01

In this paper, we compare dwarf galaxies and galaxy clusters in order to elucidate which object class is the best target for gamma-ray DM searches with imaging atmospheric Cherenkov telescopes (IACTs). We have built a mixed dwarfs+clusters sample containing some of the most promising nearby dwarf galaxies (Draco, Ursa Minor, Wilman 1 and Segue 1) and local galaxy clusters (Perseus, Coma, Ophiuchus, Virgo, Fornax, NGC 5813 and NGC 5846), and then compute their DM annihilation flux profiles by making use of the latest modeling of their DM density profiles. We also include in our calculations the effect of DM substructure.more » Willman 1 appears as the best candidate in the sample. However, its mass modeling is still rather uncertain, so probably other candidates with less uncertainties and quite similar fluxes, namely Ursa Minor and Segue 1, might be better options. As for galaxy clusters, Virgo represents the one with the highest flux. However, its large spatial extension can be a serious handicap for IACT observations and posterior data analysis. Yet, other local galaxy cluster candidates with more moderate emission regions, such as Perseus, may represent good alternatives. After comparing dwarfs and clusters, we found that the former exhibit annihilation flux profiles that, at the center, are roughly one order of magnitude higher than those of clusters, although galaxy clusters can yield similar, or even higher, integrated fluxes for the whole object once substructure is taken into account. Even when any of these objects are strictly point-like according to the properties of their annihilation signals, we conclude that dwarf galaxies are best suited for observational strategies based on the search of point-like sources, while galaxy clusters represent best targets for analyses that can deal with rather extended emissions. Finally, we study the detection prospects for present and future IACTs in the framework of the constrained minimal supersymmetric standard model. We find that the level of the annihilation flux from these targets is below the sensitivities of current IACTs and the future CTA.« less

Dark Matter Searches with Cherenkov Telescopes: Nearby Dwarf Galaxies or Local Galaxy Clusters?

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

Sanchez-Conde, Miguel A.; /KIPAC, Menlo Park /SLAC /IAC, La Laguna /Laguna U., Tenerife; Cannoni, Mirco

2012-06-06

In this paper, we compare dwarf galaxies and galaxy clusters in order to elucidate which object class is the best target for gamma-ray DM searches with imaging atmospheric Cherenkov telescopes (IACTs). We have built a mixed dwarfs+clusters sample containing some of the most promising nearby dwarf galaxies (Draco, Ursa Minor, Wilman 1 and Segue 1) and local galaxy clusters (Perseus, Coma, Ophiuchus, Virgo, Fornax, NGC 5813 and NGC 5846), and then compute their DM annihilation flux profiles by making use of the latest modeling of their DM density profiles. We also include in our calculations the effect of DM substructure.more » Willman 1 appears as the best candidate in the sample. However, its mass modeling is still rather uncertain, so probably other candidates with less uncertainties and quite similar fluxes, namely Ursa Minor and Segue 1, might be better options. As for galaxy clusters, Virgo represents the one with the highest flux. However, its large spatial extension can be a serious handicap for IACT observations and posterior data analysis. Yet, other local galaxy cluster candidates with more moderate emission regions, such as Perseus, may represent good alternatives. After comparing dwarfs and clusters, we found that the former exhibit annihilation flux profiles that, at the center, are roughly one order of magnitude higher than those of clusters, although galaxy clusters can yield similar, or even higher, integrated fluxes for the whole object once substructure is taken into account. Even when any of these objects are strictly point-like according to the properties of their annihilation signals, we conclude that dwarf galaxies are best suited for observational strategies based on the search of point-like sources, while galaxy clusters represent best targets for analyses that can deal with rather extended emissions. Finally, we study the detection prospects for present and future IACTs in the framework of the constrained minimal supersymmetric standard model. We find that the level of the annihilation flux from these targets is below the sensitivities of current IACTs and the future CTA.« less

Dark matter searches with Cherenkov telescopes: nearby dwarf galaxies or local galaxy clusters?

NASA Astrophysics Data System (ADS)

Sánchez-Conde, Miguel A.; Cannoni, Mirco; Zandanel, Fabio; Gómez, Mario E.; Prada, Francisco

2011-12-01

In this paper, we compare dwarf galaxies and galaxy clusters in order to elucidate which object class is the best target for gamma-ray DM searches with imaging atmospheric Cherenkov telescopes (IACTs). We have built a mixed dwarfs+clusters sample containing some of the most promising nearby dwarf galaxies (Draco, Ursa Minor, Wilman 1 and Segue 1) and local galaxy clusters (Perseus, Coma, Ophiuchus, Virgo, Fornax, NGC 5813 and NGC 5846), and then compute their DM annihilation flux profiles by making use of the latest modeling of their DM density profiles. We also include in our calculations the effect of DM substructure. Willman 1 appears as the best candidate in the sample. However, its mass modeling is still rather uncertain, so probably other candidates with less uncertainties and quite similar fluxes, namely Ursa Minor and Segue 1, might be better options. As for galaxy clusters, Virgo represents the one with the highest flux. However, its large spatial extension can be a serious handicap for IACT observations and posterior data analysis. Yet, other local galaxy cluster candidates with more moderate emission regions, such as Perseus, may represent good alternatives. After comparing dwarfs and clusters, we found that the former exhibit annihilation flux profiles that, at the center, are roughly one order of magnitude higher than those of clusters, although galaxy clusters can yield similar, or even higher, integrated fluxes for the whole object once substructure is taken into account. Even when any of these objects are strictly point-like according to the properties of their annihilation signals, we conclude that dwarf galaxies are best suited for observational strategies based on the search of point-like sources, while galaxy clusters represent best targets for analyses that can deal with rather extended emissions. Finally, we study the detection prospects for present and future IACTs in the framework of the constrained minimal supersymmetric standard model. We find that the level of the annihilation flux from these targets is below the sensitivities of current IACTs and the future CTA.

The effect of very-low-calorie diet on mRNA expression of inflammation-related genes in subcutaneous adipose tissue and peripheral monocytes of obese patients with type 2 diabetes mellitus.

PubMed

Mraz, M; Lacinova, Z; Drapalova, J; Haluzikova, D; Horinek, A; Matoulek, M; Trachta, P; Kavalkova, P; Svacina, S; Haluzik, M

2011-04-01

Low-grade inflammation links obesity, type 2 diabetes mellitus (T2DM), and cardiovascular diseases. To explore the expression profile of genes involved in inflammatory pathways in adipose tissue and peripheral monocytes (PM) of obese patients with and without T2DM at baseline and after dietary intervention. Two-week intervention study with very-low-calorie diet (VLCD). University hospital. Twelve obese females with T2DM, 8 obese nondiabetic females (OB) and 15 healthy age-matched females. Two weeks of VLCD (2500 kJ/d). Metabolic parameters, circulating cytokines, hormones, and mRNA expression of 39 genes in sc adipose tissue (SCAT) and PM. Both T2DM and OB group had significantly increased serum concentrations of circulating proinflammatory factors (C-reactive protein, TNFα, IL-6, IL-8), mRNA expression of macrophage antigen CD68 and proinflammatory chemokines (CCL-2, -3, -7, -8, -17, -22) in SCAT and complementary chemokine receptors (CCR-1, -2, -3, -5) and other proinflammatory receptors (toll-like receptor 2 and 4, TNF receptor superfamily 1A and 1B, IL-6R) in PM, with OB group showing less pronounced chemoattracting and proinflammatory profile compared to T2DM group. In T2DM patients VLCD decreased body weight, improved metabolic profile, and decreased mRNA expression of up-regulated CCRs in PM and chemokines [CCL 8, chemokine (C-X-C motif) ligand 10] in SCAT. VLCD markedly increased mRNA expression of T-lymphocyte attracting chemokine CCL-17 in SCAT. Obese patients with and without T2DM have increased mRNA expression of chemotactic and proinflammatory factors in SCAT and expression of corresponding receptors in PM. Two weeks of VLCD significantly improved this profile in T2DM patients.

Testing the uniqueness of mass models using gravitational lensing

NASA Astrophysics Data System (ADS)

Walls, Levi; Williams, Liliya L. R.

2018-06-01

The positions of images produced by the gravitational lensing of background-sources provide insight to lens-galaxy mass distributions. Simple elliptical mass density profiles do not agree well with observations of the population of known quads. It has been shown that the most promising way to reconcile this discrepancy is via perturbations away from purely elliptical mass profiles by assuming two super-imposed, somewhat misaligned mass distributions: one is dark matter (DM), the other is a stellar distribution. In this work, we investigate if mass modelling of individual lenses can reveal if the lenses have this type of complex structure, or simpler elliptical structure. In other words, we test mass model uniqueness, or how well an extended source lensed by a non-trivial mass distribution can be modeled by a simple elliptical mass profile. We used the publicly-available lensing software, Lensmodel, to generate and numerically model gravitational lenses and “observed” image positions. We then compared “observed” and modeled image positions via root mean square (RMS) of their difference. We report that, in most cases, the RMS is ≤0.05‧‧ when averaged over an extended source. Thus, we show it is possible to fit a smooth mass model to a system that contains a stellar-component with varying levels of misalignment with a DM-component, and hence mass modelling cannot differentiate between simple elliptical versus more complex lenses.

Associations between bone-alkaline phosphatase and bone mineral density in adults with and without diabetes

PubMed Central

Chen, Hailing; Li, Jufen; Wang, Qian

2018-01-01

Abstract Insufficient evidence is available to reliably compare the roles of bone alkaline phosphatase (BAP) and bone mineral density (BMD) in diabetes. This study aimed to compare associations between BAP and BMD in adults with and without diabetes to elucidate fracture risk in diabetes. Data were extracted from the National Health and Nutrition Examination Survey (NHANES), 2001–2004, including 4197 adults aged 20 to 49 years, 143 with diabetes (DM group), and 4054 without (non-DM group). Main outcome measure was BMD and regression analyses were performed to identify serum BAP and other covariates associated with total BMD. BMD decreased significantly in DM patients when BAP was increased. In the non-DM group, all BMD results were significantly decreased when BAP was increased. Factors associated with total BMD varied with DM status. Lifestyle measures such as smoking and physical activity were also associated with BMD in the non-DM group. BAP and BMD are inversely associated in DM and non-DM patients. BAP is significantly associated with BMD after controlling for other variables, suggesting that BAP may interact with other factors altering bone metabolism in DM patients. PMID:29702995

Emergence of the mass discrepancy-acceleration relation from dark matter-baryon interactions

NASA Astrophysics Data System (ADS)

Famaey, Benoit; Khoury, Justin; Penco, Riccardo

2018-03-01

The observed tightness of the mass discrepancy-acceleration relation (MDAR) poses a fine-tuning challenge to current models of galaxy formation. We propose that this relation could arise from collisional interactions between baryons and dark matter (DM) particles, without the need for modification of gravity or ad hoc feedback processes. We assume that these interactions satisfy the following three conditions: (i) the relaxation time of DM particles is comparable to the dynamical time in disk galaxies; (ii) DM exchanges energy with baryons due to elastic collisions; (iii) the product between the baryon-DM cross section and the typical energy exchanged in a collision is inversely proportional to the DM number density. As a proof of principle, we present an example of a particle physics model that gives a DM-baryon cross section with the desired density and velocity dependence. For consistency with direct detection constraints, our DM particles must be either very light (m ll mb) or very heavy (mgg mb), corresponding respectively to heating and cooling of DM by baryons. In both cases, our mechanism applies and an equilibrium configuration can in principle be reached. In this exploratory paper, we focus on the heavy DM/cooling case because it is technically simpler, since the average energy exchanged turns out to be approximately constant throughout galaxies. Under these assumptions, we find that rotationally-supported disk galaxies could naturally settle to equilibrium configurations satisfying a MDAR at all radii without invoking finely tuned feedback processes. We also discuss issues related to the small scale clumpiness of baryons, as well as predictions for pressure-supported systems. We argue in particular that galaxy clusters do not follow the MDAR despite being DM-dominated because they have not reached their equilibrium configuration. Finally, we revisit existing phenomenological, astrophysical and cosmological constraints on baryon-DM interactions in light of the unusual density dependence of the cross section of DM particles.

Dwarf spheroidal galaxies as degenerate gas of free fermions

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

Domcke, Valerie; Urbano, Alfredo, E-mail: valerie.domcke@sissa.it, E-mail: alfredo.urbano@sissa.it

2015-01-01

In this paper we analyze a simple scenario in which Dark Matter (DM) consists of free fermions with mass m{sub f}. We assume that on galactic scales these fermions are capable of forming a degenerate Fermi gas, in which stability against gravitational collapse is ensured by the Pauli exclusion principle. The mass density of the resulting con figuration is governed by a non-relativistic Lane-Emden equation, thus leading to a universal cored profile that depends only on one free parameter in addition to m{sub f}. After reviewing the basic formalism, we test this scenario against experimental data describing the velocity dispersionmore » of the eight classical dwarf spheroidal galaxies of the Milky Way. We find that, despite its extreme simplicity, the model exhibits a good fit to the data and realistic predictions for the size of DM halos providing that m{sub f}≅ 200 eV. Furthermore, we show that in this setup larger galaxies correspond to the non-degenerate limit of the gas. We propose a concrete realization of this model in which DM is produced non-thermally via inflaton decay. We show that imposing the correct relic abundance and the bound on the free-streaming length constrains the inflation model in terms of inflaton mass, its branching ratio into DM and the reheating temperature.« less

Semiautomatic estimation of breast density with DM-Scan software.

PubMed

Martínez Gómez, I; Casals El Busto, M; Antón Guirao, J; Ruiz Perales, F; Llobet Azpitarte, R

2014-01-01

To evaluate the reproducibility of the calculation of breast density with DM-Scan software, which is based on the semiautomatic segmentation of fibroglandular tissue, and to compare it with the reproducibility of estimation by visual inspection. The study included 655 direct digital mammograms acquired using craniocaudal projections. Three experienced radiologists analyzed the density of the mammograms using DM-Scan, and the inter- and intra-observer agreement between pairs of radiologists for the Boyd and BI-RADS® scales were calculated using the intraclass correlation coefficient. The Kappa index was used to compare the inter- and intra-observer agreements with those obtained previously for visual inspection in the same set of images. For visual inspection, the mean interobserver agreement was 0,876 (95% CI: 0,873-0,879) on the Boyd scale and 0,823 (95% CI: 0,818-0,829) on the BI-RADS® scale. The mean intraobserver agreement was 0,813 (95% CI: 0,796-0,829) on the Boyd scale and 0,770 (95% CI: 0,742-0,797) on the BI-RADS® scale. For DM-Scan, the mean inter- and intra-observer agreement was 0,92, considerably higher than the agreement for visual inspection. The semiautomatic calculation of breast density using DM-Scan software is more reliable and reproducible than visual estimation and reduces the subjectivity and variability in determining breast density. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

Effects of simvastatin and ezetimibe in lowering low-density lipoprotein cholesterol in subjects with type 1 and type 2 diabetes mellitus.

PubMed

Ciriacks, Kevin; Coly, Gerard; Krishnaswami, Shanthi; Patel, Shailendra B; Kidambi, Srividya

2015-03-01

Statins are used to lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels among patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). However, there are no studies of statin efficacy among T1DM patients. T1DM patients have higher gut cholesterol absorption than synthesis; hence cholesterol absorption inhibitors such as ezetimibe may also be effective in T1DM. Here, we compare the effects of simvastatin and ezetimibe among subjects with T1DM and T2DM. Subjects with T1DM (n=20, 45% female) or T2DM (n=27, 56% female) were assigned to alternating therapy with simvastatin (40 mg) or ezetimibe (10 mg) for 6 weeks in a crossover design. Among T2DM subjects, simvastatin lowered TC and LDL-C from the baseline (-25±4% and -40±5%, respectively, P<0.001), whereas ezetimibe was not as effective (-2±4% and -3±5%, respectively). Among T1DM subjects, both statin and ezetimibe showed significant decreases in TC and LDL-C from baseline, although ezetimibe lowered LDL-C much more than simvastatin (-32±12 (P<0.001) and -19±5% (P<0.01), respectively). Effect of simvastatin on LDL-C was much lower among T1DM subjects compared to T2DM subjects (P=0.02). This study shows that the cholesterol synthesis inhibitor simvastatin was less effective in lowering LDL-C in T1DM than T2DM subjects, whereas the cholesterol absorption inhibitor ezetimibe was at least as effective in lowering LDL-C as simvastatin among T1DM subjects.

Size, density and cholesterol load of HDL predict microangiopathy, coronary artery disease and β-cell function in men with T2DM.

PubMed

Hermans, Michel P; Amoussou-Guenou, K Daniel; Bouenizabila, Evariste; Sadikot, Shaukat S; Ahn, Sylvie A; Rousseau, Michel F

The role of high-density lipoprotein cholesterol (HDL-C) as modifiable risk factor for cardiovascular (CV) disease is increasingly debated, notwithstanding the finding that small-dense and dysfunctional HDL are associated with the metabolic syndrome and T2DM. In order to better clarify the epidemiological risk related to HDL of different size/density, without resorting to direct measures, it would seem appropriate to adjust HDL-C to the level of its main apolipoprotein (apoA-I), thereby providing an [HDL-C/apoA-I] ratio. The latter allows not only to estimate an average size for HDLs, but also to derive indices on particle number, cholesterol load, and density. So far, the potential usefulness of this ratio in diabetes is barely addressed. To this end, we sorted 488 male patients with T2DM according to [HDL-C/apoA-I] quartiles (Q), to determine how the ratio relates to cardiometabolic risk, β-cell function, glycaemic control, and micro- and macrovascular complications. Five lipid parameters were derived from the combined determination of HDL-C and apoA-I, namely HDL size; particle number; cholesterol load/particle; apoA-I/particle; and particle density. An unfavorable cardiometabolic profile characterized patients from QI and QII, in which HDLs were pro-atherogenic, denser and apoA-I-depleted. By contrast, QIII patients had an [HDL-C/apoA-I] ratio close to that of non-diabetic controls. QIV patients had better than average HDL size and composition, and in those patients whose [HDL-C/apoA-I] ratio was above normal, a more favorable phenotype was observed regarding lifestyle, anthropometry, metabolic comorbidities, insulin sensitivity, MetS score/severity, glycaemic control, and target-organ damage pregalence in small or large vessels. In conclusion, [HDL-C/apoA-I] and the resulting indices of HDL composition and functionality predict macrovascular risk and β-cell function decline, as well as overall microangiopathic risk, suggesting that this ratio could serve both in cardiometabolic assessment and as biomarker of vascular complications. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

VizieR Online Data Catalog: Dark matter in dSph galaxies (Charbonnier+, 2011)

NASA Astrophysics Data System (ADS)

Charbonnier, A.; Combet, C.; Daniel, M.; Funk, S.; Hinton, J. A.; Maurin, D.; Power, C.; Read, J. I.; Sarkar, S.; Walker, M. G.; Wilkinson, M. I.

2012-07-01

Due to their large dynamical mass-to-light ratios, dwarf spheroidal galaxies (dSphs) are promising targets for the indirect detection of dark matter (DM) in γ-rays. We examine their detectability by present and future γ-ray observatories. The key innovative features of our analysis are as follows: (i) we take into account the angular size of the dSphs; while nearby objects have higher γ-ray flux, their larger angular extent can make them less attractive targets for background-dominated instruments; (ii) we derive DM profiles and the astrophysical J-factor (which parametrizes the expected γ-ray flux, independently of the choice of DM particle model) for the classical dSphs directly from photometric and kinematic data. We assume very little about the DM profile, modelling this as a smooth split-power-law distribution, with and without subclumps; (iii) we use a Markov chain Monte Carlo technique to marginalize over unknown parameters and determine the sensitivity of our derived J-factors to both model and measurement uncertainties; and (iv) we use simulated DM profiles to demonstrate that our J-factor determinations recover the correct solution within our quoted uncertainties. (6 data files).

Population prevalence and control of cardiovascular risk factors: what electronic medical records tell us.

PubMed

Catalán-Ramos, Arantxa; Verdú, Jose M; Grau, María; Iglesias-Rodal, Manuel; del Val García, José L; Consola, Alicia; Comin, Eva

2014-01-01

To analyze the prevalence, control, and management of hypertension, hypercholesterolemia, and diabetes mellitus type 2 (DM2). Cross-sectional analysis of all individuals attended in the Catalan primary care centers between 2006 and 2009. History of cardiovascular diseases, diagnosis and treatment of hypertension, hypercholesterolemia, DM2, lipid profile, glycemia and blood pressure data were extracted from electronic medical records. Age-standardized prevalence and levels of management and control were estimated. Individuals aged 35-74 years using primary care databases. A total of 2,174,515 individuals were included (mean age 52 years [SD 11], 47% men). Hypertension was the most prevalent cardiovascular risk factor (39% in women, 41% in men) followed by hypercholesterolemia (38% and 40%) and DM2 (12% and 16%), respectively. Diuretics and angiotensin-converting enzyme inhibitors were most often prescribed for hypertension control (<140/90mmHg, achieved in 68% of men and 60% of women treated). Hypercholesterolemia was controlled (low-density lipoprotein cholesterol <130mg/dl) in just 31% of men and 26% of women with no history of cardiovascular disease, despite lipid-lowering treatment, primarily (90%) with statins. The percentage of women and men with DM2 and with glycated hemoglobin <7% was 64.7% and 59.2%, respectively; treatment was predominantly with oral hypoglycemic agents alone (70%), or combined with insulin (15%). Hypertension was the most prevalent cardiovascular risk factor in the Catalan population attended at primary care centers. About two thirds of individuals with hypertension or DM2 were adequately controlled; hypercholesterolemia control was particularly low. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Risk factor profile and pregnancy outcome in women with type 1 and type 2 diabetes mellitus.

PubMed

Handisurya, Ammon; Bancher-Todesca, Dagmar; Schober, Edith; Klein, Katharina; Tobler, Karin; Schneider, Barbara; Pollak, Arnold; Husslein, Peter; Luger, Anton; Kautzky-Willer, Alexandra

2011-02-01

To assess differences in congenital anomalies, infant mortality, and obstetrical complications as well as risk factors associated with an adverse pregnancy outcome in women with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). This observational study was performed at a university clinic and included a total of 200 singleton pregnancies between January 1995 and December 2006. Outcome measures comprise the prevalence of major congenital malformations, fetal losses, stillbirths, and neonatal deaths as well as the combined end point, adverse pregnancy outcome, and obstetrical complications. Despite changes in prevailing risk factors, the rate of congenital anomalies and embryonic as well as perinatal death was comparable in type 1 diabetic women over time as well as between women with T1DM and T2DM. Outcome measures and risk factor profile were similar in women with preconception and newly diagnosed T2DM. Glycemic control and increased body mass index (BMI) during the first trimester were the strongest predictors of an adverse pregnancy outcome. Hemoglobin A1c (HbA1c) was higher in T1DM than in T2DM but similar in women with T1DM over time. BMI was highest in women with T2DM, followed by T1DM women of the most recent time period. In addition to HbA1c, other risk factors, especially high BMI, strongly influence pregnancy outcome. The higher prevalence of these risk factors in T2DM might compensate for the better glycemic control, resulting in a pregnancy outcome comparable to that of T1DM. Pregnancy outcome in T1DM remained unchanged over time, possibly because of the missing amelioration of HbA1c levels and the increasing BMI.

Modulation of Coronary Heart Disease Risk by Insulin Resistance in Subjects With Normal Glucose Tolerance or Prediabetes

PubMed Central

Ariel, Danit; Reaven, Gerald

2014-01-01

Aims/hypothesis This study is based on the hypothesis that: 1)coronary heart disease (CHD) risk is accentuated in the insulin resistant subset of persons with normal glucose tolerance (NGT) or prediabetes (PreDM); 2)the prevalence of insulin resistance, and associated abnormalities, is greater in subjects with PreDM; and 3)insulin resistance is the major contributor to increased CHD risk in these individuals. Methods A 75 g oral glucose challenge was used to classify volunteers as having NGT or PreDM. Steady-state plasma glucose (SSPG) concentrations during the insulin suppression test subdivided both groups into insulin sensitive (IS=SSPG <8.4 mmol/L) or resistant (IR=SSPG ≥8.4 mmol/L). Measurements were made of demographic characteristics, blood pressure, and lipid and lipoprotein concentrations, and comparisons made between the subgroups. Results Subjects with PreDM (n=127) were somewhat older, more likely to be non-Hispanic men, with increased adiposity than those with NGT (n=315). In addition, they had higher FPG concentrations, were insulin resistant (SSPG concentration; 11.4 vs. 7.2 mmol/L), with higher blood pressures, and a significantly more adverse CHD risk lipid profile (p<0.001). Twice as many subjects with PreDM were IR (72% vs. 35 %), and the CHD risk profile was significantly worse in the IR subgroups in those with either NGT or PreDM. Conclusions/interpretation CHD risk profile is significantly more adverse in subjects with PreDM as compared to individuals with NGT. However, glucose tolerance status is not the only determinant of CHD risk in nondiabetic individuals, and differences in degree of insulin resistance significantly modulate CHD risk in subjects with NGT or PreDM. PMID:25358836

Association between thyroid hormone parameters and dyslipidemia among type 2 diabetes mellitus patients: Comparative cross-sectional study.

PubMed

Wolide, Amare Desalegn; Zawdie, Belay; Alemayehu, Tilahun; Tadesse, Samuel

2017-11-01

The relationship between thyroid function and lipid profile has been documented in T2DM and healthy subjects. The aim of the current study was to assess the association between thyroid hormone parameters and dyslipidemia in T2DM and non-diabetic study participants. In this comparative cross-sectional study, 214 type 2 diabetic and 214 non-diabetic study participants were enrolled. Clinical and anthropometric data were collected from all study participants. After overnight fasting, 10ml of whole blood samples were drawn for the measurement of serum TSH, free thyroxine (fT4), free triiodothyronine (fT3), serum reactive C-protein levels, as well as for lipid profile test and glucose. The burden of hypothyroidism and subclinical hypothyroidism among T2DM study participants were 73 (17.05%) and 13 (3.04%) respectively. Comparatively, T2DM study participants had significantly higher serum lipid level than non-diabetics. Stratified by TSH, hypothyroid T2DM study participants had increased lipid level than euthyroid subjects. T2DM serum TSH have shown a positive significant correlation with all lipid profile parameters except HDL-C. In the final model (multivariate linear regression), diabetics serum TSH significantly and positively associated with TG and BMI. Diabetic serum fT3 and fT4 negatively associated with body mass index. In addition, diabetics serum fT3 negatively and serum fT4 positively associated with TC and HDL-C respectively. T2DM study subjects had significantly higher lipid level than nondiabetic and We identified that TSH was positively associated with serum TG and BMI among T2DM study participants. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Dextromethorphan Analogs: Receptor Binding and Pharmacological Profile of Novel Anticonvulsant/Neuroprotectant Drugs

DTIC Science & Technology

1993-05-13

AD-POO8 801 Dextromethorphan Analogs: Receptor Binding and Pharmacological Profile of Novel Anticonvulsant/Neuroprotective Drugs F.C. Tortella, L...Baltimore, MD 21224 CD ABSTRACT A series of 3-substituted 17-methylmorphinan analogs of dextromethorphan (DM) have open developed which are...nTTrTTn) INTRODUCTION The antitussives dextromethorphan (DM), caramiphen and carbetapentane have distinguished themselves as anticonvulsant drugs (1

Endurance Exercise Improves Molecular Pathways of Aerobic Metabolism in Patients With Myositis.

PubMed

Munters, Li Alemo; Loell, Ingela; Ossipova, Elena; Raouf, Joan; Dastmalchi, Maryam; Lindroos, Eva; Chen, Yi-Wen; Esbjörnsson, Mona; Korotkova, Marina; Alexanderson, Helene; Nagaraju, Kanneboyina; Crofford, Leslie J; Jakobsson, Per-Johan; Lundberg, Ingrid E

2016-07-01

Endurance exercise demonstrates beneficial effects in polymyositis/dermatomyositis (PM/DM); however, the molecular effects of exercise on skeletal muscle are incompletely understood. We undertook this controlled pilot study to investigate the effects of a 12-week endurance exercise training program on the molecular profile of skeletal muscle in patients with established PM/DM compared to a nonexercised control group of patients with established PM/DM. Fifteen patients (7 in the exercise group and 8 in the control group) with paired baseline and 12-week follow-up muscle biopsy samples were included. Messenger RNA expression profiling, mass spectrometry-based quantitative proteomics, and immunohistochemical analyses were performed on muscle biopsy samples to determine molecular adaptations associated with changes in clinical measurements induced by endurance exercise. Compared to the control group, the exercise group improved in minutes of cycling time (P < 0.01) and Vo2 max (P < 0.05). The exercise group also had reduced disease activity (P < 0.05) and reduced lactate levels at exhaustion (P < 0.05). Genes related to capillary growth, mitochondrial biogenesis, protein synthesis, cytoskeletal remodeling, and muscle hypertrophy were up-regulated in the exercise group, while genes related to inflammation/immune response and endoplasmic reticulum stress were down-regulated. Mitochondrial pathways including the oxidative phosphorylation metabolic pathway were most affected by the endurance exercise, as demonstrated by proteomics analysis. The exercise group also showed a higher number of capillaries per mm(2) in follow-up biopsy samples (P < 0.05). Our data indicate that endurance exercise in patients with established PM and DM may activate an aerobic phenotype and promote muscle growth and simultaneously suppress the inflammatory response in these patients' muscles, as supported by a combination of data on gene expression, proteomics, and capillary density in repeated muscle biopsies. © 2016, American College of Rheumatology.

Growth and dissolution of spherical density enhancements in SCDEW cosmologies

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

Bonometto, Silvio A.; Mainini, Roberto, E-mail: bonometto@oats.inaf.it, E-mail: roberto.mainini@mib.infn.it

2017-06-01

Strongly Coupled Dark Energy plus Warm dark matter (SCDEW) cosmologies are based on the finding of a conformally invariant (CI) attractor solution during the early radiative expansion, requiring then the stationary presence of ∼ 1 % of coupled-DM and DE, since inflationary reheating. In these models, coupled-DM fluctuations, even in the early radiative expansion, grow up to non-linearity, as shown in a previous associated paper. Such early non-linear stages are modelized here through the evolution of a top-hat density enhancement. As expected, its radius R increases up to a maximum and then starts to decrease. Virial balance is reached whenmore » the coupled-DM density contrast is just 25–26 and DM density enhancement is O(10 %) of total density. Moreover, we find that this is not an equilibrium configuration as, afterwards, coupling causes DM particle velocities to increase, so that the fluctuation gradually dissolves. We estimate the duration of the whole process, from horizon crossing to dissolution, and find z {sub horizon}/ z {sub erasing} ∼ 3 × 10{sup 4}. Therefore, only fluctuations entering the horizon at z ∼< 10{sup 9}–10{sup 10} are able to accrete WDM with mass ∼ 100 eV—as soon as it becomes non-relativistic—so avoiding full disruption. Accordingly, SCDEW cosmologies, whose WDM has mass ∼ 100 eV, can preserve primeval fluctuations down to stellar mass scale.« less

Clinical characteristics and beta cell function in Chinese patients with newly diagnosed type 2 diabetes mellitus with different levels of serum triglyceride.

PubMed

Zheng, Shuang; Zhou, Huan; Han, Tingting; Li, Yangxue; Zhang, Yao; Liu, Wei; Hu, Yaomin

2015-04-29

To explore clinical characteristics and beta cell function in Chinese patients with newly diagnosed drug naive type 2 diabetes mellitus (T2DM) with different levels of serum triglyceride (TG). Patients with newly diagnosed T2DM (n = 624) were enrolled and divided into different groups according to levels of serum TG. All patients underwent oral glucose tolerance tests and insulin releasing tests. Demographic data, lipid profiles, glucose levels, and insulin profiles were compared between different groups. Basic insulin secretion function index (homeostasis model assessment for beta cell function index, HOMA-β), modified beta cell function index (MBCI), glucose disposition indices (DI), and early insulin secretion function index (insulinogenic index, IGI) were used to evaluate the beta cell function. Patients of newly diagnosed T2DM with hypertriglyceridemia were younger, fatter and had worse lipid profiles, glucose profiles, and high insulin levels than those with normal TG. There is no difference in early phase insulin secretion among groups of newly diagnosed T2DM patients with different TG levels. The basal beta cell function (HOMA-β and MBCI) initially increased along rising TG levels and then decreased as the TG levels rose further. The insulin sensitivity was relatively high in patients with a low level of TG and low with a high level of TG. Hypertriglyceridemia influences clinical characteristics and β cell function of Chinese patients with newly diagnosed T2DM. A better management of dyslipidemia may, to some extent, reduce the effect of lipotoxicity, thereby improving glucose homeostasis in patients with newly diagnosed T2DM.

The Dark Matter Halo Profile Of NGC 2976 Via Stellar Kinematics

NASA Astrophysics Data System (ADS)

Adams, Joshua J.; Gebhardt, K.; Hill, G. J.; van den Bosch, R. C. E.; Blanc, G. A.

2011-01-01

The observations of kinematics in low surface brightness (LSB) and dwarf late type galaxies have stubbornly resisted giving clear evidence for the cuspy Navarro-Frenk-White (NFW) dark matter (DM) halo profiles that simulations with ΛCDM inputs predict. Instead, most LSBs and late type dwarfs suggest cored DM halos or the observations are not yet constraining enough to rule out cusps. One viable theory to explain cored DM halos relies on the gravitational perturbation of a growing baryonic disk that is then rapidly removed causing the halo to expand to a cored equilibrium. Weakly self-interacting dark matter has also been invoked to explain cored DM halos. This problem may loom large over small galaxy formation and growth. However, different measurements can be taken to further test the apparent problem. Most previous data have relied on HI or Hα as kinematic tracers. A small number of works have studied the problem with longslit stellar kinematics. Ideally, the advantages of 2D spectroscopic coverage and a collisionless kinematic tracer would be combined. So far, NGC 2976 has made one of the cleanest cases for a cored DM halo via integral field spectroscopy in Hα. We here report on observations of NGC 2976 with the large field-of-view fiber-fed Visible Integral field Replicable Unit Spectrograph Prototype (VIRUS-P) at R=3200 to concurrently measure the gaseous and stellar kinematics and probe the DM halo. We find that the gas and stellar kinematics disagree both in the magnitude of their second velocity moments and their detailed profiles. We unexpectedly find emission features in one of NGC 2976's two large star-forming regions which may be indicative of carbon-rich Wolf-Rayet stars. A putative bar further complicates the use of gaseous tracers. We solve the Jeans equations with stellar kinematics to reevaluate the DM profile in this exemplar galaxy of the core-cusp problem.

Benefit of Adding Ezetimibe to Statin Therapy on Cardiovascular Outcomes and Safety in Patients With Versus Without Diabetes Mellitus: Results From IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).

PubMed

Giugliano, Robert P; Cannon, Christopher P; Blazing, Michael A; Nicolau, José C; Corbalán, Ramón; Špinar, Jindřich; Park, Jeong-Gun; White, Jennifer A; Bohula, Erin A; Braunwald, Eugene

2018-04-10

Ezetimibe, when added to simvastatin, reduces cardiovascular events after acute coronary syndrome. We explored outcomes stratified by diabetes mellitus (DM). In IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), 18 144 patients after acute coronary syndrome with low-density lipoprotein cholesterol 50 to 125 mg/dL were randomized to 40 mg ezetimibe/simvastatin (E/S) or 40 mg placebo/simvastatin. The primary composite end point was cardiovascular death, major coronary events, and stroke. DM was a prespecified subgroup. The 4933 (27%) patients with DM were more often older and female, had had a prior myocardial infarction and revascularization, and presented more frequently with non-ST segment elevation acute coronary syndrome compared with patients without DM (each P <0.001). The median admission low-density lipoprotein cholesterol was lower among patients with DM (89 versus 97 mg/dL, P <0.001). E/S achieved a significantly lower median time-weighted average low-density lipoprotein cholesterol compared with placebo/simvastatin, irrespective of DM (DM: 49 versus 67 mg/dL; no DM: 55 versus 71 mg/dL; both P <0.001). In patients with DM, E/S reduced the 7-year Kaplan-Meier primary end point event rate by 5.5% absolute (hazard ratio, 0.85; 95% confidence interval, 0.78-0.94); in patients without DM, the absolute difference was 0.7% (hazard ratio, 0.98; 95% confidence interval, 0.91-1.04; P int =0.02). The largest relative reductions in patients with DM were in myocardial infarction (24%) and ischemic stroke (39%). No differences in safety outcomes by treatment were present regardless of DM. When stratified further by age, patients ≥75 years of age had a 20% relative reduction in the primary end point regardless of DM ( P int =0.91), whereas patients <75 years of age with DM had greater benefit than those without ( P int =0.011). When stratified by the TIMI (Thrombolysis in Myocardial Infarction) Risk Score for Secondary Prevention, all patients with DM demonstrated benefit with E/S regardless of risk. In contrast, among patients without DM, those with a high risk score experienced a significant (18%) relative reduction in the composite of cardiovascular death, myocardial infarction, and ischemic stroke with E/S compared with placebo/simvastatin, whereas patients without DM at low or moderate risk demonstrated no benefit with the addition of ezetimibe to simvastatin ( P int =0.034). In IMPROVE-IT, the benefit of adding ezetimibe to statin was enhanced in patients with DM and in high-risk patients without DM. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00202878. © 2017 American Heart Association, Inc.

PULSAR OBSERVATIONS USING THE FIRST STATION OF THE LONG WAVELENGTH ARRAY AND THE LWA PULSAR DATA ARCHIVE

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

Stovall, K.; Dowell, J.; Eftekhari, T.

2015-08-01

We present initial pulsar results from the first station of the Long Wavelength Array (LWA1) obtained during the commissioning period of LWA1 and in early science results. We present detections of periodic emission from 44 previously known pulsars, including 3 millisecond pulsars. The effects of the interstellar medium (ISM) on pulsar emission are significantly enhanced at the low frequencies of the LWA1 band (10–88 MHz), making LWA1 a very sensitive instrument for characterizing changes in the dispersion measure (DM) and other effects from the ISM. Pulsars also often have significant evolution in their pulse profile at low frequency and amore » break in their spectral index. We report DM measurements for 44 pulsars, mean flux density measurements for 36 pulsars, and multi-frequency component spacing and widths for 15 pulsars with more than one profile component. For 27 pulsars, we report spectral index measurements within our frequency range. We also introduce the LWA1 Pulsar Data Archive, which stores reduced data products from LWA1 pulsar observations. Reduced data products for the observations presented here can be found in the archive. Reduced data products from future LWA1 pulsar observations will also be made available through the archive.« less

Lipid, Fatty Acid and Energy Density Profiles of White Sharks: Insights into the Feeding Ecology and Ecophysiology of a Complex Top Predator

PubMed Central

Pethybridge, Heidi R.; Parrish, Christopher C.; Bruce, Barry D.; Young, Jock W.; Nichols, Peter D.

2014-01-01

Lipids are major sources of metabolic energy in sharks and are closely linked to environmental conditions and biological cycles, such as those related to diet, reproduction and migration. In this study, we report for the first time, the total lipid content, lipid class composition and fatty acid profiles of muscle and liver tissue of white sharks, Carcharodon carcharias, of various lengths (1.5–3.9 m), sampled at two geographically separate areas off southern and eastern Australia. Muscle tissue was low in total lipid content (<0.9% wet mass, wm) and was dominated by phospholipids (>90% of total lipid) and polyunsaturated fatty acids (34±12% of total fatty acids). In contrast, liver was high in total lipid which varied between 51–81% wm and was dominated by triacylglycerols (>93%) and monounsaturated fatty acids (36±12%). With knowledge of total lipid and dry tissue mass, we estimated the energy density of muscle (18.4±0.1 kJ g−1 dm) and liver (34.1±3.2 kJ g−1 dm), demonstrating that white sharks have very high energetic requirements. High among-individual variation in these biochemical parameters and related trophic markers were observed, but were not related to any one biological or environmental factor. Signature fatty acid profiles suggest that white sharks over the size range examined are generalist predators with fish, elasmobranchs and mammalian blubber all contributing to the diet. The ecological applications and physiological influences of lipids in white sharks are discussed along with recommendations for future research, including the use of non-lethal sampling to examine the nutritional condition, energetics and dietary relationships among and between individuals. Such knowledge is fundamental to better understand the implications of environmental perturbations on this iconic and threatened species. PMID:24871223

Lipid, fatty acid and energy density profiles of white sharks: insights into the feeding ecology and ecophysiology of a complex top predator.

PubMed

Pethybridge, Heidi R; Parrish, Christopher C; Bruce, Barry D; Young, Jock W; Nichols, Peter D

2014-01-01

Lipids are major sources of metabolic energy in sharks and are closely linked to environmental conditions and biological cycles, such as those related to diet, reproduction and migration. In this study, we report for the first time, the total lipid content, lipid class composition and fatty acid profiles of muscle and liver tissue of white sharks, Carcharodon carcharias, of various lengths (1.5-3.9 m), sampled at two geographically separate areas off southern and eastern Australia. Muscle tissue was low in total lipid content (<0.9% wet mass, wm) and was dominated by phospholipids (>90% of total lipid) and polyunsaturated fatty acids (34±12% of total fatty acids). In contrast, liver was high in total lipid which varied between 51-81% wm and was dominated by triacylglycerols (>93%) and monounsaturated fatty acids (36±12%). With knowledge of total lipid and dry tissue mass, we estimated the energy density of muscle (18.4±0.1 kJ g-1 dm) and liver (34.1±3.2 kJ g-1 dm), demonstrating that white sharks have very high energetic requirements. High among-individual variation in these biochemical parameters and related trophic markers were observed, but were not related to any one biological or environmental factor. Signature fatty acid profiles suggest that white sharks over the size range examined are generalist predators with fish, elasmobranchs and mammalian blubber all contributing to the diet. The ecological applications and physiological influences of lipids in white sharks are discussed along with recommendations for future research, including the use of non-lethal sampling to examine the nutritional condition, energetics and dietary relationships among and between individuals. Such knowledge is fundamental to better understand the implications of environmental perturbations on this iconic and threatened species.

Black hole genesis of dark matter

NASA Astrophysics Data System (ADS)

Lennon, Olivier; March-Russell, John; Petrossian-Byrne, Rudin; Tillim, Hannah

2018-04-01

We present a purely gravitational infra-red-calculable production mechanism for dark matter (DM) . The source of both the DM relic abundance and the hot Standard Model (SM) plasma is a primordial density of micro black holes (BHs), which evaporate via Hawking emission into both the dark and SM sectors. The mechanism has four qualitatively different regimes depending upon whether the BH evaporation is 'fast' or 'slow' relative to the initial Hubble rate, and whether the mass of the DM particle is 'light' or 'heavy' compared to the initial BH temperature. For each of these regimes we calculate the DM yield, Y, as a function of the initial state and DM mass and spin. In the 'slow' regime Y depends on only the initial BH mass over a wide range of initial conditions, including scenarios where the BHs are a small fraction of the initial energy density. The DM is produced with a highly non-thermal energy spectrum, leading in the 'light' DM mass regime (~260 eV and above depending on DM spin) to a strong constraint from free-streaming, but also possible observational signatures in structure formation in the spin 3/2 and 2 cases. The 'heavy' regime (~1.2 × 108 GeV to MPl depending on spin) is free of these constraints and provides new possibilities for DM detection. In all cases there is a dark radiation component predicted.

Assessing Whether Northeastern Earthquakes and Warm Springs Are Produced by the Northern Appalachian Anomaly

NASA Astrophysics Data System (ADS)

Marrero, A. M.; Abbott, D. H.; Menke, W. H.

2017-12-01

The passive margin of eastern North America has been tectonically quiescent for >100 Ma. However, earthquakes, mantle-derived 3He in ground water and warm springs hint at continued activity. The recent proposal of asthenospheric upwelling (the Northern Appalachian Anomaly, NAA) beneath southern New England (SNE) raises the possibility that this activity is due to mantle melt. Its delivery to the lithosphere may lower density and cause stress, open pathways for 3He, and heat the crust. We examine isostatic balance along the Levin et al. [2017] receiver function profile for which crustal thickness H and compressional-to-shear velocity ratio R are published. It crosses the continental margin north of the NAA and acts as a control against which regions closer to it may be compared. We use Christensen's [1996] measurements of rocks to predict crustal density Dc from R. Isostatic balance is estimated by combining H, Dc, elevation and mantle density Dm. We assume a constant Dm, which allows us to assess the imbalance due to factors other than mantle heterogeneities. The crust along the profile is not in isostatic balance, with very large disequilibrium pressure P (up to -33.6 MPa). We use the horizontal gradient of P as a proxy for crustal shear force and compare it to seismicity. The signals show significant correlation, indicating that both the isostatic imbalance and the crustal seismicity may be due to crustal features that are thought to be mostly "fossil'; that is, originating hundreds of millions of year ago when the crust was formed. While our results do not preclude the possibility that the present-day NAA is influencing isostatic disequilibria and seismicity in SNE, they indicate that distinguishing its effect from the very large ancient causes may be problematical. We also study warm springs underlain by the NAA and show that their temperatures have been stable over the last 100 years, suggesting their importance in long-term heat transport.

Review of the fermionic dark matter model applied to galactic structures

NASA Astrophysics Data System (ADS)

Krut, A.; Argüelles, C. R.; Rueda, J.; Ruffini, R.

2015-12-01

Baryonic components (e.g. bulge and disk) of galactic structures are assumed to be embedded in an isothermal dark matter halo of fermionic nature. Besides the Pauli principle only gravitational interaction is considered. Using the underlying Fermi-Dirac phase space distribution, typical of collisionless relaxation processes, it yields an one-parameter family of scaled solutions which reproduces the observed flat rotation curves in galaxies, and additionally predicts a degenerate core through their centers. In order to provide the right DM halo properties of galaxies a set of four parameters (particle mass, degeneracy parameter at the galactic center, central density and the velocity dispersion) is necessary. The more general density profile shows three regimes depending on radius: an almost uniform very dense quantum core followed by a steep fall, a plateau in the diluted regime and a Boltzmannian tail representing the halo. In contrast to purely Boltzmannian configurations the fermionic DM model containing a quantum core allows to determine the particle mass. We show that the quantum core can be well approximated by a polytrope of index n = 3/2, while the halo can be perfectly described by an isothermal sphere with a halo scale length radius equal to approximately 3/4 of the King-radius.

Review of the fermionic dark matter model applied to galactic structures

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

Krut, A.; Argüelles, C. R.; Rueda, J.

2015-12-17

Baryonic components (e.g. bulge and disk) of galactic structures are assumed to be embedded in an isothermal dark matter halo of fermionic nature. Besides the Pauli principle only gravitational interaction is considered. Using the underlying Fermi-Dirac phase space distribution, typical of collisionless relaxation processes, it yields an one-parameter family of scaled solutions which reproduces the observed flat rotation curves in galaxies, and additionally predicts a degenerate core through their centers. In order to provide the right DM halo properties of galaxies a set of four parameters (particle mass, degeneracy parameter at the galactic center, central density and the velocity dispersion)more » is necessary. The more general density profile shows three regimes depending on radius: an almost uniform very dense quantum core followed by a steep fall, a plateau in the diluted regime and a Boltzmannian tail representing the halo. In contrast to purely Boltzmannian configurations the fermionic DM model containing a quantum core allows to determine the particle mass. We show that the quantum core can be well approximated by a polytrope of index n = 3/2, while the halo can be perfectly described by an isothermal sphere with a halo scale length radius equal to approximately 3/4 of the King-radius.« less

Anatomy of the inert two-Higgs-doublet model in the light of the LHC and non-LHC dark matter searches

NASA Astrophysics Data System (ADS)

Belyaev, Alexander; Cacciapaglia, Giacomo; Ivanov, Igor P.; Rojas-Abatte, Felipe; Thomas, Marc

2018-02-01

The inert two-Higgs-doublet model (i2HDM) is a theoretically well-motivated example of a minimal consistent dark matter (DM) model which provides monojet, mono-Z , mono-Higgs, and vector-boson-fusion +ETmiss signatures at the LHC, complemented by signals in direct and indirect DM search experiments. In this paper we have performed a detailed analysis of the constraints in the full five-dimensional parameter space of the i2HDM, coming from perturbativity, unitarity, electroweak precision data, Higgs data from the LHC, DM relic density, direct/indirect DM detection, and LHC monojet analysis, as well as implications of experimental LHC studies on disappearing charged tracks relevant to a high DM mass region. We demonstrate the complementarity of the above constraints and present projections for future LHC data and direct DM detection experiments to probe further i2HDM parameter space. The model is implemented into the CalcHEP and micrOMEGAs packages, which are publicly available at the HEPMDB database, and it is ready for a further exploration in the context of the LHC, relic density, and DM direct detection.

Observation and modelling of main-sequence star chromospheres - XII. Two-component model chromospheres for five active dM1e stars

NASA Astrophysics Data System (ADS)

Houdebine, E. R.

2009-08-01

We aim to constrain the Hα, CaII H and CaII K profiles from quiescent and active regions on active dM1e stars. A preliminary analysis of all the data available for dM1e stars shows that the Hα/CaII equivalent width (EW) ratio varies by up to a factor of 7 for different stars in our sample. We find that spectroscopic binaries have a significantly smaller ratio than single dM1e stars. We also find that the pre-main-sequence stars Gl 616.2, GJ 1264 and Gl 803 have a ratio lower than main-sequence single dM1e stars. These differences imply that different chromospheric structures are present on different stars, notably the temperature minimum must decrease with an increasing Hα/CaII EW ratio. For these reasons, it is impossible to reproduce all observations with only one grid of model chromospheres. We show that the grid of model chromospheres of Paper VI is adequate to describe the physical conditions that prevail in the chromospheres of spectroscopic binaries and pre-main-sequence M1e stars, but not for the conditions in single dM1e stars. One or more additional grids of model chromospheres will be necessary to reproduce all observations. We use the method developed in Paper XI in this series, in order to build two-component model chromospheres for five M1e field stars: FF And A, FF And B, GJ 1264, AU Mic and Gl 815A. Our solutions provide an exact match of the Hα and the mean CaII H & K EWs within measurement uncertainties. We compare the theoretical profiles and the observed profiles of Hα and the CaII H & K resonance lines. On the one hand, our fits to the CaII lines are reasonably good. On the other hand, our models tend to produce Hα profiles with a central absorption that is too deep. This suggests that the column mass at the transition region for plages is underestimated, but this would imply that the contrast factor between quiescent and active regions in the CaII lines is larger than 5. We find that, except in the cases of FF And A and AU Mic, the total Hα profile is dominated by the contributions from plage regions. The Hα profiles in quiescent regions are typically filled in or slightly in emission. We also find that, as in the case of the less active dM1 stars, CaII emission in dM1e stars is generally dominated by the contribution from plage regions. We find plage filling factors typically in the range 10 to 60 per cent. These are on average (40 per cent) slightly larger than those derived for the less active dM1 stars (30 per cent). Our modelling shows that the grid of model chromospheres of Paper VI is adequate for only a subset of dM1e stars. Physical conditions that prevail in the chromospheres of dM1e stars are very different from one star to another. For this reason, this study demonstrates the critical need for several improved grids of model chromospheres as well as higher signal-to-noise ratio data. Based on observations collected at Observatoire de Haute Provence, France, and at the European Southern Observatory, Chile. E-mail: eric_houdebine@yahoo.fr

The difference in correlation between insulin resistance index and chronic inflammation in type 2 diabetes with and without metabolic syndrome.

PubMed

Pourfarzam, Morteza; Zadhoush, Fouzieh; Sadeghi, Masoumeh

2016-01-01

Insulin resistance (IR) is associated with low-grade systemic inflammation. It plays an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in patients with metabolic syndrome (MetS). It is unclear whether diabetic patients with MetS confer elevated CVD risk and outcomes beyond the impact of individual's components of MetS. The aim of this study is to highlight the central role of IR, inflammation, triglyceride/high-density lipoprotein- cholesterol (TG/HDL-C) ratio, and atherogenic index of plasma (AIP) in T2DM with MetS. This cross-sectional study comprised 130 men distributed into three groups, namely Controls: 40 nondiabetic healthy volunteers; Group I: 40 T2DM patients without MetS, and Group II: 50 T2DM patients with MetS. Fasting blood samples were collected for the measurement of blood lipid profile, glucose, insulin, hemoglobin A1c, and high-sensitivity C-reactive protein (hs-CRP). TG/HDL-C ratio, AIP, and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Significant positive association was observed between HOMA-IR and hs-CRP only in Group II and between HOMA-IR and TG/HDL-C ratio in all subjects. Significant differences were seen in waist and hip circumferences, waist/hip ratio, body mass index, systolic blood pressure, fasting blood glucose, TGs, HDL-C, insulin, hs-CRP, HOMA-IR, TG/HDL ratio, and AIP between Controls and Group I with Group II. In T2DM with MetS, coexistence of elevated atherogenic indices, systemic inflammation, and association between HOMA-IR and TG/HDL-C ratio were seen. These factors are considered having important role in elevated CVD risk beyond MetS components in these patients.

Comparison of breast percent density estimation from raw versus processed digital mammograms

NASA Astrophysics Data System (ADS)

Li, Diane; Gavenonis, Sara; Conant, Emily; Kontos, Despina

2011-03-01

We compared breast percent density (PD%) measures obtained from raw and post-processed digital mammographic (DM) images. Bilateral raw and post-processed medio-lateral oblique (MLO) images from 81 screening studies were retrospectively analyzed. Image acquisition was performed with a GE Healthcare DS full-field DM system. Image post-processing was performed using the PremiumViewTM algorithm (GE Healthcare). Area-based breast PD% was estimated by a radiologist using a semi-automated image thresholding technique (Cumulus, Univ. Toronto). Comparison of breast PD% between raw and post-processed DM images was performed using the Pearson correlation (r), linear regression, and Student's t-test. Intra-reader variability was assessed with a repeat read on the same data-set. Our results show that breast PD% measurements from raw and post-processed DM images have a high correlation (r=0.98, R2=0.95, p<0.001). Paired t-test comparison of breast PD% between the raw and the post-processed images showed a statistically significant difference equal to 1.2% (p = 0.006). Our results suggest that the relatively small magnitude of the absolute difference in PD% between raw and post-processed DM images is unlikely to be clinically significant in breast cancer risk stratification. Therefore, it may be feasible to use post-processed DM images for breast PD% estimation in clinical settings. Since most breast imaging clinics routinely use and store only the post-processed DM images, breast PD% estimation from post-processed data may accelerate the integration of breast density in breast cancer risk assessment models used in clinical practice.

Multipartite interacting scalar dark matter in the light of updated LUX data

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

Bhattacharya, Subhaditya; Ghosh, Purusottam; Poulose, Poulose, E-mail: subhab@iitg.ernet.in, E-mail: p.ghosh@iitg.ernet.in, E-mail: poulose@iitg.ernet.in

2017-04-01

We explore constraints on multipartite dark matter (DM) framework composed of singlet scalar DM interacting with the Standard Model (SM) through Higgs portal coupling. We compute relic density and direct search constraints including the updated LUX bound for two component scenario with non-zero interactions between two DM components in Z{sub 2} × Z{sub 2}{sup '} framework in comparison with the one having O(2) symmetry. We point out availability of a significantly large region of parameter space of such a multipartite model with DM-DM interactions.

SIDM on FIRE: hydrodynamical self-interacting dark matter simulations of low-mass dwarf galaxies

NASA Astrophysics Data System (ADS)

Robles, Victor H.; Bullock, James S.; Elbert, Oliver D.; Fitts, Alex; González-Samaniego, Alejandro; Boylan-Kolchin, Michael; Hopkins, Philip F.; Faucher-Giguère, Claude-André; Kereš, Dušan; Hayward, Christopher C.

2017-12-01

We compare a suite of four simulated dwarf galaxies formed in 1010 M⊙ haloes of collisionless cold dark matter (CDM) with galaxies simulated in the same haloes with an identical galaxy formation model but a non-zero cross-section for DM self-interactions. These cosmological zoom-in simulations are part of the Feedback In Realistic Environments (FIRE) project and utilize the FIRE-2 model for hydrodynamics and galaxy formation physics. We find the stellar masses of the galaxies formed in self-interacting dark matter (SIDM) with σ/m = 1 cm2 g-1 are very similar to those in CDM (spanning M⋆ ≈ 105.7-7.0M⊙) and all runs lie on a similar stellar mass-size relation. The logarithmic DM density slope (α = d log ρ/d log r) in the central 250-500 pc remains steeper than α = -0.8 for the CDM-Hydro simulations with stellar mass M⋆ ∼ 106.6 M⊙ and core-like in the most massive galaxy. In contrast, every SIDM hydrodynamic simulation yields a flatter profile, with α > -0.4. Moreover, the central density profiles predicted in SIDM runs without baryons are similar to the SIDM runs that include FIRE-2 baryonic physics. Thus, SIDM appears to be much more robust to the inclusion of (potentially uncertain) baryonic physics than CDM on this mass scale, suggesting that SIDM will be easier to falsify than CDM using low-mass galaxies. Our FIRE simulations predict that galaxies less massive than M⋆ ≲ 3 × 106 M⊙ provide potentially ideal targets for discriminating models, with SIDM producing substantial cores in such tiny galaxies and CDM producing cusps.

Streptozocin-induced type-1 diabetes mellitus results in decreased density of CGRP sensory and TH sympathetic nerve fibers that are positively correlated with bone loss at the mouse femoral neck.

PubMed

Enríquez-Pérez, Iris A; Galindo-Ordoñez, Karla E; Pantoja-Ortíz, Christian E; Martínez-Martínez, Arisaí; Acosta-González, Rosa I; Muñoz-Islas, Enriqueta; Jiménez-Andrade, Juan M

2017-08-10

Type-1 diabetes mellitus (T1DM) results in loss of innervation in some tissues including epidermis and retina; however, the effect on bone innervation is unknown. Likewise, T1DM results in pathological bone loss and increased risk of fracture. Thus, we quantified the density of calcitonin gene-related peptide (CGRP + ) sensory and tyrosine hydroxylase (TH + ) sympathetic nerve fibers and determined the association between the innervation density and microarchitecture of trabecular bone at the mouse femoral neck. Ten weeks-old female mice received 5 daily administrations of streptozocin (i.p. 50mg/kg) or citrate (control group). Twenty weeks later, femurs were analyzed by microCT and processed for immunohistochemistry. Confocal microscopy analysis revealed that mice with T1DM had a significant loss of both CGRP + and TH + nerve fibers in the bone marrow at the femoral neck. Likewise, microCT analysis revealed a significant decrease in the trabecular bone mineral density (tBMD), bone volume/total volume ratio (BV/TB), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) in mice with T1DM as compared to control mice. Analysis of correlation revealed a positive and significant association between density of CGRP + or TH + nerve fibers with tBMD, BV/TV, Tb.Th and Tb.Sp, but not with trabecular number (there was a positive association only for CGRP + ) and degree of anisotropy (DA). This study suggests an interaction between sensory and sympathetic nervous system and T1DM-induced bone loss. Identification of the factors involved in the loss of CGRP + sensory and TH + sympathetic fibers and how they regulate bone loss may result in new avenues to treat T1DM-related osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Metabolic Basis of Ethnic Differences in Diabetes Risk in Overweight and Obese Youth

PubMed Central

Alderete, TL; Toledo-Corral, CM; Goran, MI

2015-01-01

The global pandemic of childhood obesity has led to increased risk for prediabetes and type 2 diabetes mellitus (T2DM). Studies have shown decreased insulin sensitivity and/or secretion with increasing adiposity and consistently observed greater risk for T2DM in obese, non-Caucasian youth. In the current review we describe recent advances in understanding how obesity and metabolic status in children and adolescents confers various risk profiles for T2DM among Latinos, African-Americans, Caucasians, Asians and Native Americans. These possible determinants include ectopic fat distribution, adipose tissue inflammation and fibrosis, and elevated plasma levels of non-esterified free fatty acids. Future work should aim to elucidate the ethnic-specific pathophysiology of T2DM in order to develop and implement appropriate prevention and treatment strategies based on different ethnic profiles of diabetes risk. PMID:24445905

Gene expression profile of high-fat diet-fed C57BL/6J mice: in search of potential role of azelaic acid.

PubMed

Muthulakshmi, Shanmugam; Chakrabarti, Alok K; Mukherjee, Sanjay

2015-03-01

High-fat diet (HFD) elevates circulatory fatty acids and influences glucose and fat metabolism. Azelaic acid (AzA), a naturally occurring α,ω-dicarboxylic acid in wheat, rye, barley, oat seeds and sorghum, has been reported to exert antidiabetic effects in HFD-induced type 2 diabetes mellitus (T2DM) C57BL/6J mice. The present study was undertaken to identify the genes that are differentially modulated by treatment with AzA in HFD-fed mice. Mice were fed HFD for 10 weeks and subjected to intragastric administration of 80 mg/kg body weight (BW) of AzA daily along with HFD from 11 to 15 weeks. Lipid profile, adipokines and cytokines were examined in the plasma/liver of mice. Whole genome profiling was performed in the liver of mice using microarray and validated by qRT-PCR, Western blot and immunohistochemical analyses. HFD intake resulted in significantly elevated lipids (except high-density lipoproteins), resistin, tumour necrosis factor alpha and interleukin-6 with marked reduction in adiponectin. Administration of AzA to HFD-fed mice significantly restored the lipids, adipokines and cytokines to near normal. Transcript profiling revealed that HFD intake activated the genes involved in stress response, cell cycle regulation and apoptosis. Treatment with AzA caused increased expression of genes involved in reactive oxygen species (ROS) scavenging, receptor-mediated signalling, transcription, protein modification and insulin signal transduction. AzA activates insulin signal molecules leading to insulin sensitivity. The ability of AzA to modulate the expression of these genes supports the notion that AzA is a promising drug candidate for the treatment of insulin resistance associated with T2DM.

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.

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

The positive effect of moderate walking exercise on chemerin levels in Portuguese patients with type 2 diabetes mellitus.

PubMed

Neuparth, Maria João; Proença, Jorge Brandão; Santos-Silva, Alice; Coimbra, Susana

2014-02-01

Physical exercise intervention is known to be crucial in the management of type 2 diabetes mellitus (T2DM). We aimed to evaluate, in patients with T2DM, the effect of regular moderate walking exercise on markers of oxidative stress, lipid metabolism, and inflammation. We studied 30 patients with T2DM who walked regularly during the last year and 53 patients with T2DM who did not perform any type of exercise. The patients were evaluated for chemerin, adiponectin, leptin, oxidized low-density lipoprotein, and C-reactive protein (CRP) levels. The active T2DM patients showed significantly lower body mass index, as compared with the inactive patients. The active T2DM patients showed significantly lower levels of chemerin and CRP than those of the inactive T2DM patients (CRP lost significance after adjustment for body mass index). The active patients, compared with the inactive, presented a trend toward higher levels of adiponectin and lower values of oxidized low-density lipoprotein. Leptin differed significantly between sexes, and the active women presented a trend toward lower levels as compared with the inactive women. In the patients with T2DM, the practice of moderate walking in a regular basis was sufficient to reduce chemerin levels, which suggests that practice of regular physical exercise should be encouraged.

Resonance enhancement of dark matter interactions: the case for early kinetic decoupling and velocity dependent resonance width

NASA Astrophysics Data System (ADS)

Duch, M.; Grzadkowski, B.

2017-09-01

Motivated by the possibility of enhancing dark matter (DM) self-scattering cross-section σ self , we have revisited the issue of DM annihilation through a Breit-Wigner resonance. In this case thermally averaged annihilation cross-section has strong temper-ature dependence, whereas elastic scattering of DM on the thermal bath particles is sup-pressed. This leads to the early kinetic decoupling of DM and an interesting interplay in the evolution of DM density and temperature that can be described by a set of coupled Boltzmann equations. The standard Breit-Wigner parametrization of a resonance prop-agator is also corrected by including momentum dependence of the resonance width. It has been shown that this effects may change predictions of DM relic density by more than order of magnitude in some regions of the parameter space. Model independent discussion is illustrated within a theory of Abelian vector dark matter. The model assumes extra U(1) symmetry group factor and an additional complex Higgs field needed to generate a mass for the dark vector boson, which provides an extra neutral Higgs boson h 2. We discuss the resonant amplification of σ self . It turns out that if DM abundance is properly reproduced, the Fermi-LAT data favor heavy DM and constraint the enhancement of σ self to the range, which cannot provide a solution to the small-scale structure problems.

Association between body mass index and core components of metabolic syndrome in 1486 patients with type 1 diabetes mellitus in Japan (JDDM 13).

PubMed

Arai, Keiko; Yokoyama, Hiroki; Okuguchi, Fuminobu; Yamazaki, Katsuya; Takagi, Hirofumi; Hirao, Koichi; Kobayashi, Masashi

2008-12-01

There is no recent study on the prevalence of overweight and obesity in patients with type 1 diabetes mellitus (T1DM) in Japan. Being overweight has a significant effect on the metabolic condition and glycemic control of such patients. In the present cross-sectional study, we investigated the effects of body mass index (BMI) on lipid profile, blood pressure, and glycemic control in patients with T1DM. In total, 1486 patients with T1DM (including 401 patients with early onset T1DM who were <20 years of age at diagnosis) were included. Patients were divided into four groups according to their BMI, and glycosylated hemoglobin (HbA1c), daily insulin dose per kg body weight, lipid profile, and blood pressure were compared between groups. We found that 15.7% of all patients were overweight (BMI >or= 25.0 kg/m(2)) and 2.0% were obese (BMI >or= 30.0 kg/m(2)), compared with 17.5% and 2.0%, respectively, in the early onset T1DM subgroup. Significant changes in lipid profiles and blood pressure were found with increasing BMI in both the entire population and the early onset T1DM subgroup. In the entire study population HbA1c and the body weight-adjusted daily insulin dose were significantly higher in patients with a BMI >or= 23 kg/m(2) compared with those with a BMI<23 kg/m(2); however, this was not the case in the early onset T1DM subgroup. This difference may be due to the relatively small number of patients in that subgroup. In conclusion, the prevalence of overweight and obesity in patients with T1DM was less than that in the normal Japanese population. For patients with T1DM, being overweight was associated with higher blood pressure and dyslipidemia. Furthermore, we cannot exclude an association between being overweight and the need for higher daily doses of insulin.

How light a higgsino or a wino dark matter can become in a compressed scenario of MSSM

NASA Astrophysics Data System (ADS)

Chakraborti, Manimala; Chattopadhyay, Utpal; Poddar, Sujoy

2017-09-01

Higgsinos and Wino have strong motivations for being Dark Matter (DM) candidates in supersymmetry, but their annihilation cross sections are quite large. For thermal generation and a single component DM setup the higgsinos or wino may have masses of around 1 or 2-3 TeV respectively. For such DM candidates, a small amount of slepton coannihilation may decrease the effective DM annihilation cross section. This, in turn reduces the lower limit of the relic density satisfied DM mass by more than 50%. Almost a similar degree of reduction of the same limit is also seen for squark coannihilations. However, on the contrary, for near degeneracy of squarks and higgsino DM, near its generic upper limit, the associated coannihilations may decrease the relic density, thus extending the upper limit towards higher DM masses. We also compute the direct and indirect detection signals. Here, because of the quasi-mass degeneracy of the squarks and the LSP, we come across a situation where squark exchange diagrams may contribute significantly or more strongly than the Higgs exchange contributions in the spin-independent direct detection cross section of DM. For the higgsino-DM scenario, we observe that a DM mass of 600 GeV to be consistent with WMAP/PLANCK and LUX data for sfermion coannihilations. The LUX data itself excludes the region of 450 to 600 GeV, by a half order of magnitude of the cross-section, well below the associated uncertainty. The similar combined lower limit for a wino DM is about 1.1 TeV. There is hardly any collider bound from the LHC for squarks and sleptons in such a compressed scenario where sfermion masses are close to the mass of a higgsino/wino LSP.

A dark matter model that reconciles tensions between the cosmic-ray e± excess and the gamma-ray and CMB constraints

NASA Astrophysics Data System (ADS)

Xiang, Qian-Fei; Bi, Xiao-Jun; Lin, Su-Jie; Yin, Peng-Fei

2017-10-01

The cosmic-ray (CR) e± excess observed by AMS-02 can be explained by dark matter (DM) annihilation. However, the DM explanation requires a large annihilation cross section which is strongly disfavored by other observations, such as the Fermi-LAT gamma-ray observation of dwarf galaxies and the Planck observation of the cosmic microwave background (CMB). Moreover, the DM annihilation cross section required by the CR e± excess is also too large to generate the correct DM relic density with thermal production. In this work we use the Breit-Wigner mechanism with a velocity dependent DM annihilation cross section to reconcile these tensions. If DM particles accounting for the CR e± excess with v ∼ O (10-3) are very close to a resonance in the physical pole case, their annihilation cross section in the Galaxy reaches a maximal value. On the other hand, the annihilation cross section would be suppressed for DM particles with smaller relative velocities in dwarf galaxies and at recombination, which may affect the gamma-ray and CMB observations, respectively. We find a proper parameter region that can simultaneously explain the AMS-02 results and the thermal relic density, while satisfying the Fermi-LAT and Planck constraints.

Optical coherence tomography angiography discerns preclinical diabetic retinopathy in eyes of patients with type 2 diabetes without clinical diabetic retinopathy.

PubMed

Cao, Dan; Yang, Dawei; Huang, Zhongning; Zeng, Yunkao; Wang, Jun; Hu, Yunyan; Zhang, Liang

2018-05-01

To investigate changes in retinal vascular plexuses and choriocapillaris in patients with type 2 diabetes mellitus (DM2) without diabetic retinopathy (DR) and healthy controls using optical coherence tomography angiography (OCTA). A total of 71 DM2 and 67 healthy control subjects were included. All subjects underwent OCTA examination (RTVue-XR Avanti; Optovue, Fremont, CA, USA). Average vessel density in superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris, parafoveal vessel density in SCP and DCP, FAZ area (mm 2 ) in SCP, microaneurysms and capillary nonperfusion were taken into analysis. Parafoveal vessel density in both SCP and DCP decreased in the eyes without clinical DR compared to normal controls (p < 0.001). Diabetic patients with no signs of DR also had a significant reduction in average vessel density of SCP, DCP and choriocapillaris (p < 0.001, p < 0.001 and p = 0.006, respectively). No significant difference was found in FAZ area of SCP between DM2 eyes and healthy controls (p = 0.253). The average vessel density of SCP and DCP is not correlated with HbA1c or serum creatinine in DM2 patients. Microaneurysms seen in OCTA but not in fundus examination were found in 8 out of the 71 (11.3%) diabetic eyes, and capillary nonperfusion was noted in 18 of 71 diabetic eyes. We demonstrated that OCTA can identify preclinical DR before the manifestation of clinically apparent retinopathy in diabetic eyes. DM2 patients without DR have SCP, DCP and choriocapillaris impairment. Our results suggested that OCTA might be a promising tool for regular screening of diabetic eyes for DR.

Scaling Laws for Dark Matter Halos in Late-type and Dwarf Spheroidal Galaxies

NASA Astrophysics Data System (ADS)

Kormendy, John; Freeman, K. C.

2016-02-01

Dark matter (DM) halos of Sc-Im and dwarf spheroidal (dSph) galaxies satisfy scaling laws: halos in lower-luminosity galaxies have smaller core radii, higher central densities, and smaller velocity dispersions. These results are based on maximum-disk rotation curve decompositions for giant galaxies and Jeans equation analysis for dwarfs. (1) We show that spiral, Im, and Sph galaxies with absolute magnitudes MV > -18 form a sequence of decreasing baryon-to-DM surface density with decreasing luminosity. We suggest that this is a sequence of decreasing baryon retention versus supernova-driven losses or decreasing baryon capture after cosmological reionization. (2) The structural differences between S+Im and Sph galaxies are small. Both are affected mostly by the physics that controls baryon depletion. (3) There is a linear correlation between the maximum rotation velocities of baryonic disks and the outer circular velocities Vcirc of test particles in their DM halos. Baryons become unimportant at Vcirc = 42 ± 4 km s-1. Smaller galaxies are dim or dark. (4) We find that, absent baryon “depletion” and with all baryons converted into stars, dSph galaxies would be brighter by ˜4.6 mag and dIm galaxies would be brighter by ˜3.5 mag. Both have DM halos that are massive enough to help to solve the “too big to fail” problem with DM galaxy formation. (5) We suggest that there exist many galaxies that are too dark to be discovered by current techniques, as required by cold DM theory. (6) Central surface densities of DM halos are constant from MB ˜ -5 to -22. This implies a Faber-Jackson law with halo mass M ∝ (halo dispersion)4.

Dark matter self-interactions and small scale structure

NASA Astrophysics Data System (ADS)

Tulin, Sean; Yu, Hai-Bo

2018-02-01

We review theories of dark matter (DM) beyond the collisionless paradigm, known as self-interacting dark matter (SIDM), and their observable implications for astrophysical structure in the Universe. Self-interactions are motivated, in part, due to the potential to explain long-standing (and more recent) small scale structure observations that are in tension with collisionless cold DM (CDM) predictions. Simple particle physics models for SIDM can provide a universal explanation for these observations across a wide range of mass scales spanning dwarf galaxies, low and high surface brightness spiral galaxies, and clusters of galaxies. At the same time, SIDM leaves intact the success of ΛCDM cosmology on large scales. This report covers the following topics: (1) small scale structure issues, including the core-cusp problem, the diversity problem for rotation curves, the missing satellites problem, and the too-big-to-fail problem, as well as recent progress in hydrodynamical simulations of galaxy formation; (2) N-body simulations for SIDM, including implications for density profiles, halo shapes, substructure, and the interplay between baryons and self-interactions; (3) semi-analytic Jeans-based methods that provide a complementary approach for connecting particle models with observations; (4) merging systems, such as cluster mergers (e.g., the Bullet Cluster) and minor infalls, along with recent simulation results for mergers; (5) particle physics models, including light mediator models and composite DM models; and (6) complementary probes for SIDM, including indirect and direct detection experiments, particle collider searches, and cosmological observations. We provide a summary and critical look for all current constraints on DM self-interactions and an outline for future directions.

Effect of Vitamin E and omega 3 fatty acids in type 2 diabetes mellitus patients.

PubMed

Dass, Ashwitha Shruti; Narayana, Sarala; Venkatarathnamma, P N

2018-01-01

Diabetes mellitus (DM) and its complications have been implicated in hyperglycemia-induced oxidative stress. Antioxidants can improve glycemic control, lipid profile, and cognitive functions. We assessed the effect of Vitamin E and omega 3 fatty acids (OFA) on the above parameters. One hundred patients with type 2 DM receiving metformin 500 mg and glimepiride 1 mg were randomized to receive add-on therapy of Vitamin E 400 mg or OFA once daily for 12 weeks and the third group served as control. Fasting blood sugar (FBS), postprandial blood sugar (PPBS), glycated hemoglobin (HbA1c), body mass index (BMI), waist-hip ratio (WHR), lipid profile, and mini-mental state examination were done at baseline and 12 weeks. Eighty-seven patients completed the study. A significant reduction in FBS, PPBS, and HbA1c was observed in all the three groups at 12 weeks. There was significant reduction in total cholesterol and triglycerides (TG) in patients receiving either of the antioxidants and also significant reduction in low-density lipoprotein in patients receiving OFA at 12 weeks compared to baseline. BMI and WHR were significantly increased in control group. Intergroup analysis showed that in patients receiving Vitamin E and OFA, the reduction of FBS, PPBS, and HbA1c were similar. The patients receiving OFA had significant reduction in TG compared to control. There was no significant effect on cognitive function. Vitamin E and OFA had beneficial effects on lipid profile and anthropometric measurements; however, the glycemic control was similar to the patients in control group.

Effect of Vitamin E and omega 3 fatty acids in type 2 diabetes mellitus patients

PubMed Central

Dass, Ashwitha Shruti; Narayana, Sarala; Venkatarathnamma, P. N.

2018-01-01

Diabetes mellitus (DM) and its complications have been implicated in hyperglycemia-induced oxidative stress. Antioxidants can improve glycemic control, lipid profile, and cognitive functions. We assessed the effect of Vitamin E and omega 3 fatty acids (OFA) on the above parameters. One hundred patients with type 2 DM receiving metformin 500 mg and glimepiride 1 mg were randomized to receive add-on therapy of Vitamin E 400 mg or OFA once daily for 12 weeks and the third group served as control. Fasting blood sugar (FBS), postprandial blood sugar (PPBS), glycated hemoglobin (HbA1c), body mass index (BMI), waist-hip ratio (WHR), lipid profile, and mini-mental state examination were done at baseline and 12 weeks. Eighty-seven patients completed the study. A significant reduction in FBS, PPBS, and HbA1c was observed in all the three groups at 12 weeks. There was significant reduction in total cholesterol and triglycerides (TG) in patients receiving either of the antioxidants and also significant reduction in low-density lipoprotein in patients receiving OFA at 12 weeks compared to baseline. BMI and WHR were significantly increased in control group. Intergroup analysis showed that in patients receiving Vitamin E and OFA, the reduction of FBS, PPBS, and HbA1c were similar. The patients receiving OFA had significant reduction in TG compared to control. There was no significant effect on cognitive function. Vitamin E and OFA had beneficial effects on lipid profile and anthropometric measurements; however, the glycemic control was similar to the patients in control group. PMID:29441322

Nuclear magnetic resonance lipoprotein abnormalities in newly-diagnosed type 2 diabetes and their association with preclinical carotid atherosclerosis.

PubMed

Amor, Antonio J; Catalan, Marta; Pérez, Antonio; Herreras, Zoe; Pinyol, Montserrat; Sala-Vila, Aleix; Cofán, Montserrat; Gilabert, Rosa; Ros, Emilio; Ortega, Emilio

2016-04-01

Atherogenic dyslipidemia is common in type 2 diabetes (T2DM) and predicts cardiovascular disease, but information on the association of its components with atherosclerosis is scarce. We aimed to assess differences in the lipoprotein profile in newly-diagnosed T2DM and matched control individuals and their associations with preclinical carotid atherosclerosis. In a case-control study, we evaluated lipoprotein profiles by nuclear magnetic resonance (NMR) spectroscopy and determined carotid intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) by B-mode ultrasonography. We assessed 96 T2DM patients (median age 63 years, 44% women, 19% smokers, 54% hypertension, 38% dyslipidemia) and 90 non-diabetic controls matched for age, sex, and cardiovascular risk factors. In T2DM VLDL-particles (mainly large and enriched in cholesterol and triglycerides) were increased, and large HDL-particles (enriched in triglycerides and depleted in cholesterol) were reduced (p < 0.05; all comparisons). Regarding associations with preclinical atherosclerosis, VLDL triglyceride content (odds ratio [OR], 8.975; 95% confidence interval [CI], 2.330-34.576), total number of VLDL particles (OR, 2.713; CI, 1.601-4.598) and VLDL size (OR, 2.044; CI, 1.320-3.166), and the ratio cholesterol/triglycerides in HDL (OR, 0.638; CI, 0.477-0.852) were associated with plaque burden (≥3 plaques) independently of confounders, including conventional lipid levels. NMR-assessed advanced lipoprotein profile identifies lipid abnormalities associated with newly-diagnosed T2DM and preclinical atherosclerosis that are not captured by the traditional lipid profile. At this early stage of diabetes, NMR lipoproteins could be useful to identify candidates for a more comprehensive cardiovascular risk prevention strategy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluation of metabolite profiles as biomarkers for the pharmacological effects of thiazolidinediones in Type 2 diabetes mellitus patients and healthy volunteers.

PubMed

van Doorn, Martijn; Vogels, Jack; Tas, Albert; van Hoogdalem, Ewoud Jan; Burggraaf, Jacobus; Cohen, Adam; van der Greef, Jan

2007-05-01

* Many studies have investigated the effects of thiazolidinediones on isolated biochemical markers (biomarkers) or sets of markers in Type 2 diabetes mellitus (T2DM) patients and healthy volunteers. * However, a limited number of parameters is not capable of capturing the broad response to pharmacological intervention with these types of (pleiotropic) drugs, which are known to activate the nuclear transcription factor peroxisome proliferator activated receptor gamma (PPARgamma). * Our study tested the new hypothesis (primary objective) that nuclear magnetic resonance (NMR)-based metabolomics, capable of providing a readout of global metabolite concentrations in biofluids, could provide a better (more holistic) picture of the the multiparametric response to pharmacological intervention with a PPARgamma agonist and thus yield a broad array of biomarkers ('fingerprint') that could be used to support and expedite clinical development of novel thiazolidinediones. * NMR-based metabolomics coupled with sophisticated bioinformatics is indeed capable of identifying rapid changes in global metabolite profiles in urine and plasma (treatment 'fingerprints'), which may be linked to the well-documented early changes in hepatic insulin senstitivity following thiazolidinedione intervention in T2DM patients. * Consequently, this approach (upon proper validation) comprises an important new addition to the early clinical development 'proof of concept' toolbox for thiazolidinediones, and may also be applicable to other classes of drugs. To explore the usefulness of metabolomics as a method to obtain a broad array of biomarkers for the pharmacological effects of rosiglitazone (RSG) in plasma and urine samples from patients with type 2 diabetes mellitus (T2DM) and healthy volunteers (HVs). Additionally, we explored the differences in metabolite concentrations between T2DM patients and HVs to identify a putative metabolic disease fingerprint for T2DM. (1)H nuclear magnetic resonance (NMR) spectroscopy was used to profile blood plasma and urine samples of 16 T2DM patients and 16 HVs receiving RSG 4 mg or placebo twice daily for 6 weeks. Multivariate analyses were employed to identify treatment- and disease-related effects on global endogenous metabolite profiles. RSG treatment led to a rapid relative reduction in urinary hippurate and aromatic amino acids as well as an increase in plasma branched chain amino acids and alanine, glutamine and glutamate in the T2DM group. No RSG treatment effects were noted in the HV group. Exploratory baseline analyses showed that urine and plasma metabolites discriminated between genders and disease state. T2DM patients showed a relative increase in urinary concentrations of several amino acids, citrate, phospho(enol)pyruvate and hippurate. Putative T2DM-related changes in plasma were largely attributable to increased plasma lipids. The results of this study indicate that NMR-based metabolomics of urine and blood plasma samples can yield a broad array of early responding biomarkers for the effects of RSG in T2DM patients, as well as nonglucose biomarkers that may reflect the T2DM state.

IGF-1 and IGF-binding proteins and bone mass, geometry, and strength: relation to metabolic control in adolescent girls with type 1 diabetes.

PubMed

Moyer-Mileur, Laurie J; Slater, Hillarie; Jordan, Kristine C; Murray, Mary A

2008-12-01

Children and adolescents with poorly controlled type 1 diabetes mellitus (T1DM) are at risk for decreased bone mass. Growth hormone (GH) and its mediator, IGF-1, promote skeletal growth. Recent observations have suggested that children and adolescents with T1DM are at risk for decreased bone mineral acquisition. We examined the relationships between metabolic control, IGF-1 and its binding proteins (IGFBP-1, -3, -5), and bone mass in T1DM in adolescent girls 12-15 yr of age with T1DM (n = 11) and matched controls (n = 10). Subjects were admitted overnight and given a standardized diet. Periodic blood samples were obtained, and bone measurements were performed. Serum GH, IGFBP-1 and -5, glycosylated hemoglobin (HbA(1c)), glucose, and urine magnesium levels were higher and IGF-1 values were lower in T1DM compared with controls (p < 0.05). Whole body BMC/bone area (BA), femoral neck areal BMD (aBMD) and bone mineral apparent density (BMAD), and tibia cortical BMC were lower in T1DM (p < 0.05). Poor diabetes control predicted lower IGF-1 (r(2) = 0.21) and greater IGFBP-1 (r(2) = 0.39), IGFBP-5 (r(2) = 0.38), and bone-specific alkaline phosphatase (BALP; r(2) = 0.41, p < 0.05). Higher urine magnesium excretion predicted an overall shorter, lighter skeleton, and lower tibia cortical bone size, mineral, and density (r(2) = 0.44-0.75, p < 0.05). In the T1DM cohort, earlier age at diagnosis was predictive of lower IGF-1, higher urine magnesium excretion, and lighter, thinner cortical bone (r(2) >or=0.45, p < 0.01). We conclude that poor metabolic control alters the GH/IGF-1 axis, whereas greater urine magnesium excretion may reflect subtle changes in renal function and/or glucosuria leading to altered bone size and density in adolescent girls with T1DM.

Defects in cortical microarchitecture among African-American women with type 2 diabetes

PubMed Central

Yu, Elaine W.; Putman, Melissa S.; Derrico, Nicolas; Abrishamanian-Garcia, Gabriela; Finkelstein, Joel S.; Bouxsein, Mary L.

2015-01-01

Introduction/Purpose Fracture risk is increased in patients with type 2 diabetes mellitus (DM2) despite normal areal bone mineral density (aBMD). DM2 is more common in African-Americans than in Caucasians. It is not known whether African-American women with DM2 have deficits in bone microstructure. Methods We measured aBMD at the spine and hip by DXA, and volumetric BMD (vBMD) and microarchitecture at the distal radius and tibia by HR-pQCT in 22 DM2 and 78 non-diabetic African-American women participating in the Study of Women Across the Nation (SWAN). We also measured fasting glucose and HOMA-IR. Results Age, weight, and aBMD at all sites were similar in both groups. At the radius, cortical porosity was 26% greater, while cortical vBMD and tissue mineral density were lower in women with DM2 than in controls. There were no differences in radius total vBMD or trabecular vBMD between groups. Despite inferior cortical bone properties at the radius, FEA-estimated failure load was similar between groups. Tibia vBMD and microarchitecture were also similar between groups. There were no significant associations between cortical parameters and duration of DM2 or HOMA-IR. However, among women with DM2, higher fasting glucose levels were associated with lower cortical vBMD (r=−0.54, p=0.018). Conclusions DM2 and higher fasting glucose are associated with unfavorable cortical bone microarchitecture at the distal radius in African-American women. These structural deficits may contribute to the increased fracture risk among women with DM2. Further our results suggest that hyperglycemia may be involved in mechanisms of skeletal fragility associated with DM2. PMID:25398431

Whole-genome expression analyses of type 2 diabetes in human skin reveal altered immune function and burden of infection.

PubMed

Wu, Chun; Chen, Xiaopan; Shu, Jing; Lee, Chun-Ting

2017-05-23

Skin disorders are among most common complications associated with type 2 diabetes mellitus (T2DM). Although T2DM patients are known to have increased risk of infections and other T2DM-related skin disorders, their molecular mechanisms are largely unknown. This study aims to identify dysregulated genes and gene networks that are associated with T2DM in human skin. We compared the expression profiles of 56,318 transcribed genes on 74 T2DM cases and 148 gender- age-, and race-matched non-diabetes controls from the Genotype-Tissue Expression (GTEx) database. RNA-Sequencing data indicates that diabetic skin is characterized by increased expression of genes that are related to immune responses (CCL20, CXCL9, CXCL10, CXCL11, CXCL13, and CCL18), JAK/STAT signaling pathway (JAK3, STAT1, and STAT2), tumor necrosis factor superfamily (TNFSF10 and TNFSF15), and infectious disease pathways (OAS1, OAS2, OAS3, and IFIH1). Genes in cell adhesion molecules pathway (NCAM1 and L1CAM) and collagen family (PCOLCE2 and COL9A3) are downregulated, suggesting structural changes in the skin of T2DM. For the first time, to the best of our knowledge, this pioneer analytic study reports comprehensive unbiased gene expression changes and dysregulated pathways in the non-diseased skin of T2DM patients. This comprehensive understanding derived from whole-genome expression profiles could advance our knowledge in determining molecular targets for the prevention and treatment of T2DM-associated skin disorders.

Singlet-triplet fermionic dark matter and LHC phenomenology

NASA Astrophysics Data System (ADS)

Choubey, Sandhya; Khan, Sarif; Mitra, Manimala; Mondal, Subhadeep

2018-04-01

It is well known that for the pure standard model triplet fermionic WIMP-type dark matter (DM), the relic density is satisfied around 2 TeV. For such a heavy mass particle, the production cross-section at 13 TeV run of LHC will be very small. Extending the model further with a singlet fermion and a triplet scalar, DM relic density can be satisfied for even much lower masses. The lower mass DM can be copiously produced at LHC and hence the model can be tested at collider. For the present model we have studied the multi jet (≥ 2 j) + missing energy ([InlineEquation not available: see fulltext.]) signal and show that this can be detected in the near future of the LHC 13 TeV run. We also predict that the present model is testable by the earth based DM direct detection experiments like Xenon-1T and in future by Darwin.

Characterization of invisible breast cancers in digital mammography and tomosynthesis: radio-pathological correlation.

PubMed

Aguilar Angulo, P M; Romero Castellano, C; Ruiz Martín, J; Sánchez-Camacho González-Carrato, M P; Cruz Hernández, L M

To review the radio-pathologic features of symptomatic breast cancers not detected at digital mammography (DM) and digital breast tomosynthesis (DBT). Retrospective analysis of 169 lesions from symptomatic patients with breast cancer that were studied with DM, DBT, ultrasound (US) and magnetic resonance (MR). We identified occult lesions (true false negatives) in DM and DBT. Clinical data, density, US and MR findings were analyzed as well as histopathological results. We identified seven occult lesions in DM and DBT. 57% (4/7) of the lesions were identified in high-density breasts (type c and d), and the rest of them in breasts of density type b. Six carcinomas were identified at US and MR (BI-RADS 4 masses); the remaining lesion was only identified at MR. The tumor size was larger than 3cm at MRI in 57% of the lesions. All tumors were ductal infiltrating carcinomas, six of them with high stromal proportion. According to molecular classification, we found only one triple-negative breast cancer, the other lesions were luminal-type. We analyzed the tumor margins of two resected carcinomas that were not treated with neoadjuvant chemotherapy, both lesions presented margins that displaced the adjacent parenchyma without infiltrating it. Occult breast carcinomas in DM and DBT accounted for 4% of lesions detected in patients with symptoms. They were mostly masses, all of them presented the diagnosis of infiltrating ductal carcinoma (with predominance of the luminal immunophenotype) and were detected in breasts of density type b, c and d. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Gene expression profiling demonstrates WNT/β-catenin pathway genes alteration in Mexican patients with colorectal cancer and diabetes mellitus.

PubMed

Ivonne Wence-Chavez, Laura; Palomares-Chacon, Ulises; Pablo Flores-Gutierrez, Juan; Felipe Jave-Suarez, Luis; Del Carmen Aguilar-Lemarroy, Adriana; Barros-Nunez, Patricio; Esperanza Flores-Martinez, Silvia; Sanchez-Corona, Jose; Alejandra Rosales-Reynoso, Monica

2017-01-01

Several studies have shown a strong association between diabetes mellitus (DM) and increased risk of colorectal cancer (CRC). The fundamental mechanisms that support this association are not entirely understood; however, it is believed that hyperinsulinemia and hyperglycemia may be involved. Some proposed mechanisms include upregulation of mitogenic signaling pathways like MAPK, PI3K, mTOR, and WNT, which are involved in cell proliferation, growth, and cancer cell survival. The purpose of this study was to evaluate the gene expression profile and identify differently expressed genes involved in mitogenic pathways in CRC patients with and without DM. In this study, microarray analysis of gene expression followed by quantitative PCR (qPCR) was performed in cancer tissue from CRC patients with and without DM to identify the gene expression profiles and validate the differently expressed genes. Among the study groups, some differently expressed genes were identified. However, when bioinformatics clustering tools were used, a significant modulation of genes involved in the WNT pathway was evident. Therefore, we focused on genes participating in this pathway, such as WNT3A, LRP6, TCF7L2, and FRA-1. Validation of the expression levels of those genes by qPCR showed that CRC patients without type 2 diabetes mellitus (T2DM) expressed significantly more WNT3Ay LRP6, but less TCF7L2 and FRA-1 compared to controls, while in CRC patients with DM the expression levels of WNT3A, LRP6, TCF7L2, and FRA-1 were significantly higher compared to controls. Our results suggest that WNT/β-catenin pathway is upregulated in patients with CRC and DM, demonstrating its importance and involvement in both pathologies.

Serum anti-Müllerian hormone concentration in women with polycystic ovary syndrome and type 1 diabetes mellitus.

PubMed

Łebkowska, Agnieszka; Adamska, Agnieszka; Karczewska-Kupczewska, Monika; Nikołajuk, Agnieszka; Otziomek, Elżbieta; Milewski, Robert; Górska, Maria; Wołczyński, Sławomir; Kowalska, Irina

2016-05-01

A single prior study conducted in Chilean women has shown that women with type 1 diabetes mellitus (T1DM) and polycystic ovary syndrome (PCOS) have a normal serum anti-Müllerian hormone (AMH) concentrations despite polycystic ovarian morphology. As it is not clear why women with PCOS+T1DM would not have an elevated concentrations of AMH, we hypothesize that women with T1DM and PCOS have a similar hormonal profile and serum AMH levels as is observed in classic PCOS. We studied 89 women: 37 with T1DM (16 with PCOS+T1DM, 21 with T1DM/no-PCOS), 36 with PCOS (PCOS) and 16 healthy women (control group) matched for age and body mass index (BMI). A clinical examination, determination of serum AMH and sex hormones, and an ultrasonographic evaluation of the ovaries were performed for all study participants. Serum AMH concentrations were significantly higher in women with PCOS+T1DM than in those with T1DM/no-PCOS (p<0.001) and was not different between both PCOS groups (PCOS vs PCOS+T1DM). Ovarian volume and ovarian follicle count did not differ between women with PCOS+T1DM and PCOS. The number of ovarian follicles was higher in patients with PCOS+T1DM and PCOS versus the control (p=0.007, p<0.001) and versus cases of T1DM/no-PCOS (p<0.001, p<0.001, respectively). Cross-sectionally, AMH concentrations correlated positively with luteinizing hormone (LH) (r=0.4; p<0.001), testosterone (r=0.2, p=0.02), ovarian volume (r=0.4, p<0.001) and follicle count (r=0.7, p<0.001). In both groups, PCOS+T1DM and PCOS, AMH was related to LH (r=0.5; p=0.036; r=0.3; p=0.031) and to ovarian follicle number (r=0.7; p<0.001; r=0.4; p=0.006). In multivariate logistic regression analysis, serum AMH was the only predictor of PCOS in T1DM women (OR=1.73; 95% CI 1.07-2.79, p=0.023). Women with T1DM and PCOS have a similar hormonal profile and serum AMH concentrations as observed in classic PCOS. Copyright © 2016 Elsevier Inc. All rights reserved.

Implementation of digital optical capillaroscopy for quantifying and estimating the microvascular abnormalities in type 2 diabetes mellitus

NASA Astrophysics Data System (ADS)

Gurfinkel, Yu. I.; Suchkova, O. V.; Sasonko, M. L.; Priezzhev, A. V.

2016-04-01

This study is aimed to define the extent of digital capillaroscopy possibilities for the quantification and estimation of microvascular abnormalities in type 2 diabetes mellitus (T2DM). A total of 196 adult persons were enrolled in the study including the group of compensated T2DM (n = 52), decompensated diabetics (n = 68), and healthy volunteers (n = 76) with normal blood glucose and without signs of cardiovascular pathology. All participants of the study were examined with the digital optical capillaroscope ("AET", Russia). This instrument is equipped with an image-processing program allowing for quantifying the diameters of the arterial and venous segments of the capillaries and their ratio (coefficient of remodeling), perivascular zone size, capillary blood velocity, and the degree of arterial loops narrowing and the density of the capillary network. Also we estimated the relative amount of coil-shaped capillaries. The study revealed significant difference in the capillary density and the remodeling coefficient in comparison of T2DM patients with non-diabetic individuals. Significant changes are found in the decompensated T2DM group compared to the compensated group of diabetic patients. Furthermore, the number of coil-shaped capillaries differed greatly in T2DM patients as compared to the healthy subjects. The study did not reveal any statistically significant differences in the capillary density between the patients with compensated and decompensated T2DM. The digital optical capillaroscope equipped with the advanced image-processing algorithm opens up new possibilities for obtaining clinically important information on microvascular abnormalities in patients suffering from diabetes mellitus.

The relationship of body fat to metabolic disease: influence of sex and ethnicity.

PubMed

Sumner, Anne E

2008-12-01

Clinical investigations designed to determine risk profiles for the development of cardiovascular disease (CVD) and type 2 diabetes mellitus (DM) are usually performed in homogenous populations and often focus on body mass index (BMI), waist circumference (WC), and fasting triglyceride (TG) levels. However, there are major ethnic differences in the relationship of these risk factors to outcomes. For example, the BMI risk threshold may be higher in blacks than in whites and higher in women than in men. Furthermore, a WC that predicts an obese BMI in white women only predicts a BMI in the overweight category in black women. In addition, overweight black men have a greater risk of developing type 2 DM than do overweight black women. Although TG levels are excellent predictors of insulin resistance in whites, they are not effective markers of insulin resistance in blacks. Among the criteria sets currently available to predict the development of CVD and type 2 DM, the most well known is the metabolic syndrome. The metabolic syndrome has 5 criteria: central obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) levels, fasting hyperglycemia, and hypertension. To make the diagnosis of the metabolic syndrome, 3 of the 5 factors must be present. For central obesity and low HDL, the metabolic syndrome guidelines are sex specific. Diagnostic guidelines should also take ethnic differences into account, particularly in the diagnosis of central obesity and hypertriglyceridemia.

Serum microRNA profiling and bioinformatics analysis of patients with type 2 diabetes mellitus in a Chinese population.

PubMed

Yang, Ze-Min; Chen, Long-Hui; Hong, Min; Chen, Ying-Yu; Yang, Xiao-Rong; Tang, Si-Meng; Yuan, Qian-Fa; Chen, Wei-Wen

2017-04-01

Type 2 diabetes mellitus (T2DM) is characterized by islet β-cell dysfunction and insulin resistance, which leads to an inability to maintain blood glucose homeostasis. Circulating microRNAs (miRNAs) have been suggested as novel biomarkers for T2DM prediction or disease progression. However, miRNAs and their roles in the pathogenesis of T2DM remain to be fully elucidated. In the present study, the serum miRNA expression profiles of T2DM patients in Chinese cohorts were examined. Total RNA was extracted from serum samples of 10 patients with T2DM and five healthy controls, and these was used in reverse-transcription‑quantitative polymerase chain reaction analysis with the Exiqon PCR system of 384 serum/plasma miRNAs. A total of seven miRNAs were differentially expressed between the two groups (fold change >3 or <0.33; P<0.05). The serum expression levels of miR‑455‑5p, miR‑454‑3p, miR‑144‑3p and miR‑96‑5p were higher in patients with T2DM, compared with those of healthy subjects, however, the levels of miR‑409‑3p, miR‑665 and miR‑766‑3p were lower. Hierarchical cluster analysis indicated that it was possible to separate patients with T2DM and control individuals into their own similar categories by these differential miRNAs. Target prediction showed that 97 T2DM candidate genes were potentially modulated by these seven miRNAs. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that 24 pathways were enriched for these genes, and the majority of these pathways were enriched for the targets of induced and repressed miRNAs, among which insulin, adipocytokine and T2DM pathways, and several cancer‑associated pathways have been previously associated with T2DM. In conclusion, the present study demonstrated that serum miRNAs may be novel biomarkers for T2DM and provided novel insights into the pathogenesis of T2DM.

Reduced energy density of close-up diets decrease ruminal pH and increase concentration of volatile fatty acids postpartum in Holstein cows.

PubMed

Huang, Wenming; Tian, Yujia; Li, Shengli; Wu, Zhaohai; Cao, Zhijun

2017-11-01

The objective of this study was to determine the effect of reduced energy density of close-up diets on ruminal fermentation parameters in transition cows. Fourteen Holstein dry cows were blocked and assigned randomly to three groups fed a high energy density diet (HD, 1.62 Mcal of net energy for lactation (NE L )/kg dry matter (DM)), or a middle energy density diet (MD, 1.47 Mcal NE L /kg DM), or a low energy density diet (LD, 1.30 Mcal NE L /kg DM) prepartum, and were fed the same diet postpartum. The reduced energy density diets decreased the average dry matter intake (DMI) prepartum and tended to increase the DMI postpartum. The ruminal pH of the LD group was significantly higher prepartum and lower during the first week of lactation compared with the other two groups. The reduced energy density diet depressed the average ruminal concentration of propionate and butyrate prepartum, and increased the average concentration of total volatile fatty acids (VFA) postpartum. The LD group had higher populations of Butyrivibrio fibrisolvens and Ruminococcus flavefaciens relative to HD and MD groups on 7 days in milk. In conclusion, the cows fed reduced energy density diet prepartum had higher VFA concentration, but were more susceptible to subacute ruminal acidosis postpartum. © 2017 Japanese Society of Animal Science.

Doppler measurements of the ionosphere on the occasion of the Apollo-Soyuz test project. Part 1: Computer simulation of ionospheric-induced Doppler shifts

NASA Technical Reports Server (NTRS)

Grossi, M. D.; Gay, R. H.

1975-01-01

A computer simulation of the ionospheric experiment of the Apollo-Soyuz Test Project (ASTP) was performed. ASTP is the first example of USA/USSR cooperation in space and is scheduled for summer 1975. The experiment consists of performing dual-frequency Doppler measurements (at 162 and 324 MHz) between the Apollo Command Service Module (CSM) and the ASTP Docking Module (DM), both orbiting at 221-km height and at a relative distance of 300 km. The computer simulation showed that, with the Doppler measurement resolution of approximately 3 mHz provided by the instrumentation (in 10-sec integration time), ionospheric-induced Doppler shifts will be measurable accurately at all times, with some rare exceptions occurring when the radio path crosses regions of minimum ionospheric density. The computer simulation evaluated the ability of the experiment to measure changes of columnar electron content between CSM and DM (from which horizontal gradients of electron density at 221-km height can be obtained) and to measure variations in DM-to-ground columnar content (from which an averaged columnar content and the electron density at the DM can be deduced, under some simplifying assumptions).

Effects of dextromethorphan/quinidine on auditory event-related potentials in multiple sclerosis patients with pseudobulbar affect.

PubMed

Haiman, Guy; Pratt, Hillel; Miller, Ariel

2009-10-01

The purpose of this study was to characterize the brain activity and associated cortical structures involved in pseudobulbar affect (PBA), a condition characterized by uncontrollable episodes of laughing and/or crying in patients with multiple sclerosis before and after treatment with dextromethorphan/quinidine (DM/Q). Behavioral responses and event-related potentials (ERPs) in response to subjectively significant and neutral verbal stimuli were recorded from 2 groups: 6 multiple sclerosis patients with PBA before (PBA-preTx) and after (PBA-DM/Q) treatment with DM/Q and 6 healthy control (HC) subjects. Statistical nonparametric mapping comparisons of ERP source current density distributions between groups were conducted for subjectively significant and neutral stimuli separately before and after treatment with DM/Q. Treatment with DM/Q had a normalizing effect on the behavioral responses of PBA patients. Event-related potential waveform comparisons of PBA-preTx and PBA-DM/Q with HC, for both neutral and subjectively significant stimuli, revealed effects on early ERP components. Comparisons between PBA-preTx and HC, in response to subjectively significant stimuli, revealed both early and late effects. Source analysis comparisons between PBA-preTx and PBA-DM/Q indicated distinct activations in areas involved in emotional processing and high-level and associative visual processing in response to neutral stimuli and in areas involved in emotional, somatosensory, primary, and premotor processing in response to subjectively significant stimuli. In most cases, stimuli evoked higher current density in PBA-DM/Q compared with the other groups. In conclusion, differences in brain activity were observed before and after medication. Also, DM/Q administration resulted in normalization of behavioral and electrophysiological measures.

Fast Radio Bursts’ Recipes for the Distributions of Dispersion Measures, Flux Densities, and Fluences

NASA Astrophysics Data System (ADS)

Niino, Yuu

2018-05-01

We investigate how the statistical properties of dispersion measure (DM) and apparent flux density/fluence of (nonrepeating) fast radio bursts (FRBs) are determined by unknown cosmic rate density history [ρ FRB(z)] and luminosity function (LF) of the transient events. We predict the distributions of DMs, flux densities, and fluences of FRBs taking account of the variation of the receiver efficiency within its beam, using analytical models of ρ FRB(z) and LF. Comparing the predictions with the observations, we show that the cumulative distribution of apparent fluences suggests that FRBs originate at cosmological distances and ρ FRB increases with redshift resembling the cosmic star formation history (CSFH). We also show that an LF model with a bright-end cutoff at log10 L ν (erg s‑1 Hz‑1) ∼ 34 are favored to reproduce the observed DM distribution if ρ FRB(z) ∝ CSFH, although the statistical significance of the constraints obtained with the current size of the observed sample is not high. Finally, we find that the correlation between DM and flux density of FRBs is potentially a powerful tool to distinguish whether FRBs are at cosmological distances or in the local universe more robustly with future observations.

Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study.

PubMed

Paiva, Ana N; Lima, Josivan G de; Medeiros, Anna C Q de; Figueiredo, Heverton A O; Andrade, Raiana L de; Ururahy, Marcela A G; Rezende, Adriana A; Brandão-Neto, José; Almeida, Maria das G

2015-10-01

Chromium is an essential mineral that contributes to normal glucose function and lipid metabolism. This study evaluated the effect of chromium picolinate (CrPic) supplementation in patients with type 2 diabetes mellitus (T2DM). A four month controlled, single blind, randomized trial was performed with 71 patients with poorly controlled (hemoglobin A1c [HbA1c]>7%) T2DM divided into 2 groups: Control (n=39, using placebo), and supplemented (n=32, using 600μg/day CrPic). All patients received nutritional guidance according to the American Diabetes Association (ADA), and kept using prescribed medications. Fasting and postprandial glucose, HbA1c, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and serum ferritin were evaluated. CrPic supplementation significantly reduced the fasting glucose concentration (-31.0mg/dL supplemented group; -14.0mg/dL control group; p<0.05, post- vs. pre-treatment, in each group) and postprandial glucose concentration (-37.0mg/dL in the supplemented group; -11.5 mg/dL in the control group; p<0.05). HbA1c values were also significantly reduced in both groups (p<0.001, comparing post- vs. pre-treatment groups). Post-treatment HbA1c values in supplemented patients were significantly lower than those of control patients. HbA1c lowering in the supplemented group (-1.90), and in the control group (-1.00), was also significant, comparing pre- and post-treatment values, for each group (p<0.001 and p<0.05, respectively). CrPic increased serum chromium concentrations (p<0.001), when comparing the supplemented group before and after supplementation. No significant difference in lipid profile was observed in the supplemented group; however, total cholesterol, HDL-c and LDL-c were significantly lowered, comparing pre- and post-treatment period, in the control group (p<0.05). CrPic supplementation had a beneficial effect on glycemic control in patients with poorly controlled T2DM, without affecting the lipid profile. Additional studies are necessary to investigate the effect of long-term CrPic supplementation. Copyright © 2015 Elsevier GmbH. All rights reserved.

Hypertriglyceridemia in Diabetes Mellitus: Implications for Pediatric Care.

PubMed

Hartz, Jacob C; de Ferranti, Sarah; Gidding, Samuel

2018-06-01

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). It is estimated that the risk of CVD in diabetes mellitus (DM) is 2 to 10 times higher than in the general population. Much of this increased risk is thought to be related to the development of an atherogenic lipid profile, in which hypertriglyceridemia is an essential component. Recent studies suggest that dyslipidemia may be present in children and adolescents with DM, particularly in T2DM and in association with poor control in T1DM. However, the role of hypertriglyceridemia in the development of future CVD in youth with DM is unclear, as data are scarce. In this review, we will evaluate the pathophysiology of atherogenic hypertriglyceridemia in DM, the evidence regarding an independent role of triglycerides in the development of CVD, and the treatment of hypertriglyceridemia in patients with DM, highlighting the potential relevance to children and the need for more data in children and adolescents to guide clinical practice.

The child as proband for future parental cardiometabolic disease: the 26-year prospective Princeton Lipid Research Clinics Follow-up Study.

PubMed

Morrison, John A; Glueck, Charles J; Wang, Ping

2012-04-01

To evaluate children's cardiovascular disease (CVD) risk factors as predictors of parents' subsequent CVD, type 2 diabetes mellitus (T2DM), and high blood pressure (HBP). We conducted a 26-year prospective follow-up of 852 5- to 19-year-old black and white schoolchildren (mean age, 12 years; Lipid Research Clinics, 1973-8), and parents (mean age, 40 years) from 519 families in Princeton Schools, Cincinnati, Ohio. Schoolchildren were reassessed in the Princeton Follow-up study 1999-2003 at mean age 39 years; CVD, T2DM, and HBP history of their 1038 parents were reassessed by mean age 66 years. We assessed relationships of childhood risk factors with parental CVD, T2DM, and HBP. Child-probands identified with triglyceride (TG) levels, blood pressure, low-density lipoprotein cholesterol levels, body mass index (BMI), and glucose level greater than and high-density lipoprotein cholesterol levels less than established cutoff points. Pediatric HBP (P=.006) and low high-density lipoprotein cholesterol (P=.018) were predictive of parental CVD at age ≤50 years. Pediatric HBP (P=.02) and high TG (P=.03) were predictive of parental CVD at age ≤60 years. Pediatric high TG (P=.009) and high low-density lipoprotein cholesterol (P=.04) were predictive of parental CVD by age 66 years. Pediatric high BMI (P=.0006) were predictive of parental T2DM. Pediatric high BMI (P=.003) and black race (P=.004) were predictive of parental HBP. Pediatric risk factors identify families with parents at increased risk for CVD, T2DM, and HBP, emphasizing the usefulness of the child as proband. Copyright © 2012 Mosby, Inc. All rights reserved.

Association between Low-density Lipoprotein Receptor-related Protein 5 Polymorphisms and Type 2 Diabetes Mellitus in Han Chinese: a Case-control Study.

PubMed

You, Hai Fei; Zhao, Jing Zhi; Zhai, Yu Jia; Yin, Lei; Pang, Chao; Luo, Xin Ping; Zhang, Ming; Wang, Jin Jin; Li, Lin Lin; Wang, Yan; Wang, Qian; Wang, Bing Yuan; Ren, Yong Cheng; Hu, Dong Sheng

2015-07-01

To investigate the association between low-density lipoprotein receptor-related protein 5 (LRP5) variants (rs12363572 and rs4930588) and type 2 diabetes mellitus (T2DM) in Han Chinese. A total of 1842 T2DM cases (507 newly diagnosed cases and 1335 previously diagnosed cases) and 7777 controls were included in this case-control study. PCR-RFLP was conducted to detect the genotype of the two single nucleotide polymorphisms (SNPs). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to describe the strength of the association by logistic regression. In the study subjects, neither rs12363572 nor rs4930588 was significantly associated with T2DM, even after adjusting for relevant covariates. When stratified by body mass index (BMI), the two SNPs were also not associated with T2DM. Among the 3 common haplotypes, only haplotype TT was associated with reduced risk of T2DM (OR 0.820, 95% CI 0.732-0.919). In addition, rs12363572 was associated with BMI (P<0.001) and rs4930588 was associated with triglyceride levels (P=0.043) in 507 newly diagnosed T2DM cases but not in healthy controls. No LRP5 variant was found to be associated with T2DM in Han Chinese, but haplotype TT was found to be associated with T2DM. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Magnitude Differences in Bioactive Compounds, Chemical Functional Groups, Fatty Acid Profiles, Nutrient Degradation and Digestion, Molecular Structure, and Metabolic Characteristics of Protein in Newly Developed Yellow-Seeded and Black-Seeded Canola Lines.

PubMed

Theodoridou, Katerina; Zhang, Xuewei; Vail, Sally; Yu, Peiqiang

2015-06-10

Recently, new lines of yellow-seeded (CS-Y) and black-seeded canola (CS-B) have been developed with chemical and structural alteration through modern breeding technology. However, no systematic study was found on the bioactive compounds, chemical functional groups, fatty acid profiles, inherent structure, nutrient degradation and absorption, or metabolic characteristics between the newly developed yellow- and black-seeded canola lines. This study aimed to systematically characterize chemical, structural, and nutritional features in these canola lines. The parameters accessed include bioactive compounds and antinutrition factors, chemical functional groups, detailed chemical and nutrient profiles, energy value, nutrient fractions, protein structure, degradation kinetics, intestinal digestion, true intestinal protein supply, and feed milk value. The results showed that the CS-Y line was lower (P ≤ 0.05) in neutral detergent fiber (122 vs 154 g/kg DM), acid detergent fiber (61 vs 99 g/kg DM), lignin (58 vs 77 g/kg DM), nonprotein nitrogen (56 vs 68 g/kg DM), and acid detergent insoluble protein (11 vs 35 g/kg DM) than the CS-B line. There was no difference in fatty acid profiles except C20:1 eicosenoic acid content (omega-9) which was in lower in the CS-Y line (P < 0.05) compared to the CS-B line. The glucosinolate compounds differed (P < 0.05) in terms of 4-pentenyl, phenylethyl, 3-CH3-indolyl, and 3-butenyl glucosinolates (2.9 vs 1.0 μmol/g) between the CS-Y and CS-B lines. For bioactive compounds, total polyphenols tended to be different (6.3 vs 7.2 g/kg DM), but there were no differences in erucic acid and condensed tannins with averages of 0.3 and 3.1 g/kg DM, respectively. When protein was portioned into five subfractions, significant differences were found in PA, PB1 (65 vs 79 g/kg CP), PB2, and PC fractions (10 vs 33 g/kg CP), indicating protein degradation and supply to small intestine differed between two new lines. In terms of protein structure spectral profile, there were no significant differences in functional groups of amides I and II, α helix, and β-sheet structure as well as their ratio between the two new lines, indicating no difference in protein structure makeup and conformation between the two lines. In terms of energy values, there were significant differences in total digestible nutrient (TDN; 149 vs 133 g/kg DM), metabolizable energy (ME; 58 vs 52 MJ/kg DM), and net energy for lactation (NEL; 42 vs 37 MJ/kg DM) between CS-Y and CS-B lines. For in situ rumen degradation kinetics, the two lines differed in soluble fraction (S; 284 vs 341 g/kg CP), potential degradation fraction (D; 672 vs 590 g/kg CP), and effective degraded organic matter (EDOM; 710 vs 684 g/kg OM), but no difference in degradation rate. CS-Y had higher digestibility of rumen bypass protein in the intestine than CS-B (566 vs 446 g/kg of RUP, P < 0.05). Modeling nutrient supply results showed that microbial protein synthesis (MCP; 148 vs 171 g/kg DM) and rumen protein degraded balance (DPB; 108 vs 127 g/kg DM) were lower in the CS-Y line, but there were no differences in total truly digested protein in small intestine (DVE) and feed milk value (FMV) between the two lines. In conclusion, the new yellow line had different nutritional, chemical, and structural features compared to the black line. CS-Y provided better nutrient utilization and availability.

The difference in correlation between insulin resistance index and chronic inflammation in type 2 diabetes with and without metabolic syndrome

PubMed Central

Pourfarzam, Morteza; Zadhoush, Fouzieh; Sadeghi, Masoumeh

2016-01-01

Background: Insulin resistance (IR) is associated with low-grade systemic inflammation. It plays an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in patients with metabolic syndrome (MetS). It is unclear whether diabetic patients with MetS confer elevated CVD risk and outcomes beyond the impact of individual's components of MetS. The aim of this study is to highlight the central role of IR, inflammation, triglyceride/high-density lipoprotein- cholesterol (TG/HDL-C) ratio, and atherogenic index of plasma (AIP) in T2DM with MetS. Materials and Methods: This cross-sectional study comprised 130 men distributed into three groups, namely Controls: 40 nondiabetic healthy volunteers; Group I: 40 T2DM patients without MetS, and Group II: 50 T2DM patients with MetS. Fasting blood samples were collected for the measurement of blood lipid profile, glucose, insulin, hemoglobin A1c, and high-sensitivity C-reactive protein (hs-CRP). TG/HDL-C ratio, AIP, and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Results: Significant positive association was observed between HOMA-IR and hs-CRP only in Group II and between HOMA-IR and TG/HDL-C ratio in all subjects. Significant differences were seen in waist and hip circumferences, waist/hip ratio, body mass index, systolic blood pressure, fasting blood glucose, TGs, HDL-C, insulin, hs-CRP, HOMA-IR, TG/HDL ratio, and AIP between Controls and Group I with Group II. Conclusions: In T2DM with MetS, coexistence of elevated atherogenic indices, systemic inflammation, and association between HOMA-IR and TG/HDL-C ratio were seen. These factors are considered having important role in elevated CVD risk beyond MetS components in these patients. PMID:27713874

Dark matter profiles and annihilation in dwarf spheroidal galaxies: prospectives for present and future γ-ray observatories - I. The classical dwarf spheroidal galaxies

NASA Astrophysics Data System (ADS)

Charbonnier, A.; Combet, C.; Daniel, M.; Funk, S.; Hinton, J. A.; Maurin, D.; Power, C.; Read, J. I.; Sarkar, S.; Walker, M. G.; Wilkinson, M. I.

2011-12-01

Due to their large dynamical mass-to-light ratios, dwarf spheroidal galaxies (dSphs) are promising targets for the indirect detection of dark matter (DM) in γ-rays. We examine their detectability by present and future γ-ray observatories. The key innovative features of our analysis are as follows: (i) we take into account the angular size of the dSphs; while nearby objects have higher γ-ray flux, their larger angular extent can make them less attractive targets for background-dominated instruments; (ii) we derive DM profiles and the astrophysical J-factor (which parametrizes the expected γ-ray flux, independently of the choice of DM particle model) for the classical dSphs directly from photometric and kinematic data. We assume very little about the DM profile, modelling this as a smooth split-power-law distribution, with and without subclumps; (iii) we use a Markov chain Monte Carlo technique to marginalize over unknown parameters and determine the sensitivity of our derived J-factors to both model and measurement uncertainties; and (iv) we use simulated DM profiles to demonstrate that our J-factor determinations recover the correct solution within our quoted uncertainties. Our key findings are as follows: (i) subclumps in the dSphs do not usefully boost the signal; (ii) the sensitivity of atmospheric Cherenkov telescopes to dSphs within ˜20 kpc with cored haloes can be up to ˜50 times worse than when estimated assuming them to be point-like. Even for the satellite-borne Fermi-Large Area Telescope (Fermi-LAT), the sensitivity is significantly degraded on the relevant angular scales for long exposures; hence, it is vital to consider the angular extent of the dSphs when selecting targets; (iii) no DM profile has been ruled out by current data, but using a prior on the inner DM cusp slope 0 ≤γprior≤ 1 provides J-factor estimates accurate to a factor of a few if an appropriate angular scale is chosen; (iv) the J-factor is best constrained at a critical integration angle αc= 2rh/d (where rh is the half-light radius and d is the distance from the dwarf) and we estimate the corresponding sensitivity of γ-ray observatories; (v) the 'classical' dSphs can be grouped into three categories: well constrained and promising (Ursa Minor, Sculptor and Draco), well constrained but less promising (Carina, Fornax and Leo I), and poorly constrained (Sextans and Leo II); and (vi) observations of classical dSphs with the Fermi-LAT integrated over the mission lifetime are more promising than observations with the planned Cherenkov Telescope Array for DM particle mass ≲ 700 GeV. However, even the Fermi-LAT will not have sufficient integrated signal from the classical dwarfs to detect DM in the 'vanilla' Minimal Supersymmetric Standard Model. Both the Galactic Centre and the 'ultrafaint' dwarfs are likely to be better targets and will be considered in future work.

Axion cosmology

NASA Astrophysics Data System (ADS)

Marsh, David J. E.

2016-07-01

Axions comprise a broad class of particles that can play a major role in explaining the unknown aspects of cosmology. They are also well-motivated within high energy physics, appearing in theories related to CP-violation in the standard model, supersymmetric theories, and theories with extra-dimensions, including string theory, and so axion cosmology offers us a unique view onto these theories. I review the motivation and models for axions in particle physics and string theory. I then present a comprehensive and pedagogical view on the cosmology and astrophysics of axion-like particles, starting from inflation and progressing via BBN, the CMB, reionization and structure formation, up to the present-day Universe. Topics covered include: axion dark matter (DM); direct and indirect detection of axions, reviewing existing and future experiments; axions as dark radiation; axions and the cosmological constant problem; decays of heavy axions; axions and stellar astrophysics; black hole superradiance; axions and astrophysical magnetic fields; axion inflation, and axion DM as an indirect probe of inflation. A major focus is on the population of ultralight axions created via vacuum realignment, and its role as a DM candidate with distinctive phenomenology. Cosmological observations place robust constraints on the axion mass and relic density in this scenario, and I review where such constraints come from. I next cover aspects of galaxy formation with axion DM, and ways this can be used to further search for evidence of axions. An absolute lower bound on DM particle mass is established. It is ma > 10-24eV from linear observables, extending to ma ≳ 10-22eV from non-linear observables, and has the potential to reach ma ≳ 10-18eV in the future. These bounds are weaker if the axion is not all of the DM, giving rise to limits on the relic density at low mass. This leads to the exciting possibility that the effects of axion DM on structure formation could one day be detected, and the axion mass and relic density measured from cosmological observables.

SCALING LAWS FOR DARK MATTER HALOS IN LATE-TYPE AND DWARF SPHEROIDAL GALAXIES

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

Kormendy, John; Freeman, K. C., E-mail: kormendy@astro.as.utexas.edu, E-mail: kenneth.freeman@anu.edu.au

2016-02-01

Dark matter (DM) halos of Sc–Im and dwarf spheroidal (dSph) galaxies satisfy scaling laws: halos in lower-luminosity galaxies have smaller core radii, higher central densities, and smaller velocity dispersions. These results are based on maximum-disk rotation curve decompositions for giant galaxies and Jeans equation analysis for dwarfs. (1) We show that spiral, Im, and Sph galaxies with absolute magnitudes M{sub V} > −18 form a sequence of decreasing baryon-to-DM surface density with decreasing luminosity. We suggest that this is a sequence of decreasing baryon retention versus supernova-driven losses or decreasing baryon capture after cosmological reionization. (2) The structural differences betweenmore » S+Im and Sph galaxies are small. Both are affected mostly by the physics that controls baryon depletion. (3) There is a linear correlation between the maximum rotation velocities of baryonic disks and the outer circular velocities V{sub circ} of test particles in their DM halos. Baryons become unimportant at V{sub circ} = 42 ± 4 km s{sup −1}. Smaller galaxies are dim or dark. (4) We find that, absent baryon “depletion” and with all baryons converted into stars, dSph galaxies would be brighter by ∼4.6 mag and dIm galaxies would be brighter by ∼3.5 mag. Both have DM halos that are massive enough to help to solve the “too big to fail” problem with DM galaxy formation. (5) We suggest that there exist many galaxies that are too dark to be discovered by current techniques, as required by cold DM theory. (6) Central surface densities of DM halos are constant from M{sub B} ∼ −5 to −22. This implies a Faber–Jackson law with halo mass M ∝ (halo dispersion){sup 4}.« less

Serum Myostatin Is Reduced in Individuals with Metabolic Syndrome

PubMed Central

Chiang, Chih-Kang; Tseng, Fen-Yu; Tseng, Ping-Huei; Chen, Chi-Ling; Wu, Kwan-Dun; Yang, Wei-Shiung

2014-01-01

Aims Myostatin is a negative regulator of skeletal muscle mass and may also modulate energy metabolism secondarily. We aim to investigate the relationship between serum myostatin and the metabolic variables in diabetic (DM) and non-diabetic subjects. Materials and Methods A cross-sectional study recruiting 246 consecutive DM patients and 82 age- and gender-matched non-diabetic individuals at a medical center was conducted. The variables of anthropometry and blood chemistry were obtained. Serum myostatin level was measured with enzyme immunoassay. Results DM group had lower serum myostatin compared with non-diabetics (7.82 versus 9.28 ng/ml, p<0.01). Sixty-two percent of the recruited individuals had metabolic syndrome (MetS). The patients with MetS had significantly lower serum myostatin than those without (7.39 versus 9.49 ng/ml, p<0.001). The serum myostatin level decreased with increasing numbers of the MetS components (p for trend<0.001). The patients with higher body mass index, larger abdominal girth, lower high-density lipoprotein cholesterol (HDL-C), and higher triglycerides had lower serum myostatin than those without. The serum myostatin level was independently negatively related to larger abdominal girth, higher triglycerides, and lower HDL-C after adjustment. The odds ratios for MetS, central obesity, low HDL-C, high triglycerides, and DM were 0.85, 0.88, 0.89, 0.85, and 0.92, respectively, when serum myostatin increased per 1 ng/mL, in the binary logistic regression models. Conclusions Lower serum myostatin independently associated with MetS, central obesity, low HDL-C, and high triglycerides after adjustment. Higher serum myostatin is associated with favorable metabolic profiles. PMID:25254550

Hidden from view: coupled dark sector physics and small scales

NASA Astrophysics Data System (ADS)

Elahi, Pascal J.; Lewis, Geraint F.; Power, Chris; Carlesi, Edoardo; Knebe, Alexander

2015-09-01

We study cluster mass dark matter (DM) haloes, their progenitors and surroundings in a coupled dark matter-dark energy (DE) model and compare it to quintessence and Λ cold dark matter (ΛCDM) models with adiabatic zoom simulations. When comparing cosmologies with different expansions histories, growth functions and power spectra, care must be taken to identify unambiguous signatures of alternative cosmologies. Shared cosmological parameters, such as σ8, need not be the same for optimal fits to observational data. We choose to set our parameters to ΛCDM z = 0 values. We find that in coupled models, where DM decays into DE, haloes appear remarkably similar to ΛCDM haloes despite DM experiencing an additional frictional force. Density profiles are not systematically different and the subhalo populations have similar mass, spin, and spatial distributions, although (sub)haloes are less concentrated on average in coupled cosmologies. However, given the scatter in related observables (V_max,R_{V_max}), this difference is unlikely to distinguish between coupled and uncoupled DM. Observations of satellites of Milky Way and M31 indicate a significant subpopulation reside in a plane. Coupled models do produce planar arrangements of satellites of higher statistical significance than ΛCDM models; however, in all models these planes are dynamically unstable. In general, the non-linear dynamics within and near large haloes masks the effects of a coupled dark sector. The sole environmental signature we find is that small haloes residing in the outskirts are more deficient in baryons than their ΛCDM counterparts. The lack of a pronounced signal for a coupled dark sector strongly suggests that such a phenomena would be effectively hidden from view.

Pharmacokinetic profile of dextromethorphan hydrobromide in a syrup formulation in children and adolescents.

PubMed

Guenin, Eric; Armogida, Marianna; Riff, Dennis

2014-09-01

Dextromethorphan hydrobromide (DM) is a widely used antitussive. This study determined, for the first time, the basic pharmacokinetic profile of DM and its active metabolite, dextrorphan (DP) in children and adolescents. Thirty-eight male and female subjects at risk for developing an upper respiratory tract infection (URTI), or symptomatic with cough due to URTI, were enrolled in this single-dose, open-label study: ages 2-5 years (Group A, n = 8), 6-11 years (Group B, n = 17), 12-17 years (Group C, n = 13). Subjects were genotyped for cytochrome P450 (CYP) 2D6 polymorphisms and characterized as poor (PM) or non-poor metabolizers (non-PM). Groups A and B were dosed using an age-weight dosing schedule (DM range 7.5-24.75 mg); a 30-mg dose was used for Group C. Average exposures to total DP increased as age group increased, and average exposure to DM was highest in the adolescent group. One subject in that group was a PM. The terminal half-life (t ½) values were longer in the adolescent group due in part to the single PM subject. No relationship between body weight and pharmacokinetic parameters was noted. This is the first evaluation of the pharmacokinetic characteristics of DM in children and adolescents. A single dose of DM in this population was safe, and well tolerated at all doses tested. The data are used to model and compare pediatric DM exposures with those of adults.

Direct phase selection of initial phases from single-wavelength anomalous dispersion (SAD) for the improvement of electron density and ab initio structure determination.

PubMed

Chen, Chung-De; Huang, Yen-Chieh; Chiang, Hsin-Lin; Hsieh, Yin-Cheng; Guan, Hong-Hsiang; Chuankhayan, Phimonphan; Chen, Chun-Jung

2014-09-01

Optimization of the initial phasing has been a decisive factor in the success of the subsequent electron-density modification, model building and structure determination of biological macromolecules using the single-wavelength anomalous dispersion (SAD) method. Two possible phase solutions (φ1 and φ2) generated from two symmetric phase triangles in the Harker construction for the SAD method cause the well known phase ambiguity. A novel direct phase-selection method utilizing the θ(DS) list as a criterion to select optimized phases φ(am) from φ1 or φ2 of a subset of reflections with a high percentage of correct phases to replace the corresponding initial SAD phases φ(SAD) has been developed. Based on this work, reflections with an angle θ(DS) in the range 35-145° are selected for an optimized improvement, where θ(DS) is the angle between the initial phase φ(SAD) and a preliminary density-modification (DM) phase φ(DM)(NHL). The results show that utilizing the additional direct phase-selection step prior to simple solvent flattening without phase combination using existing DM programs, such as RESOLVE or DM from CCP4, significantly improves the final phases in terms of increased correlation coefficients of electron-density maps and diminished mean phase errors. With the improved phases and density maps from the direct phase-selection method, the completeness of residues of protein molecules built with main chains and side chains is enhanced for efficient structure determination.

Clinical Safety and Tolerability of Vildagliptin - Insights from Randomised Trials, Observational Studies and Post-marketing Surveillance.

PubMed

Mathieu, Chantal; Kozlovski, Plamen; Paldánius, Päivi M; Foley, James E; Modgill, Vikas; Evans, Marc; Serban, Carmen

2017-08-01

Vildagliptin is one of the most extensively studied dipeptidyl peptidase-4 (DPP-4) inhibitors in terms of its clinical utility. Over the last decade, a vast panorama of evidence on the benefit-risk profile of vildagliptin has been generated in patients with type 2 diabetes mellitus (T2DM). In this article, we review the cumulative evidence on the safety of vildagliptin from the clinical development programme, as well as reports of rare adverse drug reactions detected during the post-marketing surveillance of the drug. Across clinical studies, the overall safety and tolerability profile of vildagliptin was similar to placebo, and it was supported by real-world data in a broad population of patients with T2DM, making DPP-4 inhibitors, like vildagliptin, a safe option for managing patients with T2DM.

Parametric strong gravitational lensing analysis of Abell 1689

NASA Astrophysics Data System (ADS)

Halkola, A.; Seitz, S.; Pannella, M.

2006-11-01

We have derived the mass distribution of galaxy cluster Abell 1689 within 0.3h-170Mpc of the cluster centre using its strong lensing (SL) effect on 32 background galaxies, which are mapped in altogether 107 multiple images. The multiple images are based on some from the literature with modifications to both include new and exclude some of the original image systems. The cluster profile is explored further out to ~2.5h-170Mpc with weak lensing (WL) shear measurements from the literature. The masses of ~200 cluster galaxies are measured with the Fundamental Plane (FP) in order to model accurately the small-scale mass structure in the cluster. The cluster galaxies are modelled as elliptical truncated isothermal spheres. The scalings of the truncation radii with the velocity dispersions of galaxies are assumed to match those of: (i) field galaxies; and (ii) theoretical expectations for galaxies in dense environments. The dark matter (DM) component of the cluster is described by either non-singular isothermal ellipsoids (NSIE) or elliptical versions of the universal DM profile (elliptical Navarro, Frenk & White, ENFW). To account for substructure in the DM we allow for two DM haloes. The fitting of a non-singular isothermal sphere (NSIS) to the smooth DM component results in a velocity dispersion of 1450+39-31kms-1 and a core radius of 77+10-8h-170kpc, while a Navarro, Frenk & White (NFW) profile has an r200 of 2.86 +/- 0.16h-170Mpc (M200 = 3.2 × 1015Msolarh70) and a concentration of 4.7+0.6-0.5. The total mass profile is well described by either a NSIS profile with σ = 1514+18-17kms-1 and a core radius of rc = 71 +/- 5h-170kpc, or an NFW profile with C = 6.0 +/- 0.5 and r200 = 2.82 +/- 0.11h-170Mpc (M200 = 3.0 × 1015Msolarh70). The errors are assumed to be due to the error in assigning masses to the individual galaxies in the galaxy component. Their small size is due to the very strong constraints imposed by multiple images and the ability of the smooth DM component to adjust to uncertainties in the galaxy masses. The agreement in the total mass profile between this work and that of the literature is better than 1σ at all radii, despite the considerable differences in the methodology used. Using the same image configuration as used in the literature, we obtain a SL model that is superior to some in the literature (rms of 2.7 compared to 3.2arcsec). This is very surprising considering the larger freedom in the surface mass profile in their grid modelling. The difference is most likely a result of the careful inclusion of the cluster galaxies. Using also WL shear measurements from the literature, we can constrain the profile further out to r ~ 2.5h-170Mpc. The best-fitting parameters change to σ = 1499 +/- 15kms-1 and rc = 66 +/- 5h-170kpc for the NSIS profile and C = 7.6 +/- 0.5 and r200 = 2.55 +/- 0.07h-170Mpc (M200 = 2.3 × 1015Msolarh70) for the NFW profile.

Metabolomic Insight into Lipid and Protein Profile in Diabetes Using Mass Spectrometry.

PubMed

Bukowiecka-Matusiak, Malgorzata; Chmielewska-Kassassir, Malgorzata; Szczesna, Dorota; Wozniak, Lucyna A

2016-01-01

In recent years, metabolomics has become a necessary tool for understanding the impact of external and pathological factors on the operation of biological systems. The first reports of metabolomics date back to the 1970s, however, the area only began to develop dynamically at the beginning of this century and has proved effective only during the present decade. The five primary tools used in this form of analysis are NMR spectrometry, HPLC, TLC-UV, GC-MS and LC-MS/MS, with MS as the most universal approach, particularly when used together with chromatographic separation and NMR. Diabetes mellitus type 2 (T2DM) is a rapidly growing problem with global consequences. The metabolomic approach has been extensively applied to examining T2DM, insulin resistance and obesity, not only to assess the development of the disease, but also to discover its potential biomarkers. The presented review summarizes current studies on lipidomic and proteomic profiles in the context of different types of diabetes mellitus disease (T1DM, T2DM and GDM), as determined by chromatography-coupled mass spectrometry.

Safety Profile and Costs of Related Adverse Events of Trastuzumab Emtansine for the Treatment of HER2-Positive Locally Advanced or Metastatic Breast Cancer Compared to Capecitabine Plus Lapatinib from the Perspective of the Canadian Health-Care System.

PubMed

Piwko, Charles; Prady, Catherine; Yunger, Simon; Pollex, Erika; Moser, Aurelie

2015-08-01

Trastuzumab emtansine (T-DM1, KADCYLA(®)) is an antibody-drug conjugate comprised of the cytotoxic agent DM1 and trastuzumab (HERCEPTIN(®)). The safety profile of T-DM1 in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane was investigated in the phase III EMILIA trial. The trial demonstrated clinically and statistically meaningful differences in the safety profile between T-DM1 and capecitabine plus lapatinib (CAP + LAP). The objective of this study was to estimate the costs of managing treatment-related grade ≥ 3 adverse events (AEs) that occurred in ≥ 2% of patients and grade 2 AEs that occurred in ≥ 5% of patients taking T-DM1 compared with patients taking CAP + LAP based on the EMILIA trial, from the perspective of Canadian public payers. An Excel-based model was utilized to estimate the relevant costs. Clinical data were obtained from the EMILIA trial. Cost information was obtained from the literature, clinical experts, and standard cost sources. The analysis was conducted from the Canadian public-payer perspective and reported in 2014 Canadian dollars (CAD). The management of included treatment-related AEs resulted in higher estimated per-patient costs of CAD6901 for CAP + LAP versus CAD3380 for T-DM1, resulting in savings of CAD3521. From a Canadian perspective, this analysis demonstrated that utilizing T-DM1 for the management of HER2-positive metastatic breast cancer results in substantial savings to the public health-care system when considering the costs of treatment-related AEs, due to fewer amount of toxicities compared with CAP + LAP. Results of various sensitivity analyses investigating changes in number and costs of AEs confirmed the findings; however, the magnitude of cost savings varied. Further analyses are necessary to determine whether these cost savings would occur in other countries and health-care systems.

Hemostasis and Lipoprotein Indices Signify Exacerbated Lung Injury in TB With Diabetes Comorbidity.

PubMed

Dong, Zhengwei; Shi, Jingyun; Dorhoi, Anca; Zhang, Jie; Soodeen-Lalloo, Adiilah K; Tan, WenLing; Yin, Hongyun; Sha, Wei; Li, Weitong; Zheng, Ruijuan; Liu, Zhonghua; Yang, Hua; Qin, Lianhua; Wang, Jie; Huang, Xiaochen; Wu, Chunyan; Kaufmann, Stefan H E; Feng, Yonghong

2018-05-01

Exacerbated immunopathology is a frequent consequence of TB that is complicated by diabetes mellitus (DM); however, the underlying mechanisms are still poorly defined. In the two groups of age- and sex-matched patients with TB and DM (DM-TB) and with TB and without DM, we microscopically evaluated the areas of caseous necrosis and graded the extent of perinecrotic fibrosis in lung biopsies from the sputum smear-negative (SN) patients. We scored acid-fast bacilli in sputum smear-positive (SP) patients and compiled CT scan data from both the SN and SP patients. We compared inflammatory biomarkers and routine hematologic and biochemical parameters. Binary logistic regression analyses were applied to define the indices associated with the extent of lung injury. Enlarged caseous necrotic areas with exacerbated fibrotic encapsulations were found in SN patients with DM-TB, consistent with the higher ratio of thick-walled cavities and more bacilli in the sputum from SP patients with DM-TB. Larger necrotic foci were detected in men compared with women within the SN TB groups. Significantly higher fibrinogen and lower high-density lipoprotein cholesterol (HDL-C) were observed in SN patients with DM-TB. Regression analyses revealed that diabetes, activation of the coagulation pathway (shown by increased platelet distribution width, decreased mean platelet volume, and shortened prothrombin time), and dyslipidemia (shown by decreased low-density lipoprotein cholesterol, HDL-C, and apolipoprotein A) are risk factors for severe lung lesions in both SN and SP patients with TB. Hemostasis and dyslipidemia are associated with granuloma necrosis and fibroplasia leading to exacerbated lung damage in TB, especially in patients with DM-TB. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

THE INNER STRUCTURE OF DWARF-SIZED HALOS IN WARM AND COLD DARK MATTER COSMOLOGIES

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

González-Samaniego, A.; Avila-Reese, V.; Colín, P.

2016-03-10

By means of N-body + hydrodynamic zoom-in simulations we study the evolution of the inner dark matter and stellar mass distributions of central dwarf galaxies formed in halos of virial masses M{sub v} = (2–3) × 10{sup 10} h{sup −1} M{sub ⊙} at z = 0, both in a warm dark matter (WDM) and cold dark matter (CDM) cosmology. The half-mode mass in the WDM power spectrum of our simulations is M{sub f} = 2 × 10{sup 10} h{sup −1} M{sub ⊙}. In the dark matter (DM) only simulations halo density profiles are well described by the Navarro–Frenk–White parametric fit in both cosmologies, though the WDM halos have concentrations lower bymore » factors of 1.5–2.0 than their CDM counterparts. In the hydrodynamic simulations, the effects of baryons significantly flatten the inner density, velocity dispersion, and pseudo phase space density profiles of the WDM halos but not of the CDM ones. The density slope, measured at ≈0.02R{sub v}, α{sub 0.02}, becomes shallow in periods of 2–5 Gyr in the WDM runs. We explore whether this flattening process correlates with the global star formation (SF), M{sub s}/M{sub v} ratio, gas outflow, and internal specific angular momentum histories. We do not find any clear trends, but when α{sub 0.02} is shallower than −0.5, M{sub s}/M{sub v} is always between 0.25% and 1%. We conclude that the main reason for the formation of the shallow core is the presence of strong gas mass fluctuations inside the inner halo, which are a consequence of the feedback driven by a very bursty and sustained SF history in shallow gravitational potentials. Our WDM halos, which assemble late and are less concentrated than the CDM ones, obey these conditions. There are also (rare) CDM systems with extended mass assembly histories that obey these conditions and form shallow cores. The dynamical heating and expansion processes behind the DM core flattening apply also to the stars in such a way that the stellar age and metallicity gradients of the dwarfs are softened, their stellar half-mass radii strongly grow with time, and their central surface densities decrease.« less

Variation of inflammatory parameters after sibutramine treatment compared to placebo in type 2 diabetic patients.

PubMed

Derosa, G; Maffioli, P; Ferrari, I; Palumbo, I; Randazzo, S; D'Angelo, A; Cicero, A F G

2011-10-01

The efficacy of sibutramine has been demonstrated in randomized trials in obese/overweight patients including those with type 2 diabetes mellitus (T2DM). Our objective was to evaluate the effects of 1-year treatment with sibutramine compared to placebo on body weight, glycaemic control, lipid profile, and inflammatory parameters in type 2 diabetic patients. Two hundred and forty-six patients with uncontrolled T2DM [glycated haemoglobin (HbA(1c) ) > 8·0%] in therapy with different oral hypoglycaemic agents or insulin were randomized to take 10 mg of sibutramine or placebo for 12 months. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA(1c) , fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), leptin, tumour necrosis factor-α (TNF-α), adiponectin (ADN), vaspin, high sensitivity C-reactive protein (Hs-CRP). We observed a decrease of body weight after 9 and 12 months in the group treated with sibutramine, but not in the control group. Regarding glycaemic and lipid profile, although there are differences seen over time within each of the groups, we did not obtain any significant differences between the two groups. Both placebo and sibutramine gave a similar improvement of HOMA-IR, leptin, TNF-α, ADN, and Hs-CRP. No vaspin variations were observed in either group. Sibutramine resulted in a decrease in body weight at 9 months and at 12 months that was not observed with placebo. Although there were differences seen over time within each of the groups, there were no significant differences between groups for any other parameter that we measured. © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.

Effect of garlic supplement in the management of type 2 diabetes mellitus (T2DM): a meta-analysis of randomized controlled trials.

PubMed

Wang, Juan; Zhang, Xiuming; Lan, Haili; Wang, Weijia

2017-01-01

The present study was designed to systematically evaluate the clinical efficacy and safety of garlic supplement in the management of type 2 diabetes mellitus (T2DM). PubMed, EMBASE, the Cochrane Library, and China National Knowledge Internet (CNKI) were searched for relevant randomized controlled trials (RCTs) by using the terms garlic and T2DM up to April 2017. The quality of included RCTs was assessed by the Cochrane tool of risk of bias, and data of outcomes were pooled by REVMAN 5.3. Clinical factors were handled by meta-regression and subgroup analysis, and risk of publication bias was explored by inverted funnel plots. Nine RCTs involving 768 T2DM patients were included in the meta-analysis, and the dose of daily garlic (allicin) supplement ranged from 0.05g to 1.5g. A significant reduction in the level of fasting blood glucose in 1-2 weeks [SMD = -1.61, 95%CI (-2.89, -0.32)], 3-4 weeks [SMD = -2.87, 95%CI (-4.74, -1.00)], 12 weeks [SMD = -9.57, 95%CI (-12.39, -6.75)], and 24 weeks [SMD = -21.02, 95%CI (-32.47, -9.57)] was achieved in favour of the garlic group rather than the control group. Significantly decreased fructosamine and glycated hemoglobin (both in 12 and 24 weeks) were also found in garlic group. Meanwhile, significantly improved blood liquids of total cholesterol [SMD = -1.93, 95%CI (-2.98, -0.87), 3-4 weeks], high density lipoprotein [SMD = -0.41, 95%CI (-0.83, -0.00), 3-4 weeks] and low density lipoprotein [SMD = -3.47, 95%CI (-5.76, -1.18), 12 weeks] were confirmed after garlic administration. There was no significant difference in complications. Current data confirms that garlic supplement plays positive and sustained roles in blood glucose, total cholesterol, and high/low density lipoprotein regulation in the management of T2DM. Abbreviations : T2DM = type 2 diabetes mellitus; RCT = randomized controlled trial; SMD = standard mean difference; CI = confidence interval; FBG = fasting blood glucose; HbA1c = glycated hemoglobin; HDL = high density lipoprotein; LDL = low density lipoprotein.

Effect of Larval Density on Food Utilization Efficiency of Tenebrio molitor (Coleoptera: Tenebrionidae).

PubMed

Morales-Ramos, Juan A; Rojas, M Guadalupe

2015-10-01

Crowding conditions of larvae may have a significant impact on commercial production efficiency of some insects, such as Tenebrio molitor L. (Coleoptera: Tenebrionidae). Although larval densities are known to affect developmental time and growth in T. molitor, no reports were found on the effects of crowding on food utilization. The effect of larval density on food utilization efficiency of T. molitor larvae was studied by measuring efficiency of ingested food conversion (ECI), efficiency of digested food conversion (EDC), and mg of larval weight gain per gram of food consumed (LWGpFC) at increasing larval densities (12, 24, 36, 48, 50, 62, 74, and 96 larvae per dm(2)) over four consecutive 3-wk periods. Individual larval weight gain and food consumption were negatively impacted by larval density. Similarly, ECI, ECD, and LWGpFC were negatively impacted by larval density. Larval ageing, measured as four consecutive 3-wk periods, significantly and independently impacted ECI, ECD, and LWGpFC in a negative way. General linear model analysis showed that age had a higher impact than density on food utilization parameters of T. molitor larvae. Larval growth was determined to be responsible for the age effects, as measurements of larval mass density (in grams of larvae per dm(2)) had a significant impact on food utilization parameters across ages and density treatments (in number of larvae per dm(2)). The importance of mass versus numbers per unit of area as measurements of larval density and the implications of negative effects of density on food utilization for insect biomass production are discussed. Published by Oxford University Press on behalf of Entomological Society of America 2015. This work is written by US Government employees and is in the public domain in the US.

Compatibility of a dark matter discovery at XENONnT or LZ with the WIMP thermal production mechanism

NASA Astrophysics Data System (ADS)

Catena, Riccardo; Conrad, Jan; Krauss, Martin B.

2018-05-01

The discovery of dark matter (DM) at XENONnT or LZ would place constraints on DM particle mass and coupling constants. It is interesting to ask when these constraints can be compatible with the DM thermal production mechanism. We address this question within the most general set of renormalizable models that preserve Lorentz and gauge symmetry, and that extend the standard model by one DM candidate of mass mDM and one particle of mass Mmed mediating DM-quark interactions. Our analysis divides into two parts. First, we postulate that XENONnT/LZ has detected μS˜O (100 ) signal events, and use this input to calculate the DM relic density, ΩDMh2. Then, we identify the regions in the Mmed-ΩDMh2 plane which are compatible with the observed signal and with current CMB data. We find that for most of the models considered here, O (100 ) signal events at XENONnT/LZ and the DM thermal production are only compatible for resonant DM annihilations, i.e. for Mmed≃2 mDM. In this case, XENONnT/LZ would be able to simultaneously measure mDM and Mmed. We also discuss the dependence of our results on mDM, μS and the DM spin, and provide analytic expressions for annihilation cross sections and mediator decay widths for all models considered in this study.

Ashanti pepper (Piper guineense Schumach et Thonn) attenuates carbohydrate hydrolyzing, blood pressure regulating and cholinergic enzymes in experimental type 2 diabetes rat model.

PubMed

Adefegha, Stephen Adeniyi; Oboh, Ganiyu; Adefegha, Omowunmi Monisola

2017-01-01

Ashanti pepper (Piper guineense Schumach et Thonn) seed is well known in folkloric medicine in the management of type 2 diabetes (T2DM) with little or no scientific documentation for its action. This study investigated the effect of Ashanti pepper seed on some enzymes relevant to carbohydrate hydrolysis, blood regulation and the cholinergic system, as well as the blood glucose level, lipid profile, antioxidant parameters, and hepatic and renal function markers in T2DM rats. T2DM was induced by feeding rats with high-fat diet (HFD) for 14 days followed by a single intraperitoneal dose of 35 mg/kg body weight of streptozotocin (STZ). Three days after STZ induction, diabetic rats were placed on a dietary regimen containing 2%-4% Ashanti pepper. Reduced blood glucose level with decreased α-amylase, α-glucosidase and angiotensin I converting enzyme (ACE) activities were observed in Ashanti pepper seed and acarbose-treated rat groups when compared to that of the diabetic control rat group. Furthermore, the results revealed that inclusion of 2%-4% Ashanti pepper seed in diabetic rat fed group diets may ameliorate the lipid profile, antioxidant status, and hepatic and renal function in T2DM rats as much as in the acarbose-treated groups. In addition, a chromatographic profile of the seed revealed the presence of quercitrin (116.51 mg/g), capsaicin (113.94 mg/g), dihydrocapsaicin (88.29 mg/g) and isoquercitrin (74.89 mg/g). The results from this study clearly suggest that Ashanti pepper could serve as a promising source of phenolic compounds with great alternative therapeutic potentials in the management of T2DM.

Serum metabolomics differentiating pancreatic cancer from new-onset diabetes

PubMed Central

He, Xiangyi; Zhong, Jie; Wang, Shuwei; Zhou, Yufen; Wang, Lei; Zhang, Yongping; Yuan, Yaozong

2017-01-01

To establish a screening strategy for pancreatic cancer (PC) based on new-onset diabetic mellitus (NO-DM), serum metabolomics analysis and a search for the metabolic pathways associated with PC related DM were performed. Serum samples from patients with NO-DM (n = 30) and patients with pancreatic cancer and NO-DM were examined by liquid chromatography-mass spectrometry. Data were analyzed using principal components analysis (PCA) and orthogonal projection to latent structures (OPLS) of the most significant metabolites. The diagnostic model was constructed using logistic regression analysis. Metabolic pathways were analyzed using the web-based tool MetPA. PC patients with NO-DM were older and had a lower BMI and shorter duration of DM than those with NO-DM. The metabolomic profiles of patients with PC and NO-DM were significantly different from those of patients with NO-DM in the PCA and OPLS models. Sixty two differential metabolites were identified by the OPLS model. The logistic regression model using a panel of two metabolites including N_Succinyl_L_diaminopimelic_acid and PE (18:2) had high sensitivity (93.3%) and specificity (93.1%) for PC. The top three metabolic pathways associated with PC related DM were valine, leucine and isoleucine biosynthesis and degradation, primary bile acid biosynthesis, and sphingolipid metabolism. In conclusion, screening for PC based on NO-DM using serum metabolomics in combination with clinic characteristics and CA19-9 is a potential useful strategy. Several metabolic pathways differed between PC related DM and type 2 DM. PMID:28418859

Time-dependent changes in the plasma amino acid concentration in diabetes mellitus.

PubMed

Mochida, Taiga; Tanaka, Takayuki; Shiraki, Yasuko; Tajiri, Hiroko; Matsumoto, Shirou; Shimbo, Kazutaka; Ando, Toshihiko; Nakamura, Kimitoshi; Okamoto, Masahiro; Endo, Fumio

2011-08-01

We investigated longitudinal change in the amino acid (AA) profile in type 1 diabetes mellitus (DM) using AKITA mice, which develop DM as a result of insulin deficiency. The plasma concentrations of valine, leucine, isoleucine, as well as the total branched chain amino acids, alanine, citrulline and proline, were significantly higher in the diabetic mice. We show that the degree and timing of the changes were different among the plasma amino acid concentrations (pAAs) during the development of type 1 DM. Copyright © 2011 Elsevier Inc. All rights reserved.

Active vitamin D3, 1,25-(OH)2D3, protects against macrovasculopathy in a rat model of type 2 diabetes mellitus.

PubMed

Ma, R; Deng, X L; Du, G L; Li, C; Xiao, S; Aibibai, Y; Zhu, J

2016-06-03

To investigate the protective effect of the active form of vitamin D3, 1,25-(OH)2D3, on macrovasculopathy in rats with type 2 diabetes mellitus (T2DM), 8-week-old male Sprague-Dawley rats were randomly divided into control group, T2DM group, and treatment group. The T2DM model was established after 6 weeks by administering an intraperitoneal injection of streptozotocin (30 mg/kg). 1,25-(OH)2D3 was administered by gavage to rats in the treatment group, and an equal volume of peanut oil was administered to rats in the T2DM group. Fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterols were measured in all rats. The morphology of the thoracic aorta was examined, and the expression of tumor necrosis factor alpha (TNF-α), endothelin (ET), endothelial nitric oxide synthase (eNOS), CD54, and CD106 in the thoracic aorta was determined by immunohistochemistry. The expression of FPG, TG, TC, and LDL-C in rats from the T2DM and treatment groups was significantly elevated compared with rats from the control group (P < 0.05). Compared with that in control group, the expression of TNF-α, ET, eNOS, and CD106 was significantly upregulated in the T2DM group and the treatment group, while the expression of CD54 was increased only in the T2DM group (P < 0.05). Moreover, the levels of TNF-α, CD54, and CD106 in rats from the treatment group were lower than those in the T2DM group (P < 0.05). These data suggest that 1,25-(OH)2D3 may protect the macrovessels from injury in T2DM rats by inhibiting the expression of TNF-α, CD54, and CD106.

Effect of moisture of municipal biowaste on start-up and efficiency of mesophilic and thermophilic dry anaerobic digestion.

PubMed

Li, Chaoran; Mörtelmaier, Christoph; Winter, Josef; Gallert, Claudia

2014-09-01

Methane production from biowaste with 20-30% dry matter (DM) by box-type dry anaerobic digestion and contributing bacteria were determined for incubation at 20, 37 and 55 °C. The same digestion efficiency as for wet anaerobic digestion of biowaste was obtained for dry anaerobic digestion with 20% DM content at 20, 37 and 55 °C and with 25% DM content at 37 and 55 °C. No or only little methane was produced in dry anaerobic reactors with 30% DM at 20, 37 or 55 °C. Population densities in the 20-30% DM-containing biowaste reactors were similar although in mesophilic and thermophilic biowaste reactors with 30% DM content significantly less but phylogenetically more diverse archaea existed. Biogas production in the 20% and 25% DM assays was catalyzed by Methanosarcinales and Methanomicrobiales. In all assays Pelotomaculum and Syntrophobacter species were dominant propionate degraders. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dark Matter's secret liaisons: phenomenology of a dark U(1) sector with bound states

NASA Astrophysics Data System (ADS)

Cirelli, Marco; Panci, Paolo; Petraki, Kalliopi; Sala, Filippo; Taoso, Marco

2017-05-01

Dark matter (DM) charged under a dark U(1) force appears in many extensions of the Standard Model, and has been invoked to explain anomalies in cosmic-ray data, as well as a self-interacting DM candidate. In this paper, we perform a comprehensive phenomenological analysis of such a model, assuming that the DM abundance arises from the thermal freeze-out of the dark interactions. We include, for the first time, bound-state effects both in the DM production and in the indirect detection signals, and quantify their importance for FERMI, AMS-02, and CMB experiments. We find that DM in the mass range 1 GeV to 100 TeV, annihilating into dark photons of MeV to GeV mass, is in conflict with observations. Instead, DM annihilation into heavier dark photons is viable. We point out that the late decays of multi-GeV dark photons can produce significant entropy and thus dilute the DM density. This can lower considerably the dark coupling needed to obtain the DM abundance, and in turn relax the existing constraints.

Dark Matter's secret liaisons: phenomenology of a dark U(1) sector with bound states

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

Cirelli, Marco; Petraki, Kalliopi; Sala, Filippo

Dark matter (DM) charged under a dark U(1) force appears in many extensions of the Standard Model, and has been invoked to explain anomalies in cosmic-ray data, as well as a self-interacting DM candidate. In this paper, we perform a comprehensive phenomenological analysis of such a model, assuming that the DM abundance arises from the thermal freeze-out of the dark interactions. We include, for the first time, bound-state effects both in the DM production and in the indirect detection signals, and quantify their importance for FERMI, AMS-02, and CMB experiments. We find that DM in the mass range 1 GeVmore » to 100 TeV, annihilating into dark photons of MeV to GeV mass, is in conflict with observations. Instead, DM annihilation into heavier dark photons is viable. We point out that the late decays of multi-GeV dark photons can produce significant entropy and thus dilute the DM density. This can lower considerably the dark coupling needed to obtain the DM abundance, and in turn relax the existing constraints.« less

Soluble tumor necrosis factor receptor 1 is associated with diminished estimated glomerular filtration rate in colombian patients with type 2 diabetes.

PubMed

Gómez-Banoy, Nicolás; Cuevas, Virginia; Higuita, Andrea; Aranzález, Luz Helena; Mockus, Ismena

2016-07-01

The tumor necrosis factor α (TNF-α) family of inflammatory molecules plays a crucial role in the pathogenesis of type 2 diabetes mellitus (DM2) complications. TNF-α soluble receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated with chronic kidney disease in DM2 patients. This cross-sectional study intended to determine serum concentrations of sTNFR1 and sTNFR2 in Colombian patients and correlated them with various clinical variables, especially kidney function. 92 Colombian patients with DM2 were recruited. Anthropometric variables, glycemic control parameters, lipid profile and renal function were assessed for each patient. Levels of sTNFR1 and sTNFR2 were determined using ELISA. Patients were stratified in two groups according to reduced estimated glomerular filtration rate (eGFR) (<60ml/min/1.73m(2)) and normal eGFR (≥60ml/min/1.73m(2)). Significantly elevated levels of sTNFR1 and sTNFR2 were observed in the diminished versus normal eGFR group. Also, significant differences were noticed between both groups in haemoglobin A1c (HbA1c) values, percentage of hypertensive subjects treated with angiotensin receptor blocker (ARB) and subjects treated with metformin. No differences were observed regarding body mass index (BMI), albuminuria and lipid profile. Multivariable linear regression analysis revealed that sTNFR1 alone showed a significant association with low eGFR (p=0.009). However, after adjusting for age, the association weakens. Moreover, sTNFR1 and sTNFR2 showed a linear negative correlation with eGFR (r=-0.448, p<0.001 and r=-0.376, p<0.001, respectively). A positive correlation was also seen between sTNFR1 and HbA1c, whereas a negative correlation between both sTNFRs and high-density lipoprotein (HDL) cholesterol was found. Elevated levels of sTNFRs, especially sTNFR1, are associated with loss of kidney function in Hispanic patients with DM2. Future studies should focus on social and genetic determinants of inflammation and their association with CKD in this ethnicity. Copyright © 2016 Elsevier Inc. All rights reserved.

[Relationship between brachial-ankle pulse wave velocity and glycemic control of type 2 diabetes mellitus patients in Beijing community population].

PubMed

Sun, Ke-xin; Liu, Zhi-ke; Cao, Ya-ying; Juan, Juan; Xiang, Xiao; Yang, Cheng; Huang, Shao-ping; Liu, Xiao-fen; Li, Na; Tang, Xun; Li, Jin; Wu, Tao; Chen, Da-fang; Hu, Yong-hua

2015-06-18

To explore the correlation between glycemic control of type 2 diabetes mellitus (T2DM) patients and brachial-ankle pulse velocity (baPWV). A community-based cross-sectional study was conducted in Beijing, China. Every subject underwent physical examinations, glycated hemoglobin (HbA1c), blood lipid and baPWV measurements and completed a standardized questionnaire. T2DM patients were divided into well controlled and poorly controlled groups according to HbA1c levels. The correlation between glycemic control of T2DM patients and baPWV was analyzed. In this study, 1 341 subjects were recruited, including 733 T2DM patients and 608 non-diabetes subjects. Compared with non-diabetes subjects, abnormal baPWV (baPWV≥1 700 cm/s) rate for T2DM patients was higher (40.8% vs. 26.8%, P<0.001). With HbA1c<6.5% or <7.0% as the aim of glycemic control in T2DM patients, the abnormal baPWV rates for non-diabetes subjects, well controlled and poorly controlled T2DM patients were significantly different (non-diabetes vs. HbA1c<6.5% T2DM vs. HbA1c≥6.5% T2DM: 26.8% vs. 32.8% vs. 42.6%, P<0.001; non-diabetes vs. HbA1c<7.0% T2DM vs. HbA1c≥7.0% T2DM: 26.8% vs. 36.1% vs. 43.4%, P<0.001). After being adjusted for gender, age, smoking status, diabetes mellitus family history, T2DM duration, cardiovascular diseases (CVD), waist hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), total triglycerides (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C), the Logistic regression models suggested that glycemic control status of T2DM patients was associated with abnormal baPWV. Compared with non-diabetes subjects, the ORs for abnormal baPWV in HbA1c<6.5% T2DM patients and HbA1c≥6.5% T2DM patients were 0.927(95%CI 0.560-1.537) and 1.826 (95%CI 1.287-2.591). Compared with non-diabetes subjects, the ORs for abnormal baPWV in HbA1c<7.0% T2DM patients and HbA1c≥7.0% T2DM patients were 1.210 (95%CI 0.808-1.811) and 1.898 (95%CI 1.313-2.745). The glycemic control status of T2DM patients from communities is significantly associated with baPWV. Poor glycemic control is a risk factor for abnormal baPWV. Keeping HbA1c under control might lower the risk of cardiovascular diseases in T2DM patients.

Evaluation of immunogenicity of LY2963016 insulin glargine compared with Lantus® insulin glargine in patients with type 1 or type 2 diabetes mellitus.

PubMed

Ilag, L L; Deeg, M A; Costigan, T; Hollander, P; Blevins, T C; Edelman, S V; Konrad, R J; Ortmann, R A; Pollom, R K; Huster, W J; Zielonka, J S; Prince, M J

2016-02-01

To compare the immunogenicity profiles and the potential effects on clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus® insulin glargine (IGlar), products with identical primary amino acid sequences, in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). To assess immunogenicity, anti-insulin glargine antibodies (measured as percent binding) were compared between treatments in 52-week (open-label) and 24-week (double-blind) randomized studies in total study populations of patients with T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients with T2DM: insulin-naïve patients and those reporting prestudy IGlar treatment (prior IGlar). Relationships between insulin antibody levels and clinical outcomes were assessed using analysis of covariance and partial correlations. Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment comparisons for treatment-emergent antibody response (TEAR) and incidence of detectable antibodies were analysed using Fisher's exact test. No significant treatment differences were observed for insulin antibody levels, incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR [overall and endpoint, by last-observation-carried-forward (LOCF)] in patients with T1DM or patients with T2DM, including the insulin-naïve subgroup. A statistically significant difference was noted in the overall incidence of detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar subgroup of patients with T2DM. Insulin antibody levels were low (<5%) in both treatment groups. Insulin antibody levels or developing TEAR was not associated with clinical outcomes. LY IGlar and IGlar have similar immunogenicity profiles; anti-insulin glargine antibody levels were low for both treatments, with no observed effect on efficacy and safety outcomes. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Stellar model chromospheres. XIII - M dwarf stars

NASA Technical Reports Server (NTRS)

Giampapa, M. S.; Worden, S. P.; Linsky, J. L.

1982-01-01

Single-component, homogeneous model chromospheres that are consistent with high-resolution profiles of the Ca II K line calibrated in surface flux units for three dMe and 2 dM stars observed at quiescent times are constructed. The models reveal several systematic trends. Large values of the ratio of T(min) to T(eff) are derived, indicating a large amount of nonradiative heating present in the upper photospheres of M dwarf stars. It is also found that the lower chromospheric temperature gradient is similar for all the M dwarf stars. Since for the models here the chromospheric K line emission strength is most sensitive to the total amount of chromospheric material present within the approximate temperature range T(min)-6000 K, increasing the emission strength is not simply due to increasing chromospheric temperature gradients. It is also found that both the electron density and electron temperature at one thermalization length in the K line below the top of the chromospheres are greater in the dMe stars than in the dM stars. The M dwarf models here have microturbulent velocities between 1 and 2 km/sec, which are much smaller than for solar chromosphere models.

Dark gamma-ray bursts

NASA Astrophysics Data System (ADS)

Brdar, Vedran; Kopp, Joachim; Liu, Jia

2017-03-01

Many theories of dark matter (DM) predict that DM particles can be captured by stars via scattering on ordinary matter. They subsequently condense into a DM core close to the center of the star and eventually annihilate. In this work, we trace DM capture and annihilation rates throughout the life of a massive star and show that this evolution culminates in an intense annihilation burst coincident with the death of the star in a core collapse supernova. The reason is that, along with the stellar interior, also its DM core heats up and contracts, so that the DM density increases rapidly during the final stages of stellar evolution. We argue that, counterintuitively, the annihilation burst is more intense if DM annihilation is a p -wave process than for s -wave annihilation because in the former case, more DM particles survive until the supernova. If among the DM annihilation products are particles like dark photons that can escape the exploding star and decay to standard model particles later, the annihilation burst results in a flash of gamma rays accompanying the supernova. For a galactic supernova, this "dark gamma-ray burst" may be observable in the Čerenkov Telescope Array.

iTRAQ-based quantitative protein expression profiling and MRM verification of markers in type 2 diabetes.

PubMed

Kaur, Prabhjit; Rizk, Nasser M; Ibrahim, Sereen; Younes, Noura; Uppal, Arushi; Dennis, Kevin; Karve, Tejaswita; Blakeslee, Kenneth; Kwagyan, John; Zirie, Mahmoud; Ressom, Habtom W; Cheema, Amrita K

2012-11-02

The pathogenesis of Type 2 diabetes mellitus (T2DM) is complex owing to molecular heterogeneity in the afflicted population. Current diagnostic methods rely on blood glucose measurements, which are noninformative with respect to progression of the disease to other associated pathologies. Thus, predicting the risk and development of T2DM-related complications, such as cardiovascular disease, remains a major challenge. We have used a combination of quantitative methods for characterization of circulating serum biomarkers of T2DM using a cohort of nondiabetic control subjects (n = 76) and patients diagnosed with T2DM (n = 106). In this case-control study, the samples were randomly divided as training and validation data sets. In the first step, iTRAQ (isobaric tagging for relative and absolute quantification) based protein expression profiling was performed for identification of proteins displaying a significant differential expression in the two study groups. Five of these protein markers were selected for validation using multiple reaction-monitoring mass spectrometry (MRM-MS) and further confirmed with Western blot and QPCR analysis. Functional pathway analysis identified perturbations in lipid and small molecule metabolism as well as pathways that lead to disruption of glucose homeostasis and blood coagulation. These putative biomarkers may be clinically useful for subset stratification of T2DM patients as well as for the development of novel therapeutics targeting the specific pathology.

Phenolic compounds in hawthorn (Crataegus grayana) fruits and leaves and changes during fruit ripening.

PubMed

Liu, Pengzhan; Kallio, Heikki; Yang, Baoru

2011-10-26

Phenolics in the fruits and leaves of Crataegus grayana were identified by HPLC-UV-ESI-MS. The contents of these compounds and their changes during autumn were also analyzed. Epicatechin [1-7 mg/g dry mass (DM) in fruits and 1-10 mg/g DM in leaves), procyanidins B2 (2-4 and 1-8 mg/g DM) and C1 (2-4 and 1-8 mg/g DM), hyperoside (0.5-1 and 2-11 mg/g DM), and a quercetin-pentoside (0.3-0.5 and 2-6 mg/g DM) were the major phenolics in both fruits and leaves. C-Glycosyl flavones were present in leaves (2-5 mg/g DM), whereas only trace levels were found in fruits. Ideain and 5-O-caffeoylquinic acid were found only in fruits. An additional 11 phenolics were identified/tentatively identified. Total phenolic contents reached highest levels by the end of August in fruits and by the end of September in leaves. The compositional profiles of phenolics in fruits and leaves of C. grayana were different from those of other Crataegus species.

Effect of Korean Red Ginseng treatment on the gene expression profile of diabetic rat retina

PubMed Central

Yang, Hana; Son, Gun Woo; Park, Hye Rim; Lee, Seung Eun; Park, Yong Seek

2015-01-01

Background Korean Red Ginseng (KRG) is a herbal medicine used in Asian countries and is very popular for its beneficial biological properties. Diabetes mellitus (DM) and its complications are rapidly becoming a global public health concern. The literature on transcriptional changes induced by KRG in rat models of diabetic retinopathy is limited. Considering these facts, we designed this study to determine whether retinopathy-associated genes are altered in retinas of rats with DM and whether the induced changes are reversed by KRG. Methods Male Sprague–Dawley rats were intravenously injected with streptozotocin (50 mg/kg body weight) to induce DM, following which, KRG powder (200 mg/kg body weight) was orally administered to the KRG-treated DM rat group for 10 wks. The rats were then sacrificed, and their retinas were harvested for total RNA extraction. Microarray gene expression profiling was performed on the extracted RNA samples. Results From among > 31,000 genes investigated, the expression of 268 genes was observed to be upregulated and that of 58 genes was downregulated, with twofold altered expression levels in the DM group compared with those in the control group. Moreover, 39 genes were upregulated more than twofold and 84 genes were downregulated in the KRG-treated group compared to the DM group. The expression of the genes was significantly reversed by KRG treatment; some of these genes were analyzed further to verify the results of the microarray experiments. Conclusion Taken together, our data suggest that reversed changes in the gene expression may mediate alleviating activities of KRG in rats with diabetic retinopathy. PMID:26843816

Neuropsychological function in type 2 diabetes mellitus.

PubMed

Nici, Janice; Hom, Jim

2018-05-04

Type 2 diabetes mellitus (DM) is a major and growing health problem. Brain-related effects of type 2 DM have been studied in several ways over the past few decades. Results have shown effects on brain structure, incidence of dementia, and impairment of various cognitive functions. The present study examined a sample of clinically-referred patients with type 2 DM and compared them with a sample of control patients who were matched on a pairwise basis on age, education, and gender. Each patient was tested using a comprehensive, integrated neuropsychological test battery. Results showed a pattern of generalized and specific neuropsychological dysfunction affecting a broad range of neurocognitive and sensorimotor abilities. However, no differences were found on measures of attention/concentration, memory, or abstract reasoning. Nevertheless, the DM group consistently performed worse on all measures. The DM group's score on a summary measure of neuropsychological function (GNDS) reflected moderate brain-related impairment. A neurocognitive profile is identified that may help clinicians understand their DM patients.

Gene Polymorphisms of Glutathione S-Transferase T1/M1 in Egyptian Children and Adolescents with Type 1 Diabetes Mellitus.

PubMed

Barseem, Naglaa; Elsamalehy, Mona

2017-06-01

Oxidative stress plays an important role in the pathogenesis of type 1 diabetes mellitus (T1DM). To evaluate the association of glutathione S-transferase mu 1 (GST M1) and glutathione S-transferase theta 1 (GST T1) polymorphisms with development of T1DM and disease-related risk factors. Measurement of fasting glucose, serum creatinine, lipid profile, and glycosylated hemoglobin (HbA1c), as well as evaluation of GST T1 and M1 genetic polymorphisms using polymerase chain reaction were done in 64 diabetic children and 41 controls. The diabetic group had significantly higher fasting glucose, HbA1c, and cholesterol levels. GST T1 null genotype was more frequent in the diabetic than the control group with 4.2-fold increased risk of T1DM (odds ratio=4.2; 95% confidence interval=1.6-11.5; p=0.03). Significant positive associations were found with lipid profile, HbA1c, and duration of illness but not with age, age at onset, and body mass index. Gene polymorphisms of the enzyme GST are associated with development of T1DM and disease-related risk factors.

Plasma triglyceride determination can identify increased risk of statin-induced type 2 diabetes: a hypothesis.

PubMed

Armato, J; Ruby, R; Reaven, G

2015-04-01

To evaluate the ability of plasma triglyceride (TG) measurements to identify statin-treated persons at accentuated risk of statin-induced type 2 diabetes (T2DM). The experimental population consisted of nondiabetic, statin-treated patients (n = 469), classified as being at high risk for T2DM, subdivided on the basis of a plasma TG concentration of 1.7 mmol/L. Comparisons were made of demographic characteristics, concentrations of fasting glucose, insulin, HbA1c, and hs-CRP, oral glucose tolerance tests, estimates of insulin action and secretion, and lipid/lipoprotein profiles. Despite similar fasting glucose and HbA1c concentrations, patients with elevated TG concentrations displayed markers of increased risk of T2DM (insulin resistance and compensatory hyperinsulinemia), more adverse lipid/lipoprotein profiles, and increased prevalence of abnormal hs-CRP values. These findings demonstrate that plasma TG concentrations ≥ 1.7 mmol/L identified a subset of individuals at enhanced risk of developing statin-induced diabetes within a population classified prior to statin treatment as being at high risk of T2DM. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Achievement of national clinical practice recommendations among those in the Puerto Rican population with diabetes mellitus.

PubMed

Rodríguez-Vigil, Efraín; Rodríguez-Chacón, Migdalia; Trabanco, Cesar; Irizarry-Ramos, Jessica

2014-12-01

To analyze glycemic control among patients with diabetes mellitus (DM) in Puerto Rico (PR) using the 2011 American Diabetes Association (ADA) recommendations and glycemic goals as standards. We also explored other factors that are related to glycemic control. Glycemic data were obtained from 600 adults with DM from 5 different regions in PR. The patient's health insurance coverage, type of health care provider, type of diabetes treatment, gender, age, physical activity, weight, degree of hypertension and degree and type of dyslipidemia comorbidities (when one or both were applicable), and disease duration were variables of interest. Univariate and bivariate analyses were conducted to describe the population and determine the statistical differences in the glycemic control of the subjects. Fewer than half of the participants achieved the ADA-recommended levels for HbA1c (37.3%) and blood pressure (34%). However, relatively more participants met the goals for high-density lipoprotein cholesterol (51.7%), low-density lipoprotein cholesterol (59.9%), and triglycerides (61.5%). The percentage of participants reaching the HbA1c, blood pressure, and low-density lipoprotein cholesterol goals at the same time was 9.9%. Patients with private health insurance achieved better glycemic control than did patients in the public-managed healthcare system. Half of the population presented simultaneous hypertension, dyslipidemia, and DM comorbidities. Only 50% of the participants were physically active. In the sample population, glycemic control levels and blood pressure levels in adults with DM were far from the ADA-recommended standards. Physical activity levels, type of medical insurance, and type of DM medical treatment were the main modifiable factors associated with the goal of attaining glycemic control. Barriers that limit the achievement of this goal should be analyzed in more detail to improve the medical care for people with DM.

[Diabetes mellitus and osteoporosis. How to start drug therapy for osteoporosis in patients with diabetes mellitus].

PubMed

Yamaguchi, Toru

2012-09-01

Drug treatment for osteoporosis is intended to prevent osteoporotic fractures. Physicians should assess fracture risk in patients with diabetes not only by measuring bone mineral density (BMD) but also by taking a fracture history and evaluating prior vertebral fractures using spinal X-rays when starting drug therapy. Accumulating evidence shows that patients with diabetes (DM) have a high risk for fragility fractures independent of BMD. Thus, when DM patients have osteopenia, fracture risk could become higher than non-DM counterparts, and drug therapy should be considered to prevent fragility fractures. The criteria for starting drug treatment to prevent fragility fractures in DM patients, albeit tentative, are shown in this article.

Circulating adipokines data associated with insulin secretagogue use in breast cancer patients.

PubMed

Wintrob, Zachary A P; Hammel, Jeffrey P; Nimako, George K; Fayazi, Zahra S; Gaile, Dan P; Forrest, Alan; Ceacareanu, Alice C

2017-02-01

Oral drugs stimulating endogenous insulin production (insulin secretagogues) may have detrimental effects on breast cancer outcomes. The data presented shows the relationship between pre-existing insulin secretagogues use, adipokine profiles at the time of breast cancer (BC) diagnosis and subsequent cancer outcomes in women diagnosed with BC and type 2 diabetes mellitus (T2DM). The Pearson correlation analysis evaluating the relationship between adipokines stratified by T2DM pharmacotherapy and controls is also provided. This information is the extension of the data presented and discussed in " Insulin use, adipokine profiles and breast cancer prognosis " (Wintrob et al., in press) [1].

Association of larger holes in the trabecular bone at the distal radius in postmenopausal women with type 2 diabetes mellitus compared to controls.

PubMed

Pritchard, Janet M; Giangregorio, Lora M; Atkinson, Stephanie A; Beattie, Karen A; Inglis, Dean; Ioannidis, George; Punthakee, Zubin; Adachi, J D; Papaioannou, Alexandra

2012-01-01

Adults with type 2 diabetes mellitus (DM) have an elevated fracture risk despite normal areal bone mineral density (aBMD). The study objective was to compare trabecular bone microarchitecture of postmenopausal women with type 2 DM and women without type 2 DM. An extremity 1T magnetic resonance imaging system was used to acquire axial images (195 × 195 × 1,000 μm(3) voxel size) of the distal radius of women recruited from outpatient clinics or by community advertisement. Image segmentation yielded geometric, topologic, and stereologic outcomes, i.e., number and size of trabecular bone network holes (marrow spaces), endosteal area, trabecular bone volume fraction, nodal and branch density, and apparent trabecular thickness, separation, and number. Lumbar spine (LS) and proximal femur BMD were measured with dual x-ray absorptiometry. Microarchitectural differences were assessed using linear regression and adjusted for percent body fat, ethnicity, timed up-and-go test, Charlson Index, and calcium and vitamin D intake; aBMD differences were adjusted for body mass index (BMI). Women with type 2 DM (n = 30, mean ± SD age 71.0 ± 4.8 years) had larger holes (+13.3%; P = 0.001) within the trabecular bone network than women without type 2 DM (n = 30, mean ± SD age 70.7 ± 4.9 years). LS aBMD was greater in women with type 2 DM; however, after adjustment for BMI, LS aBMD did not differ between groups. In women with type 2 DM, the average hole size within the trabecular bone network at the distal radius is greater compared to controls. This may explain the elevated fracture risk in this population. Copyright © 2012 by the American College of Rheumatology.

Meta-analyses of structural regional cerebral effects in type 1 and type 2 diabetes.

PubMed

Moulton, Calum D; Costafreda, Sergi G; Horton, Paul; Ismail, Khalida; Fu, Cynthia H Y

2015-12-01

Diabetes is associated with macrovascular and microvascular complications and is a major risk factor for neurological and psychiatric disorders, such as dementia and depression. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) have distinct etiologies and pathophysiological effects while sharing a common endpoint of persistent hyperglycemia. Neuroimaging studies in T1DM have revealed reductions in numerous regions, including the parahippocampal and occipital regions, while in T2DM there have been numerous reports of hippocampal atrophy. This meta-analysis aimed to identify consistent regional abnormalities in cerebral structures in T1DM and T2DM respectively, and also to examine the impact of potential confounds, including age, depression and vascular risk factors. Neuroimaging studies of both voxel-based morphometry (VBM) data and volumetric data were included. Ten T1DM studies (n = 613 patients) and 23 T2DM studies (n = 1364 patients) fulfilled inclusion criteria. The T1DM meta-analysis revealed reduced bilateral thalamus grey matter density in adults. The T2DM meta-analysis revealed reduced global brain volume and regional atrophy in the hippocampi, basal ganglia, and orbitofrontal and occipital lobes. Moreover, hippocampal atrophy in T2DM was not modified by hypertension, although there were more marked reductions in younger patients relative to healthy controls. In conclusion, T1DM and T2DM demonstrated distinct cerebral effects with generalised and specific target areas of grey matter reduction. Thalamic atrophy in T1DM may be a substrate of associated cognitive deficits. In T2DM, global cerebral atrophy may reflect atherosclerotic factors, while hippocampal atrophy was an independent effect providing a potential common neuropathological etiology for the comorbidity of T2DM with dementia and depression.

DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1.

PubMed

Ogitani, Yusuke; Aida, Tetsuo; Hagihara, Katsunobu; Yamaguchi, Junko; Ishii, Chiaki; Harada, Naoya; Soma, Masako; Okamoto, Hiromi; Oitate, Masataka; Arakawa, Shingo; Hirai, Takehiro; Atsumi, Ryo; Nakada, Takashi; Hayakawa, Ichiro; Abe, Yuki; Agatsuma, Toshinori

2016-10-15

An anti-HER2 antibody-drug conjugate with a novel topoisomerase I inhibitor, DS-8201a, was generated as a new antitumor drug candidate, and its preclinical pharmacologic profile was assessed. In vitro and in vivo pharmacologic activities of DS-8201a were evaluated and compared with T-DM1 in several HER2-positive cell lines and patient-derived xenograft (PDX) models. The mechanism of action for the efficacy was also evaluated. Pharmacokinetics in cynomolgus monkeys and the safety profiles in rats and cynomolgus monkeys were assessed. DS-8201a exhibited a HER2 expression-dependent cell growth-inhibitory activity and induced tumor regression with a single dosing at more than 1 mg/kg in a HER2-positive gastric cancer NCI-N87 model. Binding activity to HER2 and ADCC activity of DS-8201a were comparable with unconjugated anti-HER2 antibody. DS-8201a also showed an inhibitory activity to Akt phosphorylation. DS-8201a induced phosphorylation of Chk1 and Histone H2A.X, the markers of DNA damage. Pharmacokinetics and safety profiles of DS-8201a were favorable and the highest non-severely toxic dose was 30 mg/kg in cynomolgus monkeys, supporting DS-8201a as being well tolerated in humans. DS-8201a was effective in a T-DM1-insensitive PDX model with high HER2 expression. DS-8201a, but not T-DM1, demonstrated antitumor efficacy against several breast cancer PDX models with low HER2 expression. DS-8201a exhibited a potent antitumor activity in a broad selection of HER2-positive models and favorable pharmacokinetics and safety profiles. The results demonstrate that DS-8201a will be a valuable therapy with a great potential to respond to T-DM1-insensitive HER2-positive cancers and low HER2-expressing cancers. Clin Cancer Res; 22(20); 5097-108. ©2016 AACR. ©2016 American Association for Cancer Research.

Comparative analysis of quantum cascade laser modeling based on density matrices and non-equilibrium Green's functions

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

Lindskog, M., E-mail: martin.lindskog@teorfys.lu.se; Wacker, A.; Wolf, J. M.

2014-09-08

We study the operation of an 8.5 μm quantum cascade laser based on GaInAs/AlInAs lattice matched to InP using three different simulation models based on density matrix (DM) and non-equilibrium Green's function (NEGF) formulations. The latter advanced scheme serves as a validation for the simpler DM schemes and, at the same time, provides additional insight, such as the temperatures of the sub-band carrier distributions. We find that for the particular quantum cascade laser studied here, the behavior is well described by simple quantum mechanical estimates based on Fermi's golden rule. As a consequence, the DM model, which includes second order currents,more » agrees well with the NEGF results. Both these simulations are in accordance with previously reported data and a second regrown device.« less

Density matrix modeling of quantum cascade lasers without an artificially localized basis: A generalized scattering approach

NASA Astrophysics Data System (ADS)

Pan, Andrew; Burnett, Benjamin A.; Chui, Chi On; Williams, Benjamin S.

2017-08-01

We derive a density matrix (DM) theory for quantum cascade lasers (QCLs) that describes the influence of scattering on coherences through a generalized scattering superoperator. The theory enables quantitative modeling of QCLs, including localization and tunneling effects, using the well-defined energy eigenstates rather than the ad hoc localized basis states required by most previous DM models. Our microscopic approach to scattering also eliminates the need for phenomenological transition or dephasing rates. We discuss the physical interpretation and numerical implementation of the theory, presenting sets of both energy-resolved and thermally averaged equations, which can be used for detailed or compact device modeling. We illustrate the theory's applications by simulating a high performance resonant-phonon terahertz (THz) QCL design, which cannot be easily or accurately modeled using conventional DM methods. We show that the theory's inclusion of coherences is crucial for describing localization and tunneling effects consistent with experiment.

Study protocol: a randomised controlled trial of supervised resistance training versus aerobic training in Sri Lankan adults with type 2 diabetes mellitus: SL-DART study.

PubMed

Ranasinghe, C; Hills, A P; Constantine, G R; Finlayson, G; Katulanda, P; King, N A

2018-01-24

The prevalence of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) is rising globally. T2DM is particularly problematic in South Asia with an estimated 10-15% of Sri Lankans diagnosed with the disease. Exercise is known to improve blood glucose, lipid profiles, blood pressure and adiposity, key goals in the management of T2DM. However, much of the evidence to date has been gained from white Caucasians who have a different body composition and disease profile compared to South Asians. Similarly, the recreational exercise culture is new to Sri Lankans and the effects of exercise on T2DM has not been studied in this population. The Sri Lanka Diabetes Aerobic and Resistance Training (SL-DART) Study will be comprised of 2 components. Component 1 is a 12-week randomized controlled trial (RCT) to compare the effects of a supervised progressive resistance exercise program (RT) and aerobic exercise program (AT) with standard treatment/control (CN). Sedentary Sri Lankan adults with T2DM (aged 35-65 years) and with no contraindications to exercise will be randomized into one of 3 groups (AT, RT, CN). Exercise sessions will be conducted 2 days/week for 3 months. Baseline and post-intervention biochemical (glycemic control, lipid and liver profiles, inflammatory markers), anthropometric (height, weight, body circumferences), body composition, physical fitness, food preference (liking and wanting food) and quality of life parameters will be measured and compared between groups. Component 2 will be a qualitative study conducted immediately post-intervention via in-depth interviews to assess the barriers and facilitators for adherence to each exercise program. SL-DART Study represents one of the first adequately powered methodologically sound RCTs conducted in South Asia to assess the effects of resistance and aerobic exercise in participants with T2DM. Triangulation of quantitative and qualitative outcomes will enable the design of a culturally appropriate therapeutic physical activity intervention for Sri Lankans with T2DM, and the initiation of a professionally driven and specialized clinical exercise prescription service. Sri Lanka Clinical Trials Registry; SLCTR/2016/017 . Date registered 17.06.2016. Universal trial number U1111-1181-7561.

Effect of garlic supplement in the management of type 2 diabetes mellitus (T2DM): a meta-analysis of randomized controlled trials

PubMed Central

Wang, Juan; Zhang, Xiuming; Lan, Haili; Wang, Weijia

2017-01-01

ABSTRACT The present study was designed to systematically evaluate the clinical efficacy and safety of garlic supplement in the management of type 2 diabetes mellitus (T2DM). PubMed, EMBASE, the Cochrane Library, and China National Knowledge Internet (CNKI) were searched for relevant randomized controlled trials (RCTs) by using the terms garlic and T2DM up to April 2017. The quality of included RCTs was assessed by the Cochrane tool of risk of bias, and data of outcomes were pooled by REVMAN 5.3. Clinical factors were handled by meta-regression and subgroup analysis, and risk of publication bias was explored by inverted funnel plots. Nine RCTs involving 768 T2DM patients were included in the meta-analysis, and the dose of daily garlic (allicin) supplement ranged from 0.05g to 1.5g. A significant reduction in the level of fasting blood glucose in 1–2 weeks [SMD = −1.61, 95%CI (−2.89, −0.32)], 3–4 weeks [SMD = −2.87, 95%CI (−4.74, −1.00)], 12 weeks [SMD = −9.57, 95%CI (−12.39, −6.75)], and 24 weeks [SMD = −21.02, 95%CI (−32.47, −9.57)] was achieved in favour of the garlic group rather than the control group. Significantly decreased fructosamine and glycated hemoglobin (both in 12 and 24 weeks) were also found in garlic group. Meanwhile, significantly improved blood liquids of total cholesterol [SMD = −1.93, 95%CI (−2.98, −0.87), 3–4 weeks], high density lipoprotein [SMD = −0.41, 95%CI (−0.83, −0.00), 3–4 weeks] and low density lipoprotein [SMD = −3.47, 95%CI (−5.76, −1.18), 12 weeks] were confirmed after garlic administration. There was no significant difference in complications. Current data confirms that garlic supplement plays positive and sustained roles in blood glucose, total cholesterol, and high/low density lipoprotein regulation in the management of T2DM. Abbreviations: T2DM = type 2 diabetes mellitus; RCT = randomized controlled trial; SMD = standard mean difference; CI = confidence interval; FBG = fasting blood glucose; HbA1c = glycated hemoglobin; HDL = high density lipoprotein; LDL = low density lipoprotein. PMID:29056888

The effect of pomegranate fresh juice versus pomegranate seed powder on metabolic indices, lipid profile, inflammatory biomarkers, and the histopathology of pancreatic islets of Langerhans in streptozotocin-nicotinamide induced type 2 diabetic Sprague-Dawley rats.

PubMed

Taheri Rouhi, Seyedeh Zeinab; Sarker, Md Moklesur Rahman; Rahmat, Asmah; Alkahtani, Saad Ahmed; Othman, Fauziah

2017-03-14

Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia, inflammatory disorders and abnormal lipid profiles. Several functional foods have therapeutic potential to treat chronic diseases including diabetes. The therapeutic potential of pomegranate has been stated by multitudinous scientists. The present study aimed to evaluate the effects of pomegranate juice and seed powder on the levels of plasma glucose and insulin, inflammatory biomarkers, lipid profiles, and health of the pancreatic islets of Langerhans in streptozotocin (STZ)-nicotinamide (NAD) induced T2DM Sprague Dawley (SD) rats. Forty healthy male SD rats were induced to diabetes with a single dose intra-peritoneal administration of STZ (60 mg/kg b.w.) - NAD (120 mg/kg b.w.). Diabetic rats were orally administered with 1 mL of pomegranate fresh juice (PJ) or 100 mg pomegranate seed powder in 1 mL distilled water (PS), or 5 mg/kg b.w. of glibenclamide every day for 21 days. Rats in all groups were sacrificed on day 22. The obtained data was analyzed by SPSS software (v: 22) using One-way analysis of variance (ANOVA). The results showed that PJ and PS treatment had slight but non-significant reduction of plasma glucose concentration, and no impact on plasma insulin compared to diabetic control (DC) group. PJ lowered the plasma total cholesterol (TC) and triglyceride (TG) significantly, and low-density lipoproteins (LDL) non-significantly compared to DC group. In contrast, PS treatment significantly raised plasma TC, LDL, and high-density lipoproteins (HDL) levels compared to the DC rats. Moreover, the administration of PJ and PS significantly reduced the levels of plasma inflammatory biomarkers, which were actively raised in diabetic rats. Only PJ treated group showed significant repairment and restoration signs in islets of Langerhans. Besides, PJ possessed preventative impact against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals almost 2.5 folds more than PS. Our findings suggest that active constituents with high antioxidant properties present in PJ are responsible for its anti-hyperlipidemic and anti-inflammatory effects, likewise the restoration effect on the damaged islets of Langerhans in experimental rats. Hence, the pharmacological, biochemical, and histopathological profiles of PJ treated rats obviously indicated its helpful effects in amelioration of diabetes-associated complications.

[Soil macropore characteristics under typical vegetations in Liupan Mountains].

PubMed

Shi, Zhong-Jie; Wang, Yan-Hui; Xu, Li-Hong; Yu, Peng-Tao; Xiong, Wei; Xu, Da-Ping

2007-12-01

The radius and density of soil macropores under eight typical vegetations in Liupan Mountains of Northwest China were studied by using water breakthrough curves and Poiseuille equation. The results indicated that the radii of soil macropores ranged from 0.4 mm to 2.3 mm, and the weighted mean radii ranged from 0.57 mm to 1.21 mm, with a mean of 0.89 mm. The density of soil macropores ranged from 57 individuals per dm2 to 1 117 individuals per dm2, with a mean of 408 individuals per dm2. The macropores with radii bigger than 1.4 mm had a lower density, accounting for only 6.86% of the total. The area proportion of soil macropores ranged from 0.76% to 31.26%, with a mean of 10.82%. In study area, the density of soil macropores was higher in broadleaf forest than in coniferous forest, but basically the same in sub-alpine meadow and in broadleaf forest, as well as in shrubs and in coniferous forest. As for the area proportion of soil macropores, it was also higher in broadleaf forest than in coniferous forest, but basically the same in shrubs and in broadleaf forest soil, as well as in sub-alpine meadow and in coniferous forest.

Real-world crude incidence of hypoglycemia in adults with diabetes: Results of the InHypo-DM Study, Canada.

PubMed

Ratzki-Leewing, Alexandria; Harris, Stewart B; Mequanint, Selam; Reichert, Sonja M; Belle Brown, Judith; Black, Jason Edward; Ryan, Bridget L

2018-01-01

Very few real-world studies have been conducted to assess the incidence of diabetes-related hypoglycemia. Moreover, there is a paucity of studies that have investigated hypoglycemia among people taking secretagogues as a monotherapy or in combination with insulin. Accordingly, our research team developed and validated the InHypo-DM Person with Diabetes Mellitus Questionnaire (InHypo-DMPQ) with the aim of capturing the real-world incidence of self-reported, symptomatic hypoglycemia. The questionnaire was administered online to a national sample of Canadians (≥18 years old) with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) treated with insulin and/or insulin secretagogues. Self-report data obtained from the InHypo-DMPQ were descriptively analyzed to ascertain the crude incidence proportions and annualized incidence densities (rates) of 30-day retrospective non-severe and 1-year retrospective severe hypoglycemia, including daytime and nocturnal events. A total of 552 people (T2DM: 83%; T1DM: 17%) completed the questionnaire. Over half (65.2%) of the total respondents reported experiencing at least one event (non-severe or severe) at an annualized crude incidence density of 35.1 events per person-year. The incidence proportion and rate of non-severe events were higher among people with T1DM versus T2DM (77% and 55.7 events per person-year vs 54% and 28.0 events per person-year). Severe hypoglycemia was reported by 41.8% of all respondents, at an average rate of 2.5 events per person-year. The results of the InHypo-DMPQ, the largest real-world investigation of hypoglycemia epidemiology in Canada, suggest that the incidence of hypoglycemia among adults with diabetes taking insulin and/or insulin secretagogues is higher than previously thought.

Circulating C1q complement/TNF-related protein (CTRP) 1, CTRP9, CTRP12 and CTRP13 concentrations in Type 2 diabetes mellitus: In vivo regulation by glucose

PubMed Central

Zhang, Man Man; Tan, Bee Kang; Chen, Jing

2017-01-01

Objectives The C1q complement/TNF-related protein (CTRP) superfamily, which includes the adipokine adiponectin, has been shown in animal models to have positive metabolic and cardiovascular effects. We sought to investigate circulating CTRP1, CTRP9, CTRP12 and CTRP13 concentrations in persons with type 2 diabetes mellitus (T2DM), with age and BMI matched controls, and to examine the effects of a 2 hour 75g oral glucose tolerance test (OGTT) on serum CTRP1, CTRP9, CTRP12 and CTRP13 levels in persons with T2DM. Design Cross-sectional study [newly diagnosed T2DM (n = 124) and control (n = 139) participants]. Serum CTRP1, CTRP9, CTRP12 and CTRP13 were measured by ELISA. Results Systolic and diastolic blood pressure, total cholesterol (TCH), Low-density lipoprotein (LDL)-cholesterol, triglycerides, TCH/High-density lipoprotein (HDL) ratio, triglycerides/HDL ratio, glucose, insulin, homeostatic model assessment–insulin resistance (HOMA-IR), C-reactive protein and endothelial lipase were significantly higher, whereas leptin and adiponectin were significantly lower in T2DM participants. Serum CTRP1 were significantly higher and CTRP12 significantly lower in T2DM participants. Age, diastolic blood pressure, glucose and CTRP12 were predictive of serum CTRP1; leptin was predictive of serum CTRP9; glucose and CTRP1 were predictive of serum CTRP12; endothelial lipase was predictive of serum CTRP13. Finally, serum CTRP1 were significantly higher and CTRP12 significantly lower in T2DM participants after a 2 hour 75g OGTT. Conclusions Our data supports CTRP1 and CTRP12 as potential novel biomarkers for the prediction and early diagnosis of T2DM. Furthermore, pharmacological agents that target CTRP1 and CTRP12 could represent a new strategy in the treatment of T2DM. PMID:28207876

Study of the boxlike dark matter signals from dwarf spheroidal galaxies with Fermi-LAT data

NASA Astrophysics Data System (ADS)

Li, Shang; Liang, Yun-Feng; Xia, Zi-Qing; Zu, Lei; Duan, Kai-Kai; Shen, Zhao-Qiang; Feng, Lei; Yuan, Qiang; Fan, Yi-Zhong

2018-04-01

The observation of a special spectral feature in the gamma-ray data would be one of the best ways to identify dark matter (DM). The box-shaped gamma-ray spectra could be generated by the decay of intermediate particles produced by DM annihilation or decay. It provides another kind of signal that can be relatively easily distinguished from astrophysical backgrounds besides the linelike signals. Dwarf spheroidal galaxies are expected to be dominated by DM and may be one of the most promising targets for indirect DM searches. In this paper, we study the box-shaped DM signals with Fermi-LAT observations of dwarf spheroidal galaxies. We analyze 106 months of Fermi-LAT data to derive the upper limits on the annihilation cross section or the decay timescale of DM. In addition, we compare the results for different sample selections and DM density distributions. We expect that more dwarf spheroidal galaxies will be found and the sensitivity of box-shaped gamma-ray signal searches will be significantly improved in the future.

Multiverse dark matter: SUSY or axions

NASA Astrophysics Data System (ADS)

D'Eramo, Francesco; Hall, Lawrence J.; Pappadopulo, Duccio

2014-11-01

The observed values of the cosmological constant and the abundance of Dark Matter (DM) can be successfully understood, using certain measures, by imposing the anthropic requirement that density perturbations go non-linear and virialize to form halos. This requires a probability distribution favoring low amounts of DM, i.e. low values of the PQ scale f for the QCD axion and low values of the superpartner mass scale for LSP thermal relics. In theories with independent scanning of multiple DM components, there is a high probability for DM to be dominated by a single component. For example, with independent scanning of f and , TeV-scale LSP DM and an axion solution to the strong CP problem are unlikely to coexist. With thermal LSP DM, the scheme allows an understanding of a Little SUSY Hierarchy with multi-TeV superpartners. Alternatively, with axion DM, PQ breaking before (after) inflation leads to f typically below (below) the projected range of the current ADMX experiment of f = (3 - 30) × 1011 GeV, providing strong motivation to develop experimental techniques for probing lower f.

Phase-space mass bound for fermionic dark matter from dwarf spheroidal galaxies

NASA Astrophysics Data System (ADS)

Di Paolo, Chiara; Nesti, Fabrizio; Villante, Francesco L.

2018-04-01

We reconsider the lower bound on the mass of a fermionic dark matter (DM) candidate resulting from the existence of known small dwarf spheroidal galaxies, in the hypothesis that their DM halo is constituted by degenerate fermions, with phase-space density limited by the Pauli exclusion principle. By relaxing the common assumption that the DM halo scale radius is tied to that of the luminous stellar component and by marginalizing on the unknown stellar velocity dispersion anisotropy, we prove that observations lead to rather weak constraints on the DM mass, which could be as low as tens of eV. In this scenario, however, the DM haloes would be quite large and massive, so that a bound stems from the requirement that the time of orbital decay due to dynamical friction in the hosting Milky Way DM halo is longer than their lifetime. The smallest and nearest satellites Segue I and Willman I lead to a final lower bound of m ≳ 100 eV, still weaker than previous estimates but robust and independent on the model of DM formation and decoupling. We thus show that phase-space constraints do not rule out the possibility of sub-keV fermionic DM.

Association between Cardiometabolic Profile and Dietary Characteristics among Adults with Type 1 Diabetes Mellitus.

PubMed

Gingras, Véronique; Leroux, Catherine; Desjardins, Katherine; Savard, Valérie; Lemieux, Simone; Rabasa-Lhoret, Rémi; Strychar, Irene

2015-12-01

The Mediterranean-style dietary pattern has been associated with several cardiometabolic benefits, yet no study has assessed the potential benefits of this diet in adults with type 1 diabetes mellitus (T1DM). The objective of the present study was to examine the association between cardiometabolic profile and alignment of the diet with 1) Canadian nutrient recommendations for T1DM in terms of fat, protein, carbohydrate, saturated fat, dietary fiber, and sodium and 2) a Mediterranean-style dietary pattern among adults with T1DM. This is a cross-sectional analysis including 118 adults with T1DM recruited between 2011 and 2013 in Montreal, Canada. Body mass index (calculated as kg/m(2)), waist circumference, truncal fat percentage (dual-energy x-ray absorptiometry), blood pressure, and lipid profile values were measured. Insulin sensitivity was estimated (estimated glucose disposal rate). A 3-day food record was completed and physical activity was measured with a motion sensor. Differences for the cardiometabolic profile between groups with a diet meeting the Canadian nutrient recommendations for T1DM (percentage of energy from fat, protein, carbohydrate, saturated fat, as well as grams of dietary fiber and milligrams of sodium) or not were examined with general linear models. A Mediterranean diet score was calculated (range=0 to 44) and Pearson correlations between this score and cardiometabolic variables were computed. Significance was set at P≤0.05. Participants' mean ± standard deviation age was 44.3±12.3 years, glycated hemoglobin was 8.0%±1.1%, and Mediterranean diet score was 20.2±5.0. Having a diet that meets at least three nutritional recommendations was associated with a lower truncal fat percentage (28.0% vs 32.2%; P=0.01) only. In contrast, the Mediterranean diet score was inversely correlated with body mass index (r=-0.30, P=0.002), waist circumference (r=-0.31, P=0.002), truncal fat percentage (r=-0.38, P<0.001), systolic (r=-0.20, P=0.03) and diastolic blood pressure (r=-0.23, P=0.01), and was directly correlated with estimated glucose disposal rate (r=0.22, P=0.03), after adjustments for energy intake, sex, and age. The association with estimated glucose disposal rate was no longer significant (P=0.055) after adjustment for physical activity level. These results suggest that a higher Mediterranean diet score in the context of T1DM is associated with a favorable cardiometabolic profile. Further research is needed to confirm these findings. Copyright © 2015 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Sleep-Wake Cycle and Daytime Sleepiness in the Myotonic Dystrophies

PubMed Central

Romigi, A.; Albanese, M.; Liguori, C.; Placidi, F.; Marciani, M. G.; Massa, R.

2013-01-01

Myotonic dystrophy is the most common type of muscular dystrophy in adults and is characterized by progressive myopathy, myotonia, and multiorgan involvement. Two genetically distinct entities have been identified, myotonic dystrophy type 1 (DM1 or Steinert's Disease) and myotonic dystrophy type 2 (DM2). Myotonic dystrophies are strongly associated with sleep dysfunction. Sleep disturbances in DM1 are common and include sleep-disordered breathing (SDB), periodic limb movements (PLMS), central hypersomnia, and REM sleep dysregulation (high REM density and narcoleptic-like phenotype). Interestingly, drowsiness in DM1 seems to be due to a central dysfunction of sleep-wake regulation more than SDB. To date, little is known regarding the occurrence of sleep disorders in DM2. SDB (obstructive and central apnoea), REM sleep without atonia, and restless legs syndrome have been described. Further polysomnographic, controlled studies are strongly needed, particularly in DM2, in order to clarify the role of sleep disorders in the myotonic dystrophies. PMID:26316996

Higgs boson mass and complex sneutrino dark matter in the supersymmetric inverse seesaw models

NASA Astrophysics Data System (ADS)

Guo, Jun; Kang, Zhaofeng; Li, Tianjun; Liu, Yandong

2014-02-01

The discovery of a relatively heavy Standard Model (SM)-like Higgs boson challenges naturalness of the minimal supersymmetric standard model (MSSM) from both Higgs and dark matter (DM) sectors. We study these two aspects in the MSSM extended by the low-scale inverse seesaw mechanism. Firstly, it admits a sizable radiative contribution to the Higgs boson mass m h , up to ~4 GeV in the case of an IR-fixed point of the coupling Y ν LH u ν c and a large sneutrino mixing. Secondly, the lightest sneutrino, highly complex as expected, is a viable thermal DM candidate. Owing to the correct DM relic density and the XENON100 experimental constraints, two scenarios survive: a Higgs-portal complex DM with mass lying around the Higgs pole or above W threshold, and a coannihilating DM with slim prospect of detection. Given an extra family of sneutrinos, both scenarios naturally work when we attempt to suppress the DM left-handed sneutrino component, confronting with enhancing m h .

A Search for Fast Radio Bursts with the GBNCC Pulsar Survey

NASA Astrophysics Data System (ADS)

Chawla, P.; Kaspi, V. M.; Josephy, A.; Rajwade, K. M.; Lorimer, D. R.; Archibald, A. M.; DeCesar, M. E.; Hessels, J. W. T.; Kaplan, D. L.; Karako-Argaman, C.; Kondratiev, V. I.; Levin, L.; Lynch, R. S.; McLaughlin, M. A.; Ransom, S. M.; Roberts, M. S. E.; Stairs, I. H.; Stovall, K.; Swiggum, J. K.; van Leeuwen, J.

2017-08-01

We report on a search for fast radio bursts (FRBs) with the Green Bank Northern Celestial Cap (GBNCC) Pulsar Survey at 350 MHz. Pointings amounting to a total on-sky time of 61 days were searched to a dispersion measure (DM) of 3000 pc cm-3, while the rest (23 days; 29% of the total time) were searched to a DM of 500 pc cm-3. No FRBs were detected in the pointings observed through 2016 May. We estimate a 95% confidence upper limit on the FRB rate of 3.6× {10}3 FRBs sky-1 day-1 above a peak flux density of 0.63 Jy at 350 MHz for an intrinsic pulse width of 5 ms. We place constraints on the spectral index α by running simulations for different astrophysical scenarios and cumulative flux density distributions. The nondetection with GBNCC is consistent with the 1.4 GHz rate reported for the Parkes surveys for α > +0.35 in the absence of scattering and free-free absorption and α > -0.3 in the presence of scattering, for a Euclidean flux distribution. The constraints imply that FRBs exhibit either a flat spectrum or a spectral turnover at frequencies above 400 MHz. These constraints also allow estimation of the number of bursts that can be detected with current and upcoming surveys. We predict that CHIME may detect anywhere from several to ˜50 FRBs per day (depending on model assumptions), making it well suited for interesting constraints on spectral index, the log N-log S slope, and pulse profile evolution across its bandwidth (400-800 MHz).

[Atherogenic dyslipidemia in patients with type 1 diabetes mellitus].

PubMed

Chillarón, Juan J; Sales, María P; Flores Le-Roux, Juana A; Castells, Ignasi; Benaiges, David; Sagarra, Enric; Pedro-Botet, Juan

2013-12-07

To assess the prevalence of lipid abnormalities, with special emphasis on atherogenic dyslipidemia and its relationship with chronic complications in patients with type 1 diabetes mellitus (T1DM). Cross-sectional study including all patients aged 18 and over, diagnosed of T1DM attending the outpatient clinic at Hospital del Mar and Hospital de Granollers, in Barcelona, during 2008. Of the 291 enrolled patients, 17.2 and 7.9% had high density lipoproteins (HDL) cholesterol<40 mg/dL (men) or<50mg/dL (women) and triglycerides>150 mg/dL, respectively. Hypoalphalipoproteinemic patients had a higher prevalence of peripheral neuropathy (28 vs. 7.1%, P<.001), macroalbuminuria (14 vs. 2.5%, P<.001) and higher concentrations of triglycerides (107.5 [55.8] vs. 82.7 [36] mg/dL, P<.0001) compared with those with normal/high HDL cholesterol levels. Hypertriglyceridemia was associated with increasing age (43.6 [11.2] vs. 37.6 [11.8] yr, P<.02), higher prevalence of hypertension (47.8 vs. 22.8%, P<.008), metabolic syndrome (82.6 vs. 22%, P<.001) and microangiopathic complications, lower insulin sensitivity (6.75 [2.1] vs. 8.54 [2.6] mg/Kg(-1)/min(-1), P<.004) compared with the normotriglyceridemic group. One in 5 patients with T1DM has hypoalphalipoproteinemia or hypertriglyceridemia and these conditions are associated with 3 fold-increase microangiopathy. Thus, in these patients glycemic and blood pressure but also lipid profile control must be optimum. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Effects of 12-month, 2000IU/day vitamin D supplementation on treatment naïve and vitamin D deficient Saudi type 2 diabetic patients

PubMed Central

Al-Shahwan, May A.; Al-Othman, Abdulaziz M.; Al-Daghri, Nasser M.; Sabico, Shaun B.

2015-01-01

Objectives: To determine whether 12-month, 2000IU/day vitamin D supplementation cardiometabolically improves treatment naïve type 2 diabetes mellitus (T2DM) Saudi patients with vitamin D deficiency. Methods: This 12-month interventional study was conducted at primary health centers in 5 different residential areas in Riyadh, Saudi Arabia between January 2013 and January 2014. Forty-five Saudi T2DM patients were enrolled. Baseline anthropometrics, glycemic, and lipid profiles were measured and repeated after 6 and 12 months. All subjects were provided with 2000IU vitamin D supplements for one year. Results: Vitamin D deficiency at baseline was 46.7%, 31.8% after 6 months, and 35.6% after 12 months, indicating an overall improvement in the vitamin D status in the entire cohort. Insulin and homeostatic model assessment-insulin resistance (HOMA-IR) after 12 months were significantly lower than a 6 months (p<0.05), but comparable to baseline values. Mean levels of triglycerides increased overtime from baseline (1.9±0.01 mmol/l) to 12 months (2.1±0.2 mmol). This modest increase in serum triglycerides was parallel to the insignificant decrease in circulating high-density lipoprotein -cholesterol levels. Conclusion: Twelve-month vitamin D supplementation of 2000IU per day in a cohort of treatment naïve Saudi patients with T2DM resulted in improvement of several cardiometabolic parameters including systolic blood pressure, insulin, and HOMA-IR. Further studies that include a placebo group are suggested to reinforce findings. PMID:26620985

Rotation curves of high-resolution LSB and SPARC galaxies with fuzzy and multistate (ultralight boson) scalar field dark matter

NASA Astrophysics Data System (ADS)

Bernal, T.; Fernández-Hernández, L. M.; Matos, T.; Rodríguez-Meza, M. A.

2018-04-01

Cold dark matter (CDM) has shown to be an excellent candidate for the dark matter (DM) of the Universe at large scales; however, it presents some challenges at the galactic level. The scalar field dark matter (SFDM), also called fuzzy, wave, Bose-Einstein condensate, or ultralight axion DM, is identical to CDM at cosmological scales but different at the galactic ones. SFDM forms core haloes, it has a natural cut-off in its matter power spectrum, and it predicts well-formed galaxies at high redshifts. In this work we reproduce the rotation curves of high-resolution low surface brightness (LSB) and SPARC galaxies with two SFDM profiles: (1) the soliton+NFW profile in the fuzzy DM (FDM) model, arising empirically from cosmological simulations of real, non-interacting scalar field (SF) at zero temperature, and (2) the multistate SFDM (mSFDM) profile, an exact solution to the Einstein-Klein-Gordon equations for a real, self-interacting SF, with finite temperature into the SF potential, introducing several quantum states as a realistic model for an SFDM halo. From the fits with the soliton+NFW profile, we obtained for the boson mass 0.212 < mψ/(10-23 eV/c2) < 27.0 and for the core radius 0.326 < rc/kpc < 8.96. From the combined analysis with the LSB galaxies, we obtained mψ = 0.554 × 10-23 eV, a result in tension with the severe cosmological constraints. Also, we show the analytical mSFDM model fits the observations as well as or better than the empirical soliton+NFW profile, and it reproduces naturally the wiggles present in some galaxies, being a theoretically motivated framework additional or alternative to the FDM profile.

Effect of Diabetes Mellitus and Metformin on Central Corneal Endothelial Cell Density in Eye Bank Eyes.

PubMed

Chocron, Isaac M; Rai, Dinesh K; Kwon, Ji-Won; Bernstein, Nicole; Hu, Jimmy; Heo, Moonseong; Lee, Jimmy K; Gore, Patrick K; McCartney, Mitchell D; Chuck, Roy S

2018-05-04

To determine whether metformin use and diabetes mellitus (DM) affect central corneal endothelial cell density (ECD) by examining an eye bank corneal donor database. The Lions Eye Institute corneal donor database, which consists of 38,318 corneal samples, was examined. Associations of ECD with metformin use and DM were tested by mixed effects linear models that account for correlations of outcomes between eyes within subjects adjusting for age, intraocular lens status, and glaucoma. Subjects (N = 17,056) with observed ECD counts for both eyes are included for analysis. Average donor age was 56.3 (SD = 15.0). ECD was not associated with metformin use (mean ± SE = 2592 ± 11.9 (N = 1014) versus nonuse [2592 ± 3.0 (N = 16,042), P = 0.302]; further analysis showed that ECD was not significantly associated with metformin use in patients with diabetes. However, metformin use was significantly associated with lower ECD among patients with glaucoma: [2658 ± 50.7 (N = 27) for use versus 2789 ± 19.0 (N = 164) for nonuse, P = 0.018]. The presence of DM was significantly associated with lower ECD 2581 ± 5.6 (N = 4766) for DM versus 2595 ± 3.4 (N = 12,290) for non-DM, P = 0.031). Lower ECD was associated with DM. Lower ECD was not associated with metformin use except in a subgroup of patients with glaucoma, in which subgroup analysis showed lower ECD. The differences in ECD observed were small and unlikely to affect the suitability for transplantation of donor corneas.

Long-term streptozotocin-induced diabetes in rats leads to severe damage of brain blood vessels and neurons via enhanced oxidative stress.

PubMed

Yang, Hongying; Fan, Shourui; Song, Dianping; Wang, Zhuo; Ma, Shungao; Li, Shuqing; Li, Xiaohong; Xu, Mian; Xu, Min; Wang, Xianmo

2013-02-01

The aim of this study was to investigate pathophysiological alterations and oxidative stress in various stages of streptozotocin (STZ)‑induced diabetes mellitus (DM) in rats. Male Sprague-Dawley rats (120) were randomized into DM and control groups. Body mass, plasma glucose, glycated hemoglobin (HbA1c), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels, as well as aldose reductase (AR) activities, in brain tissue and serum were determined. Electron microscopy was used to observe neuron and vessel changes in the brain. In STZ‑treated rats, blood glucose, low density lipoproteins, triglycerides and total cholesterol levels increased 1.43‑3.0‑fold and high density lipoprotein, HbA1c and insulin sensitivity index increased 1.1‑1.23‑fold compared with control. At week 16 following treatment, DM rat serum H2O2 concentration was increased, indicating oxidative stress and mRNA levels of GPx and SOD were 2‑fold higher than the control. Protein GPx and SOD levels were reduced (P<0.01). DM rats were identified to exhibit early irregular glomerular capillary basement membrane thickening and vacuolization in the mitochondria and epithelial cells. Neuron cells and blood vessels in the DM rat brains became increasingly abnormal over time with altered Golgi bodies, mitochondria and endoplasmic reticulum cisterns, concurrent with SOD inactivation and AR protein accumulation. Disease progression in rats with STZ‑induced DM included brain pathologies with vascular and neuron cell abnormalities, associated with the reduction of SOD, CAT and GPx activities and also AR accumulation.

Kinetic Modeling of Human Hepatic Glucose Metabolism in Type 2 Diabetes Mellitus Predicts Higher Risk of Hypoglycemic Events in Rigorous Insulin Therapy*

PubMed Central

König, Matthias; Holzhütter, Hermann-Georg

2012-01-01

A major problem in the insulin therapy of patients with diabetes type 2 (T2DM) is the increased occurrence of hypoglycemic events which, if left untreated, may cause confusion or fainting and in severe cases seizures, coma, and even death. To elucidate the potential contribution of the liver to hypoglycemia in T2DM we applied a detailed kinetic model of human hepatic glucose metabolism to simulate changes in glycolysis, gluconeogenesis, and glycogen metabolism induced by deviations of the hormones insulin, glucagon, and epinephrine from their normal plasma profiles. Our simulations reveal in line with experimental and clinical data from a multitude of studies in T2DM, (i) significant changes in the relative contribution of glycolysis, gluconeogenesis, and glycogen metabolism to hepatic glucose production and hepatic glucose utilization; (ii) decreased postprandial glycogen storage as well as increased glycogen depletion in overnight fasting and short term fasting; and (iii) a shift of the set point defining the switch between hepatic glucose production and hepatic glucose utilization to elevated plasma glucose levels, respectively, in T2DM relative to normal, healthy subjects. Intriguingly, our model simulations predict a restricted gluconeogenic response of the liver under impaired hormonal signals observed in T2DM, resulting in an increased risk of hypoglycemia. The inability of hepatic glucose metabolism to effectively counterbalance a decline of the blood glucose level becomes even more pronounced in case of tightly controlled insulin treatment. Given this Janus face mode of action of insulin, our model simulations underline the great potential that normalization of the plasma glucagon profile may have for the treatment of T2DM. PMID:22977253

Surface micromachined MEMS deformable mirror based on hexagonal parallel-plate electrostatic actuator

NASA Astrophysics Data System (ADS)

Ma, Wenying; Ma, Changwei; Wang, Weimin

2018-03-01

Deformable mirrors (DM) based on microelectromechanical system (MEMS) technology are being applied in adaptive optics (AO) system for astronomical telescopes and human eyes more and more. In this paper a MEMS DM with hexagonal actuator is proposed and designed. The relationship between structural design and performance parameters, mainly actuator coupling, is analyzed carefully and calculated. The optimum value of actuator coupling is obtained. A 7-element DM prototype is fabricated using a commercial available standard three-layer polysilicon surface multi-user-MEMS-processes (PolyMUMPs). Some key performances, including surface figure and voltage-displacement curve, are measured through a 3D white light profiler. The measured performances are very consistent with the theoretical values. The proposed DM will benefit the miniaturization of AO systems and lower their cost.

Instantaneous phase mapping deflectometry for dynamic deformable mirror characterization

NASA Astrophysics Data System (ADS)

Trumper, Isaac; Choi, Heejoo

2017-09-01

We present an instantaneous phase mapping deflectometry (PMD) system in the context of measuring a continuous surface deformable mirror (DM). Deflectometry has a high dynamic range, enabling the full range of surfaces generated by the DM to be measured. The recent development of an instantaneous PMD system leverages the simple setup of the PMD system to measure dynamic objects with accuracy similar to an interferometer. To demonstrate the capabilities of this technology, we perform a linearity measurement of the actuator motion in a continuous surface DM, which is critical for closed loop control in adaptive optics applications. We measure the entire set of actuators across the DM as they traverse their full range of motion with a Shack-Hartman wavefront sensor, thereby obtaining the influence function. Given the influence function of each actuator, the DM can produce specific Zernike terms on its surface. We then measure the linearity of the Zernike modes available in the DM software using the instantaneous PMD system. By obtaining the relationship between modes, we can more accurately generate surface profiles composed of Zernike terms. This ability is useful for other dynamic freeform metrology applications that utilize the DM as a null component.

Acids, sugars, and sugar alcohols in Chinese hawthorn (Crataegus spp.) fruits.

PubMed

Liu, Pengzhan; Kallio, Heikki; Lü, Deguo; Zhou, Chuansheng; Ou, Shiyi; Yang, Baoru

2010-01-27

Acids, sugars, and sugar alcohols in the fruits of 22 cultivars/origins of three species of hawthorn (Crataegus spp.) were analyzed by gas chromatography and mass spectrometry. Citric acid (2.0-8.4 g/100 g dry mass [DM]), quinic acid (0.5-5.6 g/100 g DM), malic acid (0.3-1.1 g/100 g DM), fructose (5.5-18.4 g/100 g DM), glucose (5.3-16.6 g/100 g DM), sorbitol (3.0-15.7 g/100 g DM), and myo-inositol (0.1-0.3 g/100 g DM) were found in all the samples. Sucrose was present only in C. scabrifolia and three cultivars of C. pinnatifida var. major. C. scabrifolia differed from other species by its high content of quinic acid. The cultivars of C. pinnatifida var. major and C. brettschneideri had a higher content of total sugars and a higher sugar/acid ratio than the natural origins of C. pinnatifida and C. scabrifolia (P < 0.05). The hawthorn samples analyzed fell into two groups rich in sugars and acids respectively. This is the first report of the profiles of sugars and sugar alcohols and the occurrence of quinic acid in hawthorn fruits.

High Prevalence of Diabetes and Prediabetes and Their Coexistence with Cardiovascular Risk Factors in a Hispanic Community.

PubMed

Pérez, Cynthia M; Soto-Salgado, Marievelisse; Suárez, Erick; Guzmán, Manuel; Ortiz, Ana Patricia

2015-08-01

This study examined the prevalence and association of diabetes mellitus (DM) and prediabetes with cardiovascular risk factors among Puerto Ricans adults. Data from a household survey of 857 adults aged 21-79 years who underwent interviews, physical exams, and blood draws were analyzed. Prevalence of total DM and prediabetes was estimated using American Diabetes Association diagnostic criteria of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). Poisson regression models were used to estimate the prevalence ratio for each cardiovascular risk factor under study. Age-standardized prevalence of total DM and prediabetes, detected by FPG and/or HbA1c, was 25.5 and 47.4 %, respectively. Compared with participants with normoglycemia, those with previously diagnosed DM, undiagnosed DM, and prediabetes had more adverse cardiovascular risk factor profiles, characterized by a higher prevalence of general and abdominal obesity, hypertension, low HDL cholesterol, elevated LDL cholesterol, elevated triglycerides, and elevated plasminogen activator inhibitor 1 (p < 0.05). The high prevalence of DM and prediabetes calls for public health actions to plan and implement lifestyle interventions to prevent or delay the onset of DM and cardiovascular disease.

High Prevalence of Diabetes and Prediabetes and Their Coexistence with Cardiovascular Risk Factors in a Hispanic Community

PubMed Central

Soto-Salgado, Marievelisse; Suárez, Erick; Guzmán, Manuel; Ortiz, Ana Patricia

2014-01-01

This study examined the prevalence and association of diabetes mellitus (DM) and prediabetes with cardiovascular risk factors among Puerto Ricans adults. Data from a household survey of 857 adults aged 21–79 years who underwent interviews, physical exams, and blood draws were analyzed. Prevalence of total DM and prediabetes was estimated using American Diabetes Association diagnostic criteria of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). Poisson regression models were used to estimate the prevalence ratio for each cardiovascular risk factor under study. Age-standardized prevalence of total DM and prediabetes, detected by FPG and/or HbA1c, was 25.5 and 47.4 %, respectively. Compared with participants with normoglycemia, those with previously diagnosed DM, undiagnosed DM, and prediabetes had more adverse cardiovascular risk factor profiles, characterized by a higher prevalence of general and abdominal obesity, hypertension, low HDL cholesterol, elevated LDL cholesterol, elevated triglycerides, and elevated plasminogen activator inhibitor 1 (p < 0.05). The high prevalence of DM and prediabetes calls for public health actions to plan and implement lifestyle interventions to prevent or delay the onset of DM and cardiovascular disease. PMID:24781780

The MCP-1 Gene A-2518G Polymorphism Confers an Increased Risk of Vascular Complications in Type 2 Diabetes Mellitus Patients.

PubMed

Xu, Jin; Liao, Yun-Fei; Zhou, Wei-Ping; Ming, Hua-Li; Wang, Qing-Hai

2015-08-01

We aimed to evaluate the correlation of the monocyte chemoattractant protein 1 (MCP-1) A-2518G polymorphism with type 2 diabetes mellitus (T2DM) and vascular complications in T2DM, to aid in understanding its role in pathogenesis. A total of 150 T2DM patients and 50 healthy controls (group A) were enrolled. The T2DM patients were divided into three groups based on the absence of complications (group B) presence of microvascular disease (group C) or macrovascular disease (group D). DNA of all enrolled subjects was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the MCP-1 A-2518G polymorphism. Serum MCP-1 levels were measured by an enzyme-linked immunosorbent assay (ELISA). Participants in group D had increased serum MCP-1 levels relative to group B, group C, and group A (all p<0.01). Compared with group A, the frequencies of the MCP-1 A-2518G G/G genotype and G allele were significantly higher in group C and group D (all p<0.05). In contrast to group B, group C had higher frequencies of the G/G genotype and G allele, while group D had higher G allele frequencies (all p<0.05). Logistic regression analysis showed that lower body-mass index (BMI) and free cholesterol (FC), as well as higher high-density lipoprotein cholesterol (HDL-C) levels may be the protective factors for T2DM, while higher levels of triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and G/G genotype frequency were independent risk factors for T2DM. Our data indicates a correlation between the MCP-1 A-2518G polymorphism with macrovascular complications in T2DM patients; lower BMI and FC, as well as higher HDL-C levels may be the protective factors for T2DM, while higher levels of TG, LDL-C, and G/G genotype frequency were independent risk factors for T2DM.

Pancreatic size and fat content in diabetes: A systematic review and meta-analysis of imaging studies.

PubMed

Garcia, Tiago Severo; Rech, Tatiana Helena; Leitão, Cristiane Bauermann

2017-01-01

Imaging studies are expected to produce reliable information regarding the size and fat content of the pancreas. However, the available studies have produced inconclusive results. The aim of this study was to perform a systematic review and meta-analysis of imaging studies assessing pancreas size and fat content in patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM). Medline and Embase databases were performed. Studies evaluating pancreatic size (diameter, area or volume) and/or fat content by ultrasound, computed tomography, or magnetic resonance imaging in patients with T1DM and/or T2DM as compared to healthy controls were selected. Seventeen studies including 3,403 subjects (284 T1DM patients, 1,139 T2DM patients, and 1,980 control subjects) were selected for meta-analyses. Pancreas diameter, area, volume, density, and fat percentage were evaluated. Pancreatic volume was reduced in T1DM and T2DM vs. controls (T1DM vs. controls: -38.72 cm3, 95%CI: -52.25 to -25.19, I2 = 70.2%, p for heterogeneity = 0.018; and T2DM vs. controls: -12.18 cm3, 95%CI: -19.1 to -5.25, I2 = 79.3%, p for heterogeneity = 0.001). Fat content was higher in T2DM vs. controls (+2.73%, 95%CI 0.55 to 4.91, I2 = 82.0%, p for heterogeneity<0.001). Individuals with T1DM and T2DM have reduced pancreas size in comparison with control subjects. Patients with T2DM have increased pancreatic fat content.

Human Milk and Donkey Milk, Compared to Cow Milk, Reduce Inflammatory Mediators and Modulate Glucose and Lipid Metabolism, Acting on Mitochondrial Function and Oleylethanolamide Levels in Rat Skeletal Muscle.

PubMed

Trinchese, Giovanna; Cavaliere, Gina; De Filippo, Chiara; Aceto, Serena; Prisco, Marina; Chun, Jong Tai; Penna, Eduardo; Negri, Rossella; Muredda, Laura; Demurtas, Andrea; Banni, Sebastiano; Berni-Canani, Roberto; Mattace Raso, Giuseppina; Calignano, Antonio; Meli, Rosaria; Greco, Luigi; Crispino, Marianna; Mollica, Maria P

2018-01-01

Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM) and donkey milk (DM) are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM), DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate. Moreover, we also evaluated the levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle, since tissue fatty acid profiles can be modulated by nutrient intervention. Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then, glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti-inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal muscle was also processed to estimate mitochondrial function, efficiency, and dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined in liver and skeletal muscle tissue. Results: We demonstrated that DM or HM administration reducing inflammation status, improves glucose disposal and insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover, HM or DM administration increases redox status, and mitochondrial uncoupling, affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM supplementation increase liver and muscle levels of the N-oleoylethanolamine (OEA), a key regulator of lipid metabolism and inflammation. Conclusions: HM and DM have a healthy nutritional effect, acting on inflammatory factors and glucose and lipid metabolism. This beneficial effect is associated to a modulation of mitochondrial function, efficiency, and dynamics and to an increase of OEA levels in skeletal muscle.

Human Milk and Donkey Milk, Compared to Cow Milk, Reduce Inflammatory Mediators and Modulate Glucose and Lipid Metabolism, Acting on Mitochondrial Function and Oleylethanolamide Levels in Rat Skeletal Muscle

PubMed Central

Trinchese, Giovanna; Cavaliere, Gina; De Filippo, Chiara; Aceto, Serena; Prisco, Marina; Chun, Jong Tai; Penna, Eduardo; Negri, Rossella; Muredda, Laura; Demurtas, Andrea; Banni, Sebastiano; Berni-Canani, Roberto; Mattace Raso, Giuseppina; Calignano, Antonio; Meli, Rosaria; Greco, Luigi; Crispino, Marianna; Mollica, Maria P.

2018-01-01

Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM) and donkey milk (DM) are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM), DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate. Moreover, we also evaluated the levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle, since tissue fatty acid profiles can be modulated by nutrient intervention. Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then, glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti-inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal muscle was also processed to estimate mitochondrial function, efficiency, and dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined in liver and skeletal muscle tissue. Results: We demonstrated that DM or HM administration reducing inflammation status, improves glucose disposal and insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover, HM or DM administration increases redox status, and mitochondrial uncoupling, affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM supplementation increase liver and muscle levels of the N-oleoylethanolamine (OEA), a key regulator of lipid metabolism and inflammation. Conclusions: HM and DM have a healthy nutritional effect, acting on inflammatory factors and glucose and lipid metabolism. This beneficial effect is associated to a modulation of mitochondrial function, efficiency, and dynamics and to an increase of OEA levels in skeletal muscle. PMID:29472867

Effect of regrowth interval and a microbial inoculant on the fermentation profile and dry matter recovery of guinea grass silages.

PubMed

Santos, E M; Pereira, O G; Garcia, R; Ferreira, C L L F; Oliveira, J S; Silva, T C

2014-07-01

The objectives of this study were to characterize and quantify the microbial populations in guinea grass (Panicum maximum Jacq. cultivar Mombasa) harvested at different regrowth intervals (35, 45, 55, and 65 d). The chemical composition and fermentation profile of silages (after 60 d) with or without the addition of a microbial inoculant were also analyzed. Before ensiling, samples of the plants were used for the isolation and identification of lactic acid bacteria (LAB) in the epiphytic microbiota. A 4 × 2 factorial arrangement of treatments (4 regrowth intervals × with/without inoculant) was used in a completely randomized design with 3 replications. Based on the morphological and biochemical characteristics and the carbohydrate fermentation profile, Lactobacillus plantarum was found to be the predominant specie of LAB in guinea grass forage. Linear increases were detected in the dry matter (DM) content and concentrations of neutral detergent fiber, acid detergent fiber, acid detergent insoluble nitrogen, and DM recovery as well as linear reductions in the concentrations of crude protein and NH3-N with regrowth interval. Additionally, linear reductions for gas and effluent losses in silages were detected with increasing regrowth interval. These results demonstrate that guinea grass plants harvested after 55 d of regrowth contain a LAB population sufficiently large to ensure good fermentation and increase the DM recovery. The use of microbial inoculant further enhanced the fermentation of guinea grass at all stages of regrowth by improving the DM recovery. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effect of diabetes mellitus on the quality and cytokine content of human semen.

PubMed

Lu, Xiaosheng; Huang, Yonggang; Zhang, Huina; Zhao, Junzhao

2017-09-01

The effects of diabetes mellitus (DM) on the quality and cytokine levels of human semen remain unknown. Sixty semen samples from 30 normal volunteers and 30 DM patients were assayed. The percentage of sperm progressive motility, sperm vitality, sperm survival rate, the rate of normal sperm morphology, semen volume, and semen pH and density of DM males were significantly lower than those of normal males (p<0.05). Moreover, semen interleukin (IL)-17 and IL-18 levels in DM males were significantly higher than those in normal males (p<0.05) and were positively correlated with blood glucose level and sperm DNA fragmentation index. DM increased blood glucose levels, consequently inducing the abnormal expression of IL-17 and IL-18. The abnormal expression of these cytokines in semen decreased semen quality and might lead to male infertility. Copyright © 2017 Elsevier B.V. All rights reserved.

Exploring spin-3 /2 dark matter with effective Higgs couplings

NASA Astrophysics Data System (ADS)

Chang, Chia-Feng; He, Xiao-Gang; Tandean, Jusak

2017-10-01

We study an economical model of weakly interacting massive particle dark matter (DM) which has spin 3 /2 and interacts with the 125 GeV Higgs boson via effective scalar and pseudoscalar operators. We apply constraints on the model from the relic density data, LHC measurements of the Higgs boson, and direct and indirect searches for DM, taking into account the effective nature of the DM-Higgs couplings. We show that this DM is currently viable in most of the mass region from about 58 GeV to 2.3 TeV and will be probed more stringently by ongoing and upcoming experiments. Nevertheless, the presence of the DM-Higgs pseudoscalar coupling could make parts of the model parameter space elusive from future tests. We find that important aspects of this scenario are quite similar to those of its more popular spin-1 /2 counterpart.

Formation and internal structure of superdense dark matter clumps and ultracompact minihaloes

NASA Astrophysics Data System (ADS)

Berezinsky, V. S.; Dokuchaev, V. I.; Eroshenko, Yu. N.

2013-11-01

We discuss the formation mechanisms and structure of the superdense dark matter clumps (SDMC) and ultracompact minihaloes (UCMH), outlining the differences between these types of DM objects. We define as SDMC the gravitationally bounded DM objects which have come into virial equilibrium at the radiation-dominated (RD) stage of the universe evolution. Such objects can be formed from the isocurvature (entropy) density perturbations or from the peaks in the spectrum of curvature (adiabatic) perturbation. The axion miniclusters (Kolb and Tkachev 1994) are the example of the former model. The system of central compact mass (e.g. in the form of SDMC or primordial black hole (PBH)) with the outer DM envelope formed in the process of secondary accretion we refer to as UCMH. Therefore, the SDMC can serve as the seed for the UCMH in some scenarios. Recently, the SDMC and UCMH were considered in the many works, and we try to systematize them here. We consider also the effect of asphericity of the initial density perturbation in the gravitational evolution, which decreases the SDMC amount and, as the result, suppresses the gamma-ray signal from DM annihilation.

The distribution of dimethylsulfoniopropionate in tropical Pacific coral reef invertebrates

NASA Astrophysics Data System (ADS)

van Alstyne, Kathryn L.; Schupp, Peter; Slattery, Marc

2006-08-01

Dimethylsulfoniopropionate (DMSP) is an important component of the global sulfur cycle and may be involved, via its cleavage product dimethylsulfide, in climate regulation. Although it is common in many algae, reports of DMSP in animals, particularly tropical invertebrates, are limited. This study examined the distribution of DMSP in a diverse group of coral reef invertebrates. DMSP was present in all 22 species of cnidarians and ranged from 9 to 723 μmol g-1 of dry mass (DM) with a mean (± 1SD) of 110 ± 180 μmol g-1 DM. It was not detected in a flatworm and an ascidian or in two of five sponges. Concentrations in sponges ranged from undetectable to 16 μmol g-1 DM with a mean of 4 ± 7 μmol g-1 DM. Within the cnidarians, DMSP concentrations did not differ among orders. Among cnidarian species, DMSP concentrations were correlated with symbiotic zooxanthellae densities. Within cnidarian species, DMSP concentrations of individuals were positively correlated with zooxanthellae densities in three of the four species examined. We speculate that DMSP is dietarily derived in sponges and derived from zooxanthellae in the cnidarians. The functions of DMSP in coral reef invertebrates are not known.

Obese with higher FNDC5/Irisin levels have a better metabolic profile, lower lipopolysaccharide levels and type 2 diabetes risk.

PubMed

Bonfante, Ivan Luiz Padilha; Chacon-Mikahil, Mara Patricia Traina; Brunelli, Diego Trevisan; Gáspari, Arthur Fernandes; Duft, Renata Garbellini; Oliveira, Alexandre Gabarra; Araujo, Tiago Gomes; Saad, Mario Jose Abdalla; Cavaglieri, Cláudia Regina

2017-12-01

Thus, the aim of this study was to compare if higher or smaller fibronectin type 3 domain-containing protein 5 (FNDC5)/irisin levels are associated with inflammatory and metabolic markers, caloric/macronutrient intake, physical fitness and type 2 diabetes mellitus (T2DM) risk in obese middle-aged men, and also to correlate all variables analyzed with FNDC5/irisin. On the basis of a cluster study, middle-aged obese men (IMC: 31.01 ± 1.64 kg/m2) were divided into groups of higher and smaller levels of FNDC5/irisin. The levels of leptin, resistin, adiponectin, tumor necrosis factor alpha (TNFα), interleukin 6 and 10 (IL6, IL10), lipopolysaccharide (LPS), glucose, insulin, glycated hemoglobin, insulin resistance and sensibility, lipid profile, risk of T2DM development, body composition, rest energy expenditure, caloric/macronutrient intake and physical fitness were measured. The higher FNDC5/ irisin group presented improved insulin sensibility (homeostasis model assessment - sensibility (HOMA-S) (p = 0.01) and QUICKI index (p < 0.01)), insulin (p = 0.02) and triglyceride levels (p = 0.01), lower insulin resistance (homeostasis model assessment - insulin resistance (HOMA-IR) (p = 0.01), triglycerides/glucose (TYG index) (p = 0.02), neck circumference (p = 0.02), risk of T2DM development (p = 0.02), tendency to decrease serum resistin (p = 0.08) and significant lower LPS levels (p = 0.02). Inverse correlations between FNDC5/irisin and body weight (r -0.46, p = 0.04), neck circumference (r -0.51, p = 0.02), free fat mass (r -0.49, p = 0.02), triglycerides (r -0.43, p = 0.05) and risk of developing T2DM (r -0.61, p = 0.04) were observed. These results suggest that higher FNDC5/irisin levels in obese middle-aged men are related to a better metabolic profile and lower risk of T2DM development and serum LPS, a potential inducer of insulin resistance.

QTL mapping of downy and powdery mildew resistances in PI 197088 cucumber with genotyping-by-sequencing in RIL population.

PubMed

Wang, Yuhui; VandenLangenberg, Kyle; Wen, Changlong; Wehner, Todd C; Weng, Yiqun

2018-03-01

Host resistances in PI 197088 cucumber to downy and powdery mildew pathogens are conferred by 11 (3 with major effect) and 4 (1 major effect) QTL, respectively, and three of which are co-localized. The downy mildew (DM) and powdery mildew (PM) are the two most important foliar diseases of cucurbit crops worldwide. The cucumber accession PI 197088 exhibits high-level resistances to both pathogens. Here, we reported QTL mapping results for DM and PM resistances with 148 recombinant inbred lines from a cross between PI 197088 and the susceptible line 'Coolgreen'. Phenotypic data on responses to natural DM and PM infection were collected in multi-year and multi-location replicated field trials. A high-density genetic map with 2780 single nucleotide polymorphisms (SNPs) from genotyping-by-sequencing and 55 microsatellite markers was developed, which revealed genomic regions with segregation distortion and mis-assemblies in the '9930' cucumber draft genome. QTL analysis identified 11 and 4 QTL for DM and PM resistances accounting for more than 73.5 and 63.0% total phenotypic variance, respectively. Among the 11 DM resistance QTL, dm5.1, dm5.2, and dm5.3 were major-effect contributing QTL, whereas dm1.1, dm2.1, and dm6.2 conferred susceptibility. Of the 4 QTL for PM resistance, pm5.1 was the major-effect QTL explaining 32.4% phenotypic variance and the minor-effect QTL pm6.1 contributed to disease susceptibility. Three PM QTL, pm2.1, pm5.1, and pm6.1, were co-localized with DM QTL dm2.1, dm5.2, and dm6.1, respectively, which was consistent with the observed linkage of PM and DM resistances in PI 197088. The genetic architecture of DM resistance in PI 197088 and another resistant line WI7120 (PI 330628) was compared, and the potential of using PI 197088 in cucumber breeding for downy and powdery mildew resistances is discussed.

Productive performance and urinary excretion of mimosine metabolites by hair sheep grazing in a silvopastoral system with high densities of Leucaena leucocephala.

PubMed

Barros-Rodríguez, Marcos; Solorio-Sánchez, Javier; Ku-Vera, Juan; Ayala-Burgos, Armín; Sandoval-Castro, Carlos; Solís-Pérez, Georgina

2012-12-01

The aim of this study was to evaluate daily weight gain (DWG), total dry matter (DM) intake, rumen degradability of forage, and urinary excretion of mimosine metabolites by hair sheep in a silvopastoral system with high densities of Leucaena leucocephala. A completely randomized design was carried out with two treatments: treatment 1 (T1) silvopastoral system with leucaena at a density of 35,000 plants/ha and treatment 2 (T2), leucaena at a density of 55,000 plants/ha. Leucaena was associated with tropical grasses Panicum maximum and Cynodon nlemfluensis. Twenty-four male Pelibuey lambs of 23.2 ± 3.4 kg live weight (LW) were used (12 lambs per treatment). Results showed differences (P < 0.05) in DWG of T1 (106.41 ± 11.66 g(-1) sheep(-1)) with respect to that of T2 (81.33 ± 11.81 g(-1) sheep). Voluntary intake was higher in lambs from T1 (83.81 ± 04.07 g DM/kg LW(0.75)) with respect to that from T2 (71.67 ± 8.12 g DM/kg LW(0.75)). There was a difference in color of urine between sheep of T1 and T2, the latter giving positive results for the presence of metabolites derived from mimosine (3-4 dihydroxypyridine and 2-3 dihydroxy pyridone). Rumen degradability of DM of L. leucocephala was higher (P < 0.05) compared to that of P. maximum and C. nlemfluensis (72.94 ± 0.40 vs. 67.06 ± 1.50 and 63.25 ± 1.51 %, respectively). It is concluded that grazing at high densities of L. leucocephala affects daily weight gain of hair sheep, possibly due to ingestion of high amounts of mimosine which may exert an adverse effect on voluntary intake.

[Prevalence of type 2 diabetes mellitus in overweight or obese outpatients in Spain. OBEDIA Study].

PubMed

Gomis, Ramón; Artola, Sara; Conthe, Pedro; Vidal, Josep; Casamor, Ricard; Font, Beatriu

2014-06-06

The increase in the prevalence of type 2 diabetes mellitus (T2DM) is related to the increase of obesity. We aimed to determine the Spanish prevalence of T2DM in patients with overweight or obesity attended by either family or specialist physicians. Cross-sectional, multicenter and simultaneous 2-phase design, performed under clinical conditions. Phase A was designed to determine T2DM prevalence: 169,023 patients were recruited. Phase B was designed to define socio-demographic, clinical and metabolic profile of T2DM according to the body mass index (BMI): 7,754 patients were included. T2DM prevalence in overweight or obese patients was 23.6%; 17.8% of overweight patients were diabetic and T2DM was present in 34.8% of obese people. According to sex, 20.2% of men and 16.4% of women had T2DM. Overall, the mean of risk factors related to T2DM was 4.4 (SD 0,8); out of them, 92.6% patients had dyslipidemia, 73.7% hypertension and 62.5% performed a low physical activity. 37.8% of diabetic patients had vascular involvement. Only 43.1% of patients showed a proper metabolic control of T2DM (glycosilated hemoglobin<7%). T2DM is related to overweight and obesity and higher the BMI is, higher the T2DM prevalence. Dyslipidemia, hypertension and a low physical activity in diabetic patients are more frequent when BMI increases. Patients with inadequate metabolic control have a higher BMI. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Dark Matter Equilibria in Galaxies and Galaxy Systems

NASA Astrophysics Data System (ADS)

Lapi, A.; Cavaliere, A.

2009-02-01

In the dark matter (DM) halos embedding galaxies and galaxy systems the "entropy" K ≡ σ2/ρ2/3 (a quantity that combines the radial velocity dispersion σ with the density ρ) is found from intensive N-body simulations to follow a power-law run K vprop r α throughout the halos' bulk, with α around 1.25. Taking up from phenomenology just that α≈ const. applies, we cut through the rich analytic contents of the Jeans equation describing the self-gravitating equilibria of the DM; we specifically focus on computing and discussing a set of novel physical solutions that we name α-profiles, marked by the entropy slope α itself, and by the maximal gravitational pull κcrit(α) required for a viable equilibrium to hold. We then use an advanced semianalytic description for the cosmological buildup of halos to constrain the values of α to within the narrow range 1.25-1.29 from galaxies to galaxy systems; these correspond to halos' current masses in the range 1011-1015 M sun. Our range of α applies since the transition time that—both in our semianalytic description and in state-of-the-art numerical simulations—separates two development stages: an early violent collapse that comprises a few major mergers and enforces dynamical mixing, followed by smoother mass addition through slow accretion. In our range of α we provide a close fit for the relation κcrit(α), and discuss a related physical interpretation in terms of incomplete randomization of the infall kinetic energy through dynamical mixing. We also give an accurate analytic representation of the α-profiles with parameters derived from the Jeans equation; this provides straightforward precision fits to recent detailed data from gravitational lensing in and around massive galaxy clusters, and thus replaces the empirical Navarro-Frenk-White formula relieving the related problems of high concentration and old age. We finally stress how our findings and predictions as to α and κcrit contribute to understanding hitherto unsolved issues concerning the fundamental structure of DM halos.

Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers in Type 2 Diabetes Mellitus Patients.

PubMed

Jacobo-Cejudo, M Gorety; Valdés-Ramos, Roxana; Guadarrama-López, Ana L; Pardo-Morales, Rosa-Virgen; Martínez-Carrillo, Beatriz E; Harbige, Laurence S

2017-06-03

Type 2 diabetes mellitus (T2DM) is accompanied by chronic low-grade inflammation, with an imbalance in the secretion of adipokines and, worsening insulin resistance. Supplementation with n- 3 PUFA in T2DM decreases inflammatory markers, the purpose of the study was to investigate the effect of n- 3 PUFA supplementation on adipokines, metabolic control, and lipid profile in T2DM Mexican adults. In a randomized, single-blind, placebo-controlled pilot study, 54 patients with T2DM received 520 mg of DHA + EPA-enriched fish-oil (FOG) or a placebo (PG) daily. Baseline and 24-week anthropometric and biochemical measurements included glucose, insulin, glycosylated hemoglobin (Hb1Ac), leptin, adiponectin, resistin, and lipid profile; n- 3 PUFA intake was calculated in g/day. Waist circumference and blood glucose showed significant reductions in the FOG group ( p = 0.001 and p = 0.011, respectively). Hb1Ac ( p = 0.009 and p = 0.004), leptin ( p < 0.000 and p < 0.000), and leptin/adiponectin ratio ( p < 0.000 and p < 0.000) decreased significantly in both groups after 24 weeks (FOG and PG respectively). Serum resistin (FOG p < 0.000 and PG p = 0.001), insulin (FOG p < 0.000 and PG p < 0.000), and HOMA-IR (FOG p = 0.000 and PG p < 0.000) increased significantly in both groups. FOG had an overall improvement in the lipid profile with a significant decrease in triacylgycerols ( p = 0.002) and atherogenic index ( p = 0.031); in contrast, the PG group had increased total cholesterol ( p < 0.000), non-HDL cholesterol ( p < 0.000), and atherogenic index ( p = 0.017). We found a beneficial effect of n- 3 PUFA supplementation on waist circumference, glucose, Hb1Ac, leptin, leptin/adiponectin ratio, and lipid profile, without significant changes in adiponectin, and increases in resistin, insulin, and HOMA-IR in both groups.

Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers in Type 2 Diabetes Mellitus Patients

PubMed Central

Jacobo-Cejudo, M. Gorety; Valdés-Ramos, Roxana; Guadarrama-López, Ana L.; Pardo-Morales, Rosa-Virgen; Martínez-Carrillo, Beatriz E.; Harbige, Laurence S.

2017-01-01

Background: Type 2 diabetes mellitus (T2DM) is accompanied by chronic low-grade inflammation, with an imbalance in the secretion of adipokines and, worsening insulin resistance. Supplementation with n-3 PUFA in T2DM decreases inflammatory markers, the purpose of the study was to investigate the effect of n-3 PUFA supplementation on adipokines, metabolic control, and lipid profile in T2DM Mexican adults. Methods: In a randomized, single-blind, placebo-controlled pilot study, 54 patients with T2DM received 520 mg of DHA + EPA-enriched fish-oil (FOG) or a placebo (PG) daily. Baseline and 24-week anthropometric and biochemical measurements included glucose, insulin, glycosylated hemoglobin (Hb1Ac), leptin, adiponectin, resistin, and lipid profile; n-3 PUFA intake was calculated in g/day. Results: Waist circumference and blood glucose showed significant reductions in the FOG group (p = 0.001 and p = 0.011, respectively). Hb1Ac (p = 0.009 and p = 0.004), leptin (p < 0.000 and p < 0.000), and leptin/adiponectin ratio (p < 0.000 and p < 0.000) decreased significantly in both groups after 24 weeks (FOG and PG respectively). Serum resistin (FOG p < 0.000 and PG p = 0.001), insulin (FOG p < 0.000 and PG p < 0.000), and HOMA-IR (FOG p = 0.000 and PG p < 0.000) increased significantly in both groups. FOG had an overall improvement in the lipid profile with a significant decrease in triacylgycerols (p = 0.002) and atherogenic index (p = 0.031); in contrast, the PG group had increased total cholesterol (p < 0.000), non-HDL cholesterol (p < 0.000), and atherogenic index (p = 0.017). Conclusions: We found a beneficial effect of n-3 PUFA supplementation on waist circumference, glucose, Hb1Ac, leptin, leptin/adiponectin ratio, and lipid profile, without significant changes in adiponectin, and increases in resistin, insulin, and HOMA-IR in both groups. PMID:28587203

Combining insulins for optimal blood glucose control in type 1 and 2 diabetes: Focus on insulin glulisine

PubMed Central

Ulrich, Heather; Snyder, Benjamin; K Garg, Satish

2007-01-01

Normalization of blood glucose is essential for the prevention of diabetes mellitus (DM)-related microvascular and macrovascular complications. Despite substantial literature to support the benefits of glucose lowering and clear treatment targets, glycemic control remains suboptimal for most people with DM in the United States. Pharmacokinetic limitations of conventional insulins have been a barrier to achieving treatment targets secondary to adverse effects such as hypoglycemia and weight gain. Recombinant DNA technology has allowed modification of the insulin molecule to produce insulin analogues that overcome these pharmacokinetic limitations. With time action profiles that more closely mimic physiologic insulin secretion, rapid acting insulin analogues (RAAs) reduce post-prandial glucose excursions and hypoglycemia when compared to regular human insulin (RHI). Insulin glulisine (Apidra®) is a rapid-acting insulin analogue created by substituting lysine for asparagine at position B3 and glutamic acid for lysine at position B29 on the B chain of human insulin. The quick absorption of insulin glulisine more closely reproduces physiologic first-phase insulin secretion and its rapid acting profile is maintained across patient subtypes. Clinical trials have demonstrated comparable or greater efficacy of insulin glulisine versus insulin lispro or RHI, respectively. Efficacy is maintained even when insulin glulisine is administered post-meal. In addition, glulisine appears to have a more rapid time action profile compared with insulin lispro across various body mass indexes (BMIs). The safety and tolerability profile of insulin glulisine is also comparable to that of insulin lispro or RHI in type 1 or 2 DM and it has been shown to be as safe and effective when used in a continuous subcutaneous insulin infusion (CSII). In summary, insulin glulisine is a safe, effective, and well tolerated rapid-acting insulin analogue across all BMIs and a worthy option for prandial glucose control in type 1 or 2 DM. PMID:17703632

Proregenerative Microenvironment Triggered by Donor Mesenchymal Stem Cells Preserves Renal Function and Structure in Mice with Severe Diabetes Mellitus.

PubMed

Ezquer, Fernando; Giraud-Billoud, Maximiliano; Carpio, Daniel; Cabezas, Fabián; Conget, Paulette; Ezquer, Marcelo

2015-01-01

The aim of our work was to evaluate, in an animal model of severe diabetes mellitus, the effect of mesenchymal stem cells (MSCs) administration on diabetic nephropathy (DN) progression. After diabetes induction, one group of mice received the vehicle (DM) and other group received a single dose of MSCs (DM + MSCs). DM + MSCs mice showed a significant improvement in functional parameters of the kidney compared with untreated mice. While DM mice presented marked histopathological changes characteristics of advanced stages of DN (fibrosis, glomerulosclerosis, glomerular basement membrane thickening, capillary occlusion, decreased podocyte density, and effacement of foot processes), DM + MSCs mice showed only slight tubular dilatation. The renoprotection was not associated with an improvement in diabetic condition and very low number of donor cells was found in the kidney of DM + MSCs mice, suggesting that renoprotection could be mediated by paracrine effects. Indeed, DM + MSC mice presented increased renal proliferation index, decreased renal apoptotic index and the restoration of proregenerative factors, and anti-inflammatory cytokines levels. Moreover, macrophage infiltration and oxidative stress damage were also reduced in DM + MSCs mice. Our data demonstrate that MSC administration triggers a proregenerative microenvironment in DN kidney, which allows the preservation of the renal function even if diabetes was uncorrected.

Proregenerative Microenvironment Triggered by Donor Mesenchymal Stem Cells Preserves Renal Function and Structure in Mice with Severe Diabetes Mellitus

PubMed Central

Ezquer, Fernando; Giraud-Billoud, Maximiliano; Carpio, Daniel; Cabezas, Fabián; Conget, Paulette

2015-01-01

The aim of our work was to evaluate, in an animal model of severe diabetes mellitus, the effect of mesenchymal stem cells (MSCs) administration on diabetic nephropathy (DN) progression. After diabetes induction, one group of mice received the vehicle (DM) and other group received a single dose of MSCs (DM + MSCs). DM + MSCs mice showed a significant improvement in functional parameters of the kidney compared with untreated mice. While DM mice presented marked histopathological changes characteristics of advanced stages of DN (fibrosis, glomerulosclerosis, glomerular basement membrane thickening, capillary occlusion, decreased podocyte density, and effacement of foot processes), DM + MSCs mice showed only slight tubular dilatation. The renoprotection was not associated with an improvement in diabetic condition and very low number of donor cells was found in the kidney of DM + MSCs mice, suggesting that renoprotection could be mediated by paracrine effects. Indeed, DM + MSC mice presented increased renal proliferation index, decreased renal apoptotic index and the restoration of proregenerative factors, and anti-inflammatory cytokines levels. Moreover, macrophage infiltration and oxidative stress damage were also reduced in DM + MSCs mice. Our data demonstrate that MSC administration triggers a proregenerative microenvironment in DN kidney, which allows the preservation of the renal function even if diabetes was uncorrected. PMID:26167475

Type 2 diabetes mellitus unawareness, prevalence, trends and risk factors: National Health and Nutrition Examination Survey (NHANES) 1999-2010.

PubMed

Zhang, Nana; Yang, Xin; Zhu, Xiaolin; Zhao, Bin; Huang, Tianyi; Ji, Qiuhe

2017-04-01

Objectives To determine whether the associations with key risk factors in patients with diagnosed and undiagnosed type 2 diabetes mellitus (T2DM) are different using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. Methods The study analysed the prevalence and association with risk factors of undiagnosed and diagnosed T2DM using a regression model and a multinomial logistic regression model. Data from the NHANES 1999-2010 were used for the analyses. Results The study analysed data from 10 570 individuals. The overall prevalence of diagnosed and undiagnosed T2DM increased significantly from 1999 to 2010. The prevalence of undiagnosed T2DM was significantly higher in non-Hispanic whites, in individuals <30 years old and in those with near optimal (130-159 mg/dl) or very high (≥220 mg/dl) non-high-density lipoprotein cholesterol levels compared with diagnosed T2DM. Body mass index, low economic status or low educational level had no effect on T2DM diagnosis rates. Though diagnosed T2DM was associated with favourable diet/carbohydrate intake behavioural changes, it had no effect on physical activity levels. Conclusion The overall T2DM prevalence increased between 1999 and 2010, particularly for undiagnosed T2DM in patients that were formerly classified as low risk.

Type 2 diabetes mellitus unawareness, prevalence, trends and risk factors: National Health and Nutrition Examination Survey (NHANES) 1999–2010

PubMed Central

Zhang, Nana; Yang, Xin; Zhu, Xiaolin; Zhao, Bin; Huang, Tianyi

2017-01-01

Objectives To determine whether the associations with key risk factors in patients with diagnosed and undiagnosed type 2 diabetes mellitus (T2DM) are different using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. Methods The study analysed the prevalence and association with risk factors of undiagnosed and diagnosed T2DM using a regression model and a multinomial logistic regression model. Data from the NHANES 1999–2010 were used for the analyses. Results The study analysed data from 10 570 individuals. The overall prevalence of diagnosed and undiagnosed T2DM increased significantly from 1999 to 2010. The prevalence of undiagnosed T2DM was significantly higher in non-Hispanic whites, in individuals <30 years old and in those with near optimal (130–159 mg/dl) or very high (≥220 mg/dl) non-high-density lipoprotein cholesterol levels compared with diagnosed T2DM. Body mass index, low economic status or low educational level had no effect on T2DM diagnosis rates. Though diagnosed T2DM was associated with favourable diet/carbohydrate intake behavioural changes, it had no effect on physical activity levels. Conclusion The overall T2DM prevalence increased between 1999 and 2010, particularly for undiagnosed T2DM in patients that were formerly classified as low risk. PMID:28415936

Likelihood Analysis of the Minimal AMSB Model

DOE PAGES

Bagnaschi, E.; Borsato, M.; Sakurai, K.; ...

2017-04-27

We perform a likelihood analysis of the minimal Anomaly-Mediated Supersymmetry Breaking (mAMSB) model using constraints from cosmology and accelerator experiments. We find that a wino-like or a Higgsino-like neutralino LSP,more » $$m_{\\tilde \\chi^0_{1}}$$, may provide the cold dark matter (DM) with similar likelihood. The upper limit on the DM density from Planck and other experiments enforces $$m_{\\tilde \\chi^0_{1}} \\lesssim 3~TeV$$ after the inclusion of Sommerfeld enhancement in its annihilations. If most of the cold DM density is provided by the $$\\tilde \\chi_0^1$$, the measured value of the Higgs mass favours a limited range of $$\\tan \\beta \\sim 5$$ (or for $$\\mu > 0$$, $$\\tan \\beta \\sim 45$$) but the scalar mass $$m_0$$ is poorly constrained. In the wino-LSP case, $$m_{3/2}$$ is constrained to about $900~TeV$ and $${m_{\\tilde \\chi^0_{1}}}$$ to $$2.9\\pm0.1~TeV$$, whereas in the Higgsino-LSP case $$m_{3/2}$$ has just a lower limit $$\\gtrsim 650TeV$$ ($$\\gtrsim 480TeV$$) and $$m_{\\tilde \\chi^0_{1}}$$ is constrained to $$1.12 ~(1.13) \\pm0.02~TeV$$ in the $$\\mu>0$$ ($$\\mu<0$$) scenario. In neither case can the anomalous magnetic moment of the muon, $${(g-2)_\\mu}$$, be improved significantly relative to its Standard Model (SM) value, nor do flavour measurements constrain the model significantly, and there are poor prospects for discovering supersymmetric particles at the LHC, {though there} are some prospects for direct DM detection. On the other hand, if the $${m_{\\tilde \\chi^0_{1}}}$$ contributes only a fraction of the cold DM density, {future LHC $$E_T$$-based searches for gluinos, squarks and heavier chargino and neutralino states as well as disappearing track searches in the wino-like LSP region will be relevant}, and interference effects enable $${\\rm BR}(B_{s, d} \\to \\mu^+\\mu^-)$$ to agree with the data better than in the SM in the case of wino-like DM with $$\\mu > 0$$.« less

Higgs naturalness and dark matter stability by scale invariance

NASA Astrophysics Data System (ADS)

Guo, Jun; Kang, Zhaofeng

2015-09-01

Extending the spacetime symmetries of standard model (SM) by scale invariance (SI) may address the Higgs naturalness problem. In this article we attempt to embed accidental dark matter (DM) into SISM, requiring that the symmetry protecting DM stability is accidental due to the model structure rather than imposed by hand. In this framework, if the light SM-like Higgs boson is the pseudo Goldstone boson of SI spontaneously breaking, we can even pine down the model, two-Higgs-doublets plus a real singlet: The singlet is the DM candidate and the extra Higgs doublet triggers electroweak symmetry breaking via the Coleman-Weinberg mechanism; Moreover, it dominates DM dynamics. We study spontaneously breaking of SI using the Gillard-Weinberg approach and find that the second doublet should acquire vacuum expectation value near the weak scale. Moreover, its components should acquire masses around 380 GeV except for a light CP-odd Higgs boson. Based on these features, we explore viable ways to achieve the correct relic density of DM, facing stringent constraints from direct detections of DM. For instance, DM annihilates into b b bar near the SM-like Higgs boson pole, or into a pair of CP-odd Higgs boson with mass above that pole.

Periodontal Microorganisms and Cardiovascular Risk Markers in Youth With Type 1 Diabetes and Without Diabetes.

PubMed

Merchant, Anwar T; Nahhas, Georges J; Wadwa, R Paul; Zhang, Jiajia; Tang, Yifan; Johnson, Lonnie R; Maahs, David M; Bishop, Franziska; Teles, Ricardo; Morrato, Elaine H

2016-04-01

A subset of periodontal microorganisms has been associated with cardiovascular disease (CVD), which is the leading complication of type 1 diabetes (t1DM). The authors therefore evaluated the association between periodontal microorganism groups and early markers of CVD in youth with t1DM. A cross-sectional analysis was conducted among youth aged 12 to 19 years at enrollment; 105 had t1DM for ≥5 years and were seeking care at the Barbara Davis Center, University of Colorado, from 2009 to 2011, and 71 did not have diabetes. Subgingival plaque samples were assessed for counts of 41 periodontal microorganisms using DNA-DNA hybridization. Microorganisms were classified using cluster analysis into four groups named red-orange, orange-green, blue/other, and yellow/other, modified from Socransky's color scheme for periodontal microorganisms. Subsamples (54 with t1DM and 48 without diabetes) also received a periodontal examination at the University of Colorado School of Dental Medicine. Participants were ≈15 years old on average, and 74% were white. Mean periodontal probing depth was 2 mm (SE 0.02), and 17% had bleeding on probing. In multivariable analyses, glycated hemoglobin (HbA1c) was inversely associated with the yellow/other cluster (microorganisms that are not associated with periodontal disease) among youth with t1DM. Blood pressure, triglycerides, low-density lipoprotein, high-density lipoprotein, and total cholesterol were not associated with microorganism clusters in this group. HbA1c was not associated with periodontal microorganism clusters among youth without diabetes. Among youth with t1DM who had good oral health, periodontal microorganisms were not associated with CVD risk factors.

Association analysis of SLC30A8 rs13266634 and rs16889462 polymorphisms with type 2 diabetes mellitus and repaglinide response in Chinese patients.

PubMed

Huang, Qiong; Yin, Ji-Ye; Dai, Xing-Ping; Wu, Jing; Chen, Xiang; Deng, Cai-Shu; Yu, Min; Gong, Zhi-Cheng; Zhou, Hong-Hao; Liu, Zhao-Qian

2010-12-01

Genome-wide association studies (GWASs) identified that SLC30A8 genetic polymorphism was a risk of type 2 diabetes mellitus (T2DM) in several populations. This study aimed to investigate whether the SLC30A8 rs13266634 and rs16889462 polymorphisms were associated with T2DM susceptibility and repaglinide therapeutic efficacy in Chinese T2DM patients. We conducted a case-control study of 443 T2DM patients and 229 healthy volunteers to identify SLC30A8 rs13266634 and rs16889462 genotypes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-eight patients were randomly selected and underwent an 8-week repaglinide treatment (3 mg/d). Fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbAlc), fasting serum insulin (FINS), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), serum triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c) and high-density lipoprotein-cholesterol (HDL-c) were determined before and after repaglinide treatment. SLC30A8 rs13266634 risk C allele frequency was higher in T2DM patients than in healthy controls (P < 0.05). There was a better repaglinide response on FINS (P < 0.05) and PINS (P < 0.01) in patients with rs13266634 CT+TT genotypes compared with CC genotype carriers. Patients with rs16889462 GA genotype showed an enhanced repaglinide efficacy on FPG (P < 0.01), PPG (P < 0.01) and HbAlc (P < 0.05) compared with GG genotype individuals. SLC30A8 rs13266634 and rs16889462 polymorphisms were associated with repaglinide therapeutic efficacy in Chinese T2DM patients.

LIGO GRAVITATIONAL WAVE DETECTION, PRIMORDIAL BLACK HOLES, AND THE NEAR-IR COSMIC INFRARED BACKGROUND ANISOTROPIES

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

Kashlinsky, A., E-mail: Alexander.Kashlinsky@nasa.gov

LIGO's discovery of a gravitational wave from two merging black holes (BHs) of similar masses rekindled suggestions that primordial BHs (PBHs) make up the dark matter (DM). If so, PBHs would add a Poissonian isocurvature density fluctuation component to the inflation-produced adiabatic density fluctuations. For LIGO's BH parameters, this extra component would dominate the small-scale power responsible for collapse of early DM halos at z ≳ 10, where first luminous sources formed. We quantify the resultant increase in high- z abundances of collapsed halos that are suitable for producing the first generation of stars and luminous sources. The significantly increasedmore » abundance of the early halos would naturally explain the observed source-subtracted near-IR cosmic infrared background (CIB) fluctuations, which cannot be accounted for by known galaxy populations. For LIGO's BH parameters, this increase is such that the observed CIB fluctuation levels at 2–5 μ m can be produced if only a tiny fraction of baryons in the collapsed DM halos forms luminous sources. Gas accretion onto these PBHs in collapsed halos, where first stars should also form, would straightforwardly account for the observed high coherence between the CIB and unresolved cosmic X-ray background in soft X-rays. We discuss modifications possibly required in the processes of first star formation if LIGO-type BHs indeed make up the bulk or all of DM. The arguments are valid only if the PBHs make up all, or at least most, of DM, but at the same time the mechanism appears inevitable if DM is made of PBHs.« less

CYTOKINE PROFILING FOR CHEMICAL RESPIRATORY SENSITIZERS

EPA Science Inventory

CYTOKINE PROFILING FOR CHEMICAL RESPIRATORY SENSITIZERS. LM Plitnick1, SE Loveless2, GS Ladics2, MP Holsapple3, MJ Selgrade4, DM Sailstad4 & RJ Smialowicz4. 1UNC, Chapel Hill, NC; 2DuPont Co., Haskell Laboratory, Newark, DE; 3Dow Chemical, Midland, MI & 4USEPA, NHEERL, RTP, NC.

Liver Proteome in Diabetes Type 1 Rat Model: Insulin-Dependent and -Independent Changes.

PubMed

Braga, Camila Pereira; Boone, Cory H T; Grove, Ryan A; Adamcova, Dana; Fernandes, Ana Angélica Henrique; Adamec, Jiri; de Magalhães Padilha, Pedro

2016-12-01

Diabetes mellitus type 1 (DM1) is a major public health problem that continues to burden the healthcare systems worldwide, costing exponentially more as the epidemic grows. Innovative strategies and omics system diagnostics for earlier diagnosis or prognostication of DM1 are essential to prevent secondary complications and alleviate the associated economic burden. In a preclinical study design that involved streptozotocin (STZ)-induced DM1, insulin-treated STZ-induced DM1, and control rats, we characterized the insulin-dependent and -independent changes in protein profiles in liver samples. Digested proteins were subjected to LC-MS E for proteomic data. Progenesis QI data processing and analysis of variance were utilized for statistical analyses. We found 305 proteins with significantly altered abundance among the control, DM1, and insulin-treated DM1 groups (p < 0.05). These differentially regulated proteins were related to enzymes that function in key metabolic pathways and stress responses. For example, gluconeogenesis appeared to return to control levels in the DM1 group after insulin treatment, with the restoration of gluconeogenesis regulatory enzyme, FBP1. Insulin administration to DM1 rats also restored the blood glucose levels and enzymes of general stress and antioxidant response systems. These observations are crucial for insights on DM1 pathophysiology and new molecular targets for future clinical biomarkers, drug discovery, and development. Additionally, we underscore that proteomics offers much potential in preclinical biomarker discovery for diabetes as well as common complex diseases such as cancer, dementia, and infectious disorders.

Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis

PubMed Central

Rato, L.; Alves, M. G.; Dias, T. R.; Cavaco, J. E.; Oliveira, Pedro F.

2015-01-01

Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM) induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ) T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by 1H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters. PMID:26064993

Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis.

PubMed

Rato, L; Alves, M G; Dias, T R; Cavaco, J E; Oliveira, Pedro F

2015-01-01

Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM) induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ) T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by (1)H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters.

Defining and characterizing the critical transition state prior to the type 2 diabetes disease

PubMed Central

Zhu, Chunqing; Zhou, Xin; Chen, Pei; Fu, Tianyun; Hu, Zhongkai; Wu, Qian; Liu, Wei; Liu, Daowei; Yu, Yunxian; Zhang, Yan; McElhinney, Doff B.; Li, Yu-Ming; Culver, Devore S; Alfreds, Shaun T.; Stearns, Frank; Sylvester, Karl G.; Widen, Eric

2017-01-01

Background Type 2 diabetes mellitus (T2DM), with increased risk of serious long-term complications, currently represents 8.3% of the adult population. We hypothesized that a critical transition state prior to the new onset T2DM can be revealed through the longitudinal electronic medical record (EMR) analysis. Method We applied the transition-based network entropy methodology which previously identified a dynamic driver network (DDN) underlying the critical T2DM transition at the tissue molecular biological level. To profile pre-disease phenotypical changes that indicated a critical transition state, a cohort of 7,334 patients was assembled from the Maine State Health Information Exchange (HIE). These patients all had their first confirmative diagnosis of T2DM between January 1, 2013 and June 30, 2013. The cohort’s EMRs from the 24 months preceding their date of first T2DM diagnosis were extracted. Results Analysis of these patients’ pre-disease clinical history identified a dynamic driver network (DDN) and an associated critical transition state six months prior to their first confirmative T2DM state. Conclusions This 6-month window before the disease state provides an early warning of the impending T2DM, warranting an opportunity to apply proactive interventions to prevent or delay the new onset of T2DM. PMID:28686739

Burden and spectrum of disease in people with diabetes in Tonga

PubMed Central

Viney, K.; Roseveare, C.; Colaguiri, R.; Marais, B. J.

2014-01-01

Setting: National Diabetes Centre, Tonga. Objective: To describe the diabetes patient profile and disease spectrum, assess the impact of diabetic care and evaluate diabetes-attributable adverse outcomes. Design: Retrospective descriptive study of patients registered in the National Diabetes Registry from its inception in May 2004 to 2012, and review of the National Deaths Registry (2011–2012). Results: Of 4653 patients with diabetes mellitus (DM) identified, 95.8% had type 2 DM, 0.2% type 1, 1.2% gestational DM and 2.9% pre-DM. Of the 4409 patients with type 2 DM, 64.7% were female, 82.7% were aged ⩾40 years, 25.3% had hypertension and 53.3% were obese. Among those in care for >2 years, no positive impact on body mass index or glycosylated haemoglobin could be demonstrated, but there was significant improvement in hypertension control. Morbidity included lower limb amputations in 272 (6.1%) patients. DM was listed as a contributory cause of death due to sepsis (15/30, 50.0%), kidney failure (16/28, 57.1%), stroke (7/16, 43.8%) and ischaemic heart disease (20/59, 33.9%). Conclusion: DM was associated with high levels of morbidity and mortality. DM care improved hypertension control, but had little impact on other comorbid conditions. Enhanced monitoring and greater patient involvement should improve care; creative strategies are required to prevent and reduce obesity. PMID:26477287

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

Blennow, Mattias; Herrero-Garcia, Juan; Schwetz, Thomas, E-mail: emb@kth.se, E-mail: juhg@kth.se, E-mail: schwetz@fysik.su.se

We show that a positive signal in a dark matter (DM) direct detection experiment can be used to place a lower bound on the DM capture rate in the Sun, independent of the DM halo. For a given particle physics model and DM mass we obtain a lower bound on the capture rate independent of the local DM density, velocity distribution, galactic escape velocity, as well as the scattering cross section. We illustrate this lower bound on the capture rate by assuming that upcoming direct detection experiments will soon obtain a significant signal. When comparing the lower bound on themore » capture rate with limits on the high-energy neutrino flux from the Sun from neutrino telescopes, we can place upper limits on the branching fraction of DM annihilation channels leading to neutrinos. With current data from IceCube and Super-Kamiokande non-trivial limits can be obtained for spin-dependent interactions and direct annihilations into neutrinos. In some cases also annihilations into ττ or b b start getting constrained. For spin-independent interactions current constraints are weak, but they may become interesting for data from future neutrino telescopes.« less

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

Blennow, Mattias; Herrero-Garcia, Juan; Schwetz, Thomas

We show that a positive signal in a dark matter (DM) direct detection experiment can be used to place a lower bound on the DM capture rate in the Sun, independent of the DM halo. For a given particle physics model and DM mass we obtain a lower bound on the capture rate independent of the local DM density, velocity distribution, galactic escape velocity, as well as the scattering cross section. We illustrate this lower bound on the capture rate by assuming that upcoming direct detection experiments will soon obtain a significant signal. When comparing the lower bound on themore » capture rate with limits on the high-energy neutrino flux from the Sun from neutrino telescopes, we can place upper limits on the branching fraction of DM annihilation channels leading to neutrinos. With current data from IceCube and Super-Kamiokande non-trivial limits can be obtained for spin-dependent interactions and direct annihilations into neutrinos. In some cases also annihilations into ττ or bb start getting constrained. For spin-independent interactions current constraints are weak, but they may become interesting for data from future neutrino telescopes.« less

Type 2 Diabetes in Relation to Hip Bone Density, Area, and Bone Turnover in Swedish Men and Women: A Cross-Sectional Study.

PubMed

Mitchell, Adam; Fall, Tove; Melhus, Håkan; Wolk, Alicja; Michaëlsson, Karl; Byberg, Liisa

2018-06-26

Men and women with type 2 diabetes mellitus (T2DM) have higher risk of hip fracture, but the mechanisms are not fully understood. We aimed to investigate how T2DM, glucose, and insulin were associated with femoral bone mineral density (BMD), bone mineral area (BMA), and bone turnover markers. We used two cross-sectional cohorts: the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 452, mean age 82 years) and the Swedish Mammography Cohort Clinical (SMCC, n = 4713, mean age 68 years). We identified men and women with normal fasting glucose (NFG), impaired fasting plasma glucose (IFG), and T2DM. BMD and BMA at the total hip and femoral shaft were measured using dual energy X-ray absorptiometry (DXA). Bone turnover markers; CrossLaps and osteocalcin were measured in women. Linear regression models were applied. Men and women showed a progressively higher BMD following the clinical cutoffs of fasting glucose from NFG to IFG to T2DM. In contrast, there was a progressively lower BMA. Men and women with T2DM, compared to those with NFG, had lower BMA at the total hip (- 1.7%; 95% CI - 3.2, - 0.2 and - 1.0%; 95% CI - 1.6, - 0.4) and the femoral shaft (- 2.0%; 95% CI - 3.5, - 0.4 and - 0.6%; 95% CI - 1.2, - 0.01), respectively. T2DM was associated with lower concentrations of CrossLaps (- 8.1%; 95% CI - 12.7, - 3.6) and osteocalcin (- 15.2%; 95% CI - 19.0, - 11.2). These cross-sectional results indicate that those with T2DM have smaller bone area and lower bone turnover, which could increase the risk of hip fracture.

Electrodeposition and Characterization of Mn-Cu-Zn Alloys for Corrosion Protection Coating

NASA Astrophysics Data System (ADS)

Tsurtsumia, Gigla; Gogoli, David; Koiava, Nana; Kakhniashvili, Izolda; Jokhadze, Nunu; Lezhava, Tinatin; Nioradze, Nikoloz; Tatishvili, Dimitri

2017-12-01

Mn-Cu-Zn alloys were electrodeposited from sulphate bath, containing citrate or EDTA and their mixtures as complexing ligands. The influence of bath composition and deposition parameters on alloys composition, cathodic current efficiency and structural and electrochemical properties were studied. At a higher current density (≥ 37.5 A dm-2) a uniform surface deposit of Mn-Cu-Zn was obtained. Optimal pH of electrolyte (0.3 mol/dm3Mn2+ + 0.6 mol/dm3 (NH4)2SO4 +0.1 mol/dm3Zn2++0.005 mol/dm3 Cu2++ 0.05mol/dm3Na3Cit + 0.15mol/dm3 EDTA; t=300C; τ=20 min) for silvery, nonporous coating of Mn-Cu-Zn alloy was within 6.5-7.5; coating composition: 71-83% Mn, 6-7.8% Cu, 11.5-20% Zn, current efficiency up to 40%. XRD patterns revealed BCT (body centred tetragonal) γ-Mn solid phase solution (lattice constants a=2.68 Å c=3.59 Å). Corrosion measurements of deposited alloys were performed in aerated 3.5% NaCl solution. The corrosion current density (icorr) of the electrodeposited alloys on carbon steel was 10 times lower than corrosion rate of pure zinc and manganese coatings. Triple alloy coatings corrosion potential (Ecorr = -1140 mV vs. Ag/AgCl) preserved negative potential value longer (more than three months) compared to carbon steel substrate (Ecorr = -670 mV vs. Ag/AgCl). Tafel polarization curves taken on Mn-Cu-Zn alloy coating in aerated 3.5% NaCl solution did not show a typical passivation behaviour which can be explained by formation oflow solubility of adherent corrosion products on the alloy surface. Corrosion test of Mn-Cu-Zn electrocoating in chlorine environment shows that it is the best cathodic protective coating for a steel product.

Biochemical profile of stone-forming patients with diabetes mellitus.

PubMed

Pak, Charles Y C; Sakhaee, Khashayar; Moe, Orson; Preminger, Glenn M; Poindexter, John R; Peterson, Roy D; Pietrow, Paul; Ekeruo, Wesley

2003-03-01

To test the hypothesis that stone-forming patients with type II diabetes (DM-II) have a high prevalence of uric acid (UA) stones and present with some of the biochemical features of gouty diathesis (GD). The demographic and initial biochemical data from 59 stone-forming patients with DM-II (serum glucose greater than 126 mg/dL, no insulin therapy, older than 35 years of age) from Dallas, Texas and Durham, North Carolina were retrieved and compared with data from 58 patients with GD and 116 with hyperuricosuric calcium oxalate urolithiasis (HUCU) without DM. UA stones were detected in 33.9% of patients with DM-II compared with 6.2% of stone-forming patients without DM (P <0.001). Despite similar ingestion of alkali, the urinary pH in patients with DM-II and UA stones (n = 20) was low (pH = 5.5), as it is in patients with GD, and was significantly lower than in patients with HUCU. The urinary pH in patients with DM-II and calcium stones (n = 39) was intermediate between that in those with DM-II and UA stones and those with HUCU. However, both DM groups had fractional excretion of urate that was not depressed, as it is in those with GD, and was comparable to the value obtained in those with HUCU. The urinary content of undissociated UA was significantly higher, and the saturation of calcium phosphate (brushite) and sodium urate was significantly lower in those with DM-II and UA stones than in those with HUCU. Stone-forming patients with DM-II have a high prevalence of UA stones. Diabetic patients with UA stones share a key feature of those with GD, namely the passage of unusually acid urine, but not the low fractional excretion of urate.

The cognitive profile of myotonic dystrophy type 1: A systematic review and meta-analysis.

PubMed

Okkersen, Kees; Buskes, Melanie; Groenewoud, Johannes; Kessels, Roy P C; Knoop, Hans; van Engelen, Baziel; Raaphorst, Joost

2017-10-01

To examine the cognitive profile of patients with myotonic dystrophy type 1 (DM1) on the basis of a systematic review and meta-analysis of the literature. Embase, Medline and PsycInfo were searched for studies reporting ≥1 neuropsychological test in both DM1 patients and healthy controls. Search, data extraction and risk of bias analysis were independently performed by two authors to minimize error. Neuropsychological tests were categorized into 12 cognitive domains and effect sizes (Hedges' g) were calculated for each domain and for tests administered in ≥5 studies. DM1 participants demonstrated a significantly worse performance compared to controls in all cognitive domains. Effect sizes ranged from -.33 (small) for verbal memory to -1.01 (large) for visuospatial perception. Except for the domains global cognition, intelligence and social cognition, wide confidence intervals (CIs) were associated with moderate to marked statistical heterogeneity that necessitates careful interpretation of results. Out of the individual tests, the Rey-Osterrieth complex figure-copy (both non-verbal memory and visuoconstruction) showed consistent impairment with acceptable heterogeneity. In DM1 patients, cognitive deficits may include a variable combination of global cognitive impairment with involvement across different domains, including social cognition, memory and visuospatial functioning. Although DM1 is a heterogeneous disorder, our study shows that meta-analysis is feasible, contributes to the understanding of brain involvement and may direct bedside testing. The protocol for this study has been registered in PROSPERO (International prospective register of systematic reviews) under ID: 42016037415. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metabolic risk factors in adolescent girls with type 1 diabetes.

PubMed

Castro-Correia, Cíntia; Santos-Silva, Rita; Pinheiro, Marta; Costa, Carla; Fontoura, Manuel

2018-06-27

The incidence of pediatric metabolic syndrome (MS) has progressively increased. The incidence of type 1 diabetes mellitus (T1DM) has also increased. Thus, some children and adolescents with T1DM exhibit MS parameters. The aim of the study was to evaluate the presence of MS parameters in female adolescents with T1DM based on their nutritional status. We evaluated 44 adolescents with T1DM (consecutive non-randomized sample) aged between 14 and 18 years, who were on intensive therapy with insulin. Patients were subdivided according to their body mass index (BMI). Variables evaluated include: age, age at diagnosis, weight, height, BMI, abdominal circumference, blood pressure, glycated hemoglobin (HbA1c), abdominal and pelvic ultrasound and lipoprotein profile. Gynecological history data were also collected. Lipid profile changes were identified in 32% of overweight or obese girls and in 23% of those with an adequate weight. Hypertension (HT) was observed in 19% of overweight or obese girls and in 14% of those with a BMI≥85th percentile (Pc). The only statistically significant difference between the groups was the presence of abdominal adiposity. All other features, including the presence of dyslipidemia, HT, abdominal adiposity, non-alcoholic steatohepatitis (NASH) and polycystic ovarian syndrome (PCOS), were present in both groups. Although being overweight and/or obese aggravates the risk of cardiovascular disease, MS is already present in many young adolescents with T1DM of normal weight. It is necessary that MS risk factors are routinely evaluated in all diabetic adolescents, including those with an adequate BMI.

Biochemical and microstructural Ccharacteristics of insoluble and soluble dietary fiber prepared from mushroom sclerotia of Pleurotus tuber-regium, Polyporus rhinocerus, and Wolfiporia cocos.

PubMed

Wong, Ka-Hing; Cheung, Peter C K; Wu, Jin-Zhong

2003-11-19

The proximate composition of sclerotia of Pleurotus tuber-regium, Polyporus rhinoceros, and Wolfiporia cocos, together with the yield, purity, monosaccharide profile, and microstructure of their insoluble dietary fiber (IDF) and soluble dietary fiber (SDF) fractions prepared from AOAC enzymatic-gravimetric methods were investigated and compared. All three sclerotia were typical carbohydrate rich sclerotia [ranging from 90.5 to 98.1% dry matter (DM)] with an exceptionally low amount of crude lipid content (ranging from 0.02 to 0.14% DM). Besides, all three sclerotia possessed substantial amounts of IDF (ranging from 77.4 to 94.6% DM) with notably high levels of nonstarch polysaccharides (NSP) (89.9-92.2% DM) in which glucose was the predominant sugar residue (90.6-97.2% of NSP DM). On the contrary, both the yield (only ranging from 1.45 to 2.50% DM) and the amount of NSP (ranging from 22.4 to 29.6% DM) of the three sclerotial SDF fractions were very low. Scanning electron micrographs showed fragments of interwoven hyphae and insoluble materials in the three sclerotial IDF fractions, but only an amorphous structure of soluble materials was observed in the SDF fractions. The potential use of these fiber preparations was discussed.

Direct and Indirect Dark Matter Detection in Gauge Theories (in Portuguese)

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

Queiroz, Farinaldo

The Dark matter (DM) problem constitutes a key question at the interface among Particle Physics, Astrophysics and Cosmology. The observational data which have been accumulated in the last years point to an existence of non baryonic amount of DM. Since the Standard Model (SM) does not provide any candidate for such non-baryonic DM, the evidence of DM is a major indication for new physics beyond the SM. We will study in this work one of the most popular DM candidates, the so called WIMPs (Weakly Interacting Massive Particles) from a direct and indirect detection perspective. In order to approach themore » direct and indirect dection of DM in the context of Particle Physics in a more pedagogic way, we will begin our discussion talking about a minimal extension of the SM. Later we will work on the subject in a 3-3-1 model. Next, we will study the role of WIMPs in the Big Bang Nucleosynthesis. Lastly, we will look for indirect DM signals in the center of our galaxy using the NASA Satellite, called Fermi-LAT. Through a comprehensive analysis of the data events observed by Fermi-LAT and some background models, we will constrain the dark matter annihilation cross section for several annihilation channels and dark matter halo profiles.« less

Predictors of completing a primary health care diabetes prevention intervention programme in people at high risk of type 2 diabetes: Experiences of the DE-PLAN project.

PubMed

Gilis-Januszewska, Aleksandra; Lindström, Jaana; Barengo, Noël C; Tuomilehto, Jaakko; Schwarz, Peter Eh; Wójtowicz, Ewa; Piwońska-Solska, Beata; Szybiński, Zbigniew; Windak, Adam; Hubalewska-Dydejczyk, Alicja

2018-02-01

It has been shown that real-life implementation studies for the prevention of type 2 diabetes (DM2) performed in different settings and populations can be effective. However, not enough information is available on factors influencing the reach of DM2 prevention programmes. This study examines the predictors of completing an intervention programme targeted at people at high risk of DM2 in Krakow, Poland as part of the DE-PLAN project.A total of 262 middle-aged people, everyday patients of 9 general practitioners' (GP) practices, at high risk of DM2 (Finnish Diabetes Risk Score (FINDRISK) >14) agreed to participate in the lifestyle intervention to prevent DM2. Intervention consisted of 11 lifestyle counseling sessions, organized physical activity sessions followed by motivational phone calls and letters. Measurements were performed at baseline and 1 year after the initiation of the intervention.Seventy percent of the study participants enrolled completed the core curriculum (n = 184), 22% were men. When compared to noncompleters, completers had a healthier baseline diabetes risk profile (P <.05). People who completed the intervention were less frequently employed versus noncompleters (P = .037), less often had hypertension (P = .043), and more frequently consumed vegetables and fruit daily (P = .055).In multiple logistic regression model, employment reduced the likelihood of completing the intervention 2 times (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.25-0.81). Higher glucose 2 hours after glucose load and hypertension were the independent factors decreasing the chance to participate in the intervention (OR 0.79, 95% 0.69-0.92 and OR 0.52, 95% CI 0.27-0.99, respectively). Daily consumption of vegetables and fruits increased the likelihood of completing the intervention (OR 1.86, 95% 1.01-3.41).In conclusion, people with healthier behavior and risk profile are more predisposed to complete diabetes prevention interventions. Male, those who work and those with a worse health profile, are less likely to participate and complete interventions. Targeted strategies are needed in real-life diabetes prevention interventions to improve male participation and to reach those who are working as well as people with a higher risk profile.

HLA-DRB1*08 allele may help to distinguish between type 1 diabetes mellitus and type 2 diabetes mellitus in Mexican children.

PubMed

Rodríguez-Ventura, Ana L; Yamamoto-Furusho, Jesus K; Coyote, Ninel; Dorantes, Luis M; Ruiz-Morales, Jorge A; Vargas-Alarcón, Gilberto; Granados, Julio

2007-02-01

It may be difficult to distinguish type 1 diabetes mellitus (T1DM) from type 2 diabetes mellitus (T2DM) in the pediatric population. Autoantibodies may help to differentiate both types of diabetes, but sometimes these are positive in patients with T2DM and negative in patients with T1DM. The human leukocyte antigen (HLA)-DR genotype has been associated with T1DM and with T2DM only in adults and in determined cases. To determine the differences in HLA class II allele frequencies in Mexican children with T1DM and T2DM. We included 72 children with T1DM, 28 children with T2DM, and 99 healthy controls. All were Mexican, and diabetes was diagnosed according to the clinical and laboratory criteria established by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. The HLA-DRB1 typing was performed using polymerase chain reaction-sequence-specific oligonucleotide probe and polymerase chain reaction sequence-specific primers. We found an increased frequency of HLA-DRB1*08 and a decreased frequency of HLA-DRB1*04 in the group with T2DM vs. T1DM [p = 0.0001, odds ratio (OR) = 10.58, 95% confidence interval (CI) = 3-40.8 and p = 0.0006, OR = 0.24, 95% CI = 0.11-0.53, respectively]. No significant differences were found between HLA-DRB1 alleles in T2DM vs. controls. In the group with T1DM, there was a significantly increased frequency of the HLA-DR4 and HLA-DR3 alleles relative to controls (p = 0.0000001, OR = 3.59, 95% CI = 2.2-5.8 and p = 0.00009, OR = 4.66, 95% CI = 2.1-10.3, respectively). There are significant differences in the HLA profile in Mexican children with T1DM and T2DM. HLA typing could play a role in the differentiation between both types of diabetes in this population.

Resolving the Problem of Stellar Orbital Anisotropy

NASA Astrophysics Data System (ADS)

Humphrey, Philip

2006-09-01

Mass profiles of elliptical galaxies provide an insight into dark matter (DM) halo formation, while orbital structure is tied to evolutionary history. Unfortunately the mass-anisotropy degeneracy prevents either from being uniquely determined by stellar kinematics measurements alone. A recent controversy suggesting no DM in elliptical galaxies may be explained by this effect, illustrating the urgent need for better constraints. We propose a 75ks Chandra exposure of NGC4649 to break this degeneracy in a carefully-chosen galaxy. Combined with our deep optical spectra and PN and GC kinematics, this will provide definitive constraints on the mass and orbital anisotropy profiles. By combining all techniques for one galaxy, this will provide a textbook example of how to overcome the degeneracy.

GHASP: an H α kinematical survey of spiral galaxies - XI. Distribution of luminous and dark matter in spiral and irregular nearby galaxies using WISE photometry

NASA Astrophysics Data System (ADS)

Korsaga, M.; Carignan, C.; Amram, P.; Epinat, B.; Jarrett, T. H.

2018-07-01

We present the mass distribution of a sample of 121 nearby galaxies with high-quality optical velocity fields and available infrared Wide-field Infrared Survey Explorer(WISE) 3.4 μm data. Contrary to previous studies, this sample covers all morphological types and is not biased towards late-type galaxies. These galaxies are part of the Fabry-Perot kinematical Gassendi HAlpha survey of SPirals survey of spirals and irregular nearby galaxies. Combining the kinematical data to the WISE surface brightness data probing the emission from the old stellar population, we derive mass models allowing us to compare the luminous to the dark matter (DM) halo mass distribution in the optical regions of those galaxies. DM models are constructed using the isothermal core profile and the Navarro-Frenk-White cuspy profile. We allow the mass-to-light ratio (M/L) of the baryonic disc to vary or we keep it fixed, constrained by stellar evolutionary models (WISE W1-W2 colour) and we carry out best fit (BFM) and pseudo-isothermal maximum disc (MDM) models. We found that the MDM provides M/L values four times higher than the BFM, suggesting that disc components, on average, tend to be maximal. The main results are: (i) the rotation curves of most galaxies are better fitted with core rather than cuspy profiles; and (ii) the relation between the parameters of the DM and of the luminous matter components mostly depends on morphological types. More precisely, the distribution of the DM inside galaxies depends on whether or not the galaxy has a bulge.

Factors associated with consumption of diabetic diet among type 2 diabetic subjects from Ahmedabad, Western India.

PubMed

Patel, Mayur; Patel, Ina M; Patel, Yash M; Rathi, Suresh K

2012-12-01

This cross-sectional study assessed the current situation of and factors associated with consumption of diabetic diet among 399 type 2 diabetes mellitus (T2DM) subjects from Ahmedabad, Western India. The study was performed with diagnosed (at least one year old) diabetic subjects who attended the Department of Diabetology, All India Institute of Diabetes and Research and Yash Diabetes Specialties Centre (Swasthya Hospital), Ahmedabad during July 2010-November 2010. The subjects completed an interviewer-administered questionnaire. The questionnaire included variables, such as sociodemographic factors, family history of diabetes, behavioural profile, risk profile (glycaemic status, hypertension, and obesity), and diet-related history (consumption of diabetic diet, consumption of low fat/skimmed milk, method of cooking, and sources for diet advice). Blood pressure, body mass index, glycosylated haemoglobin (HbA1c) level, and fasting lipid profile were measured. All analyses including multivariate logistic regression were conducted using SPSS, version 11.5. In total, 399 T2DM subjects (65% male, 35% female) with mean age of 53.16 +/- 7.95 years were studied. Although 73% of T2DM subjects were consuming diabetic diet, the good glycaemic control (HbA1c level < 7%) was achieved only in 35% of the subjects. The majority (75%) of the subjects had a positive family history of diabetes, and 52% were obese. In 77%, the main source of dietary advice was doctor. In 36%, the main methods of cooking were: boiling and roasting. The final multivariate model showed that visit to dietician, level of education, intake of low fat, and family history of diabetes were independent predictors for diabetic diet consumption among T2DM subjects. However, longitudinal and cohort studies are required to establish the association between consumption of diabetic diet and glycaemic control.

Circulating PCSK9 in patients with type 2 diabetes and related metabolic disorders.

PubMed

Ibarretxe, Daiana; Girona, Josefa; Plana, Núria; Cabré, Anna; Ferré, Raimón; Amigó, Núria; Guaita, Sandra; Mallol, Roger; Heras, Mercedes; Masana, Luis

2016-01-01

PCSK9 is a pivotal molecule in the regulation of lipid metabolism. Previous studies have suggested that PCSK9 expression and its function in LDL receptor regulation could be altered in the context of diabetes. The aim was to assess PCSK9 plasma levels in patients with type 2 diabetes (T2DM) and other related metabolic disorders as well as its relation to the metabolomic profile generated by nuclear magnetic resonance (NMR) and glucose homeostasis. There were recruited a total of 457 patients suffering from T2DM and other metabolic disorders (metabolic syndrome (MetS), obesity and atherogenic dyslipidaemia (AD) and other disorders). Anamnesis, anthropometry and physical examinations were conducted, and vascular and abdominal adiposity imaging were carried out. Biochemical studies were performed to determine PCSK9 plasma levels 6 weeks after lipid lowering drug wash-out in treated patients. A complete metabolomic lipid profile was also generated by NMR. The rs505151 and rs11591147 genetic variants of PCSK9 gene were identified in patients. The results showed that PCSK9 levels are increased in patients with T2DM and MetS (14% and 13%; p<0.005, respectively). Circulating PCSK9 levels were correlated with an atherogenic lipid profile and with insulin resistance parameters. PCSK9 levels were also positively associated with AD, as defined by lipoprotein particle number and size. The rs11591147 genetic variant resulted in lower levels of circulating PCSK9 and LDL cholesterol (LDL-C). PCSK9 plasma levels are increased in T2DM and MetS patients and are associated with LDL-C and other parameters of AD and glucose metabolism. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Clinical and metabolic profile of patients with latent autoimmune diabetes in adults in specialized care in Madrid.

PubMed

Arranz Martín, Alfonso; Lecumberri Pascual, Edurne; Brito Sanfiel, Miguel Ángel; Andía Melero, Víctor; Nattero Chavez, Lia; Sánchez López, Iván; Cánovas Molina, Gloria; Arrieta Blanco, Francisco; González Perez Del Villar, Noemí

2017-01-01

To report the clinical characteristics of patients with latent autoimmune diabetes in adults (LADA), and to ascertain their metabolic control and associated chronic complications. Patients with DM attending specialized medical care in Madrid who met the following criteria: age at diagnosis of DM >30years, initial insulin independence for at least 6months and positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis, associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic control, and presence of chronic complications were analyzed. Number of patients; 193; 56% females. Family history of DM: 62%. Age at DM diagnosis: 49years. Delay in confirmation of LADA: 3.5years. Insulin-independence time: 12months. Baseline serum C-peptide levels: 0.66ng/ml. Basal-bolus regimen: 76.7%. Total daily dose: 35.1U/day, corresponding to 0.51U/Kg. With no associated oral antidiabetic drugs: 33.5%. Other autoimmune diseases: 57%. Fasting plasma glucose: 160.5mg/dL. HbA1c: 7.7%. BMI: 25.4kg/m 2 (overweight, 31.5%; obesity, 8%). Blood pressure: 128/75. HDL cholesterol: 65mg/dL. LDL cholesterol: 96mg/dL. Triglycerides: 89mg/dL. Known chronic complications: 28%. Recognition of LADA may be delayed by several years. There is a heterogeneous pancreatic insulin reserve which is negative related to glycemic parameters. Most patients are poorly controlled despite intensive insulin therapy. They often have overweight, but have adequate control of BP and lipid profile and a low incidence of macrovascular complications. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

The HLA profiles of mixed connective tissue disease differ distinctly from the profiles of clinically related connective tissue diseases.

PubMed

Flåm, Siri Tennebø; Gunnarsson, Ragnar; Garen, Torhild; Lie, Benedicte Alexandra; Molberg, Øyvind

2015-03-01

The Norwegian nationwide MCTD cohort was established to obtain unbiased data on key disease issues, and thereby reappraise the concept of MCTD. In the current study, the aims were to obtain detailed HLA profile data on the large Norwegian MCTD cohort and compare these with the HLA profiles of ethnically matched healthy controls and related CTD controls. HLA profiles, determined by sequence-based typing of HLA-B* and DRB1*, were compared between four control groups of Norwegian ancestry, SLE (n = 96), SSc (n = 95), PM/DM (n = 84), healthy individuals (n = 282), the complete MCTD cohort (n = 155) and MCTD subsets defined by key clinical parameters. HLA-B*08 [odds ratio (OR) 2.05, P = 1.31 × 10(-4)) and DRB1*04:01 (OR 2.82, P = 3.64 × 10(-8)) were identified as risk alleles for MCTD, while DRB1*04:04, DRB1*13:01 and DRB1*13:02 were protective. Risk alleles for SLE and PM/DM were B*08 and DRB1*03:01. SSc risk was associated with DRB1*08:01. Analyses of MCTD subsets identified B*18 [OR 3.32 (95% CI 1.38, 8.01)] and DRB1*03:01 [OR 1.83 (95% CI 1.03, 3.25)] as independent risk factors for lung fibrosis. Novel HLA alleles associated with MCTD and disease subsets were identified and DRB1*04:01 was confirmed as a major risk allele. Altogether, the data reinforce the notion of MCTD as a disease entity distinct from SLE, SSc and PM/DM. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Discordance between Prevalent Vertebral Fracture and Vertebral Strength Estimated by the Finite Element Method Based on Quantitative Computed Tomography in Patients with Type 2 Diabetes Mellitus

PubMed Central

2015-01-01

Background Bone fragility is increased in patients with type 2 diabetes mellitus (T2DM), but a useful method to estimate bone fragility in T2DM patients is lacking because bone mineral density alone is not sufficient to assess the risk of fracture. This study investigated the association between prevalent vertebral fractures (VFs) and the vertebral strength index estimated by the quantitative computed tomography-based nonlinear finite element method (QCT-based nonlinear FEM) using multi-detector computed tomography (MDCT) for clinical practice use. Research Design and Methods A cross-sectional observational study was conducted on 54 postmenopausal women and 92 men over 50 years of age, all of whom had T2DM. The vertebral strength index was compared in patients with and without VFs confirmed by spinal radiographs. A standard FEM procedure was performed with the application of known parameters for the bone material properties obtained from nondiabetic subjects. Results A total of 20 women (37.0%) and 39 men (42.4%) with VFs were identified. The vertebral strength index was significantly higher in the men than in the women (P<0.01). Multiple regression analysis demonstrated that the vertebral strength index was significantly and positively correlated with the spinal bone mineral density (BMD) and inversely associated with age in both genders. There were no significant differences in the parameters, including the vertebral strength index, between patients with and without VFs. Logistic regression analysis adjusted for age, spine BMD, BMI, HbA1c, and duration of T2DM did not indicate a significant relationship between the vertebral strength index and the presence of VFs. Conclusion The vertebral strength index calculated by QCT-based nonlinear FEM using material property parameters obtained from nondiabetic subjects, whose risk of fracture is lower than that of T2DM patients, was not significantly associated with bone fragility in patients with T2DM. This discordance may indirectly suggest that patients with T2DM have deteriorated bone material compared with nondiabetic subjects, a potential cause of bone fragility in T2DM patients. PMID:26642210

Coagulation and oxidative stress plasmatic levels in a type 2 diabetes population.

PubMed

Barillari, Giovanni; Fabbro, Elisabetta; Pasca, Samantha; Bigotto, Enrico

2009-06-01

Type 2 diabetes mellitus (DM2) is a metabolic disorder characterized by relative insulin deficiency, insulin resistance and hyperglycemia. DM2 improperly managed can cause severe complications such as renal failure, blindness or arterial disease. In addition to serious complications due to DM2, in the past 20 years, several studies have demonstrated the association between DM2, insulin resistance and prothrombotic risk. In our study, we wanted to evaluate the correlation between coagulation factor levels, oxidative plasmatic levels and DM2. We considered 20 DM2 patients (65% women and 35% men), 40-65 years of age, who had a BMI between 25 and 40 kg/m2 and followed a diet with or without oral antidiabetic treatment and 20 controls, blood donors, 15 men (75%) and five women (25%), who had a BMI between 25 and 40 kg/m2 and their age was between 40 and 65 years. Plasmatic levels of oxidative stress markers (tumor necrosis factor-alpha, nitrotyrosine, oxidized low-density lipoprotein) and coagulation markers (factors VII, VIII, IX, XI, XII, antithrombin III and fibrinogen) of both populations were analyzed following statistic criteria. The analyzed data of this study related to oxidative stress and coagulation factors proved that the differences observed between diabetic patients and controls were not statistically significant (P < 0.05) for tumor necrosis factor-alpha, nitrotyrosine, oxidized low-density lipoprotein, factor VII and factor XI; conversely for factor VIII, factor IX, factor XII, antithrombin III and fibrinogen, the results gave a difference statistically significant (P < 0.01). In patients with DM2, factor VIII increased from 79 to 103%, factor IX from 88 to 103%, factor XII from 87 to 105% and finally, antithrombin III from 81 to 103%. Different results between literature and our study could be due to fact that the patients considered were in the early stage of diabetes when endothelial damage is absent and vascular complications are not clinically expressed. In this study, it is still shown that DM2 is a multifactor disease and its physiopathologic mechanisms are not completely known today.

Plasma lipids, lipoprotein metabolism and HDL lipid transfers are equally altered in metabolic syndrome and in type 2 diabetes.

PubMed

Silva, Vanessa M; Vinagre, Carmen G C; Dallan, Luis A O; Chacra, Ana P M; Maranhão, Raul C

2014-07-01

Metabolic syndrome (MetS) refers to states of insulin resistance that predispose to development of cardiovascular disease and type 2 diabetes (T2DM). The aim was to investigate whether plasma lipids and lipid metabolism differ in MetS patients compared to those with T2DM with poor glycemic control (glycated hemoglobin > 7.0). Eighteen patients with T2DM, 18 with MetS and 14 controls, paired for age (40-70 years) and body mass index (BMI), were studied. Plasma lipids and the kinetics of a triacylglycerol-rich emulsion labeled with [(3)H]-triolein ([(3)H]-TAG) and [(14)C]-cholesteryl esters ([(14)C]-CE) injected intravenously followed by one-hour blood sampling were determined. Lipid transfers from an artificial nanoemulsion donor to high-density lipoprotien (HDL) were assayed in vitro. Low-density lipoprotein (LDL) and HDL cholesterol (mg/dl) were not different in T2DM (128 ± 7; 42 ± 7) and MetS (142 ± 6; 39 ± 3), but triacylglycerols were even higher in MetS (215 ± 13) than in T2DM (161 ±11, p < 0.05). Fractional clearance rate (FCR, in min(1)) of [(3)H]-TAG and [(14)C]-CE were equal in T2DM (0.008 ± 0.018; 0.005 ± 0.024) and MetS (0.010 ± 0.016; 0.006 ± 0.013), and both were reduced compared to controls. The transfer of non-esterified cholesterol, phospholipids and triacylglycerols to HDL was higher in MetS and T2DM than in controls (p < 0.01). Cholesteryl ester transfer and HDL size were equal in all groups. Results imply that MetS is equal to poorly controlled T2DM concerning the disturbances of plasma lipid metabolism examined here, and suggest that there are different thresholds for the insulin action on glucose and lipids. These findings highlight the magnitude of the lipid disturbances in MetS, and may have implications in the prevention of cardiovascular diseases.

Combined pancreas-kidney transplantation for patients with end-stage nephropathy caused by type-2 diabetes mellitus.

PubMed

Margreiter, Christian; Resch, Thomas; Oberhuber, Rupert; Aigner, Felix; Maier, Herbert; Sucher, Robert; Schneeberger, Stefan; Ulmer, Hanno; Bösmüller, Claudia; Margreiter, Raimund; Pratschke, Johann; Öllinger, Robert

2013-04-27

Simultaneous pancreas-kidney (SPK) transplantation is widely accepted as an optimal therapeutic option for patients with type 1 diabetes mellitus (T1DM) and end-stage renal disease, but the indication for patients with type 2 diabetes mellitus (T2DM) is still controversially discussed. Twenty-one T2DM recipients of a first combined pancreas-kidney graft performed at our center during a 9-year period were retrospectively analyzed with regard to demographic characteristics; cardiovascular risk factors; surgical, immunological, and infectious complications; and patient and graft survivals and compared with T1DM recipients (n=195) and 32 T2DM patients who received a kidney transplant alone (KTA) during the same period. Patient survival at 1 and 5 years was 96.9% and 91.6% for the T1DM group, 90.5% and 80.1% for the T2DM group, and 87.1% and 54.2% for the T2DM KTA group, respectively (P<0.001). Actuarial pancreas graft survival for SPK recipients at 1 and 5 years was calculated to be 92.6% and 80.7% for the T1DM group and 81.0% and 75.9% for the T2DM group, respectively (P=0.19). Kidney allograft survival at 5 years was 83.6% for T1DM, 80.4% for T2DM, and 52.7% for T2DM KTA (P<0.0001). Multivariate analysis adjusting for donor and recipient age, secondary complications of diabetes, body mass index, waiting time, cold ischemic time, delayed graft function, and coronary risk factors showed that differences did not remain statistically significant. Favorable results can be achieved with SPK transplantation in type 2 diabetics with a low coronary risk profile. A high cardiac death rate impacts results of KTA and calls for stringent selection.

Effects of Growth Temperature and Postharvest Cooling on Anthocyanin Profiles in Juvenile and Mature Brassica oleracea.

PubMed

Socquet-Juglard, Didier; Bennett, Alexandra A; Manns, David C; Mansfield, Anna Katharine; Robbins, Rebecca J; Collins, Thomas M; Griffiths, Phillip D

2016-02-24

The effects of growth temperatures on anthocyanin content and profile were tested on juvenile cabbage and kale plants. The effects of cold storage time were evaluated on both juvenile and mature plants. The anthocyanin content in juvenile plants ranged from 3.82 mg of cyanidin-3,5-diglucoside equivalent (Cy equiv)/g of dry matter (dm) at 25 °C to 10.00 mg of Cy equiv/g of dm at 16 °C, with up to 76% diacylated anthocyanins. Cold storage of juvenile plants decreased the total amount of anthocyanins but increased the diacylated anthocyanin content by 3-5%. In mature plants, cold storage reduced the total anthocyanin content from 22 to 12.23 mg/g after 5 weeks of storage in red cabbage, while the total anthocyanin content increased after 2 weeks of storage from 2.34 to 3.66 mg of Cy equiv/g of dm in kale without having any effect on acylation in either morphotype. The results obtained in this study will be useful for optimizing anthocyanin production.

Effect of grape seed extract, Cistus ladanifer L., and vegetable oil supplementation on fatty acid composition of abomasal digesta and intramuscular fat of lambs.

PubMed

Jerónimo, Eliana; Alves, Susana P; Dentinho, Maria T P; Martins, Susana V; Prates, José A M; Vasta, Valentina; Santos-Silva, José; Bessa, Rui J B

2010-10-13

Thirty-six lambs were used in a 6 week experiment to evaluate the effect of vegetable oil blend supplementation (0 vs 60 g/kg of dry matter (DM)) and two dietary condensed tannin sources, grape seed extract (0 vs 25 g/kg of DM) and Cistus ladanifer L. (0 vs 250 g/kg of DM), on fatty acid (FA) composition of abomasal digesta and intramuscular polar and neutral lipids. Grape seed extract did not affect the FA profile of abomasal digesta or muscle lipid fractions. C. ladanifer had a minor effect in lambs fed diets with no oil but greatly changed the abomasal and muscle FA profiles in oil-supplemented lambs. It decreased 18:0 and increased 18:1 trans-11 in abomasal digesta and increased 18:1 trans-11 and 18:2 cis-9,trans-11 (P = 0.062) in muscle neutral lipids, resulting in an important enrichment of meat 18:2 cis-9,trans-11 when compared to other oil-supplemented diets (19.2 vs 41.7 mg/100 g of muscle).

Observation and modelling of main-sequence star chromospheres - X. Radiative budgets on Gl 867A and AU Mic (dM1e), and a two-component model chromosphere for Gl 205 (dM1)

NASA Astrophysics Data System (ADS)

Houdebine, E. R.

2010-04-01

We report on high-resolution observations of two dM1 stars: Gl 867A, an active dM1e star, and Gl 205, a less active dM1 star. The wavelength coverage is from 3890 to 6820Å with a resolving power of about 45000. The difference spectrum of these two stars allows us to make a survey of spectral lines sensitive to magnetic activity. We chose these two stars because, to within measurement errors, they have very close properties: Gl 867A has R = 0.726Rsolar, [M/H] = 0.080 dex and Teff = 3416 K, and Gl 205 has R = 0.758Rsolar, [M/H] = 0.101 dex and Teff = 3493 K. We find that besides traditional chromospheric lines, many photospheric lines are `filled-in' in the active star spectrum. These differences are, most of the time, weak in absolute fluxes but can be large in terms of differences in the spectral-line equivalent widths. We calculate the differences in surface fluxes between these two stars for many spectral lines. We derive the radiative budgets for two dM1e stars: Gl 867A and AU Mic. We show that the sum of the numerous spectral lines represents a significant fraction of the radiative cooling of the outer atmosphere. We also re-investigate the cooling from the continuum from the visible to the extreme ultraviolet; we find that earlier predictions of the calculations of Houdebine et al. (Paper V) are in good agreement with observations. We emphasize that if this radiative cooling is chromospheric in character, then in chromospheric model calculations, we should include the radiative losses in CaI, CrI, VI, TiI and FeI. From simple constraints, we derive model chromospheres for quiescent and active regions on Gl 205. We show that the quiescent regions have a strong absorption Hα profile. The plage regions show a filled-in intermediate activity Hα profile. We also present possible spectral line profiles of quiescent and active regions on Gl 867A. Based on observations collected at Observatoire de Haute Provence, France. E-mail: eric_houdebine@yahoo.fr

Possible dark matter origin of the gamma ray emission from the Galactic Center observed by HESS

NASA Astrophysics Data System (ADS)

Cembranos, J. A. R.; Gammaldi, V.; Maroto, A. L.

2012-11-01

We show that the gamma ray spectrum observed with the HESS array of Cherenkov telescopes coming from the Galactic Center region and identified with the source HESS J1745-290 is well fitted by the secondary photons coming from dark matter (DM) annihilation over a diffuse power law background. The amount of photons and morphology of the signal localized within a region of few parsecs, require compressed DM profiles as those resulting from baryonic contraction, which offer ˜103 enhancements in the signal over DM alone simulations. The fitted background from HESS data is consistent with recent Fermi-LAT observations of the same region.

Hidden U (1 ) gauge symmetry realizing a neutrinophilic two-Higgs-doublet model with dark matter

NASA Astrophysics Data System (ADS)

Nomura, Takaaki; Okada, Hiroshi

2018-04-01

We propose a neutrinophilic two-Higgs-doublet model with hidden local U (1 ) symmetry, where active neutrinos are Dirac type, and a fermionic dark matter (DM) candidate is naturally induced as a result of remnant symmetry even after the spontaneous symmetry breaking. In addition, a physical Goldstone boson arises as a consequence of two types of gauge singlet bosons and contributes to the DM phenomenologies as well as an additional neutral gauge boson. Then, we analyze the relic density of DM within the safe range of direct detection searches and show the allowed region of dark matter mass.

Linking axionlike dark matter to neutrino masses

NASA Astrophysics Data System (ADS)

Carvajal, C. D. R.; Sánchez-Vega, B. L.; Zapata, O.

2017-12-01

We present a framework linking axionlike particles (ALPs) to neutrino masses through the minimal inverse seesaw (ISS) mechanism in order to explain the dark matter (DM) puzzle. Specifically, we explore three minimal ISS cases where mass scales are generated through gravity-induced operators involving a scalar field hosting ALPs. In all of these cases, we find gravity-stable models that provide the observed DM relic density and, simultaneously, are consistent with the phenomenology of neutrinos and ALPs. Remarkably, in one of the ISS cases, the DM can be made of ALPs and sterile neutrinos. Furthermore, other considered ISS cases have ALPs with parameters that are within the reach of proposed ALP experiments.

Effect of topical rebamipide on conjunctival goblet cell recovery after vitrectomy

PubMed Central

Kato, Kumiko; Takashima, Yuko; Matsunaga, Koichi; Sugimoto, Masahiko; Matsubara, Hisashi; Hirano, Koji; Kondo, Mineo

2016-01-01

In vitro and in vivo experiments have shown that topical rebamipide will increase the number of goblet cells in the bulbar conjunctiva. The purpose of this study was to determine whether topical rebamipide will enhance the recovery of conjunctival goblet cells that were damaged during vitrectomy. Forty patients who underwent vitrectomy surgery were studied. The 40 patients consisted of 20 with diabetes mellitus (DM) and 20 patients without DM. They were randomized in a 1:1 ratio into groups that were treated or not treated with topical 2% rebamipide after the surgery. Impression cytology was performed at the end of surgery and at 14 days after the surgery. The mean goblet cell density of each specimen was determined by averaging the total number of goblet cells obtained from three consecutive high magnification microscopic images. In patients without DM, the mean goblet cell density at 14 days after the vitrectomy was significantly higher in eyes with topical rebemipide than in eyes without rebemipide (P < 0.01). In patients with DM, a similar tendency was observed but the difference was not significant (P = 0.09). These results suggest that topical rebamipide can be helpful in patients with globlet cell damage that occur during and after vitrectomy. PMID:26762482

Effect of topical rebamipide on conjunctival goblet cell recovery after vitrectomy.

PubMed

Kato, Kumiko; Takashima, Yuko; Matsunaga, Koichi; Sugimoto, Masahiko; Matsubara, Hisashi; Hirano, Koji; Kondo, Mineo

2016-01-14

In vitro and in vivo experiments have shown that topical rebamipide will increase the number of goblet cells in the bulbar conjunctiva. The purpose of this study was to determine whether topical rebamipide will enhance the recovery of conjunctival goblet cells that were damaged during vitrectomy. Forty patients who underwent vitrectomy surgery were studied. The 40 patients consisted of 20 with diabetes mellitus (DM) and 20 patients without DM. They were randomized in a 1:1 ratio into groups that were treated or not treated with topical 2% rebamipide after the surgery. Impression cytology was performed at the end of surgery and at 14 days after the surgery. The mean goblet cell density of each specimen was determined by averaging the total number of goblet cells obtained from three consecutive high magnification microscopic images. In patients without DM, the mean goblet cell density at 14 days after the vitrectomy was significantly higher in eyes with topical rebemipide than in eyes without rebemipide (P < 0.01). In patients with DM, a similar tendency was observed but the difference was not significant (P = 0.09). These results suggest that topical rebamipide can be helpful in patients with globlet cell damage that occur during and after vitrectomy.

A mixed acid based vanadium-cerium redox flow battery with a zero-gap serpentine architecture

NASA Astrophysics Data System (ADS)

Leung, P. K.; Mohamed, M. R.; Shah, A. A.; Xu, Q.; Conde-Duran, M. B.

2015-01-01

This paper presents the performance of a vanadium-cerium redox flow battery using conventional and zero-gap serpentine architectures. Mixed-acid solutions based on methanesulfonate-sulfate anions (molar ratio 3:1) are used to enhance the solubilities of the vanadium (>2.0 mol dm-3) and cerium species (>0.8 mol dm-3), thus achieving an energy density (c.a. 28 Wh dm-3) comparable to that of conventional all-vanadium redox flow batteries (20-30 Wh dm-3). Electrochemical studies, including cyclic voltammetry and galvanostatic cycling, show that both vanadium and cerium active species are suitable for energy storage applications in these electrolytes. To take advantage of the high open-circuit voltage (1.78 V), improved mass transport and reduced internal resistance are facilitated by the use of zero-gap flow field architecture, which yields a power density output of the battery of up to 370 mW cm-2 at a state-of-charge of 50%. In a charge-discharge cycle at 200 mA cm-2, the vanadium-cerium redox flow battery with the zero-gap architecture is observed to discharge at a cell voltage of c.a. 1.35 V with a coulombic efficiency of up to 78%.

Relationship between Two Types of Coil Packing Densities Relative to Aneurysm Size.

PubMed

Park, Keun Young; Kim, Byung Moon; Ihm, Eun Hyun; Baek, Jang Hyun; Kim, Dong Joon; Kim, Dong Ik; Huh, Seung Kon; Lee, Jae Whan

2015-01-01

Coil packing density (PD) can be calculated via a formula (PDF ) or software (PDS ). Two types of PD can be different from each other for same aneurysm. This study aimed to evaluate the interobserver agreement and relationships between the 2 types of PD relative to aneurysm size. Consecutive 420 saccular aneurysms were treated with coiling. PD (PDF , [coil volume]/[volume calculated by formula] and PDS, [coil volume]/[volume measured by software]) was calculated and prospectively recorded. Interobserver agreement was evaluated between PDF and PDS . Additionally, the relationships between PDF and PDS relative to aneurysm size were subsequently analyzed. Interobserver agreement for PDF and PDS was excellent (Intraclass correlation coefficient, PDF ; 0.967 and PDS ; 0.998). The ratio of PDF and PDS was greater for smaller aneurysms and converged toward 1.0 as the maximum dimension (DM ) of aneurysm increased. Compared with PDS , PDF was overestimated by a mean of 28% for DM < 5 mm, by 17% for 5 mm ≤ DM < 10 mm, and by 9% for DM ≥ 10 mm (P < 0.01). Interobserver agreement for PDF and PDS was excellent. However, PDF was overestimated in smaller aneurysms and converged to PDS as aneurysm size increased. Copyright © 2014 by the American Society of Neuroimaging.

Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus.

PubMed

Sohn, Elliott H; van Dijk, Hille W; Jiao, Chunhua; Kok, Pauline H B; Jeong, Woojin; Demirkaya, Nazli; Garmager, Allison; Wit, Ferdinand; Kucukevcilioglu, Murat; van Velthoven, Mirjam E J; DeVries, J Hans; Mullins, Robert F; Kuehn, Markus H; Schlingemann, Reinier Otto; Sonka, Milan; Verbraak, Frank D; Abràmoff, Michael David

2016-05-10

Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 μm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 μm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 μm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 μm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced "type 1" and B6.BKS(D)-Lepr(db)/J "type 2" diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications.

Adipokines, oxidized low-density lipoprotein, and C-reactive protein levels in lean, overweight, and obese portuguese patients with type 2 diabetes.

PubMed

Neuparth, Maria João; Proença, Jorge Brandão; Santos-Silva, Alice; Coimbra, Susana

2013-01-01

Aim. Our aim was to study how different BMI scores may influence the levels of inflammation, oxidative stress, adipogenesis, glucose, and lipid metabolism, in lean, overweight, and obese Portuguese patients with type 2 diabetes mellitus (T2DM). Methods. We studied 28 lean, 38 overweight, and 17 obese patients with T2DM and 20 controls (gender and age matched). The circulating levels of oxLDL, CRP, and some adipokines-adiponectin, leptin, and chemerin-and the lipid profile were evaluated. Results. Obese patients presented significantly lower levels of adiponectin and higher leptin, oxLDL, and chemerin levels, as compared to the overweight, lean, and control groups. Overweight, compared to lean and control, subjects showed significantly lower adiponectin and higher leptin and chemerin levels; oxLDL values were significantly higher in overweight than in lean patients. Lean patients presented significantly higher chemerin values than the control. Obese patients presented significantly higher CRP values, as compared to lean patients and the control group. Obese and overweight patients presented significantly higher triglycerides values than lean patients. Except for CRP, all the observed significant changes between control and patients remained significant after statistical adjustment for the body mass index (BMI). Conclusion. The levels of leptin, adiponectin, oxLDL, CRP, and triglycerides in patients with T2DM seem to be more associated with obesity and less with diabetes. Chemerin levels were raised in lean, overweight, and obese patients, suggesting that, independently of BMI, an adipocyte dysfunction occurs. Moreover, chemerin may provide an important early biomarker of adipocyte dysfunction and a link between obesity and type 2 diabetes mellitus.

Adipokines, Oxidized Low-Density Lipoprotein, and C-Reactive Protein Levels in Lean, Overweight, and Obese Portuguese Patients with Type 2 Diabetes

PubMed Central

Neuparth, Maria João; Proença, Jorge Brandão; Santos-Silva, Alice; Coimbra, Susana

2013-01-01

Aim. Our aim was to study how different BMI scores may influence the levels of inflammation, oxidative stress, adipogenesis, glucose, and lipid metabolism, in lean, overweight, and obese Portuguese patients with type 2 diabetes mellitus (T2DM). Methods. We studied 28 lean, 38 overweight, and 17 obese patients with T2DM and 20 controls (gender and age matched). The circulating levels of oxLDL, CRP, and some adipokines—adiponectin, leptin, and chemerin—and the lipid profile were evaluated. Results. Obese patients presented significantly lower levels of adiponectin and higher leptin, oxLDL, and chemerin levels, as compared to the overweight, lean, and control groups. Overweight, compared to lean and control, subjects showed significantly lower adiponectin and higher leptin and chemerin levels; oxLDL values were significantly higher in overweight than in lean patients. Lean patients presented significantly higher chemerin values than the control. Obese patients presented significantly higher CRP values, as compared to lean patients and the control group. Obese and overweight patients presented significantly higher triglycerides values than lean patients. Except for CRP, all the observed significant changes between control and patients remained significant after statistical adjustment for the body mass index (BMI). Conclusion. The levels of leptin, adiponectin, oxLDL, CRP, and triglycerides in patients with T2DM seem to be more associated with obesity and less with diabetes. Chemerin levels were raised in lean, overweight, and obese patients, suggesting that, independently of BMI, an adipocyte dysfunction occurs. Moreover, chemerin may provide an important early biomarker of adipocyte dysfunction and a link between obesity and type 2 diabetes mellitus. PMID:24634792

Glucose and cholesterol stabilization in patients with type 2 diabetes mellitus with depressive and anxiety symptoms by problem-solving therapy in primary care centers in Mexico City.

PubMed

Villamil-Salcedo, Valerio; Vargas-Terrez, Blanca E; Caraveo-Anduaga, Jorge; González-Olvera, Jorge; Díaz-Anzaldúa, Adriana; Cortés-Sotres, José; Pérez-Ávila, Magdalena

2018-01-01

Aim The aim of this study was to determine if the problem-solving therapy (PST) helps control metabolic variables in patients with type 2 diabetes mellitus (T2DM) who show depressive and anxiety symptoms. T2DM is a chronic-degenerative multifactorial disease. It is considered one of the main public health problems in the world, and it represents an important social and economic burden. It is frequently associated with major depression and anxiety disorders, which are related with high glycated hemoglobin (HbA1c) concentrations and poor metabolic control. We initially included 123 patients diagnosed with T2DM from five primary care centers (PCC) in Mexico City. HbA1c, central glucose, and lipid profile were measured in each patient. In addition, the Kessler psychological distress scale (K-10), the Beck Depression Inventory, and the Beck Anxiety Inventory were applied at the beginning and, to those who continued, at the end of the PST, as well as four months later. Findings In total, 36 patients completed the PST and the follow-up. There was a significant decrease in depressive and anxiety symptoms (P<0.001), as well as in total cholesterol (P=0.002), HbA1c (P=0.05), and low-density lipoprotein (LDL) (P=0.022). The PST helps reduce depressive and anxiety symptoms and may help stabilize glucose and cholesterol up to four months. Further studies on this area are recommended. If our findings are confirmed, the PST could help improve the quality of life of thousands of individuals with psychiatric-metabolic co-morbidity who only visit PCC.

Tissue- and age-specific DNA replication patterns at the CTG/CAG-expanded human myotonic dystrophy type 1 locus.

PubMed

Cleary, John D; Tomé, Stéphanie; López Castel, Arturo; Panigrahi, Gagan B; Foiry, Laurent; Hagerman, Katharine A; Sroka, Hana; Chitayat, David; Gourdon, Geneviève; Pearson, Christopher E

2010-09-01

Myotonic dystrophy, caused by DM1 CTG/CAG repeat expansions, shows varying instability levels between tissues and across ages within patients. We determined DNA replication profiles at the DM1 locus in patient fibroblasts and tissues from DM1 transgenic mice of various ages showing different instability. In patient cells, the repeat is flanked by two replication origins demarcated by CTCF sites, with replication diminished at the expansion. In mice, the expansion replicated from only the downstream origin (CAG as lagging template). In testes from mice of three different ages, replication toward the repeat paused at the earliest age and was relieved at later ages-coinciding with increased instability. Brain, pancreas and thymus replication varied with CpG methylation at DM1 CTCF sites. CTCF sites between progressing forks and repeats reduced replication depending on chromatin. Thus, varying replication progression may affect tissue- and age-specific repeat instability.

The Surface Density Profile of the Galactic Disk from the Terminal Velocity Curve

NASA Astrophysics Data System (ADS)

McGaugh, Stacy S.

2016-01-01

The mass distribution of the Galactic disk is constructed from the terminal velocity curve and the mass discrepancy-acceleration relation. Mass models numerically quantifying the detailed surface density profiles are tabulated. For R0 = 8 kpc, the models have stellar mass 5 < M* < 6 × 1010 {M}⊙ , scale length 2.0 ≤ Rd ≤ 2.9 kpc, LSR circular velocity 222 ≤ Θ0 ≤ 233 {km} {{{s}}}-1, and solar circle stellar surface density 34 ≤ Σd(R0) ≤ 61 {M}⊙ {{pc}}-2. The present interarm location of the solar neighborhood may have a somewhat lower stellar surface density than average for the solar circle. The Milky Way appears to be a normal spiral galaxy that obeys scaling relations like the Tully-Fisher relation, the size-mass relation, and the disk maximality-surface brightness relation. The stellar disk is maximal, and the spiral arms are massive. The bumps and wiggles in the terminal velocity curve correspond to known spiral features (e.g., the Centaurus arm is a ˜50% overdensity). The rotation curve switches between positive and negative over scales of hundreds of parsecs. The rms amplitude {< {| {dV}/{dR}| }2> }1/2≈ 14 {km} {{{s}}}-1 {{kpc}}-1, implying that commonly neglected terms in the Jeans equations may be nonnegligible. The spherically averaged local dark matter density is ρ0,DM ≈ 0.009 {M}⊙ {{pc}}-3 (0.34 {GeV} {{cm}}-3). Adiabatic compression of the dark matter halo may help reconcile the Milky Way with the c-V200 relation expected in ΛCDM while also helping to mitigate the too-big-to-fail problem, but it remains difficult to reconcile the inner bulge/bar-dominated region with a cuspy halo. We note that NGC 3521 is a near twin to the Milky Way, having a similar luminosity, scale length, and rotation curve.

Microstructure and properties of ceramic coatings prepared by micro-arc oxidation on 7075 aluminum alloy

NASA Astrophysics Data System (ADS)

Cao, G. P.; Song, R. G.

2018-02-01

Micro-arc oxidation (MAO) ceramic coatings were prepared in silicate-based electrolyte on 7075 aluminum alloy. The effects of current density on microstructure and properties of the MAO coatings were studied by scanning electron microscopy (SEM), stereoscopic microscopy, x-ray diffraction (XRD), electrochemical tests as well as tribological and wear tests. The results showed that the current density plays an important role in affecting the quality of the MAO coatings. XRD results showed that the α-Al2O3 phase first increased then decreased with increasing the current density, which matched well with the micro-hardness test and the wearing test results. On the other hand, the coalescent strength measurements revealed that the coating prepared at the current density of 12 A dm-2 is of the highest adhesion force. The potentiodynamic polarization test proved that the coating obtained under 10 A dm-2 exhibits the best corrosion resistance, which is directly related to the morphology of coating.

Seasonal quality profile and production of foliage from trees grown on degraded cropland in arid Uzbekistan, Central Asia.

PubMed

Lamers, J P A; Khamzina, A

2010-10-01

Feed shortages hamper livestock rearing and thus impede the development of rural livelihoods in Central Asia. The production and in vitro quality of foliage from Ulmus pumila, Elaeagnus angustifolia and Populus euphratica on degraded cropland were examined to determine the potential of these species to supplement diary cattle diets. Leaf dry matter (DM) production of the species, respectively, averaged 6, 8 and 17 t DM/ha, 4 years after planting. Over seasons and years, crude protein concentrations (g/kg DM) ranged within 151-257 for E. angustifolia, 70-241 for U. pumila and 92-187 for P. euphratica. The metabolizable energy concentrations (MJ/kg DM) were the highest in U. pumila and ranged within 9-10, followed by 7-10 of E. angustifolia and 7-9 of P. euphratica. The organic matter digestibility (%) ranged within 58-70, 54-66, and 51-66, respectively, for these species. These indicators combined denoted a medium-to-good feed quality of E. angustifolia and U. pumila leaves as a cheap protein supplement to roughages. The foliage of P. euphratica was the least suitable. The seasonal profile of in vitro indicators revealed the highest feed quality in spring but early fall seems most appropriate for forage collection given the peak leaf production and an adequate quality. © 2010 Blackwell Verlag GmbH.

Constraints on dark matter annihilations from diffuse gamma-ray emission in the Galaxy

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

Tavakoli, Maryam; Evoli, Carmelo; Cholis, Ilias

2014-01-01

Recent advances in γ-ray cosmic ray, infrared and radio astronomy have allowed us to develop a significantly better understanding of the galactic medium properties in the last few years. In this work using the DRAGON code, that numerically solves the CR propagation equation and calculating γ-ray emissivities in a 2-dimensional grid enclosing the Galaxy, we study in a self consistent manner models for the galactic diffuse γ-ray emission. Our models are cross-checked to both the available CR and γ-ray data. We address the extend to which dark matter annihilations in the Galaxy can contribute to the diffuse γ-ray flux towardsmore » different directions on the sky. Moreover we discuss the impact that astrophysical uncertainties of non DM nature, have on the derived γ-ray limits. Such uncertainties are related to the diffusion properties on the Galaxy, the interstellar gas and the interstellar radiation field energy densities. Light ∼ 10 GeV dark matter annihilating dominantly to hadrons is more strongly constrained by γ-ray observations towards the inner parts of the Galaxy and influenced the most by assumptions of the gas distribution; while TeV scale DM annihilating dominantly to leptons has its tightest constraints from observations towards the galactic center avoiding the galactic disk plane, with the main astrophysical uncertainty being the radiation field energy density. In addition, we present a method of deriving constraints on the dark matter distribution profile from the diffuse γ-ray spectra. These results critically depend on the assumed mass of the dark matter particles and the type of its end annihilation products.« less

Circulating CTRP9 levels are increased in patients with newly diagnosed type 2 diabetes and correlated with insulin resistance.

PubMed

Jia, Yanjun; Luo, Xiaohe; Ji, Ying; Xie, Jingwen; Jiang, Han; Fu, Mao; Li, Xiaoqiang

2017-09-01

C1q/TNF-related protein-9 (CTRP9) is a novel adipokine that has been shown to promote lipid metabolism, enhance insulin sensitivity and protect against cardiovascular disease. However, previous studies in humans have produced controversial results regarding the association between CTRP9 and insulin resistance. The objective of this study was to evaluate the relationships between CTRP9 and insulin resistance in Chinese population. Subjects with normal glucose tolerance (NGT, n=108), impaired glucose tolerance (IGT, n=92), and newly diagnosed type 2 diabetes mellitus (nT2DM, n=106) were recruited to determining the circulating CTRP9 and adiponectin levels by enzyme linked immunosorbent assay. Anthropometric and biochemical measurements related to insulin resistance, adiposity and lipid profile were examined for all participants. Oral glucose tolerance test was performed in healthy subjects (17 male and 17 female). Circulating CTRP9 level was significantly higher in both IGT and nT2DM than in individuals with NGT. Overweight/obese subjects had much higher CTRP9 levels than lean individuals, and in all subjects, females also had higher CTRP9 levels than males. In addition, circulating CTRP9 level was positively correlated with markers of obesity and insulin resistance, including body mass index, fasting blood glucose, insulin, HbA1c, homeostasis model assessment of insulin resistance and low-density lipoprotein-cholesterol, while was inversely correlated with high-density lipoprotein-cholesterol and adiponectin. Moreover, hyperglycemia during an oral glucose challenge increased circulating CTRP9 concentrations. We conclude that CTRP9 was strongly associated with insulin resistance, suggesting that CTRP9 might be important in the development of type 2 diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

Universal scaling relations in scale-free structure formation

NASA Astrophysics Data System (ADS)

Guszejnov, Dávid; Hopkins, Philip F.; Grudić, Michael Y.

2018-07-01

A large number of astronomical phenomena exhibit remarkably similar scaling relations. The most well-known of these is the mass distribution dN/dM ∝ M-2 which (to first order) describes stars, protostellar cores, clumps, giant molecular clouds, star clusters, and even dark matter haloes. In this paper we propose that this ubiquity is not a coincidence and that it is the generic result of scale-free structure formation where the different scales are uncorrelated. We show that all such systems produce a mass function proportional to M-2 and a column density distribution with a power-law tail of dA/dln Σ ∝ Σ-1. In the case where structure formation is controlled by gravity the two-point correlation becomes ξ2D ∝ R-1. Furthermore, structures formed by such processes (e.g. young star clusters, DM haloes) tend to a ρ ∝ R-3 density profile. We compare these predictions with observations, analytical fragmentation cascade models, semi-analytical models of gravito-turbulent fragmentation, and detailed `full physics' hydrodynamical simulations. We find that these power laws are good first-order descriptions in all cases.

Universal Scaling Relations in Scale-Free Structure Formation

NASA Astrophysics Data System (ADS)

Guszejnov, Dávid; Hopkins, Philip F.; Grudić, Michael Y.

2018-04-01

A large number of astronomical phenomena exhibit remarkably similar scaling relations. The most well-known of these is the mass distribution dN/dM∝M-2 which (to first order) describes stars, protostellar cores, clumps, giant molecular clouds, star clusters and even dark matter halos. In this paper we propose that this ubiquity is not a coincidence and that it is the generic result of scale-free structure formation where the different scales are uncorrelated. We show that all such systems produce a mass function proportional to M-2 and a column density distribution with a power law tail of dA/d lnΣ∝Σ-1. In the case where structure formation is controlled by gravity the two-point correlation becomes ξ2D∝R-1. Furthermore, structures formed by such processes (e.g. young star clusters, DM halos) tend to a ρ∝R-3 density profile. We compare these predictions with observations, analytical fragmentation cascade models, semi-analytical models of gravito-turbulent fragmentation and detailed "full physics" hydrodynamical simulations. We find that these power-laws are good first order descriptions in all cases.

Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2-Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study.

PubMed

Perez, Edith A; Barrios, Carlos; Eiermann, Wolfgang; Toi, Masakazu; Im, Young-Hyuck; Conte, Pierfranco; Martin, Miguel; Pienkowski, Tadeusz; Pivot, Xavier; Burris, Howard; Petersen, Jennifer A; Stanzel, Sven; Strasak, Alexander; Patre, Monika; Ellis, Paul

2017-01-10

Purpose Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) -targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study. Methods In the MARIANNE study, 1,095 patients with centrally assessed, HER2-positive, advanced breast cancer and no prior therapy for advanced disease were randomly assigned 1:1:1 to control (trastuzumab plus taxane), T-DM1 plus placebo, hereafter T-DM1, or T-DM1 plus pertuzumab at standard doses. Primary end point was progression-free survival (PFS), as assessed by independent review. Results T-DM1 and T-DM1 plus pertuzumab showed noninferior PFS compared with trastuzumab plus taxane (median PFS: 13.7 months with trastuzumab plus taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab). Neither experimental arm showed PFS superiority to trastuzumab plus taxane. Response rate was 67.9% in patients who were treated with trastuzumab plus taxane, 59.7% with T-DM1, and 64.2% with T-DM1 plus pertuzumab; median response duration was 12.5 months, 20.7 months, and 21.2 months, respectively. The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms. Conclusion T-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast cancer.

Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2–Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study

PubMed Central

Perez, Edith A.; Barrios, Carlos; Eiermann, Wolfgang; Toi, Masakazu; Im, Young-Hyuck; Conte, Pierfranco; Martin, Miguel; Pienkowski, Tadeusz; Pivot, Xavier; Burris, Howard; Petersen, Jennifer A.; Stanzel, Sven; Strasak, Alexander; Patre, Monika; Ellis, Paul

2017-01-01

Purpose Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) –targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody–drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study. Methods In the MARIANNE study, 1,095 patients with centrally assessed, HER2-positive, advanced breast cancer and no prior therapy for advanced disease were randomly assigned 1:1:1 to control (trastuzumab plus taxane), T-DM1 plus placebo, hereafter T-DM1, or T-DM1 plus pertuzumab at standard doses. Primary end point was progression-free survival (PFS), as assessed by independent review. Results T-DM1 and T-DM1 plus pertuzumab showed noninferior PFS compared with trastuzumab plus taxane (median PFS: 13.7 months with trastuzumab plus taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab). Neither experimental arm showed PFS superiority to trastuzumab plus taxane. Response rate was 67.9% in patients who were treated with trastuzumab plus taxane, 59.7% with T-DM1, and 64.2% with T-DM1 plus pertuzumab; median response duration was 12.5 months, 20.7 months, and 21.2 months, respectively. The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms. Conclusion T-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast cancer. PMID:28056202

Dark Matter characterization at the LHC in the Effective Field Theory approach

NASA Astrophysics Data System (ADS)

Belyaev, Alexander; Panizzi, Luca; Pukhov, Alexander; Thomas, Marc

2017-04-01

We have studied the complete set of dimension 5 and dimension 6 effective operators involving the interaction of scalar, fermion and vector Dark Matter (DM) with SM quarks and gluons, to explore the possibility to distinguish these operators and characterise the spin of DM at the LHC. We have found that three factors — the effective dimension of the operator, the structure of the SM part of the operator and the parton densities of the SM particles connected to the operator — uniquely define the shape of the (unobservable) invariant mass distribution of the DM pair and, consequently, the shape of the (observable) E T miss distribution related to it. Using χ2 analysis, we found that at the LHC, with a luminosity of 300 fb-1, certain classes of EFT operators can be distinguished from each other. Hence, since DM spin is partly correlated with the factors defining the shape of E T miss , the LHC can potentially shed a light also on DM spin. We have also observed a drastic difference in the efficiencies (up to two orders of magnitude) for large E T miss cuts scenarios with different DM spin, thus indicating that the DM discovery potential strongly depends on it. The study we perform here can be applied more generally than within the EFT paradigm, where the DM mediator is not produced on-the-mass-shell, such as the case of t-channel mediator or mediator with mass below 2 M DM, where the invariant mass of the DM pair is not fixed.

CYTOKINE MRNA PROFILES FOR ISOCYANATES WITH KNOWN AND UNKNOWN POTENTIAL TO INDUCE RESPIRATORY SENSITIZATION

EPA Science Inventory

Cytokine mRNA Profiles for Isocyanates with Known and Unknown Potential to Induce Respiratory Sensitization. Plitnick, L.M., Loveless, S.E., Ladics, G.S., Holsapple, M.P., Smialowicz, R.J., Woolhiser, M.R., Anderson, P.K., Smith, C., Sailstad, D.M. and Selgrade, M.J.K (2002) Tox...

Charged composite scalar dark matter

NASA Astrophysics Data System (ADS)

Balkin, Reuven; Ruhdorfer, Maximilian; Salvioni, Ennio; Weiler, Andreas

2017-11-01

We consider a composite model where both the Higgs and a complex scalar χ, which is the dark matter (DM) candidate, arise as light pseudo Nambu-Goldstone bosons (pNGBs) from a strongly coupled sector with TeV scale confinement. The global symmetry structure is SO(7)/SO(6), and the DM is charged under an exact U(1)DM ⊂ SO(6) that ensures its stability. Depending on whether the χ shift symmetry is respected or broken by the coupling of the top quark to the strong sector, the DM can be much lighter than the Higgs or have a weak-scale mass. Here we focus primarily on the latter possibility. We introduce the lowest-lying composite resonances and impose calculability of the scalar potential via generalized Weinberg sum rules. Compared to previous analyses of pNGB DM, the computation of the relic density is improved by fully accounting for the effects of the fermionic top partners. This plays a crucial role in relaxing the tension with the current DM direct detection constraints. The spectrum of resonances contains exotic top partners charged under the U(1)DM, whose LHC phenomenology is analyzed. We identify a region of parameters with f = 1.4 TeV and 200 GeV ≲ m χ ≲ 400 GeV that satisfies all existing bounds. This DM candidate will be tested by XENON1T in the near future.

Derangement of calcium metabolism in diabetes mellitus: negative outcome from the synergy between impaired bone turnover and intestinal calcium absorption.

PubMed

Wongdee, Kannikar; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2017-01-01

Both types 1 and 2 diabetes mellitus (T1DM and T2DM) are associated with profound deterioration of calcium and bone metabolism, partly from impaired intestinal calcium absorption, leading to a reduction in calcium uptake into the body. T1DM is associated with low bone mineral density (BMD) and osteoporosis, whereas the skeletal changes in T2DM are variable, ranging from normal to increased and to decreased BMD. However, both types of DM eventually compromise bone quality through production of advanced glycation end products and misalignment of collagen fibrils (so-called matrix failure), thereby culminating in a reduction of bone strength. The underlying cellular mechanisms (cellular failure) are related to suppression of osteoblast-induced bone formation and bone calcium accretion, as well as to enhancement of osteoclast-induced bone resorption. Several other T2DM-related pathophysiological changes, e.g., osteoblast insulin resistance, impaired productions of osteogenic growth factors (particularly insulin-like growth factor 1 and bone morphogenetic proteins), overproduction of pro-inflammatory cytokines, hyperglycemia, and dyslipidemia, also aggravate diabetic osteopathy. In the kidney, DM and the resultant hyperglycemia lead to calciuresis and hypercalciuria in both humans and rodents. Furthermore, DM causes deranged functions of endocrine factors related to mineral metabolism, e.g., parathyroid hormone, 1,25-dihydroxyvitamin D 3 , and fibroblast growth factor-23. Despite the wealth of information regarding impaired bone remodeling in DM, the long-lasting effects of DM on calcium metabolism in young growing individuals, pregnant women, and neonates born to women with gestational DM have received scant attention, and their underlying mechanisms are almost unknown and worth exploring.

Proximate analysis and physico-chemical properties of flour from the seeds of the China chestnut, Sterculia monosperma Ventenat.

PubMed

Noitang, S; Sooksai, S A; Foophow, T; Petsom, A

2009-10-01

The aim of this study was to evaluate nutritional composition of China chestnut seeds, Sterculia monosperma Vent. and analyze the physico-chemical properties of flour from the seeds. The results obtained on proximate analysis of China chestnut seeds, S. monosperma, revealed that they contained mostly carbohydrate (73.7% dm), followed by fat (12.0% dm), protein (7.8% dm), fiber (5.5% dm) and ash (1.0% dm). They have a relatively high content of potassium (12.3 mg g(-1) dm) following by phosphorus (2.30 mg g(-1) dm), magnesium (1.87 mg g(-1) dm), sulfur (0.88 mg g(-1) dm) and calcium (0.14 mg g(-1) dm). The fatty acids profile was found to be composed of mainly palmitic (42%) and oleic acids (34%), with general long-chain fatty acids the other significant component by mass (13%). Glutamic acid (17.4%), aspartic acid (12.5%) and arginine (12.5%) were the three major amino acid constituents. The purified seed starch was investigated for its morphological, starch content and physico-chemical properties, such as amylose content, swelling power, solubility and pasting properties. The starch granules were quite round, about 10-15 micron diameter and composed of more than 35% (w/w) of amylose. The pasting properties of flour from the seeds of S. monosperma revealed that gelatinization began at 72.6-73.2 degrees C and the maximum viscosity in the holding period at 95 degrees C was 633 BU. Interestingly and potentially of use, was that the viscosity at the cooling period was more than two-fold higher than that in the holding period.

Management of diabetes mellitus and associated cardiovascular risk factors in Brazil – the Brazilian study on the practice of diabetes care

PubMed Central

2013-01-01

Background The Brazilian Study on the Practice of Diabetes Care main objective was to provide an epidemiological profile of individuals with type 1 and 2 diabetes mellitus (DM) in Brazil, concerning therapy and adherence to international guidelines in the medical practice. Methods This observational, cross-sectional, multicenter study collected and analyzed data from individuals with type 1 and 2 DM attending public or private clinics in Brazil. Each investigator included the first 10 patients with type 2 DM who visited his/her office, and the first 5 patients with type 1 DM. Results A total of 1,358 patients were analyzed; 375 (27.6%) had type 1 and 983 (72.4%) had type 2 DM. Most individuals were women, Caucasian, and private health care users. High prevalence rates of hypertension, dyslipidemia and central obesity were observed, particularly in type 2 DM. Only 7.3% and 5.1% of the individuals with types 1 and 2 DM, respectively, had optimal control of blood pressure, plasma glucose and lipids. The absence of hypertension and female sex were associated with better control of type 1 DM and other cardiovascular risk factors. In type 2 DM, older age was also associated with better control. Conclusions Female sex, older age, and absence of hypertension were associated with better metabolic control. An optimal control of plasma glucose and other cardiovascular risk factors are obtained only in a minority of individuals with diabetes. Local numbers, compared to those from other countries are worse. PMID:23972112

An integrated metabonomic and proteomic study on Kidney-Yin Deficiency Syndrome patients with diabetes mellitus in China.

PubMed

Jiang, Ning; Liu, Hong-fang; Li, Si-di; Zhou, Wen-xia; Zhang, Yong-xiang; Zhang, Qi; Yan, Xian-zhong

2015-06-01

To investigate specific changes in metabolites and proteins of Kidney-Yin Deficiency Syndrome (KYDS) patients with diabetes mellitus (DM) in China. KYDS (n=29) and non-KYDS (n=23) patients with DM were recruited for this study. The KYDS was diagnosed by two senior TCM clinicians separately. The metabonomic and proteomic profiles of the patients were assessed using a metabonomic strategy based on NMR with multivariate analysis and a proteomic strategy based on MALDI-TOF-MS, respectively. Eighteen upregulated peptides and thirty downregulated peptides were observed in the plasma of the KYDS patients. Comparing the proteomic profiles of the KYDS and non-KYDS groups, however, no significantly differentially expressed peptides were found. At the same time, major metabolic alterations were found to distinguish the two groups, including eight significantly changed metabolites (creatinine, citrate, TMAO, phenylalanine, tyrosine, alanine, glycine and taurine). The levels of creatinine, citrate, TMAO, phenylalanine and tyrosine were decreased, whereas the levels of alanine, glycine and taurine were increased in the KYDS patients. These biochemical changes were found to be associated with alterations in amino acid metabolism, energy metabolism and gut microflora. The identification of distinct expression profiles of metabolites and signaling pathways in KYDS patients with DM suggests that there are indeed molecular signatures underlying the principles of 'Syndrome Differentiation' in traditional Chinese medicine.

Metabolic control in patients with type 2 diabetes mellitus in a public hospital in Peru: a cross-sectional study in a low-middle income country.

PubMed

Huayanay-Espinoza, Irma Elizabeth; Guerra-Castañon, Felix; Lazo-Porras, María; Castaneda-Guarderas, Ana; Thomas, Nimmy Josephine; Garcia-Guarniz, Ana-Lucia; Valdivia-Bustamante, Augusto A; Málaga, Germán

2016-01-01

The objective of this study was to assess patients' achievement of ADA (American Diabetes Association) guideline recommendations for glycosylated hemoglobin, lipid profile, and blood pressure in a type 2 diabetes mellitus (T2DM) outpatient clinic in a low-middle income country (LMIC) setting. This is a descriptive cross-sectional study with 123 ambulatory T2DM patients who are being treated at a public hospital in Lima, Peru. Data was gathered via standardized interviews, clinical surveys, and anthropomorphic measurements for each patient. Blood samples were drawn in fasting state for measures of glucose, glycosylated hemoglobin (HbA1c), and lipid profile. Laboratory parameters and blood pressure were evaluated according to ADA recommendations. Of the 123 patients, 81 were women and the mean age was 61.8 years. Glycemic control was abnormal in 82 (68.33%) participants, and 45 (37.50%) were unable to control their blood pressure. Lipid profile was abnormal in 73 (60.83%) participants. Only nine (7.50%) participants fulfilled ADA recommendations for glycemic, blood pressure, and lipid control. Amongst individuals with type 2 diabetes, there was poor attainment of the ADA recommendations (HbA1c, blood pressure and LDL-cholesterol) for ambulatory T2DM patients. Interventions are urgently needed in order to prevent long-term diabetic complications.

Metabolic control in patients with type 2 diabetes mellitus in a public hospital in Peru: a cross-sectional study in a low-middle income country

PubMed Central

Guerra-Castañon, Felix; Lazo-Porras, María; Castaneda-Guarderas, Ana; Thomas, Nimmy Josephine; Garcia-Guarniz, Ana-Lucia; Valdivia-Bustamante, Augusto A.; Málaga, Germán

2016-01-01

Objective The objective of this study was to assess patients’ achievement of ADA (American Diabetes Association) guideline recommendations for glycosylated hemoglobin, lipid profile, and blood pressure in a type 2 diabetes mellitus (T2DM) outpatient clinic in a low-middle income country (LMIC) setting. Methods This is a descriptive cross-sectional study with 123 ambulatory T2DM patients who are being treated at a public hospital in Lima, Peru. Data was gathered via standardized interviews, clinical surveys, and anthropomorphic measurements for each patient. Blood samples were drawn in fasting state for measures of glucose, glycosylated hemoglobin (HbA1c), and lipid profile. Laboratory parameters and blood pressure were evaluated according to ADA recommendations. Results Of the 123 patients, 81 were women and the mean age was 61.8 years. Glycemic control was abnormal in 82 (68.33%) participants, and 45 (37.50%) were unable to control their blood pressure. Lipid profile was abnormal in 73 (60.83%) participants. Only nine (7.50%) participants fulfilled ADA recommendations for glycemic, blood pressure, and lipid control. Conclusions Amongst individuals with type 2 diabetes, there was poor attainment of the ADA recommendations (HbA1c, blood pressure and LDL-cholesterol) for ambulatory T2DM patients. Interventions are urgently needed in order to prevent long-term diabetic complications. PMID:27761351

Solubility enhancement of simvastatin by arginine: thermodynamics, solute-solvent interactions, and spectral analysis.

PubMed

Meor Mohd Affandi, M M R; Tripathy, Minaketan; Shah, Syed Adnan Ali; Majeed, A B A

2016-01-01

We examined the solubility of simvastatin in water in 0.01 mol·dm(-3), 0.02 mol·dm(-3), 0.04 mol·dm(-3), 0.09 mol·dm(-3), 0.18 mol·dm(-3), 0.36 mol·dm(-3), and 0.73 mol·dm(-3) arginine (ARG) solutions. The investigated drug is termed the solute, whereas ARG the cosolute. Phase solubility studies illustrated a higher extent of solubility enhancement for simvastatin. The aforementioned system was subjected to conductometric and volumetric measurements at temperatures (T) of 298.15 K, 303.15 K, 308.15 K, and 313.15 K to illustrate the thermodynamics involved and related solute-solvent interactions. The conductance values were used to evaluate the limiting molar conductance and association constants. Thermodynamic parameters (ΔG (0), ΔH (0), ΔS (0), and E s) for the association process of the solute in the aqueous solutions of ARG were calculated. Limiting partial molar volumes and expansibilities were evaluated from the density values. These values are discussed in terms of the solute-solvent and solute-cosolute interactions. Further, these systems were analyzed using ultraviolet-visible analysis, Fourier-transform infrared spectroscopy, and (13)C, (1)H, and two-dimensional nuclear overhauser effect spectroscopy nuclear magnetic resonance to complement thermophysical explanation.

Latent autoimmune diabetes in adults is perched between type 1 and type 2: evidence from adults in one region of Spain.

PubMed

Mollo, Angels; Hernandez, Marta; Marsal, Josep R; Esquerda, Aureli; Rius, Ferran; Blanco-Vaca, Francisco; Verdaguer, Joan; Pozzilli, Paolo; de Leiva, Alberto; Mauricio, Didac

2013-09-01

The aim of this study was to characterize the clinical characteristics and insulin secretion in adults with latent autoimmune diabetes in adults (LADA). We also compared these characteristics in subjects with antibody-negative type 2 diabetes (T2DM) or adult-onset type 1 diabetes (T1DM) to subjects with LADA. In this cross-sectional study, 82 patients with LADA, 78 with T1DM and 485 with T2DM were studied. Clinical and metabolic data, in particular those that related to metabolic syndrome, fasting C-peptide and islet-cell autoantibodies [glutamic acid decarboxylase (GADAb) and IA2 (IA2Ab)] were measured. The frequency of metabolic syndrome in patients with LADA (37.3%) was higher than in those with T1DM (15.5%; p = 0.005) and lower than in patients with T2DM (67.2%; p < 0.001). During the first 36 months of the disease, the C-peptide concentration in LADA patients was higher than in subjects with T1DM but was lower than in T2DM patients (p < 0.01 for comparisons). Glycemic control in LADA patients (HbA1c 8.1%) was worse than in patients with T2DM (HbA1c 7.6%; p =0.007). An inverse association between GADAb titers and C-peptide concentrations was found in subjects with LADA (p < 0.001). Finally, LADA patients rapidly progressed to insulin treatment. As in other European populations, patients with LADA in Spain have a distinct metabolic profile compared with patients with T1DM or T2DM. LADA is also associated with higher impairment of beta-cell function and has worse glycemic control than in T2DM. Beta cell function is related to GADAb titers in patients with LADA. Copyright © 2013 John Wiley & Sons, Ltd.

Implications in the difference of anti-Mi-2 and -p155/140 autoantibody prevalence in two dermatomyositis cohorts from Mexico City and Guadalajara

PubMed Central

2013-01-01

Introduction Autoantibodies and clinical manifestations in polymyositis/dermatomyositis (PM/DM) are affected by both genetic and environmental factors. The high prevalence of DM and anti-Mi-2 in Central America is thought to be associated with the high UV index of the area. The prevalences of autoantibodies and the clinical manifestations of PM/DM were evaluated comparing two cohorts in Mexico. Methods Ninety-five Mexican patients with PM/DM (66 DM, 29 PM; 67 Mexico City, 28 Guadalajara) were studied. Autoantibodies were characterized by immunoprecipitation using 35S-methionine labeled K562 cell extract. Clinical information was obtained from medical records. Results DM represented 69% of PM/DM and anti-Mi-2 was the most common autoantibody (35%), followed by anti-p155/140 (11%); however, anti-Jo-1 was only 4%. The autoantibody profile in adult-onset DM in Mexico City versus Guadalajara showed striking differences: anti-Mi-2 was 59% versus 12% (P = 0.0012) whereas anti-p155/140 was 9% versus 35% (P = 0.02), respectively. A strong association of anti-Mi-2 with DM was confirmed and when clinical features of anti-Mi-2 (+) DM (n = 30) versus anti-Mi-2 (-) DM (n = 36) were compared, the shawl sign (86% versus 64%, P < 0.05) was more common in the anti-Mi-2 (+) group (P = 0.0001). Levels of creatine phosphokinase (CPK) were higher in those who were anti-Mi-2 (+) but they responded well to therapy. Conclusions Anti-Mi-2 has a high prevalence in Mexican DM and is associated with the shawl sign and high CPK. The prevalence of anti-Mi-2 and anti-p155/140 was significantly different in Mexico City versus Guadalajara, which have a similar UV index. This suggests roles of factors other than UV in anti-Mi-2 antibody production. PMID:23557279

Exercise improves gait, reaction time and postural stability in older adults with type 2 diabetes and neuropathy.

PubMed

Morrison, Steven; Colberg, Sheri R; Parson, Henri K; Vinik, Aaron I

2014-01-01

For older adults with type 2 diabetes (T2DM), declines in balance and walking ability are risk factors for falls, and peripheral neuropathy magnifies this risk. Exercise training may improve balance, gait and reduce the risk of falling. This study investigated the effects of 12weeks of aerobic exercise training on walking, balance, reaction time and falls risk metrics in older T2DM individuals with/without peripheral neuropathy. Adults with T2DM, 21 without (DM; age 58.7±1.7years) and 16 with neuropathy (DM-PN; age 58.9±1.9years), engaged in either moderate or intense supervised exercise training thrice-weekly for 12weeks. Pre/post-training assessments included falls risk (using the physiological profile assessment), standing balance, walking ability and hand/foot simple reaction time. Pre-training, the DM-PN group had higher falls risk, slower (hand) reaction times (232 vs. 219ms), walked at a slower speed (108 vs. 113cm/s) with shorter strides compared to the DM group. Following training, improvements in hand/foot reaction times and faster walking speed were seen for both groups. While falls risk was not significantly reduced, the observed changes in gait, reaction time and balance metrics suggest that aerobic exercise of varying intensities is beneficial for improving dynamic postural control in older T2DM adults with/without neuropathy. Copyright © 2014 Elsevier Inc. All rights reserved.

Goal attainments and their discrepancies for low density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) in over 2,000 Chinese patients with known coronary artery disease or type 2 diabetes.

PubMed

He, Yong-Ming; Yang, Xiang-Jun; Zhao, Xin; Xu, Hai-Feng

2015-04-01

Low density lipoprotein cholesterol (LDL-C) is primary treatment target for patients with dislipidemia. The apolipoprotein B (apo B), an emerging biomarker for cardiovascular risk prediction, appears to be superior to the LDL-C. However, little is known about goal attainments and their discrepancies for LDL-C and apo B in Chinese patients with known CAD or DM. A total of 2,172 hospitalized patients with known coronary artery disease (CAD) or DM, aged >27 years of old, were enrolled. The success rates for apo B and LDL-C goal attainments were evaluated and compared by categorization and by sex. When the success rates for apo B were compared with the ones for LDL-C, the former was higher than the latter across all categorizations, with the statistically significant differences seen in all patients, CAD alone and DM alone (P<0.0001), but not in coexistence of CAD and DM (P=0.190). The trend toward to higher success rates for LDL-C and apo B goal attainments in men than in women were noteworthy across all categorizations although only in all patients and in DM alone patients were the statistically significant differences found (P<0.01). The LDL-C lags behind the apo B in goal attainments in Chinese patients. Whether these discrepancies are associated with the occurrence differences for CAD and for stroke between the East Asia and the Western countries warrants further study.

Freeze-in production of sterile neutrino dark matter in U(1){sub B−L} model

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

Biswas, Anirban; Gupta, Aritra

2016-09-27

With the advent of new and more sensitive direct detection experiments, scope for a thermal WIMP explanation of dark matter (DM) has become extremely constricted. The non-observation of thermal WIMP in these experiments has put a strong upper bound on WIMP-nucleon scattering cross section and within a few years it is likely to overlap with the coherent neutrino-nucleon cross section. Hence in all probability, DM may have some non-thermal origin. In this work we explore in detail this possibility of a non-thermal sterile neutrino DM within the framework of U(1){sub B−L} model. The U(1){sub B−L} model on the other handmore » is a well-motivated and minimal way of extending the standard model so that it can explain the neutrino masses via Type-I see-saw mechanism. We have shown, besides explaining the neutrino mass, it can also accommodate a non-thermal sterile neutrino DM with correct relic density. In contrast with the existing literature, we have found that W{sup ±} decay can also be a dominant production mode of the sterile neutrino DM. To obtain the comoving number density of dark matter, we have solved here a coupled set of Boltzmann equations considering all possible decay as well as annihilation production modes of the sterile neutrino dark matter. The framework developed here though has been done for a U(1){sub B−L} model, can be applied quite generally for any models with an extra neutral gauge boson and a fermionic non-thermal dark matter.« less

Application of the integrated glucose–insulin model for cross‐study characterization of T2DM patients on metformin background treatment

PubMed Central

Hamrén, Bengt; Kjellsson, Maria C.; Skrtic, Stanko

2016-01-01

Aim The integrated glucose–insulin (IGI) model is a semi‐mechanistic physiological model which can describe the glucose–insulin homeostasis system following various glucose challenge settings. The aim of the present work was to apply the model to a large and diverse population of metformin‐only‐treated type 2 diabetes mellitus (T2DM) patients and identify patient‐specific covariates. Methods Data from four clinical studies were pooled, including glucose and insulin concentration–time profiles from T2DM patients on stable treatment with metformin alone following mixed‐meal tolerance tests. The data were collected from a wide range of patients with respect to the duration of diabetes and level of glycaemic control. Results The IGI model was expanded by four patient‐specific covariates. The level of glycaemic control, represented by baseline glycosylated haemoglobin was identified as a significant covariate for steady‐state glucose, insulin‐dependent glucose clearance and the magnitude of the incretin effect, while baseline body mass index was a significant covariate for steady‐state insulin levels. In addition, glucose dose was found to have an impact on glucose absorption rate. The developed model was used to simulate glucose and insulin profiles in different groups of T2DM patients, across a range of glycaemic control, and it was found accurately to characterize their response to the standard oral glucose challenge. Conclusions The IGI model was successfully applied to characterize differences between T2DM patients across a wide range of glycaemic control. The addition of patient‐specific covariates in the IGI model might be valuable for the future development of antidiabetic treatment and for the design and simulation of clinical studies. PMID:27450071

Effects of first- and second-generation tyrosine kinase inhibitor therapy on glucose and lipid metabolism in chronic myeloid leukemia patients: a real clinical problem?

PubMed

Iurlo, Alessandra; Orsi, Emanuela; Cattaneo, Daniele; Resi, Veronica; Bucelli, Cristina; Orofino, Nicola; Sciumè, Mariarita; Elena, Chiara; Grancini, Valeria; Consonni, Dario; Orlandi, Ester Maria; Cortelezzi, Agostino

2015-10-20

Tyrosine kinase inhibitors (TKIs) have dramatically changed the prognosis of patients with chronic myeloid leukemia (CML). They have a distinct toxicity profile that includes glycometabolic alterations: i.e. diabetes mellitus (DM), impaired fasting glucose (IFG), and the metabolic syndrome (MS). The aim of this study was to evaluate the prevalence of these alterations in a cohort of CML-chronic phase patients treated with imatinib, dasatinib or nilotinib. The study involved 168 consecutive CML-chronic phase patients with no history of DM/IFG or MS. Anthropometric and metabolic parameters were assessed, and DM/IFG and MS were diagnosed based on the criteria of the American Diabetes Association and the National Cholesterol Education Program-Adult Treatment Panel III, respectively. The nilotinib group had significantly higher levels of fasting plasma glucose, insulin, C-peptide, insulin resistance, and total and LDL cholesterol than the imatinib and dasatinib groups. DM/IFG were identified in 25% of the imatinib- and dasatinib-treated patients, and 33% of those in the nilotinib cohort (p = 0.39 vs imatinib and p = 0.69 vs dasatinib). A diagnosis of MS was made in 42.4% of the imatinib-treated patients, 37.5% of the dasatinib-treated patients, and 36.1% of the nilotinib-treated patients (p = 0.46 vs imatinib and p = 0.34 vs dasatinib). Treatment with nilotinib does not seem to induce DM/IFG or the MS to a significantly higher extent than imatinib or dasatinib, though it causes a worse glycometabolic profile. These findings suggest the need for a close monitoring of glucose and lipid metabolism and a multidisciplinary approach in patients treated with nilotinib.

Profiling of cardio-metabolic risk factors and medication utilisation among Type II diabetes patients in Ghana: a prospective cohort study.

PubMed

Adua, Eric; Roberts, Peter; Sakyi, Samuel Asamoah; Yeboah, Francis Agyemang; Dompreh, Albert; Frimpong, Kwasi; Anto, Enoch Odame; Wang, Wei

2017-09-07

Type II diabetes mellitus (T2DM) is complicated by multiple cardio-metabolic risk factors. Controlling these factors requires lifestyle modifications alongside utilisation of anti-diabetic medications. Different glucose lowering [(biguanides (BIGs), sulfonylureas (SUAs), thiazolidinediones (TNZ)], lipid lowering (statins), and anti-hypertensive medicines [angiotensin converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs) and central acting drugs (CADs)] have been approved for controlling hyperglycaemia, dyslipidaemia and hypertension respectively. Here, we examined factors that characterise T2DM and explored the response to medication therapy among T2DM patients. This prospective cohort study recruited 241 T2DM patients reporting at a clinic in Ghana, from January through to August, 2016. Each patient's demographic, medications and anthropometric data was obtained while information on medication adherence was captured using Morisky adherence scale-8 (MMAS-8). Fasting blood samples were collected for biochemical analysis. The mean age of participants was 57.82 years for baseline and six-month follow-up. Physical activity differed at baseline and follow up (p < 0.05) but not body mass index (BMI). BIG alone, or in combination with SUA and TNZ did not improve glycaemic status at follow up (p > 0.05). Many participants using either ACEI or ARB were able to control their blood pressures. Among dyslipidaemia patients under statin treatment, there was an improved lipid profile at follow-up. Statin medications are effective for reducing dyslipidaemia in T2DM patients. However, control of modifiable risk factors, particularly blood glucose and to a lesser degree blood pressure is suboptimal. Addressing these will require concomitant interventions including education on medication adherence and correct dietary plans, lifestyle modifications and physical activity.

Mechanistic characterization of the HDV genomic ribozyme: a mutant of the C41 motif provides insight into the positioning and thermodynamic linkage of metal ions and protons.

PubMed

Nakano, Shu-ichi; Bevilacqua, Philip C

2007-03-20

Binding of two Mg2+ and two H+ ions influences the self-cleavage activity of the genomic HDV ribozyme. The positioning of these four ligands and their thermodynamic linkage are not fully resolved. Protonated C41 engages in a base triple, whereas protonated C75 has been implicated as an acid-base catalyst in bond cleavage. Prior studies led to the identification of one structural inner-sphere ion and one catalytic outer-sphere ion. In the present study, the contributions of the C41 base triple to the metal ion- and pH-dependence of the reaction are examined. Experiments were conducted on a CG to UA double mutant (DM), which changes the base triple to one involving an unprotonated C41. Below pH 6, the DM has a steeper dependence on pH than the wild-type (WT), consistent with a single protonation misfolding the core; this conclusion is also supported by thermal denaturation studies. Between pH 6 and 8, the WT and DM display nearly identical catalytic metal ion and H+ binding profiles. In contrast, over the same pH range, the WT and DM have distinct structural ion binding profiles; for the WT, binding is favored at lower pH, whereas the DM shows no pH dependence. These data localize the structural ion to the vicinity of the C41 motif. An overall model is presented that accommodates binding affinity, coupling, and positioning of the two metal ions and the two protons within the ribozyme. The data suggest that a protonated base triple allows the WT ribozyme to maintain appreciable activity at acidic pH, which could play an important role in the life cycle of the virus.

Culture of bovine ovarian follicle wall sections maintained the highly estrogenic profile under basal and chemically defined conditions

PubMed Central

Vasconcelos, R.B.; Salles, L.P.; Silva, I. Oliveira e; Gulart, L.V.M.; Souza, D.K.; Torres, F.A.G.; Bocca, A.L.; Silva, A.A.M. Rosa e

2013-01-01

Follicle cultures reproduce in vitro the functional features observed in vivo. In a search for an ideal model, we cultured bovine antral follicle wall sections (FWS) in a serum-free defined medium (DM) known to induce 17β-estradiol (E2) production, and in a nondefined medium (NDM) containing serum. Follicles were sectioned and cultured in NDM or DM for 24 or 48 h. Morphological features were determined by light microscopy. Gene expression of steroidogenic enzymes and follicle-stimulating hormone (FSH) receptor were determined by RT-PCR; progesterone (P4) and E2 concentrations in the media were measured by radioimmunoassay. DM, but not NDM, maintained an FWS morphology in vitro that was similar to fresh tissue. DM also induced an increase in the expression of all steroidogenic enzymes, except FSH receptor, but NDM did not. In both DM and NDM, there was a gradual increase in P4 throughout the culture period; however, P4 concentration was significantly higher in NDM. In both media, E2 concentration was increased at 24 h, followed by a decrease at 48 h. The E2:P4 ratio was higher in DM than in NDM. These results suggest that DM maintains morphological structure, upregulates the expression of steroidogenic enzyme genes, and maintains steroid production with a high E2:P4 ratio in FWS cultures. PMID:23969977

Metabolic Syndrome and Serum Liver Enzymes Level at Patients with Type 2 Diabetes Mellitus

PubMed Central

Music, Miralem; Dervisevic, Amela; Pepic, Esad; Lepara, Orhan; Fajkic, Almir; Ascic-Buturovic, Belma; Tuna, Enes

2015-01-01

Objectives: The aim of this study was to evaluate liver function in patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MS) by determining serum levels of gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). We also investigated correlation between levels of liver enzymes and some components of MS in both groups of patients. Methods: This cross-sectional study included 96 patients (age 47–83 years) with T2DM. All patients were divided according to the criteria of the National Cholesterol Education Program (NCEP) in two groups: 50 patients with T2 DM and MS (T2DM-MS) and 46 patients with T2DM without MS (T2DM-Non MS). The analysis included blood pressure monitoring and laboratory tests: fasting blood glucose (FBG), total lipoprotein cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), fibrinogen and liver enzymes: GGT, ALT and AST. T2DM-MS group included patients which had FBG ≥ 6,1 mmol/L, TG ≥ 1,7 mmol/L and blood pressure ≥ 130/85 mm Hg. Results: T2DM-MS patients had significant higher values of systolic blood pressure, diastolic blood pressure and medium arterial pressure compared to T2DM-Non MS patients. Serum levels of TC, TG, LDL-C, VLDL-C and FBG were significantly higher in the T2DM-MS group compared to the T2DM-Non MS group. Serum fibrinogen level and GGT level were significantly higher in patients with T2DM-MS compared to the serum fibrinogen level and GGT level in T2DM-Non MS patients. Mean serum AST and ALT level were higher, but not significantly, in patients with T2DM and MS compared to the patients with T2DM without MS. Significant negative correlations were observed between TC and AST (r= -0,28, p<0,05), as well as between TC and ALT level (r= -0,29, p<0,05) in T2DM-MS group of patients. Conclusion: These results suggest that patients with T2DM and MS have markedly elevated liver enzymes. T2DM and MS probably play a role in increasing the risk of liver injury. PMID:26543313

QEEG-based neural correlates of decision making in a well-trained eight year-old chess player.

PubMed

Alipour, Abolfazl; Seifzadeh, Sahar; Aligholi, Hadi; Nami, Mohammad

2017-10-25

The neurocognitive substrates of decision making (DM) in the context of chess has appealed to researchers' interest for decades. Expert and beginner chess players are hypothesized to employ different brain functional networks when involved in episodes of critical DM upon chess. Cognitive capacities including, but not restricted to pattern recognition, visuospatial search, reasoning, planning and DM are perhaps the key determinants of rewarding and judgmental decisions in chess. Meanwhile, the precise neural correlates of DM in this context has largely remained elusive. The quantitative electroencephalography (QEEG) is an investigation tool possessing a proper temporal resolution in the study of neural correlates of cognitive tasks at cortical level. Here, we used a 22-channel EEG setup and digital polygraphy in a well-trained 8 year-old boy while engaged in playing chess against the computer. Quantitative analyses were done to map and source-localize the EEG signals. Our analyses indicated a lower power spectral density (PSD) for higher frequency bands in the right hemisphere upon DM-related epochs. Moreover, the information flow upon DM blocks in this particular case was more of posterior towards anterior brain regions.

Effects of volcano profile on dilute pyroclastic density currents: Numerical simulations

NASA Astrophysics Data System (ADS)

Doronzo, D. M.; Valentine, G. A.; Dellino, P.; de Tullio, M. D.

2012-04-01

Explosive activity and lava dome collapse at stratovolcanoes can lead to pyroclastic density currents (PDCs; mixtures of volcanic gas, air, and volcanic particles) that produce complex deposits and pose a hazard to surrounding populations. Two-dimensional numerical simulations of dilute PDCs (characterized by a turbulent suspended load and deposition through a bed load) are carried out with the Euler-Lagrange approach of multiphase physics. The fluid phase is modeled as a dusty gas (1.88 kg/m3 dense), and the solid phase is modeled as discrete particles (1 mm, 5 mm, and 10 mm; 1500 kg/m3 dense and irregularly-shaped), which are two-way coupled to the gas, i.e. they affect the fluid turbulence. The initial PDC, which enters a volcano domain 5 km long and 1.9 km high, has the following characteristics: thickness of 200 m, velocity of 20 m/s, temperature of 573 K, turbulence of 5 %, and sediment concentration of 3 % by volume. The actual physics of flow boundary zone is simulated at the PDC base, by monitoring the sediment flux toward the substrate, which acts through the flow boundary zone, and the grain-size distribution. Also, the PDC velocity and dynamic pressure are calculated. The simulations show that PDC transport, deposition, and hazard potential are sensitive to the shape of the volcano slope (profile) down which they flow. In particular, three generic volcano profiles, straight, concave-upward, and convex-upward are focused on. Dilute PDCs that flow down a constant slope gradually decelerate over the simulated run-out distance (5 km in the horizontal direction) due to a combination of sedimentation, which reduces the density of the PDC, and mixing with the atmosphere. However, dilute PDCs down a concave-upward slope accelerate high on the volcano flanks and have less sedimentation until they begin to decelerate over the shallow lower slopes. A convex-upward slope causes dilute PDCs to lose relatively more of their pyroclast load on the upper slopes of a volcano, and although they accelerate as they reach the lower, steeper slopes, the acceleration is reduced because of the upstream loss of pyroclasts (lower density contrast with the atmosphere). The dynamic pressure, a measure of the damage that can be caused by PDCs, reflects these complex relations. Details are found in Valentine et al. (2011). Reference Valentine G.A., Doronzo D.M., Dellino P., de Tullio M.D. (2011), Effects of volcano profile on dilute pyroclastic density currents: Numerical simulations, Geology, 39, 947-950.

Analyses of Factors Affecting Endothelial Cell Density in an Eye Bank Corneal Donor Database.

PubMed

Kwon, Ji Won; Cho, Kyong Jin; Kim, Hong Kyu; Lee, Jimmy K; Gore, Patrick K; McCartney, Mitchell D; Chuck, Roy S

2016-09-01

To analyze the factors affecting central corneal endothelial cell density (ECD) in an eye bank corneal donor database. The Lion's Eye Institute corneal donor database consisting of 18,665 donors (34,234 corneas) aged 20 years or older was analyzed. In particular, differences in the ECD based on age, sex, race, prior ocular surgery, a history of systemic diseases, and smoking were investigated. Furthermore, risk factors for donor cell count inadequacy (defined here as ECD less than 2000/mm) were identified. ECD decreased with age. Regarding race, the average ECD of African American donors was higher than those of white or Hispanic donors. A history of diabetes mellitus (DM) and ocular surgery were associated with a lower ECD. Donor medical history of hypertension, glaucoma, depression, dementia, Parkinson disease, hyper- or hypothyroidism, or smoking did not seem to affect the ECD. The risk factors for donor cell count inadequacy, based on binary logistic regression analyses were advanced age [65-74 years yielded an odds ratio of 17.8; confidence interval (CI), 10.6-29.8; P < 0.001; and 75-99 years yielded an odds ratio of 24.6 (CI, 14.5-41.61; P < 0.001) when compared with 20-34 years], cataract surgery (odds ratio, 4.3; CI, 4.0-4.8; P < 0.001), and DM (odds ratio, 1.2; CI, 1.1-1.3; P = 0.001). Age, race, ocular surgery (cataract and refractive), and DM seem to significantly affect donor corneal ECD. Of these variables, age, a history of cataract surgery, and DM were found to be the greatest risk factors for inadequate donor cell density (less than 2000/mm).

High dietary cholesterol masks type 2 diabetes-induced osteopenia and changes in bone microstructure in rats.

PubMed

Lapmanee, Sarawut; Charoenphandhu, Narattaphol; Aeimlapa, Ratchaneevan; Suntornsaratoon, Panan; Wongdee, Kannikar; Tiyasatkulkovit, Wacharaporn; Kengkoom, Kanchana; Chaimongkolnukul, Khuanjit; Seriwatanachai, Dutmanee; Krishnamra, Nateetip

2014-10-01

Type 2 diabetes mellitus (T2DM) often occurs concurrently with high blood cholesterol or dyslipidemia. Although T2DM has been hypothesized to impair bone microstructure, several investigations showed that, when compared to age-matched healthy individuals, T2DM patients had normal or relatively high bone mineral density (BMD). Since cholesterol and lipids profoundly affect the function of osteoblasts and osteoclasts, it might be cholesterol that obscured the changes in BMD and bone microstructure in T2DM. The present study, therefore, aimed to determine bone elongation, epiphyseal histology, and bone microstructure in non-obese T2DM Goto-Kakizaki rats treated with normal (GK-ND) and high cholesterol diet. We found that volumetric BMD was lower in GK-ND rats than the age-matched wild-type controls. In histomorphometric study of tibial metaphysis, T2DM evidently suppressed osteoblast function as indicated by decreases in osteoblast surface, mineral apposition rate, and bone formation rate in GK-ND rats. Meanwhile, the osteoclast surface and eroded surface were increased in GK-ND rats, thus suggesting an activation of bone resorption. T2DM also impaired bone elongation, presumably by retaining the chondrogenic precursor cells in the epiphyseal resting zone. Interestingly, several bone changes in GK rats (e.g., increased osteoclast surface) disappeared after high cholesterol treatment as compared to wild-type rats fed high cholesterol diet. In conclusion, high cholesterol diet was capable of masking the T2DM-induced osteopenia and changes in several histomorphometric parameters that indicated bone microstructural defect. Cholesterol thus explained, in part, why a decrease in BMD was not observed in T2DM, and hence delayed diagnosis of the T2DM-associated bone disease.

SYSTEMATIC AND STOCHASTIC VARIATIONS IN PULSAR DISPERSION MEASURES

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

Lam, M. T.; Cordes, J. M.; Chatterjee, S.

2016-04-10

We analyze deterministic and random temporal variations in the dispersion measure (DM) from the full three-dimensional velocities of pulsars with respect to the solar system, combined with electron-density variations over a wide range of length scales. Previous treatments have largely ignored pulsars’ changing distances while favoring interpretations involving changes in sky position from transverse motion. Linear trends in pulsar DMs observed over 5–10 year timescales may signify sizable DM gradients in the interstellar medium (ISM) sampled by the changing direction of the line of sight to the pulsar. We show that motions parallel to the line of sight can alsomore » account for linear trends, for the apparent excess of DM variance over that extrapolated from scintillation measurements, and for the apparent non-Kolmogorov scalings of DM structure functions inferred in some cases. Pulsar motions through atomic gas may produce bow-shock ionized gas that also contributes to DM variations. We discuss the possible causes of periodic or quasi-periodic changes in DM, including seasonal changes in the ionosphere, annual variations of the solar elongation angle, structure in the heliosphere and ISM boundary, and substructure in the ISM. We assess the solar cycle’s role on the amplitude of ionospheric and solar wind variations. Interstellar refraction can produce cyclic timing variations from the error in transforming arrival times to the solar system barycenter. We apply our methods to DM time series and DM gradient measurements in the literature and assess their consistency with a Kolmogorov medium. Finally, we discuss the implications of DM modeling in precision pulsar timing experiments.« less

Tanshinone I alleviates insulin resistance in type 2 diabetes mellitus rats through IRS-1 pathway.

PubMed

Wei, Ying; Gao, Jiaqi; Qin, Lingling; Xu, Yunling; Wang, Dongchao; Shi, Haoxia; Xu, Tunhai; Liu, Tonghua

2017-09-01

Tanshinone I from tanshen has been used in traditional Chinese medicine for treating cardiovascular diseases and inflammatory diseases. Given the link between inflammation and Type 2 diabetes mellitus (T2DM), we suspect that tanshinone I may have a beneficial effect on T2DM. This study was to investigate the potential effects of tanshinone I on T2DM and its underlying mechanism. T2DM was thus induced in Sprague-Dawley (SD) rats using streptozotocin (STZ) and high-fat diet. It was observed that T2DM rats had higher levels of total cholesterol (TC), nonesterified fatty acids (NEFAs), total triglyceride (TG) and total low density lipoprotein cholesterol (LDL-C) compared with normal, healthy SD rats. Treatment with tanshinone I decreased these levels and lowered blood glucose level in T2DM rats. In addition, enzyme-linked immunosorbent assay (ELISA) analysis showed that T2DM rats had elevated levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Furthermore, Western blot analysis revealed that T2DM rats had enhanced nuclear translocation of NF-κB as well as elevated phosphorylation of Ser307 in IRS-1(insulin receptor substrate 1). Treatment by tanshinone I lowered the levels of IL-6 and TNF-α, decreased nuclear translocation of NF-κB as well as phosphorylation of Ser307 in IRS-1. These results demonstrated that tanshinone I could alleviate T2DM syndrome in rats. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Immunoscore encompassing CD3+ and CD8+ T cell densities in distant metastasis is a robust prognostic marker for advanced colorectal cancer

PubMed Central

Kwak, Yoonjin; Koh, Jiwon; Kim, Duck-Woo; Kang, Sung-Bum; Kim, Woo Ho; Lee, Hye Seung

2016-01-01

Background The immunoscore (IS), an index based on the density of CD3+ and CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor center (CT) and invasive margin (IM), has gained considerable attention as a prognostic marker. Tumor-associated macrophages (TAMs) have also been reported to have prognostic value. However, its clinical significance has not been fully clarified in patients with advanced CRC who present with distant metastases. Methods The density of CD3+, CD4+, CD8+, FOXP3+, CD68+, and CD163+ immune cells within CRC tissue procured from three sites–the primary CT, IM, and distant metastasis (DM)–was determined using immunohistochemistry and digital image analyzer (n=196). The IS was obtained by quantifying the densities of CD3+ and CD8+ TILs in the CT and IM. IS-metastatic and IS-macrophage–additional IS models designed in this study–were obtained by adding the score of CD3 and CD8 in DM and the score of CD163 in primary tumors (CT and IM), respectively, to the IS. Result Higher IS, IS-metastatic, and IS-macrophage values were significantly correlated with better prognosis (p=0.020, p≤0.001, and p=0.005, respectively). Multivariate analysis revealed that only IS-metastatic was an independent prognostic marker (p=0.012). No significant correlation was observed between KRAS mutation and three IS models. However, in the subgroup analysis, IS-metastatic showed a prognostic association regardless of the KRAS mutational status. Conclusion IS is a reproducible method for predicting the survival of patients with advanced CRC. Additionally, an IS including the CD3+ and CD8+ TIL densities at DM could be a strong prognostic marker for advanced CRC. PMID:27835889

sfDM: Open-Source Software for Temporal Analysis and Visualization of Brain Tumor Diffusion MR Using Serial Functional Diffusion Mapping.

PubMed

Ceschin, Rafael; Panigrahy, Ashok; Gopalakrishnan, Vanathi

2015-01-01

A major challenge in the diagnosis and treatment of brain tumors is tissue heterogeneity leading to mixed treatment response. Additionally, they are often difficult or at very high risk for biopsy, further hindering the clinical management process. To overcome this, novel advanced imaging methods are increasingly being adapted clinically to identify useful noninvasive biomarkers capable of disease stage characterization and treatment response prediction. One promising technique is called functional diffusion mapping (fDM), which uses diffusion-weighted imaging (DWI) to generate parametric maps between two imaging time points in order to identify significant voxel-wise changes in water diffusion within the tumor tissue. Here we introduce serial functional diffusion mapping (sfDM), an extension of existing fDM methods, to analyze the entire tumor diffusion profile along the temporal course of the disease. sfDM provides the tools necessary to analyze a tumor data set in the context of spatiotemporal parametric mapping: the image registration pipeline, biomarker extraction, and visualization tools. We present the general workflow of the pipeline, along with a typical use case for the software. sfDM is written in Python and is freely available as an open-source package under the Berkley Software Distribution (BSD) license to promote transparency and reproducibility.

Identifying candidate genes for Type 2 Diabetes Mellitus and obesity through gene expression profiling in multiple tissues or cells.

PubMed

Chen, Junhui; Meng, Yuhuan; Zhou, Jinghui; Zhuo, Min; Ling, Fei; Zhang, Yu; Du, Hongli; Wang, Xiaoning

2013-01-01

Type 2 Diabetes Mellitus (T2DM) and obesity have become increasingly prevalent in recent years. Recent studies have focused on identifying causal variations or candidate genes for obesity and T2DM via analysis of expression quantitative trait loci (eQTL) within a single tissue. T2DM and obesity are affected by comprehensive sets of genes in multiple tissues. In the current study, gene expression levels in multiple human tissues from GEO datasets were analyzed, and 21 candidate genes displaying high percentages of differential expression were filtered out. Specifically, DENND1B, LYN, MRPL30, POC1B, PRKCB, RP4-655J12.3, HIBADH, and TMBIM4 were identified from the T2DM-control study, and BCAT1, BMP2K, CSRNP2, MYNN, NCKAP5L, SAP30BP, SLC35B4, SP1, BAP1, GRB14, HSP90AB1, ITGA5, and TOMM5 were identified from the obesity-control study. The majority of these genes are known to be involved in T2DM and obesity. Therefore, analysis of gene expression in various tissues using GEO datasets may be an effective and feasible method to determine novel or causal genes associated with T2DM and obesity.

Ethnic sensitivity assessment of the antibody-drug conjugate trastuzumab emtansine (T-DM1) in patients with HER2-positive locally advanced or metastatic breast cancer.

PubMed

Li, Chunze; Wang, Bei; Lu, Dan; Jin, Jin Y; Gao, Yuying; Matsunaga, Kiyoshi; Igawa, Yuriko; Nijem, Ihsan; Lu, Michael; Strasak, Alexander; Chernyukhin, Nataliya; Girish, Sandhya

2016-09-01

Trastuzumab emtansine (T-DM1) is indicated for previously treated HER2-positive metastatic breast cancer. Ethnic sensitivity assessment of T-DM1 was conducted using data from eight clinical studies to ensure that the clinically recommended dose is appropriate across ethnicities. Four approaches were used: (1) non-compartmental analysis (NCA) comparing pharmacokinetic parameters of T-DM1 and relevant analytes across ethnic groups, (2) population pharmacokinetic (popPK) analysis assessing the impact of ethnicity on pharmacokinetics, (3) comparison of T-DM1 pharmacokinetics in Japanese patients versus the global population, and (4) exposure-response analyses assessing the impact of ethnicity on safety and efficacy. NCA pharmacokinetic parameters (T-DM1, total trastuzumab, DM1) were comparable across ethnic groups; mean cycle 1 T-DM1 AUCinf was 475, 442, and 518 day µg/mL for white (n = 461), Asian (n = 68), and others (n = 57), respectively. PopPK analysis showed that ethnicity (white, Asian, and others) was not a significant covariate for T-DM1 pharmacokinetics (n = 671). Additionally, visual predictive check plots indicated that observed pharmacokinetic profiles in Japanese patients (n = 42) were within the prediction interval generated from the final PopPK model. Exposure-response analyses showed that ethnicity was not a significant covariate impacting efficacy or hepatotoxicity risk, but there was a trend of greater thrombocytopenia risk among Asians versus non-Asians, which could not be explained by similar exposure between the ethnic groups. Most Asians with thrombocytopenia were able to continue T-DM1 using dose-adjustment rules recommended for the global population. These results suggest that T-DM1 pharmacokinetics are comparable across ethnic groups and that use of the current dosing regimen is appropriate across ethnicities.

Obese First-Degree Relatives of Patients with Type 2 Diabetes with Elevated Triglyceride Levels Exhibit Increased β-Cell Function

PubMed Central

Torres-Rasgado, Enrique; Porchia, Leonardo M.; Ruiz-Vivanco, Guadalupe; Gonzalez-Mejia, M. Elba; Báez-Duarte, Blanca G.; Pulido-Pérez, Patricia; Rivera, Alicia; Romero, Jose R.

2015-01-01

Abstract Background: Type 2 diabetes mellitus (T2DM) is characterized as a disease continuum that is marked by metabolic changes that are present for several years, sometimes well before frank diagnosis of T2DM. Genetic predisposition, ethnicity, geography, alterations in BMI, and lipid profile are considered important markers for the pathogenesis of T2DM through mechanisms that remain unresolved and controversial. The aim of this study was to investigate the relationship between triglycerides (TGs) and β-cell function, insulin resistance (IR), and insulin sensitivity (IS) in obese first-degree relatives of patients with T2DM (FDR-T2DM) among subjects from central Mexico with normal glucose tolerance (NGT). Methods: We studied 372 FDR-T2DM subjects (ages,18–65) and determined body mass index (BMI), fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), insulin, and TGs levels. Subjects were categorized based on glycemic control [NGT, prediabetes (PT2DM), or T2DM]. NGT subjects were further categorized by BMI [normal weight (Ob−) or obese (Ob+)] and TGs levels (TG−, <150 mg/dL, or TG+, ≥150 mg/dL). β-cell function, IR, and IS were determined by the homeostasis model assessment of β-cell function (HOMA2-β), homeostasis model assessment of insulin resistance (HOMA2-IR), and Quantitative Insulin Sensitivity Check Index (QUICKI) indices, respectively. Results: The obese subjects with elevated TGs levels had 21%–60% increased β-cell function when compared to all groups (P<0.05). In addition, this group had insulin levels, IS, and IR similar to PT2DM. Furthermore, only in obese subjects did TGs correlate with β-cell function (ρ=0.502, P<0.001). Conclusion: We characterized FDR-T2DM subjects from central Mexico with NGT and revealed a class of obese subjects with elevated TGs and β-cell function, which may precede PT2DM. PMID:25423015

Observational Constraints on Models of the Universe with Time Variable Gravitational and Cosmological Constants Along MOG

NASA Astrophysics Data System (ADS)

Khurshudyan, M.; Mazhari, N. S.; Momeni, D.; Myrzakulov, R.; Raza, M.

2015-02-01

The subject of this paper is to investigate the weak regime covariant scalar-tensor-vector gravity (STVG) theory, known as the MOdified gravity (MOG) theory of gravity. First, we show that the MOG in the absence of scalar fields is converted into Λ( t), G( t) models. Time evolution of the cosmological parameters for a family of viable models have been investigated. Numerical results with the cosmological data have been adjusted. We've introduced a model for dark energy (DE) density and cosmological constant which involves first order derivatives of Hubble parameter. To extend this model, correction terms including the gravitational constant are added. In our scenario, the cosmological constant is a function of time. To complete the model, interaction terms between dark energy and dark matter (DM) manually entered in phenomenological form. Instead of using the dust model for DM, we have proposed DM equivalent to a barotropic fluid. Time evolution of DM is a function of other cosmological parameters. Using sophisticated algorithms, the behavior of various quantities including the densities, Hubble parameter, etc. have been investigated graphically. The statefinder parameters have been used for the classification of DE models. Consistency of the numerical results with experimental data of S n e I a + B A O + C M B are studied by numerical analysis with high accuracy.

Impact of High-Carbohydrate Diet on Metabolic Parameters in Patients with Type 2 Diabetes

PubMed Central

Jung, Chan-Hee; Choi, Kyung Mook

2017-01-01

In patients with type 2 diabetes mellitus (T2DM), whether dietary carbohydrates have beneficial or detrimental effects on cardiometabolic risk factors has drawn attention. Although a high-carbohydrate (HC) diet and a low-carbohydrate (LC) diet have gained popularity for several decades, there is scarce review focusing on the effects of HC diet on glucose, lipids and body weight in patients with T2DM. In this review, we examined recently-published literature on the effects of HC diets on metabolic parameters in T2DM. HC diets are at least as effective as LC diets, leading to significant weight loss and a reduction in plasma glucose, HbA1c and low density lipoprotein-cholesterol (LDL-C) levels. The major concern is that HC diets may raise serum triglyceride levels and reduce high density lipoprotein-cholesterol (HDL-C) levels, increasing the risk of cardiovascular disease. However, these untoward effects were not a persistent consequence and may be ameliorated with the consumption of a low glycemic index (GI)/low glycemic load (GL) and high fiber. Carbohydrate intake should be individualized, and low caloric intake remains a crucial factor to improve insulin sensitivity and reduce body weight; however, an HC diet, rich in fiber and with a low GI/GL, may be recommendable in patients with T2DM. PMID:28338608

Impact of High-Carbohydrate Diet on Metabolic Parameters in Patients with Type 2 Diabetes.

PubMed

Jung, Chan-Hee; Choi, Kyung Mook

2017-03-24

In patients with type 2 diabetes mellitus (T2DM), whether dietary carbohydrates have beneficial or detrimental effects on cardiometabolic risk factors has drawn attention. Although a high-carbohydrate (HC) diet and a low-carbohydrate (LC) diet have gained popularity for several decades, there is scarce review focusing on the effects of HC diet on glucose, lipids and body weight in patients with T2DM. In this review, we examined recently-published literature on the effects of HC diets on metabolic parameters in T2DM. HC diets are at least as effective as LC diets, leading to significant weight loss and a reduction in plasma glucose, HbA1c and low density lipoprotein-cholesterol (LDL-C) levels. The major concern is that HC diets may raise serum triglyceride levels and reduce high density lipoprotein-cholesterol (HDL-C) levels, increasing the risk of cardiovascular disease. However, these untoward effects were not a persistent consequence and may be ameliorated with the consumption of a low glycemic index (GI)/low glycemic load (GL) and high fiber. Carbohydrate intake should be individualized, and low caloric intake remains a crucial factor to improve insulin sensitivity and reduce body weight; however, an HC diet, rich in fiber and with a low GI/GL, may be recommendable in patients with T2DM.

Effect of confounding variables on hemodynamic response function estimation using averaging and deconvolution analysis: An event-related NIRS study.

PubMed

Aarabi, Ardalan; Osharina, Victoria; Wallois, Fabrice

2017-07-15

Slow and rapid event-related designs are used in fMRI and functional near-infrared spectroscopy (fNIRS) experiments to temporally characterize the brain hemodynamic response to discrete events. Conventional averaging (CA) and the deconvolution method (DM) are the two techniques commonly used to estimate the Hemodynamic Response Function (HRF) profile in event-related designs. In this study, we conducted a series of simulations using synthetic and real NIRS data to examine the effect of the main confounding factors, including event sequence timing parameters, different types of noise, signal-to-noise ratio (SNR), temporal autocorrelation and temporal filtering on the performance of these techniques in slow and rapid event-related designs. We also compared systematic errors in the estimates of the fitted HRF amplitude, latency and duration for both techniques. We further compared the performance of deconvolution methods based on Finite Impulse Response (FIR) basis functions and gamma basis sets. Our results demonstrate that DM was much less sensitive to confounding factors than CA. Event timing was the main parameter largely affecting the accuracy of CA. In slow event-related designs, deconvolution methods provided similar results to those obtained by CA. In rapid event-related designs, our results showed that DM outperformed CA for all SNR, especially above -5 dB regardless of the event sequence timing and the dynamics of background NIRS activity. Our results also show that periodic low-frequency systemic hemodynamic fluctuations as well as phase-locked noise can markedly obscure hemodynamic evoked responses. Temporal autocorrelation also affected the performance of both techniques by inducing distortions in the time profile of the estimated hemodynamic response with inflated t-statistics, especially at low SNRs. We also found that high-pass temporal filtering could substantially affect the performance of both techniques by removing the low-frequency components of HRF profiles. Our results emphasize the importance of characterization of event timing, background noise and SNR when estimating HRF profiles using CA and DM in event-related designs. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of LDL cholesterol, statins and presence of mutations on the prevalence of type 2 diabetes in heterozygous familial hypercholesterolemia.

PubMed

Climent, Elisenda; Pérez-Calahorra, Sofía; Marco-Benedí, Victoria; Plana, Nuria; Sánchez, Rosa; Ros, Emilio; Ascaso, Juan F; Puzo, Jose; Almagro, Fátima; Lahoz, Carlos; Civeira, Fernando; Pedro-Botet, Juan

2017-07-17

Patients with heterozygous familial hypercholesterolemia (HeFH) have been reported to be less vulnerable to type 2 diabetes mellitus (T2DM), although the mechanism is unknown. The aims of the present study were to assess the effects of low density lipoprotein (LDL) cholesterol concentration and the presence of FH-causing mutations on T2DM prevalence in HeFH. Data were collected from the Dyslipidemia Registry of the Spanish Arteriosclerosis Society. Inclusion criteria were definite or probable HeFH in patients aged ≥18 years. T2DM prevalence in HeFH patients was compared with data of the general population. 1732 patients were included. The prevalence of T2DM was lower in patients with HeFH compared with the general population (5.94% vs 9.44%; OR: 0.606, 95% CI 0.486-0.755, p < 0.001). Risk factors for developing T2DM were male sex, age, body mass index, hypertension, baseline triglyceride levels and years on statin therapy. The prevalence of T2DM in HeFH patients was 40% lower than that observed in the general population. Gene mutations and LDL cholesterol concentrations were not risk factors associated with the prevalence of T2DM in patients with HeFH. The prevalence of T2DM in patients with HeFH was 40% lower than in the general population matched for age and sex.

Changes in LDL Oxidative Status and Oxidative and Inflammatory Gene Expression after Red Wine Intake in Healthy People: A Randomized Trial

PubMed Central

Di Renzo, Laura; Marsella, Luigi Tonino; Gualtieri, Paola; Gratteri, Santo; Tomasi, Diego; Gaiotti, Federica

2015-01-01

Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. Micronutrients modulate immune system and exert a protective action by reducing low density lipoproteins (LDL) oxidation via induction of antioxidant enzymes. We evaluated the gene expression of oxidative stress (HOSp), inflammasome (HIp), and human drug metabolism pathways (HDM) and ox-LDL level at baseline and after the intake of red wine naturally enriched with resveratrol (NPVRW), in association with or without a McDonald's meal (McDM). The ox-LDL levels significantly increase comparing baseline (B) versus McDM and decreased comparing McDM versus McDM + NPVRW (P ≤ 0.05). Percentages of significant genes expressed after each nutritional intervention were the following: (1) B versus McDM, 2.88% HOSp, 2.40% of HIp, and 3.37% of HDMp; (2) B versus McDM + NPVRW, 1.44% of HOSp, 4.81% of HIp, and 0.96% of HDMp; (3) McDM versus McDM + NPVRW, 2.40% of HOSp, 2.40% of HIp, and 5.77% of HDMp; (4) B versus NPVRW, 4.80% HOSp, 3.85% HIp, and 3.85% HDMp. NPVRW intake reduced postprandial ox-LDL and the expression of inflammation and oxidative stress related genes. Chronic studies on larger population are necessary before definitive conclusions. PMID:26101461

Post-prandial effects of hazelnut-enriched high fat meal on LDL oxidative status, oxidative and inflammatory gene expression of healthy subjects: a randomized trial.

PubMed

Di Renzo, L; Merra, G; Botta, R; Gualtieri, P; Manzo, A; Perrone, M A; Mazza, M; Cascapera, S; De Lorenzo, A

2017-04-01

Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. Micronutrients modulate the immune system and exert a protective action by reducing low-density lipoproteins oxidation (ox-LDL) via induction of antioxidant enzymes. The clinical study was a randomized and cross-over trial, conducted through the CONSORT flowchart. We evaluated the gene expression of 103 genes related to oxidative stress (HOSp) and human inflammasome pathways (HIp), and ox-LDL level at fasting and after 40 g raw "Tonda Gentile delle Langhe" hazelnut consumption, in association with a McDonald's® Meal (McDM) in 22 healthy human volunteers. Ox-LDL levels significantly increased comparing no dietary treatment (NDT) vs. McDM, and decreased comparing McDM vs. McDM + H (p<0.05). Percentage of significant genes expressed after each dietary treatment were the follows: (A) NDT vs. McDM: 3.88% HIp and 17.48% HOSp; (B) NDT vs. McDM + H: 17.48% HIp and 23.30% HOSp; (C) McDM vs. McDM + H: 17.48% HIp and 33.98% HOSp. Hazelnut consumption reduced post prandial risk factors of atherosclerosis, such as ox-LDL, and the expression of inflammation and oxidative stress related genes. Chronic studies on larger population are necessary before definitive conclusions.

Salivary function impairment in type 2 Diabetes patients associated with concentration and genetic polymorphisms of chromogranin A.

PubMed

Kogawa, Evelyn Mikaela; Grisi, Daniela Corrêa; Falcão, Denise Pinheiro; Amorim, Ingrid Aquino; Rezende, Taia Maria Berto; da Silva, Izabel Cristina Rodrigues; Silva, Osmar Nascimento; Franco, Octávio Luiz; de Amorim, Rivadávio Fernandes Batista

2016-11-01

The purpose of this study was to evaluate the effect of type 2 diabetes mellitus (T2DM) on salivary function impairments according to glycemic control status and subsequently compare the concentration of chromogranin A (CHGA) with its genetic profile. Thirty-six patients with controlled T2DM, 36 with poorly controlled T2DM, and 38 nondiabetic subjects underwent salivary flow rate measurements by means of unstimulated labial (ULS), unstimulated whole (UWS), and stimulated whole saliva (SWS) collections. CHGA concentrations were determined in saliva and plasma with ELISA, and two CHGA polymorphisms (T-415C and Glu264Asp) were analyzed by polymerase chain reaction-restriction fragment length polymorphism. T2DM patients presented significantly lower ULS and UWS flow rates regardless of glycemic control status compared to controls (P = 0.002 and P = 0.027, respectively). The SWS flow rate in the poorly controlled T2DM was the lowest among the groups (P = 0.026). Significantly higher plasma and salivary CHGA levels were found in T2DM groups (P = 0.019 and P < 0.001, respectively). CHGA gene variants (T-415C and Glu264Asp) revealed significant differences between diabetics and control subjects when associated with lower salivary flow and higher salivary CHGA production (P < 0.05). T2DM causes abnormalities in the function of salivary glands. However, poorly controlled T2DM has the most influence on SWS flow rates. Our findings indicate an association between plasma and salivary CHGA levels and T2DM patients. Furthermore, the results suggest that CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary CHGA production in T2DM patients. Nevertheless, further epidemiological studies are required to elucidate this clinical implication. Salivary impairments and high levels of CHGA are associated with T2DM patients. In addition, CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary CHGA production in T2DM patients. This could be a significant insight to establish a role for salivary CHGA as a potential clinical biomarker to T2DM.

Volumetric breast density affects performance of digital screening mammography.

PubMed

Wanders, Johanna O P; Holland, Katharina; Veldhuis, Wouter B; Mann, Ritse M; Pijnappel, Ruud M; Peeters, Petra H M; van Gils, Carla H; Karssemeijer, Nico

2017-02-01

To determine to what extent automatically measured volumetric mammographic density influences screening performance when using digital mammography (DM). We collected a consecutive series of 111,898 DM examinations (2003-2011) from one screening unit of the Dutch biennial screening program (age 50-75 years). Volumetric mammographic density was automatically assessed using Volpara. We determined screening performance measures for four density categories comparable to the American College of Radiology (ACR) breast density categories. Of all the examinations, 21.6% were categorized as density category 1 ('almost entirely fatty') and 41.5, 28.9, and 8.0% as category 2-4 ('extremely dense'), respectively. We identified 667 screen-detected and 234 interval cancers. Interval cancer rates were 0.7, 1.9, 2.9, and 4.4‰ and false positive rates were 11.2, 15.1, 18.2, and 23.8‰ for categories 1-4, respectively (both p-trend < 0.001). The screening sensitivity, calculated as the proportion of screen-detected among the total of screen-detected and interval tumors, was lower in higher density categories: 85.7, 77.6, 69.5, and 61.0% for categories 1-4, respectively (p-trend < 0.001). Volumetric mammographic density, automatically measured on digital mammograms, impacts screening performance measures along the same patterns as established with ACR breast density categories. Since measuring breast density fully automatically has much higher reproducibility than visual assessment, this automatic method could help with implementing density-based supplemental screening.

Sclerostin distribution in children and adolescents with type 1 diabetes mellitus and correlation with bone metabolism and bone mineral density.

PubMed

Tsentidis, Charalampos; Gourgiotis, Dimitrios; Kossiva, Lydia; Marmarinos, Antonios; Doulgeraki, Artemis; Karavanaki, Kyriaki

2016-06-01

Sclerostin is an inhibitor of the Wnt/beta-catenin bone metabolic pathway. Increased sclerostin levels and reduced bone mineral density (BMD) have been documented in adult patients with diabetes mellitus (DM), predominantly in those with type 2 diabetes mellitus (T2DM). No relative data exist on childhood type 1 diabetes mellitus (T1DM). Our objective was to study plasma sclerostin in T1DM children and adolescents and controls and its correlations with metabolic bone markers and BMD. This was a cross-sectional study that was conducted at an outpatient clinical center. Forty T1DM children and adolescents were evaluated (mean ± SD age: 13.04 ± 3.53 yr, T1DM duration: 5.15 ± 3.33 yr), along with 40 healthy matched controls (age 12.99 ± 3.3 yr). Sclerostin, soluble receptor activator of nuclear factor-kappaB ligand (s-RANKL), osteoprotegerin, osteocalcin, C-telopeptide crosslinks, electrolytes, parathyroid hormone (PTH), and total 25(OH)D were measured. Lumbar and subcranial total body BMD were evaluated with dual energy X-ray absorptiometry (DXA). Sclerostin levels demonstrated a Gaussian distribution, with no significant difference between patients and controls (51.56 ± 12.05 vs. 50.98 ± 13.55 pmol/L, p = 0.84). Significantly lower values were found in girls and prepubertal children. Sclerostin values were significantly and gradually increased in children through pubertal Tanner stages 1-3, were reduced at stage 4 and increased again at pubertal stage 5. Sclerostin levels were positively correlated with logCTX (logarithm of C-terminal telopeptide crosslinks of type I collagen), logOsteocalcin (logarithm of Osteocalcin), magnesium, total body, and L1-L4 BMD z-score. T1DM patients had similar levels of sclerostin with controls. Sclerostin correlated with bone resorption and formation markers and also with bone mass indices, gender, and pubertal stage. The decrease in sclerostin values observed in pubertal stage 4 adolescents coincides with the concurrent growth spurt, and is consistent with sclerostin physiology as an inhibiting signal. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of NOS1AP rs12742393 polymorphism on repaglinide response in Chinese patients with type 2 diabetes mellitus.

PubMed

Wang, Tao; Wang, Yan; Lv, Dong-Mei; Song, Jin-Fang; Lu, Qian; Gao, Xing; Zhang, Fan; Guo, Hao; Li, Wei; Yin, Xiao-Xing

2014-02-01

To investigate the associations of NOS1AP rs12742393 polymorphism with the risk of type 2 diabetes mellitus (T2DM) and repaglinide therapeutic efficacy in Chinese patients with T2DM. Prospective case-control study. Academic medical center. A total of 300 patients with T2DM and 200 healthy volunteers were enrolled to identify NOS1AP rs12742393 genotypes using the polymerase chain reaction-restriction fragment length polymorphism assay. Eighty-four patients with various genotypes were randomly selected to receive oral repaglinide as a single-agent therapy (3 mg/day) for 8 weeks. Anthropometric measurements and fasting plasma glucose (FPG), postprandial plasma glucose, hemoglobin A1c , fasting serum insulin (FINS), postprandial serum insulin, homeostasis model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol tests were obtained before and after repaglinide treatment. The risk C allelic frequency of NOS1AP rs12742393 was higher in patients with T2DM than in healthy volunteers (p<0.001). Patients with T2DM and genotypes AA and AC at NOS1AP rs12742393 had a significant reduction in FPG (mmol/l) compared with those with genotype CC (p<0.01). Patients with CC homozygotes and AC heterozygotes had a greater increase in FINS (mU/l) than those with wild-type AA (p<0.05). In addition, the carriers of genotype CC at NOS1AP rs12742393 had higher differential values of HOMA-IR compared with genotypes AC and AA carriers (p<0.001). The effects of repaglinide treatment on FPG (p<0.01), FINS (p<0.05) and HOMA-IR (p<0.001) were reduced in patients with T2DM carrying the NOS1AP rs12742393 risk C allele compared with the AA genotype carriers. The NOS1AP rs12742393 polymorphism is associated with therapeutic efficacy of repaglinide in Chinese T2DM patients. © 2013 Pharmacotherapy Publications, Inc.

Spherical cows in dark matter indirect detection

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

Bernal, Nicolás; Necib, Lina; Slatyer, Tracy R., E-mail: nicolas.bernal@uan.edu.co, E-mail: lnecib@mit.edu, E-mail: tslatyer@mit.edu

2016-12-01

Dark matter (DM) halos have long been known to be triaxial, but in studies of possible annihilation and decay signals they are often treated as approximately spherical. In this work, we examine the asymmetry of potential indirect detection signals of DM annihilation and decay, exploiting the large statistics of the hydrodynamic simulation Illustris. We carefully investigate the effects of the baryons on the sphericity of annihilation and decay signals for both the case where the observer is at 8.5 kpc from the center of the halo (exemplified in the case of Milky Way-like halos), and for an observer situated wellmore » outside the halo. In the case of Galactic signals, we find that both annihilation and decay signals are expected to be quite symmetric, with axis ratios very different from 1 occurring rarely. In the case of extragalactic signals, while decay signals are still preferentially spherical, the axis ratio for annihilation signals has a much flatter distribution, with elongated profiles appearing frequently. Many of these elongated profiles are due to large subhalos and/or recent mergers. Comparing to gamma-ray emission from the Milky Way and X-ray maps of clusters, we find that the gamma-ray background appears less spherical/more elongated than the expected DM signal from the large majority of halos, and the Galactic gamma ray excess appears very spherical, while the X-ray data would be difficult to distinguish from a DM signal by elongation/sphericity measurements alone.« less

Cytokines profile and its correlation with endothelial damage and oxidative stress in patients with type 1 diabetes mellitus and nephropathy.

PubMed

Pestana, Rodrigo M C; Domingueti, Caroline P; Duarte, Rita C F; Fóscolo, Rodrigo B; Reis, Janice S; Rodrigues, Ana Maria S; Martins, Laís B; Sousa, Lirlândia P; Lage, Daniela P; Ferreira, Cláudia N; Ferreira, Adaliene V M; Fernandes, Ana P; Gomes, Karina B

2016-08-01

The aim of the present study was to investigate the association between the presence of albuminuria and cytokines profile with biomarkers of endothelial damage and oxidative stress in patients with type 1 diabetes mellitus (DM1). The sample was composed by 35 healthy individuals, 63 DM1 patients with normoalbuminuria (<30 mg of albumin/g of creatinine) and 62 DM1 patients with micro- and macroalbuminuria (≥30 mg of albumin/g of creatinine). Plasma and urinary cytokines (TNF-α, IL-6 and IL-10) and thrombomodulin levels were determined by ELISA. Oxidative status was evaluated using the TBARS and MTT assays. Diabetic patients were characterized by elevated levels of urinary cytokines TNF-α, IL-6 and IL-10. Those with macroalbuminuria presented significantly higher TNF-α and IL-10 urinary levels when compared to other groups. Urinary and plasmatic levels of TNF-α were positively correlated with plasma levels of cystatin C, creatinine, urea and albuminuria, while they were negatively correlated with estimated glomerular filtration rate. Urinary IL-10 levels proved positive correlation with fasting glucose, HbA1c, thrombomodulin and TBARS, while IL-6 plasma levels were positively correlated with HbA1c and albuminuria. Only urinary TNF-α levels were associated with the presence and severity of macroalbuminuria, after logistic regression analysis. This finding suggests that measurement of urinary TNF-α level may be helpful to evaluate progression to nephropathy in DM1 patients.

Expression of cytokine signaling genes in morbidly obese patients with non-alcoholic steatohepatitis and hepatic fibrosis.

PubMed

Estep, J Michael; Baranova, Ancha; Hossain, Noreen; Elariny, Hazem; Ankrah, Kathy; Afendy, Arian; Chandhoke, Vikas; Younossi, Zobair M

2009-05-01

White adipose tissue (WAT) from visceral adiposity plays an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Development of NASH and its progression to fibrosis is partially due to cytokines and adipokines produced by WAT. The aim of this study was to assess the association of hepatic fibrosis and NASH by evaluating the intrinsic differences in the inflammatory cytokine signaling in the visceral adipose tissue obtained from morbidly obese patients. We used targeted microarrays representing human genes involved in the inflammatory and fibrogenic reactions to profile visceral adipose samples of 15 well-matched NASH patients with and without fibrosis. Additionally, visceral adipose samples were subjected to real-time polymerase chain reaction profiling of 84 inflammations related genes. Eight genes (CCL2, CCL4, CCL18, CCR1, IL10RB, IL15RA, and LTB) were differentially expressed in NASH with fibrosis. Additionally, an overlapping but distinct list of the differentially expressed genes were found in NASH with type II diabetes (DM; IL8, BLR1, IL2RA, CD40LG, IL1RN, IL15RA, and CCL4) as compared to NASH without DM. Inflammatory cytokines are differentially expressed in the adipose tissue of NASH with fibrosis, as well in NASH with DM. These findings point at the interaction of adipose inflammatory cytokines, DM, hepatic fibrosis in NASH, and its progression to cirrhosis and end-stage liver disease.

Spherical cows in dark matter indirect detection

NASA Astrophysics Data System (ADS)

Bernal, Nicolás; Necib, Lina; Slatyer, Tracy R.

2016-12-01

Dark matter (DM) halos have long been known to be triaxial, but in studies of possible annihilation and decay signals they are often treated as approximately spherical. In this work, we examine the asymmetry of potential indirect detection signals of DM annihilation and decay, exploiting the large statistics of the hydrodynamic simulation Illustris. We carefully investigate the effects of the baryons on the sphericity of annihilation and decay signals for both the case where the observer is at 8.5 kpc from the center of the halo (exemplified in the case of Milky Way-like halos), and for an observer situated well outside the halo. In the case of Galactic signals, we find that both annihilation and decay signals are expected to be quite symmetric, with axis ratios very different from 1 occurring rarely. In the case of extragalactic signals, while decay signals are still preferentially spherical, the axis ratio for annihilation signals has a much flatter distribution, with elongated profiles appearing frequently. Many of these elongated profiles are due to large subhalos and/or recent mergers. Comparing to gamma-ray emission from the Milky Way and X-ray maps of clusters, we find that the gamma-ray background appears less spherical/more elongated than the expected DM signal from the large majority of halos, and the Galactic gamma ray excess appears very spherical, while the X-ray data would be difficult to distinguish from a DM signal by elongation/sphericity measurements alone.

The Prevalence of Osteopenia and Osteoporosis Among Malaysian Type 2 Diabetic Patients Using Quantitative Ultrasound Densitometer

PubMed Central

Abdulameer, Shaymaa Abdalwahed; Sahib, Mohanad Naji; Sulaiman, Syed Azhar Syed

2018-01-01

Background: Type 2 Diabetes Mellitus (T2DM) and osteoporosis are both chronic conditions and the relationship between them is complex. Objective: The aims of this study were to assess the prevalence of Low Bone Mineral density (LBMD, i.e., osteopenia and osteoporosis), as well as, the difference and associations between Quantitative Ultrasound Scan (QUS) parameters with socio-demographic data and clinical related data among T2DM in Penang, Malaysia. Method: An observational, cross-sectional study with a convenient sample of 450 T2DM patients were recruited from the outpatient diabetes clinic at Hospital Pulau Pinang (HPP) to measure Bone Mineral Density (BMD) at the heel bone using QUS. In addition, a self-reported structured questionnaire about the socio-demographic data and osteoporosis risk factors were collected. Moreover, the study included the retrospective collection of clinical data from patients’ medical records. Results: The mean value of T-score for normal BMD, osteopenic and osteoporotic patients’ were (-0.41±0.44), (-1.65±0.39) and (-2.76±0.27), respectively. According to QUS measurements, more than three quarters of T2DM patients (82%) were at high risk of abnormal BMD. The results showed that QUS scores were significantly associated with age, gender, menopausal duration, educational level and diabetic related data. Moreover, the QUS parameters and T-scores demonstrated significant negative correlation with age, menopausal duration, diabetic duration and glycaemic control, as well as, a positive correlation with body mass index and waist to hip ratio. The current study revealed that none of the cardiovascular disease risk factors appear to influence the prevalence of low BMD among T2DM Malaysian patients. Conclusion: The study findings revealed that the assessment of T2DM patients’ bone health and related factor are essential and future educational programs are crucial to improve osteoporosis management. PMID:29755605

The effects of increasing garlic powder and monensin supplementation on feed intake, nutrient digestibility, growth performance and blood parameters of growing calves.

PubMed

Gholipour, A; Foroozandeh Shahraki, A D; Tabeidian, S A; Nasrollahi, S M; Yang, W Z

2016-08-01

The objective of this study was to evaluate the effects of increasing garlic powder and monensin supplementation on feed intake, nutrient digestibility, growth performance and blood metabolites of growing calves. Forty Holstein calves (BW = 100 ± 11 kg) were randomly assigned to four dietary treatments (n = 10) in a complete randomized design. Experimental treatments consisted of the following: (i) basal diet (control), (ii) basal diet supplemented with 0.0003% of dietary dry matter (DM) sodium monensin, (iii) low level of garlic powder (Low-GAR; 0.5% of dietary DM) and (iv) high level of garlic powder (High-GAR; 1% of dietary DM). DM intake (DMI) and DM digestibility were (p < 0.05) decreased by High-GAR. However, calves supplemented with Low-GAR had a similar DMI to the control calves and similar DM digestibility to the control and monensin groups. The digestibility of other nutrients were not affected by the treatments. Although supplementing monensin relative to Low-GAR increased the DMI (p < 0.05), average daily gain was similar between Low-GAR and monensin supplemented calves, which were higher than the control and High-GAR groups (p < 0.05). As a result, feed conversion ratio was improved in the Low-GAR group versus other treatment groups (p < 0.05). Administrating garlic powder decreased the blood low-density lipoprotein (LDL) and non-esterified fatty acids (p < 0.05) without affecting the blood triglyceride, high-density lipoprotein and beta-hydroxybutyric acid concentrations. In conclusion, the calves fed the Low-GAR showed an improved FCR and blood metabolites without changing the DMI and nutrient digestibility. It suggests that garlic powder could be used as an alternative to monensin for growing calves under the current feeding conditions. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

IGF2BP2 variations influence repaglinide response and risk of type 2 diabetes in Chinese population.

PubMed

Huang, Qiong; Yin, Ji-ye; Dai, Xing-ping; Pei, Qi; Dong, Min; Zhou, Zhi-guang; Huang, Xi; Yu, Min; Zhou, Hong-hao; Liu, Zhao-qian

2010-06-01

To investigate whether the insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) rs1470579 and rs4402960 polymorphisms are associated with the development of type 2 diabetes mellitus (T2DM) and the repaglinide therapeutic efficacy in Chinese T2DM patients. A case-control study of a total of 350 patients with T2DM and 207 healthy volunteers was conducted to identify their genotypes for the IGF2BP2 rs1470579 and rs4402960 polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-two patients were randomly selected to undergo an 8-week repaglinide treatment (3 mg/d). Fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbAlc), fasting serum insulin (FINS), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), serum triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol (HDL-c) were determined before and after repaglinide treatment. The frequencies of the IGF2BP2 rs1470579 C allele and the rs4402960 T allele were higher in T2DM patients than in healthy controls (P<0.05 and P<0.001, respectively). The effects of the repaglinide treatment on FPG (P<0.05) and PPG (P<0.05) were reduced in patients with the rs1470579 AC+CC genotypes compared with AA genotype carriers. Patients with the rs4402960 GT+TT genotypes exhibited an enhanced effect of repaglinide treatment on PINS (P<0.01) compared with GG genotype subjects. The IGF2BP2 rs1470579 and rs4402960 polymorphisms may be associated with the development of T2DM, and these polymorphisms may affect the therapeutic efficacy of repaglinide in Chinese T2DM patients.

IGF2BP2 variations influence repaglinide response and risk of type 2 diabetes in Chinese population

PubMed Central

Huang, Qiong; Yin, Ji-ye; Dai, Xing-ping; Pei, Qi; Dong, Min; Zhou, Zhi-guang; Huang, Xi; Yu, Min; Zhou, Hong-hao; Liu, Zhao-qian

2010-01-01

Aim: To investigate whether the insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) rs1470579 and rs4402960 polymorphisms are associated with the development of type 2 diabetes mellitus (T2DM) and the repaglinide therapeutic efficacy in Chinese T2DM patients. Methods: A case-control study of a total of 350 patients with T2DM and 207 healthy volunteers was conducted to identify their genotypes for the IGF2BP2 rs1470579 and rs4402960 polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-two patients were randomly selected to undergo an 8-week repaglinide treatment (3 mg/d). Fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbAlc), fasting serum insulin (FINS), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), serum triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol (HDL-c) were determined before and after repaglinide treatment. Results: The frequencies of the IGF2BP2 rs1470579 C allele and the rs4402960 T allele were higher in T2DM patients than in healthy controls (P<0.05 and P<0.001, respectively). The effects of the repaglinide treatment on FPG (P<0.05) and PPG (P<0.05) were reduced in patients with the rs1470579 AC+CC genotypes compared with AA genotype carriers. Patients with the rs4402960 GT+TT genotypes exhibited an enhanced effect of repaglinide treatment on PINS (P<0.01) compared with GG genotype subjects. Conclusion: The IGF2BP2 rs1470579 and rs4402960 polymorphisms may be associated with the development of T2DM, and these polymorphisms may affect the therapeutic efficacy of repaglinide in Chinese T2DM patients. PMID:20523342

Interplay between the b →s l l anomalies and dark matter physics

NASA Astrophysics Data System (ADS)

Kawamura, Junichiro; Okawa, Shohei; Omura, Yuji

2017-10-01

Recently, the LHCb Collaboration has reported the excesses in the b →s l l processes. One of the promising candidates for new physics to explain the anomalies is the extended Standard Model (SM) with vectorlike quarks and leptons. In that model, Yukawa couplings between the extra fermions and SM fermions are introduced, adding extra scalars. Then, the box diagrams involving the extra fields achieve the b →s l l anomalies. It has been known that the excesses require the large Yukawa couplings of leptons, so that this kind of model can be tested by studying correlations with other observables. In this paper, we consider the extra scalar to be a dark matter (DM) candidate, and investigate DM physics as well as the flavor physics and the LHC physics. The DM relic density and the direct-detection cross section are also dominantly given by the Yukawa couplings, so that we find some explicit correlations between DM physics and the flavor physics. In particular, we find the predictions of the b →s l l anomalies against the direct detection of DM.

Predicting the short-term risk of diabetes in HIV-positive patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study

PubMed Central

Petoumenos, Kathy; Worm, Signe W; Fontas, Eric; Weber, Rainer; De Wit, Stephane; Bruyand, Mathias; Reiss, Peter; El-Sadr, Wafaa; Monforte, Antonella D'Arminio; Friis-Møller, Nina; Lundgren, Jens D; Law, Matthew G

2012-01-01

Introduction HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM and other glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV-positive populations and to compare the existing models developed in the general population. Methods All patients recruited to the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study with follow-up data, without prior DM, myocardial infarction or other CVD events and with a complete DM risk factor profile were included. Conventional risk factors identified in the general population as well as key HIV-related factors were assessed using Poisson-regression methods. Expected probabilities of DM events were also determined based on the Framingham Offspring Study DM equation. The D:A:D and Framingham equations were then assessed using an internal-external validation process; area under the receiver operating characteristic (AUROC) curve and predicted DM events were determined. Results Of 33,308 patients, 16,632 (50%) patients were included, with 376 cases of new onset DM during 89,469 person-years (PY). Factors predictive of DM included higher glucose, body mass index (BMI) and triglyceride levels, and older age. Among HIV-related factors, recent CD4 counts of<200 cells/µL and lipodystrophy were predictive of new onset DM. The mean performance of the D:A:D and Framingham equations yielded AUROC of 0.894 (95% CI: 0.849, 0.940) and 0.877 (95% CI: 0.823, 0.932), respectively. The Framingham equation over-predicted DM events compared to D:A:D for lower glucose and lower triglycerides, and for BMI levels below 25 kg/m2. Conclusions The D:A:D equation performed well in predicting the short-term onset of DM in the validation dataset and for specific subgroups provided better estimates of DM risk than the Framingham. PMID:23078769

Correlation between heat shock proteins, adiponectin, and T lymphocyte cytokine expression in type 2 diabetics.

PubMed

Mahmoud, Fadia F; Haines, David; Dashti, Ali A; El-Shazly, Sherief; Al-Najjar, Fawzia

2018-05-11

Type 2 diabetes mellitus (T2DM) features insulin resistance, hyperglycemia, dyslipidemia, overproduction of inflammatory cytokines, and systemic oxidative stress. Here, heat shock proteins Hsp70 and Hsp 90, adiponectin, and heme oxygenase-1 (HO-1, Hsp32) are profiled in peripheral blood mononuclear cells (PBMC) and serum from 25 T2DM patients and 25 healthy control subjects. Cells cultured with phorbol 12-myristate 13-acetate/ionomycin were evaluated by three-color flow cytometry for immunophenotypic biomarkers. Plasma HO-1, Hsp, and adiponectin levels were assayed by enzyme-linked immunosorbent assay (ELISA). Relative to healthy controls, T2DM patients exhibited significantly elevated plasma Hsp70, and representation of T helper immunophenotypes activated to express inflammatory cytokines, including CD4+ IFN-γ+, CD4+ TNF-α+, CD4+ IL-6+, CD4+ IL-1β+ T cells, significantly lower representation of CD4+ IL-10+ T cells, plasma adiponectin and cell-associated HO-1 expression-with no significant differences in plasma Hsp90 between T2DM and healthy controls. Plasma HO-1 and adiponectin in T2DM patients inversely correlated with TNF-α and showed inverse correlation between serum LDL and plasma HO-1. Moreover, TNF-α and Hsp90 in T2DM patients correlated positively with fasting blood glucose (FBG). These results demonstrate correlation between potentially pathogenic T cells, HO-1, and adiponectin, additionally revealing a T helper (Th)1-related character of T2DM immunopathogenesis, suggesting potential for novel T cell-related management strategies for T2DM and related co-morbidities.

Association of Plasma Ghrelin Levels with Insulin Resistance in Type 2 Diabetes Mellitus among Saudi Subjects

PubMed Central

Al Qarni, Ali Ahmed; Joatar, Faris Elbahi; Das, Nagalla; Awad, Mohamed; Eltayeb, Mona; Al-Zubair, Ahmed Gasim; Ali, Muhalab E.; Al Masaud, Abdulaziz; Shire, Abdirashid M.; Gumaa, Khalid

2017-01-01

Background Although the exact mechanism of insulin resistance (IR) has not yet been established, IR is the hallmark characteristic of type 2 diabetes mellitus (T2DM). The aim of this study was to examine the relationship between plasma ghrelin levels and IR in Saudi subjects with T2DM. Methods Patients with T2DM (n=107, cases) and non-diabetic apparently healthy subjects (n=101, controls) from Saudi Arabia were included in this study. The biochemical profiles and plasma insulin levels of all subjects were analyzed, and IR was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) index. Active ghrelin levels in plasma were measured using the radioimmunoassay technique. Results Only 46.7% (50 of 107) of the T2DM subjects had IR, including 26% (28 of 107) with severe IR (HOMA-IR ≥5), while 5.9% (six of 101) of the controls had moderate IR (3 ≤HOMA-IR <5). HOMA-IR values were not associated with age, disease duration, or gender. Importantly, T2DM itself and the co-occurrence of IR with T2DM were significantly associated with low plasma ghrelin levels. However, ghrelin levels were inversely correlated with the HOMA-IR index, body weight, and fasting plasma insulin levels, mainly in the control subjects, which was indicative of the breakdown of metabolic homeostasis in T2DM. Conclusion The prevalence of IR was relatively low, and IR may be inversely associated with plasma ghrelin levels among Saudi patients with T2DM. PMID:28555463

Galactic center gamma-ray excess from dark matter annihilation: is there a black hole spike?

PubMed

Fields, Brian D; Shapiro, Stuart L; Shelton, Jessie

2014-10-10

If the supermassive black hole Sgr A* at the center of the Milky Way grew adiabatically from an initial seed embedded in a Navarro-Frenk-White dark matter (DM) halo, then the DM profile near the hole has steepened into a spike. We calculate the dramatic enhancement to the gamma-ray flux from the Galactic center (GC) from such a spike if the 1-3 GeV excess observed in Fermi data is due to DM annihilations. We find that for the parameter values favored in recent fits, the point-source-like flux from the spike is 35 times greater than the flux from the inner 1° of the halo, far exceeding all Fermi point source detections near the GC. We consider the dependence of the spike signal on astrophysical and particle parameters and conclude that if the GC excess is due to DM, then a canonical adiabatic spike is disfavored by the data. We discuss alternative Galactic histories that predict different spike signals, including (i) the nonadiabatic growth of the black hole, possibly associated with halo and/or black hole mergers, (ii) gravitational interaction of DM with baryons in the dense core, such as heating by stars, or (iii) DM self-interactions. We emphasize that the spike signal is sensitive to a different combination of particle parameters than the halo signal and that the inclusion of a spike component to any DM signal in future analyses would provide novel information about both the history of the GC and the particle physics of DM annihilations.

Effect of increased magnesium intake on plasma cholesterol, triglyceride and oxidative stress in alloxan-diabetic rats.

PubMed

Olatunji, L A; Soladoye, A O

2007-06-01

Cardiovascular disorders are the primary causes of morbidity and mortality in patients with diabetes mellitus (DM). Agents that improve lipid profile and reduce oxidative stress have been shown to reduce the ensuing risk factors. In the present study, we investigated whether increased magnesium intake could improve hyperglycaemia, dyslipidaemia, and reduce oxidative stress in alloxan-induced diabetic rats. Male Wistar rats were divided into non-diabetic (ND), diabetic (DM) and diabetic fed on a high magnesium diet (DM-Mg) groups. Plasma concentrations of thiobarbituric acid reactive substances (TBARS) were used as markers of oxidative stress. Plasma levels of ascorbic acid, magnesium and calcium were also determined. Diabetes was induced by injecting alloxan (100 mg/kg B.W). The fasting blood glucose levels were significantly lower in the DM-Mg rats than in the DM rats. Plasma total cholesterol, triglyceride, TBARS levels were significantly higher while plasma HDL-cholesterol, HDL-cholesterol/total cholesterol ratio, ascorbic acid levels were significantly lowered in DM rats compared with the ND rats. Increased intake of magnesium significantly abrogated these alterations. There were no significant differences in the plasma levels of magnesium and calcium between the DM and ND groups. However, plasma levels of magnesium but not calcium were significantly elevated in DM-Mg rats when compared with other groups. In conclusion, these results suggest that diet rich in magnesium could exert cardioprotective effect through reduced plasma total cholesterol, triglyceride, oxidative stress and ameliorated HDL-cholesterol/total cholesterol ratio as well as increased plasma ascorbic acid and magnesium in diabetic rats.

Extended Higgs-portal dark matter and the Fermi-LAT Galactic Center Excess

NASA Astrophysics Data System (ADS)

Casas, J. A.; Gómez Vargas, G. A.; Moreno, J. M.; Quilis, J.; Ruiz de Austri, R.

2018-06-01

In the present work, we show that the Galactic Center Excess (GCE) emission, as recently updated by the Fermi-LAT Collaboration, could be explained by a mixture of Fermi-bubbles-like emission plus dark matter (DM) annihilation, in the context of a scalar-singlet Higgs portal scenario (SHP). In fact, the standard SHP, where the DM particle, S, only has renormalizable interactions with the Higgs, is non-operational due to strong constraints, especially from DM direct detection limits. Thus we consider the most economical extension, called ESHP (for extended SHP), which consists solely in the addition of a second (more massive) scalar singlet in the dark sector. The second scalar can be integrated-out, leaving a standard SHP plus a dimension-6 operator. Mainly, this model has only two relevant parameters (the DM mass and the coupling of the dim-6 operator). DM annihilation occurs mainly into two Higgs bosons, SS→ hh. We demonstrate that, despite its economy, the ESHP model provides an excellent fit to the GCE (with p-value ~ 0.6‑0.7) for very reasonable values of the parameters, in particular, mS simeq 130 GeV. This agreement of the DM candidate to the GCE properties does not clash with other observables and keep the S‑particle relic density at the accepted value for the DM content in the universe.

Design of experiments approach to engineer cell-secreted matrices for directing osteogenic differentiation.

PubMed

Decaris, Martin L; Leach, J Kent

2011-04-01

The presentation of extracellular matrix (ECM) proteins provides an opportunity to instruct the phenotype and behavior of responsive cells. Decellularized cell-secreted matrix coatings (DM) represent a biomimetic culture surface that retains the complexity of the natural ECM. Microenvironmental culture conditions alter the composition of these matrices and ultimately the ability of DMs to direct cell fate. We employed a design of experiments (DOE) multivariable analysis approach to determine the effects and interactions of four variables (culture duration, cell seeding density, oxygen tension, and media supplementation) on the capacity of DMs to direct the osteogenic differentiation of human mesenchymal stem cells (hMSCs). DOE analysis revealed that matrices created with extended culture duration, ascorbate-2-phosphate supplementation, and in ambient oxygen tension exhibited significant correlations with enhanced hMSC differentiation. We validated the DOE model results using DMs predicted to have superior (DM1) or lesser (DM2) osteogenic potential for naïve hMSCs. Compared to cells on DM2, hMSCs cultured on DM1 expressed 2-fold higher osterix levels and deposited 3-fold more calcium over 3 weeks. Cells on DM1 coatings also exhibited greater proliferation and viability compared to DM2-coated substrates. This study demonstrates that DOE-based analysis is a powerful tool for optimizing engineered systems by identifying significant variables that have the greatest contribution to the target output.

Dark-matter admixed white dwarfs

NASA Astrophysics Data System (ADS)

Leung, Shing Chi; Chu, Ming Chung; Lin, Lap Ming; Wong, Ka Wing

2014-03-01

We study the equilibrium structures of white dwarfs (WD) with dark matter cores formed by non-self-annihilating dark matter (DM) particles with masses ranging from 1 GeV to 100 GeV, assuming in form of an ideal degenerate Fermi gas inside the stars. For DM particles of mass 10 GeV and 100 GeV, we find that stable stellar models exist only if the mass of the DM core inside the star is less than O and -3)Msun , respectively. The global properties of these stars, and the corresponding Chandrasekhar mass (CM) limits, are essentially the same as those of traditional WD models without DM. Nevertheless, in the 10 GeV case, the gravitational attraction of the DM core is strong enough to squeeze the normal matter in the core region to densities above neutron drip. For the 1 GeV case, the DM core inside the star can be as massive as O and affects the global structure of the star significantly. The radius of a stellar model with DM can be about two times smaller than that of a traditional WD. Furthermore, the CM limit can be decreased by as much as 40%. Our results may have implications on the extent to which type Ia supernovae can be regarded as standard candles. This work is partially supported by a grant from the Research Grant Council of the Hong Kong Special Administrative Region, China (Project No. 400910).

Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation.

PubMed

Johannsson, G; Nilsson, A G; Bergthorsdottir, R; Burman, P; Dahlqvist, P; Ekman, B; Engström, B E; Olsson, T; Ragnarsson, O; Ryberg, M; Wahlberg, J; Biller, B M K; Monson, J P; Stewart, P M; Lennernäs, H; Skrtic, S

2012-02-01

Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release tablet with a more physiological exposure-time cortisol profile. The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of conventional hydrocortisone tablets. We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers. The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM). The same daily dose of hydrocortisone was administered as OD dual-release or TID. We evaluated cortisol pharmacokinetics. Compared with conventional TID, OD provided a sustained serum cortisol profile 0-4 h after the morning intake and reduced the late afternoon and the 24-h cortisol exposure. The mean weight (difference = -0.7 kg, P = 0.005), systolic blood pressure (difference = -5.5 mm Hg, P = 0.0001) and diastolic blood pressure (difference: -2.3 mm Hg; P = 0.03), and glycated hemoglobin (absolute difference = -0.1%, P = 0.0006) were all reduced after OD compared with TID at 12 wk. Compared with TID, a reduction in glycated hemoglobin by 0.6% was observed in patients with concomitant DM during OD (P = 0.004). The OD dual-release tablet provided a more circadian-based serum cortisol profile. Reduced body weight, reduced blood pressure, and improved glucose metabolism were observed during OD treatment. In particular, glucose metabolism improved in patients with concomitant DM.

The Effects of Chronic Aerobic Exercise on Cardiovascular Risk Factors in Persons with Diabetes Mellitus.

PubMed

Miele, Emily M; Headley, Samuel A E

2017-09-12

Aerobic exercise training is a component of diabetes mellitus (DM) care guidelines due to its favorable effects on glycemic control and cardiovascular disease (CVD) risk factors. The purpose of this review is to outline the recent evidence regarding the clinical effects of chronic aerobic exercise on CVD risk factors in persons with DM and to compare the effects of varying intensities and types of exercise. Among individuals with DM, all types of aerobic exercise training can impact positively on some traditional and non-traditional risk factors for CVD. Training programs with a higher volume or intensity induce greater improvements in vascular function, cardiorespiratory fitness (CRF), and lipid profiles. The beneficial outcomes of aerobic training include improvements in glycemic control, endothelial function, oxidative stress, dyslipidemia, myocardial function, adiposity, and CRF. Findings regarding markers of inflammation are discrepant and further research should focus on the role of exercise to impact upon the chronic inflammation associated with DM.

Woodhouse-Sakati syndrome in an Israeli-Arab family presenting with youth-onset diabetes mellitus and delayed puberty.

PubMed

Rachmiel, Marianna; Bistritzer, Tzvy; Hershkoviz, Eli; Khahil, Auni; Epstein, Orna; Parvari, Ruth

2011-01-01

Woodhouse-Sakati syndrome (WSS) is a rare autosomal-recessive disorder characterized by a combination of hypogonadism, alopecia, diabetes mellitus (DM), mental retardation and extrapyramidal signs, not described previously in Israel. Our aim was to study the clinical and genetic characteristics of the extended family of a 16-year-old female who presented with new-onset DM and had delayed puberty on physical examination. The primary physician's medical charts of 9 members of the proband's consanguineous Israeli-Arab family were reviewed. Hormonal, metabolic and antibody profile, imaging studies and molecular analysis were performed in 4 phenotypically compatible members, including the proband. Four subjects, 2 females and 2 males, had DM, absent pubertal development and similar appearance. None had extrapyramidal signs. The patients were homozygous for a one-base deletion mutation (c.436delC) in the C2orf37 gene. We describe the first Israeli-Arab family with phenotype and genotype of WSS, imitating autoimmune DM with gonadal failure. Copyright © 2011 S. Karger AG, Basel.

Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients

PubMed Central

Luo, Lin; Zhou, Wen-Hua; Cai, Jiang-Jia; Feng, Mei; Zhou, Mi; Hu, Su-Pei

2017-01-01

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). It is not diagnosed or managed properly in the majority of patients because its pathogenesis remains controversial. In this study, human whole genome microarrays identified 2898 and 4493 differentially expressed genes (DEGs) in DM and DPN patients, respectively. A further KEGG pathway analysis indicated that DPN and DM share four pathways, including apoptosis, B cell receptor signaling pathway, endocytosis, and Toll-like receptor signaling pathway. The DEGs identified through comparison of DPN and DM were significantly enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, and neurotrophin signaling pathway, while the “neurotrophin-MAPK signaling pathway” was notably downregulated. Seven DEGs from the neurotrophin-MAPK signaling pathway were validated in additional 78 samples, and the results confirmed the initial microarray findings. These findings demonstrated that downregulation of the neurotrophin-MAPK signaling pathway may be the major mechanism of DPN pathogenesis, thus providing a potential approach for DPN treatment. PMID:28900628

Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients.

PubMed

Luo, Lin; Zhou, Wen-Hua; Cai, Jiang-Jia; Feng, Mei; Zhou, Mi; Hu, Su-Pei; Xu, Jin; Ji, Lin-Dan

2017-01-01

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). It is not diagnosed or managed properly in the majority of patients because its pathogenesis remains controversial. In this study, human whole genome microarrays identified 2898 and 4493 differentially expressed genes (DEGs) in DM and DPN patients, respectively. A further KEGG pathway analysis indicated that DPN and DM share four pathways, including apoptosis, B cell receptor signaling pathway, endocytosis, and Toll-like receptor signaling pathway. The DEGs identified through comparison of DPN and DM were significantly enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, and neurotrophin signaling pathway, while the "neurotrophin-MAPK signaling pathway" was notably downregulated. Seven DEGs from the neurotrophin-MAPK signaling pathway were validated in additional 78 samples, and the results confirmed the initial microarray findings. These findings demonstrated that downregulation of the neurotrophin-MAPK signaling pathway may be the major mechanism of DPN pathogenesis, thus providing a potential approach for DPN treatment.

Lipid lowering with dietary supplements: focus on diabetes.

PubMed

Rudkowska, Iwona

2012-06-01

Cardiovascular disease (CVD) is the predominant cause of mortality in type 2 diabetic (T2DM) patients. Dyslipidemia is a modifiable risk factor that should be treated early for CVD prevention. Further, dietary supplement intake is increasing in popularity worldwide. This review examines the recent meta-analyses and clinical studies on dietary supplements, specifically psyllium, garlic and green tea, on plasma lipids levels and glycemic control, as well as other potential CVD risk factors in T2DM patients. Generally, results demonstrate that psyllium supplements improve lipid profiles as well as glycemic control beyond a traditional diet in patients with T2DM. On the other hand, the results on the usefulness of garlic and green tea supplementation for dyslipidemia and hyperglycemia are uncertain. Overall, the addition of dietary supplements may be a therapeutic alternative to lower CVD risk factors in T2DM; however, more well-designed intervention studies are needed to assess the benefit of these dietary supplements. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Partial least squares density modeling (PLS-DM) - a new class-modeling strategy applied to the authentication of olives in brine by near-infrared spectroscopy.

PubMed

Oliveri, Paolo; López, M Isabel; Casolino, M Chiara; Ruisánchez, Itziar; Callao, M Pilar; Medini, Luca; Lanteri, Silvia

2014-12-03

A new class-modeling method, referred to as partial least squares density modeling (PLS-DM), is presented. The method is based on partial least squares (PLS), using a distance-based sample density measurement as the response variable. Potential function probability density is subsequently calculated on PLS scores and used, jointly with residual Q statistics, to develop efficient class models. The influence of adjustable model parameters on the resulting performances has been critically studied by means of cross-validation and application of the Pareto optimality criterion. The method has been applied to verify the authenticity of olives in brine from cultivar Taggiasca, based on near-infrared (NIR) spectra recorded on homogenized solid samples. Two independent test sets were used for model validation. The final optimal model was characterized by high efficiency and equilibrate balance between sensitivity and specificity values, if compared with those obtained by application of well-established class-modeling methods, such as soft independent modeling of class analogy (SIMCA) and unequal dispersed classes (UNEQ). Copyright © 2014 Elsevier B.V. All rights reserved.

Exhaled methyl nitrate as a noninvasive marker of hyperglycemia in type 1 diabetes

PubMed Central

Novak, B. J.; Blake, D. R.; Meinardi, S.; Rowland, F. S.; Pontello, A.; Cooper, D. M.; Galassetti, P. R.

2007-01-01

Recent technical advances allow detection of several hundred volatile organic compounds (VOCs) in human exhaled air, many of which reflect unidentified endogenous pathways. Our group has previously estimated plasma glucose levels in healthy adults during a standard oral glucose tolerance test via exhaled VOC analysis. As a result of the metabolic characteristics of hyperglycemia in the diabetic (low insulin and increased free fatty acids and ketones), we hypothesized that different exhaled VOC profiles may be present in children with type 1 diabetes mellitus (T1DM) during spontaneous hyperglycemia. Exhaled methyl nitrate strongly correlated specifically with the acute, spontaneous hyperglycemia of T1DM children. Eighteen experiments were conducted among 10 T1DM children. Plasma glucose and exhaled gases were monitored during either constant euglycemia (n = 5) or initial hyperglycemia with gradual correction (n = 13); all subjects received i.v. insulin and glucose as needed. Gas analysis was performed on 1.9-liter breath samples via gas chromatography using electron capture, flame ionization, and mass selective detection. Among the ≈100 measured exhaled gases, the kinetic profile of exhaled methyl nitrate, commonly present in room air in the range of 5–10 parts per trillion, was most strongly statistically correlated with that of plasma glucose (P = 0.003–0.001). Indeed, the kinetic profiles of the two variables paralleled each other in 16 of 18 experiments, including repeat subjects who at different times displayed either euglycemia or hyperglycemia. PMID:17895380

Arterial stiffness evaluation by cardio-ankle vascular index in hypertension and diabetes mellitus subjects.

PubMed

Wang, Hongyu; Liu, Jinbo; Zhao, Hongwei; Fu, Xiaobao; Shang, Guangyun; Zhou, Yingyan; Yu, Xiaolan; Zhao, Xujing; Wang, Guang; Shi, Hongyan

2013-01-01

Arterial stiffness is an independent predictor for vascular diseases. Cardio-ankle vascular index (CAVI) is a new index of arterial stiffness. In the present study, we investigated the possible risk factors involving CAVI in hypertension and diabetes mellitus (DM) subjects. One thousand sixty-three subjects (M/F 533/530) from Shougang Corporation Examination Center were divided into four groups: healthy group (n = 639); hypertension group (n = 312); DM group (n = 58); and hypertension with DM group (n = 54). CAVI was measured by VS-1000 apparatus. Our results showed that CAVI was significantly higher in hypertension subjects with DM than in healthy and hypertension group, respectively (8.59 ± 1.08 vs 7.23 ± 1.10; 8.59 ± 1.08 vs 7.94 ± 1.33; both P < .05). CAVI was positively correlated with age, systolic blood pressure, diastolic blood pressure, pulse pressure, fasting plasma glucose, HbA1c, uric acid, total cholesterol, triglycerides in the entire group (r = 0.633, 0.280, 0.172, 0.269, 0.209, 0.254, 0.176, 0.129, 0.175; all P < .05, respectively). There was negatively correlation between CAVI and high-density lipoprotein cholesterol in the entire group (r = -0.167; P < .05). Multivariate analysis showed that age, body mass index, HbA1c, and high-density lipoprotein cholesterol were independent associating factors of CAVI in all subjects (β = 0.699; P < .001, β = -0.189; P = .001, β = 0.144; P = .015, β = -0.136; P = .019, respectively). Our present study suggested that CAVI was significantly higher in hypertension subjects with DM compared with healthy and hypertension groups. Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Patterns of Care and Treatment Target Success among Persons with Type 2 Diabetes Mellitus in Dubai: A Retrospective Cohort Study.

PubMed

Osenenko, Katherine M; Szabo, Shelagh M; Qatami, Lara; Korenblat Donato, Bonnie M; Al Madani, Abdulrazzak Ali; Al Awadi, Fatheya Fardallah; Al-Ansari, Jaber; Maclean, Ross; Levy, Adrian R

2015-09-01

Despite the high prevalence of type 2 diabetes mellitus (T2DM), few data exist describing its management in Dubai. This study characterized the treatment and estimated levels of glycemic, lipid, and blood pressure control among a sample with T2DM at a large Dubai Hospital. This retrospective cohort study systematically sampled charts from adults seeking care for T2DM from October 2009 to March 2010 until the target (N = 250) was reached. Data on patient characteristics, pharmacotherapy, complications, and laboratory testing were abstracted until September 2011. The frequency of treatments and modifications over the period was calculated, and measures of glycosylated hemoglobin A 1c , low-density lipoprotein, and blood pressure control were compared with guideline targets. Frequencies of complications were compared according to treatment type. One-third of the cohort comprised men, and the mean age was 58 years. At enrolment, the mean time from T2DM diagnosis was nearly 15 years and 74% had received insulin. During the study period, the most common regimens were insulin + oral combinations (55%) and oral combination therapy (39%). Overall, 67% received any insulin therapy during the study; and by study end, 78% had received insulin at any time. At the most recent assessment, guideline targets for glycosylated hemoglobin A 1c , blood pressure, and low-density lipoprotein were met by 23%, 29%, and 71%, respectively. Complications were more frequent among those treated with combination or insulin therapies. This study provides baseline data from Dubai for future comparisons of the effectiveness of new treatments, and to better understand the humanistic and economic burden of T2DM and its complications. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Parenchymal Texture Analysis in Digital Breast Tomosynthesis for Breast Cancer Risk Estimation: A Preliminary Study

PubMed Central

Kontos, Despina; Bakic, Predrag R.; Carton, Ann-Katherine; Troxel, Andrea B.; Conant, Emily F.; Maidment, Andrew D.A.

2009-01-01

Rationale and Objectives Studies have demonstrated a relationship between mammographic parenchymal texture and breast cancer risk. Although promising, texture analysis in mammograms is limited by tissue superimposition. Digital breast tomosynthesis (DBT) is a novel tomographic x-ray breast imaging modality that alleviates the effect of tissue superimposition, offering superior parenchymal texture visualization compared to mammography. Our study investigates the potential advantages of DBT parenchymal texture analysis for breast cancer risk estimation. Materials and Methods DBT and digital mammography (DM) images of 39 women were analyzed. Texture features, shown in studies with mammograms to correlate with cancer risk, were computed from the retroareolar breast region. We compared the relative performance of DBT and DM texture features in correlating with two measures of breast cancer risk: (i) the Gail and Claus risk estimates, and (ii) mammographic breast density. Linear regression was performed to model the association between texture features and increasing levels of risk. Results No significant correlation was detected between parenchymal texture and the Gail and Claus risk estimates. Significant correlations were observed between texture features and breast density. Overall, the DBT texture features demonstrated stronger correlations with breast percent density (PD) than DM (p ≤0.05). When dividing our study population in groups of increasing breast PD, the DBT texture features appeared to be more discriminative, having regression lines with overall lower p-values, steeper slopes, and higher R2 estimates. Conclusion Although preliminary, our results suggest that DBT parenchymal texture analysis could provide more accurate characterization of breast density patterns, which could ultimately improve breast cancer risk estimation. PMID:19201357

CYTOKINE PROFILING FOR CHEMICAL SENSITIZERS: APPLICATION OF THE RIBONUCLEASE PROTECTION ASSAY AND EFFECT OF DOSE

EPA Science Inventory

Cytokine Profiling for Chemical Sensitizers: Application of the Ribonuclease Protection Assay and Effect of Dose. L.M. Plitnick1, S.E. Loveless3, G.S. Ladics3, M.P. Holsapple4, M.J. Selgrade2, D.M. Sailstad2 and R.J. Smialowicz2. 1UNC, Curriculum in Toxicology, Chapel Hill, NC a...

Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics.

PubMed

Qamar, Arman; Khetarpal, Sumeet A; Khera, Amit V; Qasim, Atif; Rader, Daniel J; Reilly, Muredach P

2015-08-01

Triglyceride-rich lipoproteins have emerged as causal risk factors for developing coronary heart disease independent of low-density lipoprotein cholesterol levels. Apolipoprotein C-III (ApoC-III) modulates triglyceride-rich lipoprotein metabolism through inhibition of lipoprotein lipase and hepatic uptake of triglyceride-rich lipoproteins. Mutations causing loss-of-function of ApoC-III lower triglycerides and reduce coronary heart disease risk, suggestive of a causal role for ApoC-III. Little data exist about the relationship of ApoC-III, triglycerides, and atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Here, we examined the relationships between plasma ApoC-III, triglycerides, and coronary artery calcification in patients with T2DM. Plasma ApoC-III levels were measured in a cross-sectional study of 1422 subjects with T2DM but without clinically manifest coronary heart disease. ApoC-III levels were positively associated with total cholesterol (Spearman r=0.36), triglycerides (r=0.59), low-density lipoprotein cholesterol (r=0.16), fasting glucose (r=0.16), and glycosylated hemoglobin (r=0.12; P<0.0001 for all). In age, sex, and race-adjusted analysis, ApoC-III levels were positively associated with coronary artery calcification (Tobit regression ratio, 1.78; 95% confidence interval, 1.27-2.50 per SD increase in ApoC-III; P<0.001). As expected for an intermediate mediator, these findings were attenuated when adjusted for both triglycerides (Tobit regression ratio, 1.43; 95% confidence interval, 0.94-2.18; P=0.086) and separately for very low-density lipoprotein cholesterol (Tobit regression ratio, 1.14; 95% confidence interval, 0.75-1.71; P=0.53). In persons with T2DM, increased plasma ApoC-III is associated with higher triglycerides, less favorable cardiometabolic phenotypes, and higher coronary artery calcification, a measure of subclinical atherosclerosis. Therapeutic inhibition of ApoC-III may thus be a novel strategy for reducing plasma triglyceride-rich lipoproteins and cardiovascular risk in T2DM. © 2015 American Heart Association, Inc.

Insulin glargine 300 U/mL for basal insulin therapy in type 1 and type 2 diabetes mellitus.

PubMed

Lau, Ip Tim; Lee, Ka Fai; So, Wing Yee; Tan, Kathryn; Yeung, Vincent Tok Fai

2017-01-01

To review published clinical studies on the efficacy and safety of new insulin glargine 300 units/mL (Gla-300), a new long-acting insulin analog, for the treatment of type 1 and type 2 diabetes mellitus (T1DM, T2DM). Data sources comprised primary research articles on Gla-300, including pharmacodynamic, pharmacokinetic, and clinical studies. In pharmacodynamic and pharmacokinetic studies, Gla-300 showed a flatter time-action profile and longer duration of action than Gla-100. Noninferiority of Gla-300 versus Gla-100 for lowering of glycated hemoglobin was demonstrated in Phase III clinical studies covering a range of T1DM and T2DM patient populations. Over 6-12 months of follow-up, Gla-300 consistently showed comparable glycemic efficacy with less hypoglycemia vs Gla-100, even during the first 8 weeks of treatment. Although titrated insulin doses were 11%-17% higher with Gla-300 vs Gla-100, changes in body weight were similar or favored Gla-300. Clinical studies provide evidence that the pharmacodynamic and pharmacokinetic properties of Gla-300 may translate into clinical benefits in both T1DM and T2DM. Gla-300 may provide a new option for people initiating basal insulin, those requiring higher basal insulin doses, those with T1DM, and those who may be at increased risk for hypoglycemia, such as people with chronic kidney disease, the elderly, and those with cardiovascular comorbidities.

Separation and quantification of inulin in selected artichoke (Cynara scolymus L.) cultivars and dandelion (Taraxacum officinale WEB. ex WIGG.) roots by high-performance anion exchange chromatography with pulsed amperometric detection.

PubMed

Schütz, Katrin; Muks, Erna; Carle, Reinhold; Schieber, Andreas

2006-12-01

The profile of fructooligosaccharides and fructopolysaccharides in artichoke heads and dandelion roots was investigated. For this purpose, a suitable method for high-performance anion exchange chromatography with pulsed amperometic detection was developed. The separation of monomers, oligomers and polymers up to a chain length of 79 sugar residues was achieved in one single run. Glucose, fructose, sucrose and individual fructooligosaccharides (kestose, nystose, fructofuranosylnystose) were quantified in six different artichoke cultivars and in dandelion roots. The contents ranged from 12.9 g/kg DM to 71.7 g/kg DM for glucose, from 15.8 g/kg DM to 67.2 g/kg DM for fructose, and from 16.8 g/kg DM to 55.2 g/kg DM for sucrose in the artichoke heads. Kestose was the predominant fructooligosaccharide, followed by nystose and fructofuranosylnystose. In four cultivars fructofuranosylnystose was only detectable in traces and reached its maximum value of 3.6 g/kg DM in the cultivar Le Castel. Furthermore, an average degree of polymerization of 5.3 to 16.7 was calculated for the individual artichoke cultivars, which is noticeably lower than hitherto reported. In contrast, the contents of kestose, nystose and fructofuranosylnystose in dandelion root exceeded that of artichoke, reflecting the short chain characteristic of the inulin, which was confirmed by chromatographic analysis. Copyright (c) 2006 John Wiley & Sons, Ltd.

A Tale of Tails. Dark Matter Interpretations of the Fermi GeV Excess in Light of Background Model Systematics

DOE PAGES

Calore, Francesca; Cholis, Ilias; McCabe, Christopher; ...

2015-03-10

Several groups have identified an extended excess of gamma rays over the modeled foreground and background emissions towards the Galactic center (GC) based on observations with the Fermi Large Area Telescope. The excess emission is compatible in morphology and spectrum with a telltale sign from dark matter (DM) annihilation. Here, we present a critical reassessment of DM interpretations of the GC signal in light of the foreground and background uncertainties that some of us recently outlaid in Calore et al. (2014). We also find that a much larger number of DM models fits the gamma-ray data than previously noted. Inmore » particular: (1) In the case of DM annihilation into b¯b, we find that even large DM masses up to m χ≃74 GeV are allowed at p-value >0.05. (2) Surprisingly, annihilation into nonrelativistic hh gives a good fit to the data. (3) The inverse Compton emission from μ +μ - with m χ~60–70 GeV can also account for the excess at higher latitudes, |b|>2°, both in its spectrum and morphology. We also present novel constraints on a large number of mixed annihilation channels, including cascade annihilation involving hidden sector mediators. Finally, we show that the current limits from dwarf spheroidal observations are not in tension with a DM interpretation when uncertainties on the DM halo profile are accounted for.« less

[New therapies for type 2 diabetes mellitus].

PubMed

Puig-Domingo, Manuel; Pellitero, Silvia

2015-06-22

The increasing prevalence of obesity and type 2 diabetes mellitus (T2DM) has led to a growing interest in the investigation of new therapies. Treatment of T2DM has focused on the insulinopenia and insulin resistance. However, in the last 10 years, new lines of research have emerged for the treatment of T2DM and preclinical studies appear promising. The possibility of using these drugs in combination with other currently available drugs will enhance the antidiabetic effect and promote weight loss with fewer side effects. The data provided by post-marketing monitoring will help us to better understand their safety profile and potential long-term effects on target organs, especially the cardiovascular risk. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Interaction of prostanoid EP3 and TP receptors in guinea-pig isolated aorta: contractile self-synergism of 11-deoxy-16,16-dimethyl PGE2

PubMed Central

Jones, RL; Woodward, DF

2011-01-01

BACKGROUND AND PURPOSE Surprisingly high contractile activity was reported for 11-deoxy-16,16-dimethyl prostaglandin E2 (DX-DM PGE2) on pig cerebral artery when used as a selective EP3 receptor agonist. This study investigated the selectivity profile of DX-DM PGE2, focusing on the interaction between its EP3 and TP (thromboxane A2-like) agonist activities. EXPERIMENTAL APPROACH Contraction of guinea-pig trachea (EP1 system) and aorta (EP3 and TP systems) was measured in conventional organ baths. KEY RESULTS Strong contraction of guinea-pig aorta to sulprostone and 17-phenyl PGE2 (EP3 agonists) was only seen under priming with a second contractile agent such as phenylephrine, histamine or U-46619 (TP agonist). In contrast, DX-DM PGE2 induced strong contraction, which on the basis of treatment with (DG)-3ap (EP3 antagonist) and/or BMS-180291 (TP antagonist) was attributed to self-synergism arising from co-activation of EP3 and TP receptors. EP3/TP self-synergism also accounted for contraction induced by PGF2α and its analogues (+)-cloprostenol and latanoprost-FA. DX-DM PGE2 also showed significant EP1 agonism on guinea-pig trachea as defined by the EP1 antagonists SC-51322, (ONO)-5-methyl-1 and AH-6809, although AH-6809 exhibited poor specificity at concentrations ≥3 µM. CONCLUSIONS AND IMPLICATIONS EP3/TP self-synergism, as seen with PGE/PGF analogues in this study, may confound EP3 agonist potency comparisons and the characterization of prostanoid receptor systems. The competitive profile of a TP antagonist may be distorted by variation in the silent/overt contraction profile of the EP3 system in different studies. The relevance of self-synergism to in vivo actions of natural prostanoid receptor agonists is discussed. PMID:20955363

Neighborhood social and physical environments and type 2 diabetes mellitus in African Americans: The Jackson Heart Study.

PubMed

Gebreab, Samson Y; Hickson, DeMarc A; Sims, Mario; Wyatt, Sharon B; Davis, Sharon K; Correa, Adolfo; Diez-Roux, Ana V

2017-01-01

Using data from Jackson Heart Study, we investigated the associations of neighborhood social and physical environments with prevalence and incidence of type 2 diabetes mellitus (T2DM) in African Americans (AA). Among non-diabetic participants at baseline (n=3670), 521 (14.2%) developed T2DM during a median follow-up of 7.3 years. Measures of neighborhood social environments, and food and physical activity resources were derived using survey-and GIS-based methods. Prevalence ratios (PR) and Hazard ratios (HR) were estimated using generalized estimating equations and Cox proportional hazards models. Higher neighborhood social cohesion was associated with a 22% lower incidence of T2DM while higher density of unfavorable food stores was associated with a 34% higher incidence of T2DM after adjusting for individual-level risk factors (HR=0.78 [95% CI:0.62, 0.99] and HR=1.34 [1.12, 1.60], respectively). In addition, neighborhood problems was also associated with prevalence of T2DM (PR=1.12 [1.03, 1.21]) independent of individual-level risk factors. Our findings suggest that efforts to strengthen community ties or to attract healthy food retail outlets might be important strategies to consider for prevention of T2DM in AA. Published by Elsevier Ltd.

Improved pulmonary function in the nitrofen model of congenital diaphragmatic hernia following prenatal maternal dexamethasone and/or sildenafil.

PubMed

Burgos, Carmen Mesas; Pearson, Erik G; Davey, Marcus; Riley, John; Jia, Huimin; Laje, Pablo; Flake, Alan W; Peranteau, William H

2016-10-01

Pulmonary hypoplasia and hypertension is a leading cause of morbidity and mortality in congenital diaphragmatic hernia (CDH). The etiologic insult occurs early in gestation highlighting the potential of prenatal interventions. We evaluated prenatal pharmacologic therapies in the nitrofen CDH model. Olive oil or nitrofen were administered alone or with dexamethasone (DM), sildenafil, or DM+sildenafil to pregnant rats. Newborn pups were assessed for lung function, structure and pulmonary artery (PA) flow and resistance. Prenatal DM treatment of CDH pups increased alveolar volume density (Vva), decreased interalveloar septal thickness, increased tidal volumes and improved ventilation without improving oxygenation or PA resistance. Sildenafil decreased PA resistance and improved oxygenation without improving ventilation or resulting in significant histologic changes. DM+sildenafil decreased PA resistance, improved oxygenation and ventilation while increasing Vva and decreasing interalveolar septal and pulmonary arteriole medial wall thickness. Lung and body weights were decreased in pups treated with DM and/or sildenafil. Prenatal DM or sildenafil treatment increased pulmonary compliance and decreased pulmonary vascular resistance respectively, and was associated with improved neonatal gas exchange but had a detrimental effect on lung and fetal growth. This study highlights the potential of individual and combined prenatal pharmacologic therapies for CDH management.

FIMP and muon ( g - 2) in a U(1) Lμ- Lτ model

NASA Astrophysics Data System (ADS)

Biswas, Anirban; Choubey, Sandhya; Khan, Sarif

2017-02-01

The tightening of the constraints on the standard thermal WIMP scenario has forced physicists to propose alternative dark matter (DM) models. One of the most popular alternate explanations of the origin of DM is the non-thermal production of DM via freeze-in. In this scenario the DM never attains thermal equilibrium with the thermal soup because of its feeble coupling strength (˜10-12) with the other particles in the thermal bath and is generally called the Feebly Interacting Massive Particle (FIMP). In this work, we present a gauged U(1) Lμ- Lτ extension of the Standard Model (SM) which has a scalar FIMP DM candidate and can consistently explain the DM relic density bound. In addition, the spontaneous breaking of the U(1) Lμ- Lτ gauge symmetry gives an extra massive neutral gauge boson Z μτ which can explain the muon ( g - 2) data through its additional one-loop contribution to the process. Lastly, presence of three right-handed neutrinos enable the model to successfully explain the small neutrino masses via the Type-I seesaw mechanism. The presence of the spontaneously broken U(1) Lμ- Lτ gives a particular structure to the light neutrino mass matrix which can explain the peculiar mixing pattern of the light neutrinos.

Redefining dermatomyositis: a description of new diagnostic criteria that differentiate pure dermatomyositis from overlap myositis with dermatomyositis features.

PubMed

Troyanov, Yves; Targoff, Ira N; Payette, Marie-Pier; Raynauld, Jean-Pierre; Chartier, Suzanne; Goulet, Jean-Richard; Bourré-Tessier, Josiane; Rich, Eric; Grodzicky, Tamara; Fritzler, Marvin J; Joyal, France; Koenig, Martial; Senécal, Jean-Luc

2014-11-01

Dermatomyositis (DM) is a major clinical subset of autoimmune myositis (AIM). The characteristic DM rash (Gottron papules, heliotrope rash) and perifascicular atrophy at skeletal muscle biopsy are regarded as specific features for this diagnosis. However, new concepts are challenging the current definition of DM. A modified Bohan and Peter classification of AIM was proposed in which the core concept was the inclusion of the diagnostic significance of overlap connective tissue disease features. In this clinical classification, a DM rash in association with myositis in the absence of overlap features indicates a diagnosis of pure DM. However, overlap features in association with myositis allow a diagnosis of overlap myositis (OM), irrespective of the presence or absence of the DM rash. Perifascicular atrophy may be present in both pure DM and OM. Recently, the presence of perifascicular atrophy in myositis without a DM rash was proposed as diagnostic of a novel entity, adermatopathic DM. We conducted the present study to evaluate these new concepts to further differentiate pure DM from OM.Using the modified Bohan and Peter classification, we performed a follow-up study of a longitudinal cohort of 100 consecutive adult French Canadian patients with AIM, including 44 patients with a DM phenotype, defined as a DM rash, and/or DM-type calcinosis, and/or the presence of perifascicular atrophy on muscle biopsy. A detailed evaluation was performed for overlap features, the extent and natural history of the DM rash, adermatopathic DM, DM-specific and overlap autoantibodies by protein A immunoprecipitation on coded serum samples, and associations with cancer and survival.Two distinct subsets were identified in patients with a DM phenotype: pure DM (n = 24) and OM with DM features, or OMDM (n = 20). In pure DM, the DM rash was a dominant finding. It was the first disease manifestation, was always present at the time of myositis diagnosis, and was associated with a high cutaneous score and chronicity. Concurrent heliotrope rash and Gottron papules (positive predictive value [PPV] 91%), as well as the V-sign and/or shawl sign (PPV 100%), were diagnostic of pure DM. Anti-Mi-2, anti-MJ, and anti-p155 autoantibodies were present in 50% of pure DM patients and were restricted to this subset (PPV 100%). Cancer was present in 21% of pure DM patients. The 15-year survival was excellent (92%).In contrast, in patients with OMDM, the first manifestation was proximal muscle weakness or other skeletal muscle-related complaints. The DM rash appeared at diagnosis or at follow-up, was associated with a low cutaneous extent score and was transient. Adermatopathic DM, which was absent in pure DM, was highly predictive (PPV 100%) of OMDM. Overlap autoantibodies (including anti-Jo-1, anti-PL-7, anti-PM-Scl, anti-U1RNP, and/or anti-U5-RNP) were found in 70% of OMDM patients. OMDM was not associated with cancer, but the 15-year survival was significantly decreased (65%).Perifascicular atrophy occurred as commonly in OMDM (n = 6/20, 30%) as in pure DM (n = 4/24, 17%) patients. These 6 OMDM patients had adermatopathic DM at myositis diagnosis, and only 1 of them developed a DM rash at follow-up, emphasizing the lack of specificity of perifascicular atrophy for pure DM.In conclusion, using the modified Bohan and Peter classification of AIM allowed identification of OMDM, a new clinical subset of OM. Furthermore, identification of OMDM allowed recognition of pure DM as a new entity that was distinct from OMDM or from OM without DM features. However, the absolute specificity of a DM rash and perifascicular muscle atrophy for the diagnosis of pure DM was lost. The distinctive clinical manifestations and autoantibody profiles presented are proposed as diagnostic criteria to differentiate pure DM from OMDM.

Redefining Dermatomyositis

PubMed Central

Troyanov, Yves; Targoff, Ira N; Payette, Marie-Pier; Raynauld, Jean-Pierre; Chartier, Suzanne; Goulet, Jean-Richard; Bourré-Tessier, Josiane; Rich, Eric; Grodzicky, Tamara; Fritzler, Marvin J.; Joyal, France; Koenig, Martial; Senécal, Jean-Luc

2014-01-01

Abstract Dermatomyositis (DM) is a major clinical subset of autoimmune myositis (AIM). The characteristic DM rash (Gottron papules, heliotrope rash) and perifascicular atrophy at skeletal muscle biopsy are regarded as specific features for this diagnosis. However, new concepts are challenging the current definition of DM. A modified Bohan and Peter classification of AIM was proposed in which the core concept was the inclusion of the diagnostic significance of overlap connective tissue disease features. In this clinical classification, a DM rash in association with myositis in the absence of overlap features indicates a diagnosis of pure DM. However, overlap features in association with myositis allow a diagnosis of overlap myositis (OM), irrespective of the presence or absence of the DM rash. Perifascicular atrophy may be present in both pure DM and OM. Recently, the presence of perifascicular atrophy in myositis without a DM rash was proposed as diagnostic of a novel entity, adermatopathic DM. We conducted the present study to evaluate these new concepts to further differentiate pure DM from OM. Using the modified Bohan and Peter classification, we performed a follow-up study of a longitudinal cohort of 100 consecutive adult French Canadian patients with AIM, including 44 patients with a DM phenotype, defined as a DM rash, and/or DM-type calcinosis, and/or the presence of perifascicular atrophy on muscle biopsy. A detailed evaluation was performed for overlap features, the extent and natural history of the DM rash, adermatopathic DM, DM-specific and overlap autoantibodies by protein A immunoprecipitation on coded serum samples, and associations with cancer and survival. Two distinct subsets were identified in patients with a DM phenotype: pure DM (n = 24) and OM with DM features, or OMDM (n = 20). In pure DM, the DM rash was a dominant finding. It was the first disease manifestation, was always present at the time of myositis diagnosis, and was associated with a high cutaneous score and chronicity. Concurrent heliotrope rash and Gottron papules (positive predictive value [PPV] 91%), as well as the V-sign and/or shawl sign (PPV 100%), were diagnostic of pure DM. Anti-Mi-2, anti-MJ, and anti-p155 autoantibodies were present in 50% of pure DM patients and were restricted to this subset (PPV 100%). Cancer was present in 21% of pure DM patients. The 15-year survival was excellent (92%). In contrast, in patients with OMDM, the first manifestation was proximal muscle weakness or other skeletal muscle-related complaints. The DM rash appeared at diagnosis or at follow-up, was associated with a low cutaneous extent score and was transient. Adermatopathic DM, which was absent in pure DM, was highly predictive (PPV 100%) of OMDM. Overlap autoantibodies (including anti-Jo-1, anti-PL-7, anti-PM-Scl, anti-U1RNP, and/or anti-U5-RNP) were found in 70% of OMDM patients. OMDM was not associated with cancer, but the 15-year survival was significantly decreased (65%). Perifascicular atrophy occurred as commonly in OMDM (n = 6/20, 30%) as in pure DM (n = 4/24, 17%) patients. These 6 OMDM patients had adermatopathic DM at myositis diagnosis, and only 1 of them developed a DM rash at follow-up, emphasizing the lack of specificity of perifascicular atrophy for pure DM. In conclusion, using the modified Bohan and Peter classification of AIM allowed identification of OMDM, a new clinical subset of OM. Furthermore, identification of OMDM allowed recognition of pure DM as a new entity that was distinct from OMDM or from OM without DM features. However, the absolute specificity of a DM rash and perifascicular muscle atrophy for the diagnosis of pure DM was lost. The distinctive clinical manifestations and autoantibody profiles presented are proposed as diagnostic criteria to differentiate pure DM from OMDM. PMID:25500701

Origin of terminal voltage variations due to self-mixing in terahertz frequency quantum cascade lasers.

PubMed

Grier, Andrew; Dean, Paul; Valavanis, Alexander; Keeley, James; Kundu, Iman; Cooper, Jonathan D; Agnew, Gary; Taimre, Thomas; Lim, Yah Leng; Bertling, Karl; Rakić, Aleksandar D; Li, Lianhe H; Harrison, Paul; Linfield, Edmund H; Ikonić, Zoran; Davies, A Giles; Indjin, Dragan

2016-09-19

We explain the origin of voltage variations due to self-mixing in a terahertz (THz) frequency quantum cascade laser (QCL) using an extended density matrix (DM) approach. Our DM model allows calculation of both the current-voltage (I-V) and optical power characteristics of the QCL under optical feedback by changing the cavity loss, to which the gain of the active region is clamped. The variation of intra-cavity field strength necessary to achieve gain clamping, and the corresponding change in bias required to maintain a constant current density through the heterostructure is then calculated. Strong enhancement of the self-mixing voltage signal due to non-linearity of the (I-V) characteristics is predicted and confirmed experimentally in an exemplar 2.6 THz bound-to-continuum QCL.

Decoherence as a way to measure extremely soft collisions with dark matter

NASA Astrophysics Data System (ADS)

Riedel, C. Jess; Yavin, Itay

2017-07-01

A new frontier in the search for dark matter (DM) is based on the idea of detecting the decoherence caused by DM scattering against a mesoscopic superposition of normal matter. Such superpositions are uniquely sensitive to very small momentum transfers from new particles and forces, especially DM with a mass below 100 MeV. Here we investigate what sorts of dark sectors are inaccessible with existing methods but would induce noticeable decoherence in the next generation of matter interferometers. We show that very soft but medium range (0.1 nm - 1 μ m ) elastic interactions between nuclei and DM are particularly suitable. We construct toy models for such interactions, discuss existing constraints, and delineate the expected sensitivity of forthcoming experiments. The first hints of DM in these devices would appear as small variations in the anomalous decoherence rate with a period of one sidereal day. This is a generic signature of interstellar sources of decoherence, clearly distinguishing it from terrestrial backgrounds. The OTIMA experiment under development in Vienna will begin to probe Earth-thermalizing DM once sidereal variations in the background decoherence rate are pushed below one part in a hundred for superposed 5-nm gold nanoparticles. The proposals by Bateman et al. and Geraci et al. could be similarly sensitive although they would require at least a month of data taking. DM that is absorbed or elastically reflected by the Earth, and so avoids a greenhouse density enhancement, would not be detectable by those three experiments. On the other hand, the aggressive proposals of the MAQRO collaboration and Pino et al. would immediately open up many orders of magnitude in DM mass, interaction range, and coupling strength, regardless of how DM behaves in bulk matter.

Existence of dark matter with observed properties of cosmic microwave background radiation substantiates three conservation laws of classical physics and all principles of quantum mechanics as creates the value of Planck’s constant

NASA Astrophysics Data System (ADS)

Boriev, I. A.

2018-03-01

Astronomical data indicate a presence of dark matter (DM) in the space, what is necessary for explanation of observed dynamics of the galaxies within Newtonian mechanics. DM, at its very low density (∼10-26kg/m3), constitutes main part of the matter in the Universe, 10 times the mass of all visible cosmic bodies. No doubt, namely properties of DM, which fills space, must determine its physical properties and fundamental physical laws. Taking into account observed properties of cosmic microwave background radiation (CMBR), whose energy is ∼90% of all cosmic radiation, and understanding that this radiation is produced by DM motion, conservation laws of classical physics and principles of quantum mechanics receive their materialistic substantiation. Thus, CMBR high homogeneity and isotropy (∼10-4), and hence the same properties of DM (and space) justify momentum and angular momentum conservation laws, respectively, according to E. Noether's theorems. CMBR has black body spectrum at ∼2.7K with maximum wavelength ∼1.9·10-3m, what allows calculate the value of mechanical action produced by DM thermal motion (∼7·10-34 J·s). This value corresponds well to the Planck’s constant, which is the mechanical action too, what gives materialistic basis for all principles of quantum mechanics. Obtained results directly confirm the reality of DM existence, and show that CMBR is an observed display of DM thermal motion. Understanding that namely from DM occur known creation of electron-positron pairs as contrarily rotating material vortexes (according to their spins) let substantiate positron nature of ball lightning what first explains all its observed specific properties.

Correlation between reactive oxygen metabolites & atherosclerotic risk factors in patients with type 2 diabetes mellitus.

PubMed

Kotani, Kazuhiko; Tsuzaki, Kokoro; Taniguchi, Nobuyuki; Sakane, Naoki

2013-04-01

Oxidative stress plays important roles in the pathophysiology of type 2 diabetes mellitus (T2DM). The diacron reactive oxygen metabolites (d-ROMs) test has been used in the clinics. The present study was aimed to investigate the correlation of the oxidative stress status, as evaluated by the d-ROMs, with atherosclerotic risk factors in T2DM patients, in comparison to controls. The study included 200 subjects (100 patients with T2DM and 100 controls; 86 males/114 females; mean age 59.0 yr). Clinical variables including the body mass index, blood pressure (BP), glucose and lipid panels, in addition to the d-ROMs, were measured. Patients with T2DM showed significantly higher d-ROMs levels than controls (322 ± 60 vs. 345 ± 64 U. Carr., P<0.05). A multiple linear regression analysis revealed that systolic BP (β=0.26, P<0.05) and high-density lipoprotein cholesterol (HDL-C: β= -0.30, P<0.05) were independently and significantly correlated with the d-ROMs levels in patients with T2DM, although these correlations were not significant in the controls. The gender-based analysis showed that systolic BP (β = 0.44, P<0.05) and HDL-C (β = -0.36, P<0.05) were independently and significantly correlated with the d-ROMs levels in females with T2DM, while there was a marginally significant correlation between HDL-C and the d-ROMs levels (β = -0.36, P=0.06) in males with T2DM. The present findings may reinforce the importance of BP control in female patients with T2DM, as well as the management of HDL-C in male and female patients with T2DM, under the linkage between oxidative stress and atherosclerosis.

Management of co-existing diabetes mellitus and dyslipidemia: defining the role of thiazolidinediones.

PubMed

Florkowski, Chris M

2002-01-01

The observed reduction in macrovascular outcomes in the United Kingdom Progressive Diabetes Study (UKPDS) trial in patients with type 2 diabetes mellitus (DM), treated intensively with insulin or sulfonylureas, was of borderline significance (p = 0.052). This may be because of the role of factors other than glycemic control in the etiology of macrovascular disease. The UKPDS and other studies have suggested that lipid parameters are potent predictors of adverse outcomes in patients with type 2 DM. In patients with DM, dyslipidemia is characterized by elevated serum triglycerides and low high density lipoprotein-cholesterol (HDL-C) with normal total serum cholesterol levels and usually accompanied by an elevation of atherogenic, small, dense low density lipoprotein-cholesterol (LDL-C) particles. Dyslipidemia is only partly corrected by dietary and lifestyle modifications and pharmacological glycemic control in patients with DM. Several guidelines, including those published by the New Zealand Heart Foundation, suggest that lipid-modifying therapies are appropriate in patients considered to be at high or very high risk of a cardiac event. This includes patients with established vascular disease. Some recent studies suggest that patients with type 2 DM have risk comparable to patients without DM, but have experienced previous myocardial infarction (MI). Subgroup analysis of trials including the Scandinavian Simvastatin Survival Study (4S) and Cholesterol and Recurrent Events (CARE), which included patients with DM, have shown a significant reduction in adverse outcomes, although many patients with DM and dyslipidemia were excluded. Of lipid-lowering drugs, fibric acid derivatives are probably the most appropriate for patients with DM and dyslipidemia and their role is being evaluated in large, long-term outcome studies such as Fenofibrate Intervention and Event Lowering in Diabetes (FIELD). Thiazolidinediones, a new class of compound for treating patients with type 2 DM, primarily exert their glucose-lowering effect by increasing insulin sensitivity at the level of skeletal muscle, and to a lesser extent, at the liver by decreasing hepatic glucose output. Some of their actions are mediated through binding and activation of the peroxisome proliferator-activated receptor-gamma, a nuclear receptor that has a regulatory role in differentiation of cells, especially adipocytes. The nonhypoglycemic effects of thiazolidinediones, therefore, offer additional potential mechanisms for benefit in patients with type 2 DM and insulin resistance. Thiazolidinediones increase serum HDL-C levels. Troglitazone and pioglitazone have been shown to decrease serum triglyceride levels. Rosiglitazone, conversely has no significant effect on serum triglyceride levels. All of the thiazolidinediones increase serum LDL-C levels (pioglitazone to a lesser extent), although changes in the size of the LDL fraction may render it less susceptible to oxidation and, therefore, less atherogenic. A randomized comparative trial needs to be undertaken to determine whether true differences exist between the thiazolidinediones. Longer studies need to be undertaken to assess their effect on cardiovascular outcomes.

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.

Efficacy and Safety of Alirocumab in Individuals with Diabetes Mellitus: Pooled Analyses from Five Placebo-Controlled Phase 3 Studies.

PubMed

Ginsberg, Henry N; Farnier, Michel; Robinson, Jennifer G; Cannon, Christopher P; Sattar, Naveed; Baccara-Dinet, Marie T; Letierce, Alexia; Bujas-Bobanovic, Maja; Louie, Michael J; Colhoun, Helen M

2018-05-19

Diabetes mellitus (DM) carries an elevated risk for cardiovascular disease. Here, we assessed alirocumab efficacy and safety in people with/without DM from five placebo-controlled phase 3 studies. Data from up to 78 weeks were analyzed in individuals on maximally tolerated background statin. In three studies, alirocumab 75 mg every 2 weeks (Q2W) was increased to 150 mg Q2W at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was ≥ 70 mg/dL; two studies used alirocumab 150 mg Q2W throughout. The primary endpoint was percentage change in LDL-C from baseline to week 24. In the alirocumab 150 mg pool (n = 2416), baseline LDL-C levels were 117.4 mg/dL (DM) and 130.6 mg/dL (without DM), and in the 75/150 mg pool (n = 1043) 112.8 mg/dL (DM) and 133.0 mg/dL (without DM). In the 150 mg Q2W group, week 24 LDL-C reductions from baseline were observed in persons with DM (- 59.9%; placebo, - 1.4%) and without DM (- 60.6%; placebo, + 1.5%); 77.7% (DM) and 76.8% (without DM) of subjects achieved LDL-C < 70 mg/dL. In the alirocumab 75/150 mg group, 26% (DM) and 36% (without DM) of subjects received dose increase. In this group, week 24 LDL-C levels changed from baseline by - 43.8% (DM; placebo, + 0.3%) and - 49.7% (without DM; placebo, + 5.1%); LDL-C < 70 mg/dL was achieved by 68.3% and 65.8% of individuals, respectively. At week 24, alirocumab was also associated with improved levels of other lipids. Adverse event rates were generally comparable in all groups (79.8-82.0%). Regardless of DM status, alirocumab significantly reduced LDL-C levels; safety was generally similar. Sanofi and Regeneron Pharmaceuticals, Inc. Plain language summary available for this article.

Genetic polymorphism of estrogen receptor alpha gene in Egyptian women with type II diabetes mellitus

PubMed Central

Motawi, Tarek M.K.; El-Rehany, Mahmoud A.; Rizk, Sherine M.; Ramzy, Maggie M.; el-Roby, Doaa M.

2015-01-01

Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha gene including the XbaI and PvuII restriction enzyme polymorphisms. The aim of this study was to determine if ESRα gene polymorphisms are associated with type 2 diabetes mellitus and correlated with lipid profile. Ninety diabetic Egyptian patients were compared with forty healthy controls. ESRα genotyping of PvuII and XbaI was performed using restriction fragment length polymorphism analysis. Our study showed that there is more significant difference in the frequency of C and G polymorphic allele between patients and control groups in PvuII and XbaI respectively. Also carriers of minor C and G alleles of PvuII and XbaI gene polymorphisms were associated with increased fasting blood glucose and disturbance in lipid profile as there is an increase in total cholesterol, triglycerides and Low density lipoprotein. So findings of present study suggest the possibility that PvuII and XbaI polymorphisms in ERα are related to T2DM and with increased serum lipids among Egyptian population. PMID:26401488

Dental Cell Sheet Biomimetic Tooth Bud Model

PubMed Central

Monteiro, Nelson; Smith, Elizabeth E.; Angstadt, Shantel; Zhang, Weibo; Khademhosseini, Ali

2016-01-01

Tissue engineering and regenerative medicine technologies offer promising therapies for both medicine and dentistry. Our long-term goal is to create functional biomimetic tooth buds for eventual tooth replacement in humans. Here, our objective was to create a biomimetic 3D tooth bud model consisting of dental epithelial (DE) – dental mesenchymal (DM) cell sheets (CSs) combined with biomimetic enamel organ and pulp organ layers created using GelMA hydrogels. Pig DE or DM cells seeded on temperature-responsive plates at various cell densities (0.02, 0.114 and 0.228 cells 106/cm2) and cultured for 7, 14 and 21 days were used to generate DE and DM cell sheets, respectively. Dental CSs were combined with GelMA encapsulated DE and DM cell layers to form bioengineered 3D tooth buds. Biomimetic 3D tooth bud constructs were cultured in vitro, or implanted in vivo for 3 weeks. Analyses were performed using micro-CT, H&E staining, polarized light (Pol) microscopy, immunofluorescent (IF) and immunohistochemical (IHC) analyses. H&E, IHC and IF analyses showed that in vitro cultured multilayered DE-DM CSs expressed appropriate tooth marker expression patterns including SHH, BMP2, RUNX2, tenascin and syndecan, which normally direct DE-DM interactions, DM cell condensation, and dental cell differentiation. In vivo implanted 3D tooth bud constructs exhibited mineralized tissue formation of specified size and shape, and SHH, BMP2 and RUNX2and dental cell differentiation marker expression. We propose our biomimetic 3D tooth buds as models to study optimized DE-DM cell interactions leading to functional biomimetic replacement tooth formation. PMID:27565550

Dispersion Measure Variation of Repeating Fast Radio Burst Sources

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

Yang, Yuan-Pei; Zhang, Bing, E-mail: yypspore@gmail.com, E-mail: zhang@physics.unlv.edu

The repeating fast radio burst (FRB) 121102 was recently localized in a dwarf galaxy at a cosmological distance. The dispersion measure (DM) derived for each burst from FRB 121102 so far has not shown significant evolution, even though an apparent increase was recently seen with newly detected VLA bursts. It is expected that more repeating FRB sources may be detected in the future. In this work, we investigate a list of possible astrophysical processes that might cause DM variation of a particular FRB source. The processes include (1) cosmological scale effects such as Hubble expansion and large-scale structure fluctuations; (2)more » FRB local effects such as gas density fluctuation, expansion of a supernova remnant (SNR), a pulsar wind nebula, and an H ii region; and (3) the propagation effect due to plasma lensing. We find that the DM variations contributed by the large-scale structure are extremely small, and any observable DM variation is likely caused by the plasma local to the FRB source. In addition to mechanisms that decrease DM over time, we suggest that an FRB source in an expanding SNR around a nearly neutral ambient medium during the deceleration (Sedov–Taylor and snowplow) phases or in a growing H ii region can increase DM. Some effects (e.g., an FRB source moving in an H ii region or plasma lensing) can produce either positive or negative DM variations. Future observations of DM variations of FRB 121102 and other repeating FRB sources can provide important clues regarding the physical origin of these sources.« less

Pharmacokinetic and Pharmacodynamic Effects of Multiple-dose Administration of Omarigliptin, a Once-weekly Dipeptidyl Peptidase-4 Inhibitor, in Obese Participants With and Without Type 2 Diabetes Mellitus.

PubMed

Addy, Carol; Tatosian, Daniel; Glasgow, Xiaoli S; Gendrano, Isaias N; Kauh, Eunkyung; Martucci, Ashley; Johnson-Levonas, Amy O; Selverian, Diana; Matthews, Catherine Z; Gutierrez, Marie; Wagner, John A; Aubrey Stoch, S

2016-03-01

Omarigliptin (MK-3102) is a potent, oral, long-acting dipeptidyl peptidase (DPP)-4 inhibitor approved in Japan and in global development as a once-weekly treatment for type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the pharmacokinetic (PK) and pharmacodynamic (PD) effects of omarigliptin in obese participants with and without T2DM. This was a Phase I, randomized, double-blind, placebo-controlled, multiple-dose study of 50-mg omarigliptin administered once weekly for 4 weeks. Participants included 24 obese but otherwise healthy subjects (panel A; omarigliptin, n = 18; placebo, n = 6) and 8 obese patients with T2DM (treatment naive, hemoglobin A1c ≥ 6.5% and ≤ 10.0% [panel B]; omarigliptin, n = 6; placebo, n = 2). Participants were 45 to 65 years of age with a body mass index of ≥ 30 and ≤ 40 kg/m(2). Blood sampling occurred at select time points, depending on the study panel, to evaluate the PK properties of omarigliptin, DPP-4 activity, active glucagon-like peptide 1 levels, and plasma glucose concentrations. Body weight was an exploratory end point. Due to sparse sampling in panel A, a thorough PK analysis was performed in obese patients with T2DM (panel B) only. PD analyses were performed in the overall study population (pooled panels A and B). PK profiles in obese participants with and without T2DM were similar to those observed in nonobese reference subjects (historical data). Steady state was achieved after 1 or 2 weekly doses in obese participants with and without T2DM. In obese patients with T2DM, omarigliptin was rapidly absorbed, with a median Tmax of 1 to 2.5 hours (days 1 and 22). Compared with those in reference subjects, the geometric mean ratios (95% CI) (Obese T2DM/reference) for steady-state plasma AUC0-168h, Cmax, and C168h were 0.80 (0.65-0.98), 0.86 (0.53-1.41), and 1.08 (0.88-1.33), respectively. Trough DPP-4 activity was inhibited by ~90%; postprandial (PP) 4-hour weighted mean active GLP-1 concentrations were increased ~2-fold; and PP glucose was significantly reduced with omarigliptin versus placebo in the pooled population. Omarigliptin was generally well-tolerated in the pooled population, and there were no hypoglycemic events. Consistent with other DPP-4 inhibitors, omarigliptin had no effect on body weight in this short-duration study. The administration of omarigliptin was generally well-tolerated in obese participants with and without T2DM, and the favorable PK and PD profiles support once-weekly dosing. Omarigliptin may provide an important once-weekly treatment option for patients with T2DM. ClinicalTrials.gov identifier: NCT01088711. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

A High Level of Intestinal Alkaline Phosphatase Is Protective Against Type 2 Diabetes Mellitus Irrespective of Obesity.

PubMed

Malo, Madhu S

2015-12-01

Mice deficient in intestinal alkaline phosphatase (IAP) develop type 2 diabetes mellitus (T2DM). We hypothesized that a high level of IAP might be protective against T2DM in humans. We determined IAP levels in the stools of 202 diabetic patients and 445 healthy non-diabetic control people. We found that compared to controls, T2DM patients have approx. 50% less IAP (mean +/- SEM: 67.4 +/- 3.2 vs 35.3 +/- 2.5 U/g stool, respectively; p < 0.000001) indicating a protective role of IAP against T2DM. Multiple logistic regression analyses showed an independent association between the IAP level and diabetes status. With each 25 U/g decrease in stool IAP, there is a 35% increased risk of diabetes. The study revealed that obese people with high IAP (approx. 65 U/g stool) do not develop T2DM. Approx. 65% of the healthy population have < 65.0 U/g stool IAP, and predictably, these people might have 'the incipient metabolic syndrome', including 'incipient diabetes', and might develop T2DM and other metabolic disorders in the near future. In conclusion, high IAP levels appear to be protective against diabetes irrespective of obesity, and a 'temporal IAP profile' might be a valuable tool for predicting 'the incipient metabolic syndrome', including 'incipient diabetes'.

Anti-CD22-MCC-DM1: an antibody-drug conjugate with a stable linker for the treatment of non-Hodgkin's lymphoma.

PubMed

Polson, A G; Williams, M; Gray, A M; Fuji, R N; Poon, K A; McBride, J; Raab, H; Januario, T; Go, M; Lau, J; Yu, S-F; Du, C; Fuh, F; Tan, C; Wu, Y; Liang, W-C; Prabhu, S; Stephan, J-P; Hongo, J-A; Dere, R C; Deng, R; Cullen, M; de Tute, R; Bennett, F; Rawstron, A; Jack, A; Ebens, A

2010-09-01

Antibody-drug conjugates (ADCs) are potent cytotoxic drugs linked to antibodies through chemical linkers, and allow specific targeting of drugs to neoplastic cells. The expression of CD22 is limited to B-cells, and we show that CD22 is expressed on the vast majority of non-Hodgkin's lymphomas (NHLs). An ideal target for an ADC for the treatment of NHL would have limited expression outside the B-cell compartment and be highly effective against NHL. We generated an ADC consisting of a humanized anti-CD22 antibody conjugated to the anti-mitotic agent maytansine with a stable linker (anti-CD22-MCC-DM1). Anti-CD22-MCC-DM1 was broadly effective in in vitro killing assays on NHL B-cell lines. We did not find a strong correlation between in vitro potency and CD22 surface expression, internalization of ADC or sensitivity to free drug. We show that anti-CD22-MCC-DM1 was capable of inducing complete tumor regression in NHL xenograft mouse models. Further, anti-CD22-MCC-DM1 was well tolerated in cynomolgus monkeys and substantially decreased circulating B-cells as well as follicle size and germinal center formation in lymphoid organs. These results suggest that anti-CD22-MCC-DM1 has an efficacy, safety and pharmacodynamic profile that support its use as a treatment for NHL.

A Review of the Clinical Efficacy and Safety of Insulin Degludec and Glargine 300 U/mL in the Treatment of Diabetes Mellitus.

PubMed

Woo, Vincent C

2017-08-01

The treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) using insulin is not ideal at this time. Despite advances made with basal insulin analogues, many individuals achieve less than optimal glycemic control or are at risk for hypoglycemia. Currently available basal insulin analogues do not deliver steady, peakless, continuous insulin for >24 hours and are associated with adverse events, including hypoglycemia. The objective of this paper was to review the clinical efficacy and safety of upcoming long-acting insulin analogues such as insulin degludec and insulin glargine 300 U/mL (Gla-300). A comprehensive literature search of PubMed and Google Scholar was conducted from 1966 to 2015. The search included randomized controlled trials that specifically assessed the efficacy and safety of insulin degludec and Gla-300 in patients with T1DM and T2DM. The efficacy of insulin degludec and Gla-300 in achieving glycemic control has been reported in clinical trials in adults with T1DM and T2DM. Not only did a large number of patients succeed in meeting glycosylated hemoglobin targets, but they also experienced reductions in hypoglycemic events. These 2 therapies are associated with a reduced risk of nocturnal hypoglycemia and are generally well tolerated. The long-acting insulin analogues insulin degludec and Gla-300 are promising therapies in the treatment of T1DM and T2DM. Their improved insulin delivery for >24 hours offers glycemic control with a good safety profile. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Higher cord blood levels of fatty acids in pregnant women with type 1 diabetes mellitus.

PubMed

Djelmis, Josip; Ivaniševic, Marina; Desoye, Gernot; van Poppel, Mireille; Berberovic, Edina; Soldo, Dragan; Oreskovic, Slavko

2018-05-01

Type 1 diabetes mellitus is associated with a disturbance of carbohydrate and lipid metabolism. To determine whether type 1 diabetes mellitus (T1DM) alters maternal and neonatal fatty acid levels. Observational study. Academic hospital. Sixty pregnant women (30 women with T1DM with good glycemic control and 30 healthy women) were included in the study. Maternal blood, umbilical vein and artery blood samples were collected immediately upon delivery. Following lipid extraction, the fatty acid profiles of the total fatty acid pool of maternal serum and umbilical vein and artery serum were determined by gas chromatography. Total fatty acid concentration in maternal serum did not differ between the study groups; it was significantly higher in umbilical vein serum of the T1DM group compared with that in the control group, median (interquartile range), T1DM: 2126.2 (1446.4 - 3181.3), control: 1073.8 (657.5 - 2226.0); (P<0.001) and in umbilical artery vein serum T1DM: 1805.7 (1393.1 - 2125.0), control: 990.0 (643.3 - 1668.0); (P<0.001). Composition of fatty acids in umbilical vein serum fatty acids showed significantly higher concentrations of saturated, monounsaturated and polyunsaturated fatty acids in the T1DM group than in compared with those in the control group (P=0.001). Also cord blood levels of leptin (P<0.001), C-peptide (P<0.001), and insulin resistance (P=0.015) were higher in the T1DM group compared to controls. The neonates born to T1DM mothers had higher concentrations of total fatty acids, saturated and monounsaturated fatty acids, as well as polyunsaturated fatty acids, compared to control group newborns.

Impact of polyunsaturated vegetable oils on adiponectin levels, glycaemia and blood lipids in individuals with type 2 diabetes: a randomised, double-blind intervention study.

PubMed

Müllner, E; Plasser, E; Brath, H; Waldschütz, W; Forster, E; Kundi, M; Wagner, K-H

2014-10-01

Low adiponectin levels are discussed as risk factor for cardiovascular events. This is of special importance in individuals with type 2 diabetes (T2DM) because they are at higher risk for cardiovascular diseases. The present study aimed to investigate the effect of two plant oils rich in polyunsaturated fatty acids (PUFA), with different content of omega-3 fatty acids, on adiponectin levels, glucose and lipid metabolism in T2DM individuals treated either with insulin or oral anti-diabetics (OAD). Ninety-two subjects with T2DM [34 treated with insulin (T2DM-Ins) and 58 treated with OAD (T2DM-OAD)] participated in this randomised, double-blind, parallel intervention study. Individuals received either 9 g of nut oil (n-3:n-6 ratio: 1.3 : 6.1) or mixed oil (n-3:n-6 ratio: 0.6 : 5.7) per day for 10 weeks. The fatty acid profile, tocopherol, adiponectin levels and parameters regarding glucose and lipid metabolism were assessed at baseline, during and after the intervention. Compliance was confirmed by significant increases in γ-tocopherol and PUFA in both oil groups. An increase in adiponectin levels in T2DM-Ins participants (+6.84% in nut oil and +4.47% in mixed oil group after 10 weeks compared to baseline) was observed, albeit not significantly different from T2DM-OAD individuals (P = 0.051). Lipid and glucose metabolism were not affected by the intervention. The present study provides evidence that a small and easy change in dietary behaviour towards better fat quality moderately increases adiponectin levels in T2DM-Ins subjects, independently of the administered plant oil. © 2013 The British Dietetic Association Ltd.

Simple non-laboratory- and laboratory-based risk assessment algorithms and nomogram for detecting undiagnosed diabetes mellitus.

PubMed

Wong, Carlos K H; Siu, Shing-Chung; Wan, Eric Y F; Jiao, Fang-Fang; Yu, Esther Y T; Fung, Colman S C; Wong, Ka-Wai; Leung, Angela Y M; Lam, Cindy L K

2016-05-01

The aim of the present study was to develop a simple nomogram that can be used to predict the risk of diabetes mellitus (DM) in the asymptomatic non-diabetic subjects based on non-laboratory- and laboratory-based risk algorithms. Anthropometric data, plasma fasting glucose, full lipid profile, exercise habits, and family history of DM were collected from Chinese non-diabetic subjects aged 18-70 years. Logistic regression analysis was performed on a random sample of 2518 subjects to construct non-laboratory- and laboratory-based risk assessment algorithms for detection of undiagnosed DM; both algorithms were validated on data of the remaining sample (n = 839). The Hosmer-Lemeshow test and area under the receiver operating characteristic (ROC) curve (AUC) were used to assess the calibration and discrimination of the DM risk algorithms. Of 3357 subjects recruited, 271 (8.1%) had undiagnosed DM defined by fasting glucose ≥7.0 mmol/L or 2-h post-load plasma glucose ≥11.1 mmol/L after an oral glucose tolerance test. The non-laboratory-based risk algorithm, with scores ranging from 0 to 33, included age, body mass index, family history of DM, regular exercise, and uncontrolled blood pressure; the laboratory-based risk algorithm, with scores ranging from 0 to 37, added triglyceride level to the risk factors. Both algorithms demonstrated acceptable calibration (Hosmer-Lemeshow test: P = 0.229 and P = 0.483) and discrimination (AUC 0.709 and 0.711) for detection of undiagnosed DM. A simple-to-use nomogram for detecting undiagnosed DM has been developed using validated non-laboratory-based and laboratory-based risk algorithms. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Relationship of dental diseases with coronary artery diseases and diabetes in Bangladesh

PubMed Central

Choudhury, Arup Ratan; Choudhury, Kamrun Nahar

2016-01-01

Background Evidence suggests that dental diseases might have a role in the development and progression of coronary artery diseases (CAD) and diabetes mellitus (DM). The objective of this study was to determine the relationship of dental diseases with CAD and DM in Bangladesh. Methods We conducted a cross-sectional study among 216 consecutive patients admitted in a tertiary hospital between March and July 2011. Data were collected on socio-demographic status, smoking, blood pressure (BP), diet, physical activities, and biochemical measurements of lipid profile, glycated hemoglobin (HbA1c), C-reactive protein (CRP), fibrinogen, creatinine kinase MB (CK-MB), troponin, serum creatinine and serum glutamic-pyruvic transaminase (SGPT). CAD was detected using echocardiographic and coronary angiogram (CAG) reports. All patients underwent oral examination for dental disease. Relationship between dental disease with CAD and DM were explored statistically. Results The mean age of the participants was 57.8±12.5 years and almost two-thirds (67.1%) were male. A great majority of the patients had CAD (90.3%) and type 2 DM (83.8%), and only 44% suffered from dental diseases. Less than one-third patients presented with acute myocardial infarction (MI), 23% with old MI, 11% unstable angina (UA) and 26.4% with non-ST elevation MI. Logistic regression results indicated that patients with DM and CAD had approximately 2.6 and 4.6 times more odds of association with dental diseases than those without DM and CAD (both P value <0.001). Conclusions This study suggests a relationship of dental diseases with CAD and DM among Bangladeshi patients. Further studies are required to confirm these relationships in large clinical studies. Screening for CAD and DM should be considered among those with dental diseases and vice-versa. PMID:27054102

Family history of type 2 diabetes and prevalence of metabolic syndrome in adult Asian Indians.

PubMed

Das, Mithun; Pal, Susil; Ghosh, Arnab

2012-04-01

Our objective was to test the association between familial risk of type 2 diabetes mellitus (T2DM) and the prevalence of metabolic syndrome (MS) in adult Asian Indians. A total of 448 adult (>30 years) individuals (257 males and 191 females) participated in the study. Familial risk of T2DM was classified into three groups viz., 1=both parents affected; 2=parent and/or siblings affected and 3=none or no family history for T2DM. Anthropometric measures, blood pressures, fasting blood glucose and metabolic profiles were studied using standard techniques. MS was defined accordingly. The prevalence of MS phenotypes was estimated and compared among the three familial risk strata. Individuals with a history of both parents affected from diabetes had significantly higher (P<0.001) body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting blood glucose (FBG; P=0.035) than individuals having no family history of T2DM. Significant difference was also noticed between individuals with and without MS according to the family history of diabetes (P<0.001). Differences were evident between individuals who fulfilled all the MS criteria (P=0.001) and individuals with only one or two criteria (phenotypes) according to family history of T2DM. Family history of T2DM had significant effect on individuals with MS as compared to their counterparts (individuals having no family history of T2DM). It therefore seems reasonable to argue that family history of T2DM could be useful as a predictive tool for early diagnosis and prevention of MS in Asian Indian population.

Exploring the origins of the Dzyaloshinskii-Moriya interaction in MnSi

DOE PAGES

Dhital, C.; DeBeer-Schmitt, L.; Zhang, Q.; ...

2017-12-19

By using magnetization and small-angle neutron scattering (SANS) measurements, we have investigated the magnetic behavior of the Mn 1-xIr xSi system to explore the effect of increased carrier density and spin-orbit interaction on the magnetic properties of MnSi. We determine estimates of the spin wave stiffness and the Dzyalloshinski-Moriya (DM) interaction strength and compare with Mn 1-xCo xSi and Mn 1-xFe xSi. Despite the large differences in atomic mass and size of the substituted elements, Mn 1-xCo xSi and Mn 1-xIr xSi show nearly identical variations in their magnetic properties with substitution. We find a systematic dependence of the transitionmore » temperature, the ordered moment, the helix period, and the DM interaction strength with electron count for Mn 1-xIr xSi, Mn 1-xCo xSi, and Mn 1-xFe xSi, indicating that the magnetic behavior is primarily dependent upon the additional carrier density, rather than on the mass or size of the substituting species. This indicates that the variation in magnetic properties, including the DM interaction strength, is primarily controlled by the electronic structure, as Co and Ir are isovalent. Our work suggests that although the rigid band model of electronic structure, along with Moriya’s model of weak itinerant magnetism, describes this system surprisingly well, phenomenological models for the DM interaction strength are not adequate to describe this system.« less

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

Dhital, C.; DeBeer-Schmitt, L.; Zhang, Q.

By using magnetization and small-angle neutron scattering (SANS) measurements, we have investigated the magnetic behavior of the Mn 1-xIr xSi system to explore the effect of increased carrier density and spin-orbit interaction on the magnetic properties of MnSi. We determine estimates of the spin wave stiffness and the Dzyalloshinski-Moriya (DM) interaction strength and compare with Mn 1-xCo xSi and Mn 1-xFe xSi. Despite the large differences in atomic mass and size of the substituted elements, Mn 1-xCo xSi and Mn 1-xIr xSi show nearly identical variations in their magnetic properties with substitution. We find a systematic dependence of the transitionmore » temperature, the ordered moment, the helix period, and the DM interaction strength with electron count for Mn 1-xIr xSi, Mn 1-xCo xSi, and Mn 1-xFe xSi, indicating that the magnetic behavior is primarily dependent upon the additional carrier density, rather than on the mass or size of the substituting species. This indicates that the variation in magnetic properties, including the DM interaction strength, is primarily controlled by the electronic structure, as Co and Ir are isovalent. Our work suggests that although the rigid band model of electronic structure, along with Moriya’s model of weak itinerant magnetism, describes this system surprisingly well, phenomenological models for the DM interaction strength are not adequate to describe this system.« less

Focal Adhesion Kinase (FAK) tyrosine 397E mutation restores the vascular leakage defect in endothelium-specific FAK-kinase dead mice.

PubMed

Alexopoulou, Annika N; Lees, Delphine M; Bodrug, Natalia; Lechertier, Tanguy; Fernandez, Isabelle; D'Amico, Gabriela; Dukinfield, Matthew; Batista, Silvia; Tavora, Bernardo; Serrels, Bryan; Hodivala-Dilke, Kairbaan

2017-07-01

Focal adhesion kinase (FAK) inhibitors have been developed as potential anticancer agents and are undergoing clinical trials. In vitro activation of the FAK kinase domain triggers autophosphorylation of Y397, Src activation, and subsequent phosphorylation of other FAK tyrosine residues. However, how FAK Y397 mutations affect FAK kinase-dead (KD) phenotypes in tumour angiogenesis in vivo is unknown. We developed three Pdgfb-iCre ert -driven endothelial cell (EC)-specific, tamoxifen-inducible homozygous mutant mouse lines: FAK wild-type (WT), FAK KD, and FAK double mutant (DM), i.e. KD with a putatively phosphomimetic Y397E mutation. These ECCre+;FAK WT / WT , ECCre+;FAK KD / KD and ECCre+;FAK DM / DM mice were injected subcutaneously with syngeneic B16F0 melanoma cells. Tumour growth and tumour blood vessel functions were unchanged between ECCre+;FAK WT / WT and ECCre-;FAK WT / WT control mice. In contrast, tumour growth and vessel density were decreased in ECCre+;FAK KD / KD and ECCre+;FAK DM / DM mice, as compared with Cre - littermates. Despite no change in the percentage of perfused vessels or pericyte coverage in either genotype, tumour hypoxia was elevated in ECCre+;FAK KD / KD and ECCre+;FAK DM / DM mice. Furthermore, although ECCre+;FAK KD / KD mice showed reduced blood vessel leakage, ECCre+;FAK DM / DM and ECCre-;FAK DM / DM mice showed no difference in leakage. Mechanistically, fibronectin-stimulated Y397 autophosphorylation was reduced in Cre+;FAK KD / KD ECs as compared with Cre+;FAK WT / WT cells, with no change in phosphorylation of the known Src targets FAK-Y577, FAK-Y861, FAK-Y925, paxillin-Y118, p130Cas-Y410. Cre+;FAK DM / DM ECs showed decreased Src target phosphorylation levels, suggesting that the Y397E substitution actually disrupted Src activation. Reduced VE-cadherin-pY658 levels in Cre+;FAK KD / KD ECs were rescued in Cre+FAK DM / DM ECs, corresponding with the rescue in vessel leakage in the ECCre+;FAK DM / DM mice. We show that EC-specific FAK kinase activity is required for tumour growth, angiogenesis, and vascular permeability. The ECCre+;FAK DM/DM mice restored the KD-dependent tumour vascular leakage observed in ECCre+;FAK KD/KD mice in vivo. This study opens new fields in in vivo FAK signalling. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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.

Colder freeze-in axinos decaying into photons

NASA Astrophysics Data System (ADS)

Bae, Kyu Jung; Kamada, Ayuki; Liew, Seng Pei; Yanagi, Keisuke

2018-03-01

We point out that 7 keV axino dark matter (DM) in the R-parity violating (RPV) supersymmetric (SUSY) Dine-Fischler-Srednicki-Zhitnitsky axion model can simultaneously reproduce the 3.5 keV x-ray line excess and evade stringent constraints from the Ly -α forest data. Peccei-Quinn symmetry breaking naturally generates both the TeV-scale μ term and the MeV-scale RPV term. The RPV term introduces a tiny axino-neutrino mixing and provides axino DM as a variant of the sterile neutrino DM explaining the 3.5 keV x-ray line excess. Axinos are produced by freeze-in processes via the μ term. The resultant phase space distribution tends to be colder than the Fermi-Dirac distribution. The inherent entropy production from late-time saxion decay makes axinos even colder than those without saxion decay. The resultant axino DM takes the correct relic density and is compatible even with the latest and strongest constraint from the Ly-α forest data.

Inert Higgs Doublet Dark Matter in Type-II Seesaw

NASA Astrophysics Data System (ADS)

Chen, Chuan-Hung; Nomura, Takaaki

2016-04-01

Weakly interacting massive particle (WIMP) as a dark matter (DM) candidate is further inspired by recent AMS-02 data, which confirm the excess of positron fraction observed earlier by PAMELA and Fermi-LAT experiments. Additionally, the excess of positron+electron flux is still significant in the measurement of Fermi-LAT. For solving the problem of massive neutrinos and observed excess of cosmic-ray by DM annihilation, we study the model with an inert Higgs doublet (IHD) in the framework of type-II seesaw mechanism by imposing a Z2 symmetry on the IHD, where the lightest particle of IHD is the DM candidate while the neutrino masses origin from the Higgs triplet in type-II seesaw model. We calculate the cosmic-ray production in our model and find that if leptonic triplet decays are dominant, the observed excess of positron/electron flux could be explained well in normal ordered neutrino mass spectrum, when the constraints of DM relic density and comic-ray antiproton spectrum are taken into account.

Genome-wide association study identifies three key loci for high mesocarp oil content in perennial crop oil palm.

PubMed

Teh, Chee-Keng; Ong, Ai-Ling; Kwong, Qi-Bin; Apparow, Sukganah; Chew, Fook-Tim; Mayes, Sean; Mohamed, Mohaimi; Appleton, David; Kulaveerasingam, Harikrishna

2016-01-08

GWAS in out-crossing perennial crops is typically limited by insufficient marker density to account for population diversity and effects of population structure resulting in high false positive rates. The perennial crop oil palm is the most productive oil crop. We performed GWAS for oil-to-dry-mesocarp content (O/DM) on 2,045 genotyped tenera palms using 200K SNPs that were selected based on the short-range linkage disequilibrium distance, which is inherent with long breeding cycles and heterogeneous breeding populations. Eighty loci were significantly associated with O/DM (p ≤ 10(-4)) and three key signals were found. We then evaluated the progeny of a Deli x AVROS breeding trial and a 4% higher O/DM was observed amongst those having the beneficial genotypes at two of the three key loci (p < 0.05). We have initiated MAS and large-scale planting of elite dura and pisifera parents to generate the new commercial tenera palms with higher O/DM potential.

Probing GeV-scale MSSM neutralino dark matter in collider and direct detection experiments

NASA Astrophysics Data System (ADS)

Duan, Guang Hua; Wang, Wenyu; Wu, Lei; Yang, Jin Min; Zhao, Jun

2018-03-01

Given the recent constraints from the dark matter (DM) direct detections, we examine a light GeV-scale (2-30 GeV) neutralino DM in the alignment limit of the Minimal Supersymmetric Standard Model (MSSM). In this limit without decoupling, the heavy CP-even scalar H plays the role of the Standard Model (SM) Higgs boson while the other scalar h can be rather light so that the DM can annihilate through the h resonance or into a pair of h to achieve the observed relic density. With the current collider and cosmological constraints, we find that such a light neutralino DM above 6 GeV can be excluded by the XENON-1T (2017) limits while the survivied parameter space below 6 GeV can be fully tested by the future germanium-based light dark matter detections (such as CDEX), by the Higgs coupling precison measurements or by the production process e+e- → hA at an electron-positron collider (Higgs factory).

Dairy manure and tillage effects on soil fertility and corn yields.

PubMed

Khan, Anwar U H; Iqbal, M; Islam, K R

2007-07-01

Organic amendments have received renewed attention to improve soil fertility for crop production. A randomized complete block split plot experiment was conducted to evaluate the dairy manure (DM) amendments of soil for corn (Zea mays L. cv. Monsanto 919) production under different tillage systems. Main plot treatments were no-till (NT), conventional tillage (CT), and deep tillage (DT), and subplot treatments were chemical fertilization (DM(0)), and DM at 10Mgha(-1)yr(-1) (DM(10)) and 20Mgha(-1)yr(-1) (DM(20)) with supplemental chemical fertilization. Results show that tillage and DM had significantly reduced bulk density (rho(b)) with greater porosity (f(t)) and hydraulic conductivity (K(fs)) than soils under NT and DM(0). Manuring was effective to improve soil physical properties in all tillage treatments. While manure significantly increased C sequestration, the N concentration was influenced by both tillage and manure with significant interaction. The CT significantly increased P as did the addition of manure. However, with manure, K was significantly increased in all tillage treatments. While tilled soils produced taller plants with higher grain yields, and water-use efficiency than NT soils, manuring, in contrast, increased corn harvest index. Manure exerted significant quadratic effect on corn biomass N and K uptake. The variable effects of tillage and dairy manuring on soil properties and corn growth are most probably related to "transitional period" in which soil ecosystems may have adjusting to a new equilibrium.

Electrochemical treatment of rice grain-based distillery effluent: chemical oxygen demand and colour removal.

PubMed

Prajapati, Abhinesh Kumar; Chaudhari, Parmesh Kumar

2014-01-01

The electrochemical (EC) treatment of rice grain-based distillery wastewater was carried out in a 1.5 dm3 electrolytic batch reactor using aluminium plate electrodes. With the four-plate configurations, a current density (j) of 89.3 A/m2 and pH 8 was found to be optimal, obtaining a maximum chemical oxygen demand (COD) and colour removal of 93% and 87%, respectively. The chemical dissolution of aluminium was strongly influenced by initial pH (pHi). At higher pHi (pH 9.5) anode consumption decreased while energy consumption increased. At the optimal current density 89.3 A/m2, the aluminium electrode consumption was 16.855 g/dm3 wastewater and energy consumption was 31.4 Wh/dm3 achieving a maximum COD removal of 87%. The settling and filterability characteristics ofelectrochemically treated sludge were also analysed at different pH. It was noted that treated slurry at pHi 9.5 gave best settling characteristic, which decreased with increase in pH. EC-treated effluent at pHi 8 had provided best filterability. Characteristics of scum and residues are also analysed at different pH.

Circulating matrix modulators (MMP-9 and TIMP-1) and their association with severity of diabetic retinopathy.

PubMed

Jayashree, Kuppuswami; Yasir, Md; Senthilkumar, Gandhipuram Periyasamy; Ramesh Babu, K; Mehalingam, Vadivelan; Mohanraj, Palani Selvam

2018-05-05

Diabetic Retinopathy (DR) is the leading cause of vision loss in the working age population. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), are molecules involved in extracellular tissue matrix remodelling. They are implicated in the loss of retinal tissue integrity, a major cause of DR, that leads to retinal tissue degradation and apoptosis. This study is therefore, conducted to compare the serum levels of MMP-9 and TIMP-1 in T2DM patients without and with retinopathy, and to evaluate their association with the severity of DR. Our study comprised of 2 groups of 41 each. Group A (cases) included T2DM patients with retinopathy and Group B (controls) included T2DM patients without retinopathy. Routine parameters, mainly, fasting blood glucose, and lipid profile were measured using autoanalyzer. Serum MMP-9, TIMP-1, and insulin levels were assessed using ELISA method. Statistically significant increase in the levels of MMP-9, insulin, fasting blood glucose and lipid profile were observed in the serum of T2DM patients with retinopathy, as compared with those without retinopathy. These results help to conclude that rise in MMP-9, and associated serum markers promote disease progress in DR. These findings suggest that the elevations of our study markers in the serum of the type 2 diabetic patients with retinopathy, as compared to those without retinopathy, play important roles in aggravating tissue matrix degradation, supporting DR disease progression. Copyright © 2018. Published by Elsevier Ltd.

Cumulative incidence and risk factors of prediabetes and type 2 diabetes in a Singaporean Malay cohort.

PubMed

Man, Ryan E K; Charumathi, Sabanayagam; Gan, Alfred Tau Liang; Fenwick, Eva K; Tey, Ching Siong; Chua, Jacqueline; Wong, Tien-Yin; Cheng, Ching-Yu; Lamoureux, Ecosse L

2017-05-01

The aim of this work was to determine the cumulative incidence and independent risk factors of prediabetes and type 2 diabetes (T2DM) in a well-characterized cohort of Malays in Singapore. We included 1137 participants (mean age [SD]: 55 (10) years; 53.6% female) without diabetes (DM) at baseline from the Singapore Malay Eye Study, a population-based longitudinal study with baseline (2004-2006), and follow-up (2010-2013) examinations. Prediabetes was defined as an HbA1c between 5.7% and 6.4%, with no self-reported DM history or insulin/DM medication use. T2DM was defined as a random glucose level ≥200mg/dL or HbA1c>6.4% or use of insulin/DM medication. Age-standardized cumulative incidence was calculated as the crude 6-year cumulative incidence standardized to Singapore's Malay population census. Multivariable modified poisson regression models were utilized to determine the risk factors of incident prediabetes and T2DM. The age-standardized 6-year cumulative incidence was 11.2% (95% CI 9.5, 13.1%) for T2DM, and 20.4% (95% CI 16.4, 25.2%) for prediabetes. Hypertension, higher body mass index (BMI) and higher Hba1c levels were associated with increased risk of T2DM, while older age and higher high density lipoprotein (HDL) cholesterol were protective (all P<0.05). Only higher BMI and HbA1c levels were independently associated with incident prediabetes (all P≤0.001). While only one in ten adult Malays developed T2DM over 6-years, one in five developed prediabetes over the same time period. Our results suggest that evidence-based interventions addressing modifiable risk factors (obesity, prediabetes, hypertension, low HDL cholesterol) are needed to delay or prevent their onset. Copyright © 2017 Elsevier B.V. All rights reserved.

[Cardiovascular risk factor control in a population with longstanding diabetes attending endocrinology departments].

PubMed

Comi-Diaz, Cristina; Miralles-García, José M; Cabrerizo, Lucio; Pérez, María; Masramon, Xavier; De Pablos-Velasco, Pedro

2010-12-01

To determine the degree of control of cardiovascular risk factors (CVRF) in a sample of patients with diabetes mellitus (DM) attending Endocrinology and Nutrition Departments in Spain. An epidemiological, cross-sectional, multicenter and observational study involving 41 Departments of Endocrinology and Nutrition in Spain. Each department selected patients with DM with over 10 years of evolution, which were treated in outpatient settings. Demographic, anthropometric, clinical and biochemical data, including medication, were collected for each participant. 1159 patients who met the inclusion criteria were recruited. 52% of the participants were patients with type 2 DM. The mean duration of DM was 19.6 years. A proportion of 37%, 44%, 27.6% and 25.5% had good control of their blood pressure (BP), low density cholesterol (LDLc), lipids and glucose, respectively, and only 4.3% did well in all factors evaluated. The percentage of poorly controlled BP was four times higher in type 2 than in type 1 DM. Obesity, low cultural level and aggregation of cardiovascular risk factors were associated with poorer control. The degree of control of CVRF in diabetic patients with long disease duration is insufficient. Copyright © 2010 SEEN. Published by Elsevier Espana. All rights reserved.

PeV IceCube signals and Dark Matter relic abundance in modified cosmologies

NASA Astrophysics Data System (ADS)

Lambiase, G.; Mohanty, S.; Stabile, An.

2018-04-01

The discovery by the IceCube experiment of a high-energy astrophysical neutrino flux with energies of the order of PeV, has opened new scenarios in astroparticles physics. A possibility to explain this phenomenon is to consider the minimal models of Dark Matter (DM) decay, the 4-dimensional operator ˜ y_{α χ }\\overline{{L_{L_{α }}}} H χ , which is also able to generate the correct abundance of DM in the Universe. Assuming that the cosmological background evolves according to the standard cosmological model, it follows that the rate of DM decay Γ _χ ˜ |y_{α χ }|^2 needed to get the correct DM relic abundance (Γ _χ ˜ 10^{-58}) differs by many orders of magnitude with respect that one needed to explain the IceCube data (Γ _χ ˜ 10^{-25}), making the four-dimensional operator unsuitable. In this paper we show that assuming that the early Universe evolution is governed by a modified cosmology, the discrepancy between the two the DM decay rates can be reconciled, and both the IceCube neutrino rate and relic density can be explained in a minimal model.

Right-handed neutrino dark matter in left-right symmetric models

NASA Astrophysics Data System (ADS)

Bhupal Dev, P. S.; Mohapatra, Rabindra N.; Zhang, Yongchao

2017-07-01

We show that in a class of non-supersymmetric left-right extensions of the Standard Model (SM), the lightest right-handed neutrino (RHN) is naturally stable and can therefore play the role of thermal Dark Matter (DM) in the Universe for a wide mass range from TeV to PeV. Our model is based on the gauge group SU(3) c × SU(2) L × SU(2) R × U(1) YL × U(1) YR in which a heavy copy of the SM fermions are introduced and the stability of the RHN DM is guaranteed by an automatic Z 2 symmetry present in the leptonic sector. The active neutrino masses in the model arise from the type-II seesaw mechanism. We find a lower bound on the RHN DM mass of order TeV from relic density constraints, as well as an unitarity upper bound in the multi-TeV to PeV scale, depending on the entropy dilution factor. The RHN DM could be made long-lived by soft-breaking of the Z 2 symmetry and provides a concrete example of decaying DM interpretation of the PeV neutrinos observed at IceCube.

Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders.

PubMed

Nguyen, Linda; Thomas, Kelan L; Lucke-Wold, Brandon P; Cavendish, John Z; Crowe, Molly S; Matsumoto, Rae R

2016-03-01

Dextromethorphan (DM) is a commonly used antitussive and is currently the only FDA-approved pharmaceutical treatment for pseudobulbar affect. Its safety profile and diverse pharmacologic actions in the central nervous system have stimulated new interest for repurposing it. Numerous preclinical investigations and many open-label or blinded clinical studies have demonstrated its beneficial effects across a variety of neurological and psychiatric disorders. However, the optimal dose and safety of chronic dosing are not fully known. This review summarizes the preclinical and clinical effects of DM and its putative mechanisms of action, focusing on depression, stroke, traumatic brain injury, seizure, pain, methotrexate neurotoxicity, Parkinson's disease and autism. Moreover, we offer suggestions for future research with DM to advance the treatment for these and other neurological and psychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

A Sensitive and Effective Proteomic Approach to Identify She-Donkey’s and Goat’s Milk Adulterations by MALDI-TOF MS Fingerprinting

PubMed Central

Di Girolamo, Francesco; Masotti, Andrea; Salvatori, Guglielmo; Scapaticci, Margherita; Muraca, Maurizio; Putignani, Lorenza

2014-01-01

She-donkey’s milk (DM) and goat’s milk (GM) are commonly used in newborn and infant feeding because they are less allergenic than other milk types. It is, therefore, mandatory to avoid adulteration and contamination by other milk allergens, developing fast and efficient analytical methods to assess the authenticity of these precious nutrients. In this experimental work, a sensitive and robust matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling was designed to assess the genuineness of DM and GM milks. This workflow allows the identification of DM and GM adulteration at levels of 0.5%, thus, representing a sensitive tool for milk adulteration analysis, if compared with other laborious and time-consuming analytical procedures. PMID:25110863

Comparative study between atorvastatin and losartan on high fat diet-induced type 2 diabetes mellitus in rats.

PubMed

Mourad, Ahmed A; Heeba, Gehan H; Taye, Ashraf; El-Moselhy, Mohamed A

2013-10-01

Obesity is often associated with chronic inflammatory state which contributes to the development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM). This study investigated the effects of single and combined administration of atorvastatin (ATOR, lipid-lowering drug) and losartan (LOS, angiotensin receptor antagonist) on metabolic disorders and inflammatory status that are implicated in the development of T2DM with the use of pioglitazone (PIO) as a standard antidiabetic drug. T2DM was induced in male rats by high-fat diet (HFD) feeding for 16 weeks. Oral administrations of ATOR (10 mg/kg), LOS (20 mg/kg), PIO (3 mg/kg), their binary combinations, or vehicle were started in the last 4 weeks. Fasting serum glucose, oral glucose tolerance, fasting serum insulin, IR, serum lipid profile, serum TNF-α and body composition index were determined. Results showed that all drugs and their combinations had positive impact effect on all measured parameters, and better results were achieved from binary drug combinations than administration of each drug alone. Combination of PIO with either ATOR or LOS provided better improvements on T2DM-associated metabolic abnormalities and inflammatory status with respect to each drug alone. However, the most pronounced effects of drugs and their combinations regarding the above parameters were attributed to LOS + PIO combination. In conclusion, this study indicates that combination of ATOR + PIO and, in particular, LOS + PIO can be used as promising effective therapies in the management of HFD-induced T2DM. This concept may be attributed to the combined effects of the respective monotherapies to improve lipid profile, insulin sensitivity, and TNF-α level. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

Paternal history of diabetes mellitus and hypertension affects the prevalence and phenotype of PCOS.

PubMed

Cheng, Chen; Zhang, Haolin; Zhao, Yue; Li, Rong; Qiao, Jie

2015-12-01

The purpose of the present study is to determine if paternal or maternal history of diabetes mellitus (DM) and hypertension (HT) contributes to the prevalence and phenotype of polycystic ovary syndrome (PCOS). We performed an epidemiologic study about PCOS from four districts in Beijing, China, between 2008 and 2009. Parental histories of DM and HT were collected, and the basic characteristics and serum indices of 123 PCOS patients and 718 non-PCOS controls were tested. The prevalence of a parental history of DM and HT was significantly higher in PCOS patients than non-PCOS women (17.1 % vs. 9.2 % and 42.3 % vs. 26.0 %, P < 0.05, respectively). When paternal history was separated from maternal history, only a paternal history of DM and HT reached statistical significance between PCOS and non-PCOS patients (odds ratio (OR) = 3.42, 95 % confidence interval (CI) = 1.69-6.91; OR = 2.50, 95 % CI = 1.58-3.93, respectively). A paternal history of both DM and HT was significantly associated with sex hormone-binding globulin, fasting plasma glucose, and fasting insulin levels, the free androgen index, and the homeostatic model assessment-insulin resistance in PCOS patients (P < 0.05 for all). There was no independent association between maternal history and the clinical or biochemical phenotype of PCOS. PCOS patients with a positive paternal history of both DM and HT have an adverse endocrine and metabolic profile. A paternal history of DM and HT poses a risk to PCOS.

Association between FTO gene polymorphisms and type 2 diabetes mellitus, serum levels of apelin and androgen hormones among Iranian obese women.

PubMed

Ghafarian-Alipour, Farzaneh; Ziaee, Shayan; Ashoori, Mohamad Reza; Zakeri, Mir Saeid; Boroumand, Mohammad Ali; Aghamohammadzadeh, Naser; Abbasi-Majdi, Maryam; Shool, Fatemeh; Asbaghi, Navid Sarakhs; Mohammadi, Abolghasem; Zarghami, Nosratollah

2018-01-30

Recent studies show that FTO single nucleotide polymorphisms (SNPs) are associated with obesity and type 2 diabetes mellitus (T2DM). On the other hand, many animal models and clinical studies have demonstrated that apelin, an adipocytokine, is related to the obesity and T2DM. Additionally, obese women are at risk of Hyperandrogenemia. So, the aim of this study was to investigate the relationship between FTO variants (rs763967273, rs759031579, rs141115189, rs9926289, rs76804286 and rs9939609) with T2DM, serum apelin and androgenic hormones in Iranian obese women. 197 obese women (123 women with T2DM and 74 women as healthy control) were participated in this study. Anthropometrical and biochemical characteristics were measured. Serum apelin and androgen hormones levels were determined in 66 subjects consisting of 33 cases and 33 controls. PCR were carried out and subsequently, the PCR production was genotyped by Sanger sequencing assay. Our observations showed that all SNPs are related to T2DM. The rs9926289 FTO variant had a strong association with serum apelin and dehydroepiandrosterone-sulfate levels (P=0.04 and P=0.03, respectively) among SNPs. In addition, apelin and androgenic hormones were correlated with T2DM. Two polymorphisms including rs9939609 and rs9926289 had a strong Linkage disequilibrium (r 2 =1). FTO variants not only were associated with T2DM, but also some variants had a strong association with apelin and androgenic hormones profile. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalence and clinical profile of metabolic syndrome among type 1 diabetes mellitus patients in southern India.

PubMed

Billow, Amy; Anjana, Ranjit Mohan; Ngai, Michelle; Amutha, Anandakumar; Pradeepa, Rajendra; Jebarani, Saravanan; Unnikrishnan, Ranjit; Michael, Edwin; Mohan, Viswanathan

2015-07-01

To assess the prevalence of metabolic syndrome (MetS) among patients with type 1 diabetes mellitus(T1DM) and to look at prevalence of diabetes complications in T1DM with and without MetS. We studied 451 T1DM patients attending a tertiary diabetes centre in Chennai, South India. T1DM was diagnosed based on absence of beta cell reserve and requirement of insulin from the time of diagnosis. Data on clinical and biochemical characteristics as well as complications details to study the prevalence were also extracted from electronic records. T1DM patients were divided into those with and without MetS[diagnosed according to the harmonizing the metabolic syndrome criteria(IDF/NHLBI/AHA/WHF/IAS/IASO)]. The overall prevalence of MetS among T1DM was 22.2%(100/451). Patients with MetS were older, had longer diabetes duration, acanthosis nigricans, and increased serum cholesterol. In the unadjusted logistic regression analysis, retinopathy, nephropathy and neuropathy were associated with MetS. However after adjustment for age, gender, diabetes duration, HbA1C and BMI significant association was seen only between MetS and retinopathy [odds ratio (OR) 2.82, 95% CI 1.18-6.74, p = 0.020] and nephropathy [OR 4.92, 95% CI 2.59-9.33, p < 0.001]. Prevalence of MetS is high among Asian Indian T1DM patients, and its presence is associated with increased risk of diabetic retinopathy and nephropathy. Copyright © 2015 Elsevier Inc. All rights reserved.

Elevated alanine aminotransferase is associated with metabolic syndrome but not consistently associated with impaired fasting glucose or type 2 diabetes mellitus.

PubMed

Yueh, Chen-Yu; Chen, Jung-Hsiang; Lee, Li-Wen; Lu, Cheng-Wei; Parekh, Bhavin; Chi, Ching-Chi

2011-10-01

Abnormally elevated alanine aminotransferase (ALT) of nonspecific causes is a common outpatient problem. Without considering ethnicity, several studies had suggested that it was associated with insulin resistance (IR). To investigate whether nonspecific elevated ALT in Taiwanese population could reflect a likely underlying IR and was associated with impaired fasting glucose or type 2 diabetes mellitus (IFG/T2DM). The health examination profiles of 1313 Taiwanese were investigated cross-sectionally. The prevalence and odds ratios (ORs) for IFG/T2DM and metabolic abnormalities in relation to elevated ALT were analyzed. Subjects with metabolic syndrome (MS) all had IFG/T2DM. The elevated ALT significantly correlated with MS and IFG/T2DM (i.e., 19.9-29.2% vs. 7.8% for MS, and 27.0-31.5% vs. 16.1% for IFG/T2DM). However, after excluding MS and adjustment for age and sex, the elevated ALT alone was not consistently associated with IFG/T2DM (36 < ALT ≤ 80 IU/L with OR 0.97, 95% CI 0.58-1.61; 80 < ALT ≤ 120 IU/L with OR 0.55, 95% CI 0.13-2.37; none with ALT > 120 had IFG). In a cross-sectional analysis of Taiwanese industrial employees, elevated ALT associated with MS, but in subjects who did not meet MS criteria, elevated ALT by itself did not associate with IFG/T2DM. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Insulin glargine 300 U/mL for basal insulin therapy in type 1 and type 2 diabetes mellitus

PubMed Central

Lau, Ip Tim; Lee, Ka Fai; So, Wing Yee; Tan, Kathryn; Yeung, Vincent Tok Fai

2017-01-01

Objective To review published clinical studies on the efficacy and safety of new insulin glargine 300 units/mL (Gla-300), a new long-acting insulin analog, for the treatment of type 1 and type 2 diabetes mellitus (T1DM, T2DM) Materials and methods Data sources comprised primary research articles on Gla-300, including pharmacodynamic, pharmacokinetic, and clinical studies. Results In pharmacodynamic and pharmacokinetic studies, Gla-300 showed a flatter time–action profile and longer duration of action than Gla-100. Noninferiority of Gla-300 versus Gla-100 for lowering of glycated hemoglobin was demonstrated in Phase III clinical studies covering a range of T1DM and T2DM patient populations. Over 6–12 months of follow-up, Gla-300 consistently showed comparable glycemic efficacy with less hypoglycemia vs Gla-100, even during the first 8 weeks of treatment. Although titrated insulin doses were 11%–17% higher with Gla-300 vs Gla-100, changes in body weight were similar or favored Gla-300. Conclusion Clinical studies provide evidence that the pharmacodynamic and pharmacokinetic properties of Gla-300 may translate into clinical benefits in both T1DM and T2DM. Gla-300 may provide a new option for people initiating basal insulin, those requiring higher basal insulin doses, those with T1DM, and those who may be at increased risk for hypoglycemia, such as people with chronic kidney disease, the elderly, and those with cardiovascular comorbidities. PMID:28721081

Purine derivate content and amino acid profile in larval stages of three edible insects.

PubMed

Bednářová, Martina; Borkovcová, Marie; Komprda, Tomáš

2014-01-15

Considering their high content of protein, insects are a valuable alternative protein source. However, no evaluation of their purine content has so far been done. High content of purine derivates may lead to the exclusion of such food from the diet of people with specific diseases. The aim of this study was to analyse the content of selected purine derivates and amino acid profile in the three insect species most often used for entomophagy in Europe and compare them with the purine content in egg white and chicken breast. The content of individual purine derivates and their total content were significantly dependent on insect species. The purine content in all three species was significantly higher (P < 0.05) than in egg white, but some values were significantly lower (P < 0.05) than in chicken breast. The total protein content was 548.9 g kg(-1) dry matter (DM) in mealworm (Tenebrio molitor), 551.6 g kg(-1) DM in superworm (Zophobas atratus) and 564.9 g kg(-1) DM in cricket (Gryllus assimilis). Larvae of mealworm and superworm are protein-rich and purine-low meat alternatives. In contrast, cricket nymphs are protein-rich and purine-rich and cannot be recommended for people with hyperuricemia or gout. © 2013 Society of Chemical Industry.

Acylcarnitine Profiles in Plasma and Tissues of Hyperglycemic NZO Mice Correlate with Metabolite Changes of Human Diabetes

PubMed Central

Daniel, Hannelore

2018-01-01

The New Zealand obese (NZO) mouse is a polygenic model for obesity and diabetes with obese females and obese, diabetes-prone males, used to study traits of the metabolic syndrome like type 2 diabetes mellitus (T2DM), obesity, and dyslipidaemia. By using LC-MS/MS, we here examine the suitability of this model to mirror tissue-specific changes in acylcarnitine (AC) and amino acid (AA) species preceding T2DM which may reflect patterns investigated in human metabolism. We observed high concentrations of fatty acid-derived ACs in 11 female mice, high abundance of branched-chain amino acid- (BCAA-) derived ACs in 6 male mice, and slight increases in BCAA-derived ACs in the remaining 6 males. Principal component analysis (PCA) including all ACs and AAs confirmed our hypothesis especially in plasma samples by clustering females, males with high BCAA-derived ACs, and males with slight increases in BCAA-derived ACs. Concentrations of insulin, blood glucose, NEFAs, and triacylglycerols (TAGs) further supported the hypothesis of high BCAA-derived ACs being able to mirror the onset of diabetic traits in male individuals. In conclusion, alterations in AC and AA profiles overlap with observations from human studies indicating the suitability of NZO mice to study metabolic changes preceding human T2DM. PMID:29854816

GHASP: an Hα kinematical survey of spiral galaxies - XI. Distribution of luminous and dark matter in spiral and irregular nearby galaxies using WISE photometry.

NASA Astrophysics Data System (ADS)

Korsaga, M.; Carignan, C.; Amram, P.; Epinat, B.; Jarrett, T. H.

2018-04-01

We present the mass distribution of a sample of 121 nearby galaxies with high quality optical velocity fields and available infra-red WISE 3.4 μm data. Contrary to previous studies, this sample covers all morphological types and is not biased toward late-type galaxies. These galaxies are part of the Fabry-Perot kinematical GHASP survey of spirals and irregular nearby galaxies. Combining the kinematical data to the WISE surface brightness data probing the emission from the old stellar population, we derive mass models allowing us to compare the luminous to the dark matter halo mass distribution in the optical regions of those galaxies. Dark matter (DM) models are constructed using the isothermal core profile and the Navarro-Frenk-White cuspy profile. We allow the M/L of the baryonic disc to vary or we keep it fixed, constrained by stellar evolutionary models (WISE W1-W2 color) and we carry out best fit (BFM) and pseudo-isothermal maximum disc (MDM) models. We found that the MDM provides M/L values four times higher than the BFM, suggesting that disc components, on average, tend to be maximal. The main results are: (i) the rotation curves of most galaxies are better fitted with core rather than cuspy profiles; (ii) the relation between the parameters of the DM and of the luminous matter components mostly depends on morphological types. More precisely, the distribution of the DM inside galaxies depends on whether or not the galaxy has a bulge.

Quantitative Relationship Between Cumulative Risk Alleles Based on Genome-Wide Association Studies and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

PubMed

Kodama, Satoru; Fujihara, Kazuya; Ishiguro, Hajime; Horikawa, Chika; Ohara, Nobumasa; Yachi, Yoko; Tanaka, Shiro; Shimano, Hitoshi; Kato, Kiminori; Hanyu, Osamu; Sone, Hirohito

2018-01-05

Many epidemiological studies have assessed the genetic risk of having undiagnosed or of developing type 2 diabetes mellitus (T2DM) using several single nucleotide polymorphisms (SNPs) based on findings of genome-wide association studies (GWAS). However, the quantitative association of cumulative risk alleles (RAs) of such SNPs with T2DM risk has been unclear. The aim of this meta-analysis is to review the strength of the association between cumulative RAs and T2DM risk. Systematic literature searches were conducted for cross-sectional or longitudinal studies that examined odds ratios (ORs) for T2DM in relation to genetic profiles. Logarithm of the estimated OR (log OR) of T2DM for 1 increment in RAs carried (1-ΔRA) in each study was pooled using a random-effects model. There were 46 eligible studies that included 74,880 cases among 249,365 participants. In 32 studies with a cross-sectional design, the pooled OR for T2DM morbidity for 1-ΔRA was 1.16 (95% confidence interval [CI], 1.13-1.19). In 15 studies that had a longitudinal design, the OR for incident T2DM was 1.10 (95% CI, 1.08-1.13). There was large heterogeneity in the magnitude of log OR (P < 0.001 for both cross-sectional studies and longitudinal studies). The top 10 commonly used genes significantly explained the variance in the log OR (P = 0.04 for cross-sectional studies; P = 0.006 for longitudinal studies). The current meta-analysis indicated that carrying 1-ΔRA in T2DM-associated SNPs was associated with a modest risk of prevalent or incident T2DM, although the heterogeneity in the used genes among studies requires us to interpret the results with caution.

Quantitative Relationship Between Cumulative Risk Alleles Based on Genome-Wide Association Studies and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

PubMed Central

Kodama, Satoru; Fujihara, Kazuya; Ishiguro, Hajime; Horikawa, Chika; Ohara, Nobumasa; Yachi, Yoko; Tanaka, Shiro; Shimano, Hitoshi; Kato, Kiminori; Hanyu, Osamu; Sone, Hirohito

2018-01-01

Many epidemiological studies have assessed the genetic risk of having undiagnosed or of developing type 2 diabetes mellitus (T2DM) using several single nucleotide polymorphisms (SNPs) based on findings of genome-wide association studies (GWAS). However, the quantitative association of cumulative risk alleles (RAs) of such SNPs with T2DM risk has been unclear. The aim of this meta-analysis is to review the strength of the association between cumulative RAs and T2DM risk. Systematic literature searches were conducted for cross-sectional or longitudinal studies that examined odds ratios (ORs) for T2DM in relation to genetic profiles. Logarithm of the estimated OR (log OR) of T2DM for 1 increment in RAs carried (1-ΔRA) in each study was pooled using a random-effects model. There were 46 eligible studies that included 74,880 cases among 249,365 participants. In 32 studies with a cross-sectional design, the pooled OR for T2DM morbidity for 1-ΔRA was 1.16 (95% confidence interval [CI], 1.13–1.19). In 15 studies that had a longitudinal design, the OR for incident T2DM was 1.10 (95% CI, 1.08–1.13). There was large heterogeneity in the magnitude of log OR (P < 0.001 for both cross-sectional studies and longitudinal studies). The top 10 commonly used genes significantly explained the variance in the log OR (P = 0.04 for cross-sectional studies; P = 0.006 for longitudinal studies). The current meta-analysis indicated that carrying 1-ΔRA in T2DM-associated SNPs was associated with a modest risk of prevalent or incident T2DM, although the heterogeneity in the used genes among studies requires us to interpret the results with caution. PMID:29093303

Abnormal functional brain connectivity and personality traits in myotonic dystrophy type 1.

PubMed

Serra, Laura; Silvestri, Gabriella; Petrucci, Antonio; Basile, Barbara; Masciullo, Marcella; Makovac, Elena; Torso, Mario; Spanò, Barbara; Mastropasqua, Chiara; Harrison, Neil A; Bianchi, Maria L E; Giacanelli, Manlio; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

2014-05-01

Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy observed in adults, is a genetic multisystem disorder affecting several other organs besides skeletal muscle, including the brain. Cognitive and personality abnormalities have been reported; however, no studies have investigated brain functional networks and their relationship with personality traits/disorders in patients with DM1. To use resting-state functional magnetic resonance imaging to assess the potential relationship between personality traits/disorders and changes to functional connectivity within the default mode network (DMN) in patients with DM1. We enrolled 27 patients with genetically confirmed DM1 and 16 matched healthy control individuals. Patients underwent personality assessment using clinical interview and Minnesota Multiphasic Personality Inventory-2 administration; all participants underwent resting-state functional magnetic resonance imaging. Investigations were conducted at the Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Catholic University of Sacred Heart, and Azienda Ospedaliera San Camillo Forlanini. Resting-state functional magnetic resonance imaging. Measures of personality traits in patients and changes in functional connectivity within the DMN in patients and controls. Changes in functional connectivity and atypical personality traits in patients were correlated. We combined results obtained from the Minnesota Multiphasic Personality Inventory-2 and clinical interview to identify a continuum of atypical personality profiles ranging from schizotypal personality traits to paranoid personality disorder within our DM1 patients. We also demonstrated an increase in functional connectivity in the bilateral posterior cingulate and left parietal DMN nodes in DM1 patients compared with controls. Moreover, patients with DM1 showed strong associations between DMN functional connectivity and schizotypal-paranoid traits. Our findings provide novel biological evidence that DM1 is a clinical condition that also involves an alteration of functional connectivity of the brain. We speculate that these functional brain abnormalities, similarly to frank psychiatric disorders, may account for the atypical personality traits observed in patients with DM1.

Identification of Shared and Unique Serum Lipid Profiles in Diabetes Mellitus and Myocardial Infarction.

PubMed

Kjellqvist, Sanela; Klose, Christian; Surma, Michal A; Hindy, George; Mollet, Inês G; Johansson, Anna; Chavaux, Patrick; Gottfries, Johan; Simons, Kai; Melander, Olle; Fernandez, Céline

2016-11-29

Diabetes mellitus (DM) and cardiovascular disease are associated with dyslipidemia, but the detailed lipid molecular pattern in both diseases remains unknown. We used shotgun mass spectrometry to determine serum levels of 255 molecular lipids in 316 controls, 171 DM, and 99 myocardial infarction (MI) events from a cohort derived from the Malmö Diet and Cancer study. Orthogonal projections to latent structures analyses were conducted between the lipids and clinical parameters describing DM or MI. Fatty acid desaturases (FADS) and elongation of very long chain fatty acid protein 5 (ELOVL5) activities were estimated by calculating product to precursor ratios of polyunsaturated fatty acids in complex lipids. FADS genotypes encoding these desaturases were then tested for association with lipid levels and ratios. Differences in the levels of lipids belonging to the phosphatidylcholine and triacylglyceride (TAG) classes contributed the most to separating DM from controls. TAGs also played a dominating role in discriminating MI from controls. Levels of C18:2 fatty acids in complex lipids were lower both in DM and MI versus controls (DM, P=0.004; MI, P=6.0E-06) at least due to an acceleration in the metabolic flux from C18:2 to C20:4 (eg, increased estimated ELOVL5: DM, P=0.02; MI, P=0.04, and combined elongase-desaturase activities: DM, P=3.0E-06; MI, P=2.0E-06). Minor allele carriers of FADS genotypes were associated with increased levels of C18:2 (P≤0.007) and lower desaturase activity (P≤0.002). We demonstrate a possible relationship between decreased levels of C18:2 in complex lipids and DM or MI. We thereby highlight the importance of molecular lipids in the pathogenesis of both diseases. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Persistent organic pollutants in atmospheric deposition and biomonitoring with Tillandsia usneoides (L.) in an industrialized area in Rio de Janeiro state, southeast Brazil--Part II: PCB and PAH.

PubMed

de Souza Pereira, Márcia; Heitmann, Dieter; Reifenhäuser, Werner; Meire, Rodrigo Ornellas; Santos, Luciana Silva; Torres, João Paulo M; Malm, Olaf; Körner, Wolfgang

2007-04-01

Monitoring of immission of persistent organic pollutants in the industrialized area of Volta Redonda (V.R.) and in the National Park of Itatiaia (PNI) in southeast Brazil was performed using an endemic bromeliad species as biomonitor and measuring bulk deposition rates of polychlorinated biphenyls (PCB) and polycyclic aromatic hydrocarbons (PAH). For the sum of PCB, overall deposition rates were between 17 and 314 ng/(m2 day) in winter and between 43 and 81 ng/(m2 day) in summer, respectively. Deposition rates of dioxin-like PCBs ranged from 0.14 to 2.8 pg WHO-TEQ/(m2 day) in winter and from 0.90 to 4.3 pg WHO-TEQ/(m2 day) in summer. PCB deposition rates (total PCB and WHO-TEQ) were in the same range in winter in V.R. and PNI. In summer, contamination levels in V.R. were 6-10-folds higher than in PNI. PCB concentrations in biomonitor samples from V.R. and PNI were in the same range in summer and in winter. Concentrations of total PCB ranged from 14 to 95 microg/kg dry matter (d.m.) in winter and from 18 to 27 microg/kg d.m. in summer, respectively. The TEQ values were between 1.7 and 4.1 ng WHO-TEQ/kg d.m. in winter and between 1.9 and 2.9 ng WHO-TEQ/kg d.m. in summer. PCB concentrations of di-ortho PCB but not of non-ortho PCB were a factor of 2-4 lower in summer in both areas. PCB congener profiles resembled those from technical formulations. The profiles shifted to the higher chlorinated congeners in summer, probable due to revolatilisation of the lighter components at higher temperatures. PCB profiles in biomonitor resembled those from deposition samples and the shift to the heavier congeners in summer was even more pronounced. PAH deposition rates were in a similar range in both areas (131-2415 ng/(m2 day)). PAH levels in biomonitor samples from V.R. were about one order of magnitude higher than in samples from PNI indicating the impact of local sources. PAH profiles revealed stationary thermal processes as main source of contamination in V.R. whereas in PNI, biomass burning seems to be the main contamination source.

Torsion as a dark matter candidate from the Higgs portal

NASA Astrophysics Data System (ADS)

Belyaev, Alexander S.; Thomas, Marc C.; Shapiro, Ilya L.

2017-05-01

Torsion is a metric-independent component of gravitation, which may provide a more general geometry than the one taking place within general relativity. On the other hand, torsion could lead to interesting phenomenology in both particle physics and cosmology. In the present work it is shown that a torsion field interacting with the SM Higgs doublet and having a negligible coupling to standard model (SM) fermions is protected from decaying by a Z2 symmetry, and therefore becomes a promising dark matter (DM) candidate. This model provides a good motivation for Higgs portal vector DM scenario. We evaluate the DM relic density and explore direct DM detection and collider constraints on this model to understand its consistency with experimental data and establish the most up-to-date limits on its parameter space. We have found in the model when the Higgs boson is only partly responsible for the generation of torsion mass, there is a region of parameter space where torsion contributes 100% to the DM budget of the Universe. Furthermore, we present the first results on the potential of the LHC to probe the parameter space of minimal scenario with Higgs portal vector DM using mono-jet searches and have found that LHC at high luminosity will be sensitive to the substantial part of model parameter space which cannot be probed by other experiments.

Zingiber officinale and Type 2 Diabetes Mellitus: Evidence from Experimental Studies.

PubMed

Akash, Muhammad Sajid Hamid; Rehman, Kanwal; Tariq, Muhammad; Chen, Shuqing

2015-01-01

Zingiber officinale is being used as diet-based therapy because of its wide therapeutic potential in type 2 diabetes mellitus (T2DM) and against diabetic complications by directly interacting with different molecular and cellular pathways that provoke the pathogenesis of T2DM. This article explores the overall beneficial effects of Z. officinale on T2DM and its associated complications. Along with elucidating the beneficial facts of Z. officinale, this article may also aid in understanding the molecular basis of its effects in T2DM. The mechanistic rationale for antidiabetic effects of Z. officinale includes the inhibition of several transcriptional pathways, lipid peroxidation, carbohydrate-metabolizing enzymes, and HMG-CoA reductase and the activation of antioxidant enzyme capacity and low-density lipoprotein receptors. Consequently, by targeting these pathways, Z. officinale shows its antidiabetic therapeutic effects by increasing insulin sensitivity/synthesis, protecting β-cells of pancreatic islets, reducing fat accumulation, decreasing oxidative stress, and increasing glucose uptake by the tissues. In addition to these effects, Z. officinale also exhibits protective effects against several diabetes-linked complications, notably nephropathy and diabetic cataract, by acting as an antioxidant and antiglycating agent. In conclusion, this work suggests that consumption of Z. officinale can help to treat T2DM and diabetic complications; nevertheless, patient counseling also is required as a guiding force for the success of diet-based therapy in T2DM.

Association of Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor gamma 2 (PPARγ2) Gene with Type 2 Diabetes Mellitus in Ethnic Kashmiri Population.

PubMed

Majid, Misbah; Masood, Akbar; Kadla, Showkat Ahmad; Hameed, Iqra; Ganai, Bashir A

2017-02-01

Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia associated with insulin resistance and relative insulin deficiency. T2DM is believed to be attributable to the combined effect of genetic and environmental factors. Peroxisome proliferator-activated receptor gamma 2 (PPARγ2) is one of the main candidate genes that are implicated in T2DM. A common proline 12 alanine (Pro12Ala) polymorphism in PPARγ2 has been shown to be associated with T2DM. The aim of this work was to investigate the possible role of PPARγ2 gene polymorphism, as a genetic risk factor for T2DM. The study comprised 200 ethnic unrelated subjects (100 T2DM patients and 100 controls). PCR-RFLP technique was used for genotyping analysis. The frequency of the Pro allele was 79 and 91.5 % for controls and cases, respectively (P < 0.05; OR 3.2; 95 % CI 1.64-6.3). The Pro12Ala polymorphism was in Hardy-Weinberg equilibrium in both patients and controls (χ 2  = 0.13, P > 0.05). We found a significant association of Pro12Ala polymorphism of PPARγ2 gene with T2DM, however the genotypes showed statistically significant association only with few clinical parameters including body mass index, total cholesterol, and low-density lipoprotein (P < 0.05). The study signifies that Pro allele in PPARγ2 may be a genotypic risk factor that confers susceptibility to T2DM in ethnic Kashmiri population.

Cosmological axion and a quark nugget dark matter model

NASA Astrophysics Data System (ADS)

Ge, Shuailiang; Liang, Xunyu; Zhitnitsky, Ariel

2018-02-01

We study a dark matter (DM) model offering a very natural explanation of two (naively unrelated) problems in cosmology: the observed relation ΩDM˜Ωvisible and the observed asymmetry between matter and antimatter in the Universe, known as the "baryogenesis" problem. In this framework, both types of matter (dark and visible) have the same QCD origin, form at the same QCD epoch, and are proportional to one and the same dimensional parameter of the system, ΛQCD, which explains how these two naively distinct problems could be intimately related, and could be solved simultaneously within the same framework. More specifically, the DM in this model is composed by two different ingredients: the (well-studied) DM axions and the (less-studied) quark nuggets made of matter or antimatter. We focus on the quantitative analysis of the relation between these two distinct components contributing to the dark sector of the theory determined by ΩDM≡[ΩDM(nuggets)+ΩDM(axion)] . We argue that the nuggets' DM component always traces the visible matter density, i.e., ΩDM(nuggets)˜Ωvisible , and this feature is not sensitive to the parameters of the system such as the axion mass ma or the misalignment angle θ0. It should be contrasted with conventional axion production mechanisms due to the misalignment when ΩDM(axion) is highly sensitive to the axion mass ma and the initial misalignment angle θ0. We also discuss the constraints on this model related to the inflationary scale HI, nonobservation of the isocurvature perturbations and the tensor modes. We also comment on some constraints related to various axion search experiments.

Epigenetics and type II diabetes mellitus: underlying mechanisms of prenatal predisposition

PubMed Central

Sterns, J. David; Smith, Colin B.; Steele, John R.; Stevenson, Kimberly L.; Gallicano, G. Ian

2014-01-01

Type II diabetes mellitus (T2DM) is a widespread metabolic disorder characterized by insulin resistance precipitating abnormally high blood glucose levels. While the onset of T2DM is known to be the consequence of a multifactorial interplay with a strong genetic component, emerging research has demonstrated the additional role of a variety of epigenetic mechanisms in the development of this disorder. Heritable epigenetic modifications, such as DNA methylation and histone modifications, play a vital role in many important cellular processes, including pancreatic cellular differentiation and maintenance of normal β-cell function. Recent studies have found possible epigenetic mechanisms to explain observed risk factors, such as altered atherogenic lipid profiles, elevated body mass index (BMI), and impaired glucose tolerance (IGT), for later development of T2DM in children born to mothers experiencing both famine and hyperglycemic conditions. It is suggested that these epigenetic influences happen early during gestation and are less susceptible to the effects of postnatal environmental modification as was previously thought, highlighting the importance of early preventative measures in minimizing the global burden of T2DM. PMID:25364722

Cryptococcosis in patients with diabetes mellitus II in mainland China: 1993-2015.

PubMed

Li, Yingfang; Fang, Wenjie; Jiang, Weiwei; Hagen, Ferry; Liu, Jia; Zhang, Lei; Hong, Nan; Zhu, Yu; Xu, Xiaoguang; Lei, Xia; Deng, Danqi; Xu, Jianping; Liao, Wanqing; Boekhout, Teun; Chen, Min; Pan, Weihua

2017-11-01

Diabetes mellitus II (DM II) is a newly defined independent factor contributing to the morbidity and mortality of cryptococcosis. This retrospective case analysis aims to explore the epidemiology, clinical profile and strain characteristics of cryptococcosis in Chinese DM II patients. This study included 30 cases of cryptococcosis with DM II occurring from 1993 to 2015 in mainland China. The hospital-based prevalence of cryptococcosis in DM II was 0.21%. The mean age of the patients was 56.1 years (95% confidence interval: 51.5, 60.6), and 93% of the patients were older than 40 years. Sixty-two per cent of the patients experienced untreated or poorly controlled blood glucose before infection. Multilocus sequence typing analysis categorised all cultured strains as Cryptococcus neoformans and sequence type 5. Sixty-nine per cent of pulmonary cryptococcosis patients experienced misdiagnoses and treatment delays. Sixty per cent of cryptococcal meningitis patients received substandard antifungal therapy. The overall death rate was 33%. Considering the large population size of DM II patients in China, improved attention should be paid to the high prevalence of cryptococcosis as revealed by us. We also emphasised the importance of blood glucose control for infection prevention, especially among the elderly. © 2017 Blackwell Verlag GmbH.

An open-label study to assess safety, tolerability, and effectiveness of dextromethorphan/quinidine for pseudobulbar affect in dementia: PRISM II results.

PubMed

Doody, Rachelle S; D'Amico, Stephen; Cutler, Andrew J; Davis, Charles S; Shin, Paul; Ledon, Fred; Yonan, Charles; Siffert, João

2016-12-01

Dextromethorphan (DM)/quinidine (Q) is an approved treatment for pseudobulbar affect (PBA) based on trials in amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness and tolerability for PBA secondary to dementia, stroke, or traumatic brain injury; dementia cohort results are reported. This was an open-label, multicenter, 90 day trial; patients received DM/Q 20/10 mg twice daily. Primary outcome was change in Center for Neurologic Study-Lability Scale (CNS-LS) score. Secondary outcomes included PBA episode count and Clinical and Patient/Caregiver Global Impression of Change scores with respect to PBA (CGI-C/PGI-C). 134 patients were treated. CNS-LS improved by a mean (SD) of 7.2 (6.0) points at Day 90/Endpoint (P<.001) vs. baseline. PBA episodes were reduced 67.7% (P<.001) vs. baseline; global measures showed 77.5% CGI-C and 76.5% PGI-C "much"/"very much" improved. Adverse events included headache (7.5%), urinary tract infection (4.5%), and diarrhea (3.7%); few patients dropped out for adverse events (10.4%). DM/Q significantly reduced PBA symptoms in patients with dementia; reported adverse events were consistent with the known safety profile of DM/Q. Trial Registration clinicaltrials.gov identifier: NCT01799941.

A pilot, randomized controlled trial to examine the health outcomes of raisin consumption in patients with diabetes.

PubMed

Kanellos, P T; Kaliora, A C; Tentolouris, N K; Argiana, V; Perrea, D; Kalogeropoulos, N; Kountouri, A M; Karathanos, V T

2014-03-01

Dried fruits, like their fresh homologues, contain relatively high concentrations of antioxidants. The aim of this study was to determine the health outcomes of raisin consumption on patients with diabetes. We examined the effects of dried grapes (Vitis vinifera) cultivated in Greece, namely Corinthian Raisins (CR) on blood pressure, fasting glucose, glucated hemoglobin (HbA1c), lipid peroxidation, high-sensitivity C-reactive protein, antioxidant status, and cytokines in patients with type 2 diabetes mellitus (T2DM). Forty-eight well-controlled patients with T2DM from the diabetes outpatient clinic of our hospital were recruited to a two-armed, randomized, controlled, 24-wk prospective intervention trial in order to examine the health outcomes of CR consumption. All participants were reported to consume less fruits and vegetables than the recommended amount of five servings daily. Participants in the intervention were instructed to consume CR equal to two fruit servings (36 g/d), replacing snacks with similar energy density twice during the day. Anthropometric and blood pressure measurements, assessment of dietary intake, and fasting blood draws were conducted at baseline and at week 24. Also, phenolic compounds present in CR were analyzed in plasma of the patients. t Test for parametric data and Mann-Whitney test or Wilcoxon test for non-parametric data were performed. Significance was set at P < 0.05. Body weight, glycemic control, and lipid profile were not affected in either arm. Patients in the CR arm reduced their diastolic blood pressure and increased their total antioxidant potential significantly compared with baseline. The differences between the two groups at week 24 were significant. No change in high-sensitivity C-reactive protein was observed. A significant difference in plasma circulating p-hydroxybenzoic acid was observed between groups at the end of the trial. Our study shows that naturally CR may improve health features in patients with well-controlled T2DM. Copyright © 2014 Elsevier Inc. All rights reserved.

Log (TG)/HDL-C ratio as a predictor of decreased islet beta cell function in patients with type 2 diabetes: 6-year cohort study.

PubMed

Zhou, Meicen; Li, Zengyi; Min, Rui; Dong, Yaxiu; Sun, Qi; Li, Yuxiu

2015-09-01

The aim of the present study was to explore whether the triglyceride to high density lipoprotein cholesterol ratio [log (TG)/HDL-C] and peripheral blood leukocytes DNA telomere length could predict future islet beta cell function decreased in Chinese type 2 diabetes mellitus (T2DM) during a 6-year cohort. Sixty T2DM patients (without insulin treatment at baseline) were included in the 6-year cohort study. Peripheral blood leukocytes DNA telomere length, HbA1c, blood lipid profile, fatty fat acid, glucose, insulin and C peptide (3 h after a mixed meal) were determined. Delta C peptide area under curve (Delta CP AUC) was used to reflect change in beta cell secretion function (Delta CP AUC = baseline CP AUC - CP AUC after 6 years). Subjects were divided into slow decrease of beta cell function group (Delta CP AUCslow group) and fast decrease group (Delta CP AUCfast group) according to median of Delta CP AUC. Baseline demographic characteristics, clinical variables between two groups were compared. Correlations between baseline data and Delta CP AUC were analyzed. Baseline log (TG)/HDL-C was positively correlated with Delta CP AUC (r = 0.306, P = 0.027); log (TG)/HDL-C in Delta CP AUCfast group was higher than that in Delta CP AUCslow group (0.103 ± 0.033 vs 0.083 ± 0.030, P = 0.027). There was no significant difference in DNA telomere length between the two groups. Change in DNA telomere length over 6 years was not significantly correlated with baseline blood lipid. In Chinese T2DM patients, high baseline log (TG)/HDL-C ratio predicts fast progression of islet beta cell dysfunction. It may be a simple index to predict progression speed of islet beta cell dysfunction. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Intestinal fatty acid binding protein Ala54Thr polymorphism is associated with peripheral atherosclerosis combined with type 2 diabetes mellitus.

PubMed

Khattab, Salma A; Abo-Elmatty, Dina M; Ghattas, Maivel H; Mesbah, Noha M; Mehanna, Eman T

2017-09-01

Intestinal fatty acid-binding protein 2 (FABP2) is expressed in enterocytes and binds saturated and unsaturated long-chain fatty acids. The FABP2 Ala54Thr polymorphism has been reported to effect lipid metabolism. The aim of the present study was to assess the relationship between this polymorphism and peripheral atherosclerosis combined with type 2 diabetes mellitus (T2DM) in an Egyptian population. The study was performed on 100 T2DM patients with peripheral atherosclerosis and 100 control subjects. The Ala54Thr polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism, whereas serum FABP2 levels were determined using ELISA. Fasting blood glucose, fasting serum insulin concentrations, HbA1c, lipid profile, body mass index (BMI) and systolic and diastolic blood pressure (SBP and DBP, respectively) were determined. There was a higher frequency of the Thr54 allele among the patient group (P = 0.002). In Ala54/Thr54 heterozygotes and carriers of the rare Thr54/Thr54 genotype, there were significant increases in BMI and FABP2. Those with the Thr54/Thr54 genotype had significantly decreased high-density lipoprotein cholesterol (HDL-C) concentrations; in addition, those with the Thr54/Thr54 genotype had significantly higher SBP and DBP than subjects with the Ala54/Ala54 and Ala54/Thr54 genotypes. There was a positive correlation between FABP2 levels and BMI, SBP and DBP, and a negative correlation with HDL-C. The Thr54 allele of the FABP2 Ala54Thr polymorphism was associated with an increased incidence of peripheral atherosclerosis combined with T2DM in the population studied. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Drivers of summer oxygen depletion in the central North Sea

NASA Astrophysics Data System (ADS)

Queste, B. Y.; Fernand, L.; Jickells, T. D.; Heywood, K. J.; Hind, A. J.

2015-06-01

In stratified shelf seas, oxygen depletion beneath the thermocline is a result of a greater rate of biological oxygen demand than the rate of supply of oxygenated water. Suitably equipped gliders are uniquely placed to observe both the supply through the thermocline and the consumption of oxygen in the bottom layers. A Seaglider was deployed in the shallow (≈ 100 m) stratified North Sea in a region of known low oxygen during August 2011 to investigate the processes regulating supply and consumption of dissolved oxygen below the pycnocline. The first deployment of such a device in this area, it provided extremely high resolution observations, 316 profiles (every 16 min, vertical resolution of 1 m) of CTD, dissolved oxygen concentrations, backscatter and fluorescence during a three day deployment. The high temporal resolution observations revealed occasional small scale events that supply oxygenated water into the bottom layer at a rate of 2±1 μmol dm-3 day-1. Benthic and pelagic oxygen sinks, quantified through glider observations and past studies, indicate more gradual background consumption rates of 2.5±1 μmol dm-3 day-1. This budget revealed that the balance of oxygen supply and demand is in agreement with previous studies of the North Sea. However, the glider data show a net oxygen consumption rate of 2.8±0.3 μmol dm-3 day-1 indicating a localised or short-lived increase in oxygen consumption rates. This high rate of oxygen consumption is indicative of an unidentified oxygen sink. We propose that this elevated oxygen consumption is linked to localised depocentres and rapid remineralisation of resuspensded organic matter. The glider proved to be an excellent tool for monitoring shelf sea processes despite challenges to glider flight posed by high tidal velocities, shallow bathymetry, and very strong density gradients. The direct observation of these processes allows more up to date rates to be used in the development of ecosystem models.

Investigation of the therapy targets of Yi-Qi-Yang-Yin-Hua-Tan-Qu-Yu recipe on type 2 diabetes by serum proteome labeled with iTRAQ.

PubMed

Zhao, Jing; Xie, Ming; Liu, Jin-Na; Wang, Bang-Zhong

2018-04-11

Ethnopharmacology relevance Based on basic theories of Chinese medicine, Yi-Qi-Yang-Yin-Hua-Tan-Qu-Yu (YQYYHTQY) recipe was constituted by eleven kinds of Chinese herbs and effective in treatment of type 2 diabetes (T2DM). But the therapy target was unclear. In this study, we used the serum proteome labeled by iTRAQ to find therapy target of YQYYHTQY recipe on T2DM. The rat model was induced by high-fat diet (HFD) and streptozotocin (STZ, 30mg/kg). Drugs were administered to rats once daily for 14 days. Related laboratory parameters were observed. Serum proteome were compared between T2DM and YQYYHTQY group using the iTRAQ labeling quantitative proteomics technique. Functional differential proteins were analysis by STRING software. Target proteins were confirmed by ELISA kits. Hyperglycemia, hyperinsulinemia, insulin resistance, decrease of glucose transporter, depilation, less activity, flock together, depression, ecchymosis of tongue and tail appearance, the typical diabetic patients "a little more than three" symptoms, as well as the decrease of grip strength, serum cyclic adenosine monophosphate (cAMP)/ cyclic guanosine monophosphate (cGMP) ratio, serum high density lipoprotein-cholesterol (HDL-C) and the increase of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), thromboxane B 2 (TXB 2 )/ 6-keto prostaglandin F1α (6-keto PGF1α) ratio, endothelin-1 (ET-1) levels were found in T2DM group. After drugs treatment, all the above indexes almost were improved in different degrees and effect of YQYYHTQY recipe was superior to pioglitazone hydrochloride. In addition, there were 23 differential proteins, 5 up-regulated and 18 down-regulated proteins. Of them, there were 4 proteins related with diabetes, blood and behavior. Cell division control protein 42 homolog (CDC42) and Ras homolog gene family member A (RhoA) were the therapy targets of YQYYHTQY recipe on T2DM. YQYYHTQY recipe showed therapy effect on T2DM. CDC42 and RhoA proteins were the therapy targets of YQYYHTQY recipe. Copyright © 2018 Elsevier Ireland Ltd. All rights reserved.

Cosmological perturbations in the ΛCDM-like limit of a polytropic dark matter model

NASA Astrophysics Data System (ADS)

Kleidis, K.; Spyrou, N. K.

2017-10-01

It has recently been proposed that both dark matter (DM) and dark energy (DE) can be treated as a single component when they are considered in the context of a polytropic DM fluid with thermodynamical content. Depending on only one free parameter, that is, the polytropic exponent, - 0.103 < Γ ≤ 0, this unified DM model reproduces the distance measurements performed with the aid of the supernovae Type Ia (SNe Ia) standard candles to high accuracy. It avoids the age problem and the coincidence problem, meaning that it allows interpreting not only when, but also why the Universe so recently transited from deceleration to acceleration. However, a critical problem still remains that the polytropic DM model is also required to solve, that is, it needs to demonstrate its compatibility with current observational data on structure formation. We begin to untie this knot here by discussing the evolution of cosmological perturbations in the ΛCDM-like (I.e., Γ = 0) limit of the polytropic DM model. The corresponding results are quite encouraging because this model reproduces every major effect known from conventional (I.e., pressureless cold dark matter - CDM) structure formation theory, such as the constancy of metric perturbations in the vicinity of recombination and the (late-time) Meszaros effect on their rest-mass density counterparts. The non-zero (polytropic) pressure, on the other hand, drives the evolution of small-scale velocity perturbations along the lines of the root-mean-square velocity law of conventional statistical physics. As a consequence, peculiar velocities in this model slightly increase instead of being redshifted away by cosmic expansion. This result might comprise a convenient probe of the polytropic DM model with Γ = 0. Even more importantly, however, upon consideration of scale-invariant metric perturbations, the spectrum of their rest-mass density counterparts exhibits an effective power-law dependence on the (physical) wavenumber, kph, of the form kph3+nseff, with the associated scalar spectral index, nseff, being equal to nseff = 0.970. This theoretical value reproduces the corresponding observational Planck result, that is, nsobs = 0.968 ± 0.006.

Impact of metformin versus the prandial insulin secretagogue, repaglinide, on fasting and postprandial glucose and lipid responses in non-obese patients with type 2 diabetes.

PubMed

Lund, Søren S; Tarnow, Lise; Frandsen, Merete; Smidt, Ulla M; Pedersen, Oluf; Parving, Hans-Henrik; Vaag, Allan A

2008-01-01

Non-obese patients with type 2 diabetes (T2DM) are characterized by predominant defective insulin secretion. However, in non-obese T2DM patients, metformin, targeting insulin resistance, is non-inferior to the prandial insulin secretagogue, repaglinide, controlling overall glycaemia (HbA1c). Whether the same apply for postprandial glucose and lipid metabolism is unknown. Here, we compared the effect of metformin versus repaglinide on postprandial metabolism in non-obese T2DM patients. Single-centre, double-masked, double-dummy, crossover study during 2x4 months involving 96 non-obese (body mass index < or = 27 kg/m2) insulin-naïve T2DM patients. At enrolment, patients stopped prior oral hypoglycaemic agents therapies and after a 1-month run-in period on diet-only treatment, patients were randomized to repaglinide (2 mg) thrice daily followed by metformin (1 g) twice daily or vice versa each during 4 months with 1-month washout between interventions. Postprandial metabolism was evaluated by a standard test meal (3515 kJ; 54% fat, 13% protein and 33% carbohydrate) with blood sampling 0-6 h postprandially. Fasting levels and total area under the curve (AUC) for plasma glucose, triglycerides and free fatty acids (FFA) changed equally between treatments. In contrast, fasting levels and AUC of total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol and serum insulin were lower during metformin than repaglinide (mean (95% confidence intervals), LDL cholesterol difference metformin versus repaglinide: AUC: -0.17 mmol/l (-0.26; -0.08)). AUC differences remained significant after adjusting for fasting levels. In non-obese T2DM patients, metformin reduced postprandial levels of glycaemia, triglycerides and FFA similarly compared to the prandial insulin secretagogue, repaglinide. Furthermore, metformin reduced fasting and postprandial cholesterolaemia and insulinaemia compared with repaglinide. These data support prescription of metformin as the preferred drug in non-obese patients with T2DM targeting fasting and postprandial glucose and lipid metabolism.

Mobility and settling rate of agglomerates of polydisperse nanoparticles

NASA Astrophysics Data System (ADS)

Spyrogianni, Anastasia; Karadima, Katerina S.; Goudeli, Eirini; Mavrantzas, Vlasis G.; Pratsinis, Sotiris E.

2018-02-01

Agglomerate settling impacts nanotoxicology and nanomedicine as well as the stability of engineered nanofluids. Here, the mobility of nanostructured fractal-like SiO2 agglomerates in water is investigated and their settling rate in infinitely dilute suspensions is calculated by a Brownian dynamics algorithm tracking the agglomerate translational and rotational motion. The corresponding friction matrices are obtained using the HYDRO++ algorithm [J. G. de la Torre, G. del Rio Echenique, and A. Ortega, J. Phys. Chem. B 111, 955 (2007)] from the Kirkwood-Riseman theory accounting for hydrodynamic interactions of primary particles (PPs) through the Rotne-Prager-Yamakawa tensor, properly modified for polydisperse PPs. Agglomerates are generated by an event-driven method and have constant mass fractal dimension but varying PP size distribution, mass, and relative shape anisotropy. The calculated diffusion coefficient from HYDRO++ is used to obtain the agglomerate mobility diameter dm and is compared with that from scaling laws for fractal-like agglomerates. The ratio dm/dg of the mobility diameter to the gyration diameter of the agglomerate decreases with increasing relative shape anisotropy. For constant dm and mean dp, the agglomerate settling rate, us, increases with increasing PP geometric standard deviation σp,g (polydispersity). A linear relationship between us and agglomerate mass to dm ratio, m/dm, is revealed and attributed to the fast Brownian rotation of such small and light nanoparticle agglomerates. An analytical expression for the us of agglomerates consisting of polydisperse PPs is then derived, us=(1/-{ρf/ρp})g 3 π μ m/dm (ρf is the density of the fluid, ρp is the density of PPs, μ is the viscosity of the fluid, and g is the acceleration of gravity), valid for agglomerates for which the characteristic rotational time is considerably shorter than their settling time. Our calculations demonstrate that the commonly made assumption of monodisperse PPs underestimates us by a fraction depending on σp,g and agglomerate mass mobility exponent. Simulations are in excellent agreement with deposition rate measurements of fumed SiO2 agglomerates in water.

Cognition and event-related potentials in adult-onset non-demented myotonic dystrophy type 1.

PubMed

Tanaka, H; Arai, M; Harada, M; Hozumi, A; Hirata, K

2012-02-01

To clarify the cognitive and event-related potentials (ERPs) profiles of adult-onset genetically-proven non-demented myotonic dystrophy type 1 (DM1). Fourteen DM1 patients and matched 14 normal controls were enrolled. DM1 patients were compared with normal controls, using a variety of neuropsychological tests; an auditory "oddball" counting paradigm for the ERPs, and low-resolution brain electromagnetic tomography (LORETA). For patients, ERPs and neuropsychological parameters were correlated with CTG repeat size, duration of illness, grip strength, and arterial blood gas analysis. Frontal lobe dysfunction, prolonged N1 latency, and attenuated N2/P3 amplitudes were observed in DM1. Longer CTG repeat size was associated with fewer categories achieved on Wisconsin Card Sorting Test. Greater grip strength was associated with better scores on color-word "interference" of Stroop test. P3 latency was negatively correlated with PaO(2). LORETA revealed significant hypoactivities at the orbitofrontal and medial temporal lobe, cingulate, and insula. There was no correlation between ERPs and CTG expansion. Adult-onset non-demented DM1 presented frontal lobe dysfunction. Absence of correlations between CTG repeat size and objective ERP parameters suggested CTG expansion in lymphocytes does not directly contribute to cognitive dysfunction. CTG expansion in lymphocytes does not directly contribute to cognitive dysfunction of adult-onset non-demented DM1. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

MALDI-TOF mass spectrometry for the monitoring of she-donkey's milk contamination or adulteration.

PubMed

Cunsolo, Vincenzo; Muccilli, Vera; Saletti, Rosaria; Foti, Salvatore

2013-02-01

Donkey's milk (DM), representing a safe and alternative food in both IgE-mediated and non-IgE-mediated cow's milk protein allergy, can be categorized as precious pharma-food. Moreover, an economically relevant interest for the use of DM in cosmetology is also developing. The detection of adulterations and contaminations of DM is a matter of fundamental importance from both an economic and allergenic standpoint, and, to this aim, fast and efficient analytical approaches to assess the authenticity of this precious nutrient are desirable. Here, a rapid matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS)-based method aimed to the detection of bovine or caprine milk in raw DM is reported. The presence of the extraneous milks was revealed by monitoring the protein profiles of the most abundant whey proteins, α-lactalbumin (α-LA) and β-lactoglobulin, used as molecular markers. The possibility of obtaining a quantitative analysis of the level of cow or goat milk in DM based on the MALDI-TOF peak areas of α-LAs was also explored. The results showed that the experimental quantitative values were in good agreement with the real composition of each mixture. As pretreatment of the milk samples is not required, and owing to the speed and the high sensitivity of MALDI-MS, the protocol here reported could represent a reliable method for routine analyses aimed to assess the absence of contamination in raw fresh DM samples. Copyright © 2013 John Wiley & Sons, Ltd.

Validity of leptin receptor-deficiency (db/db) type 2 diabetes mellitus mice as a model of secondary osteoporosis.

PubMed

Huang, Le; You, Yong-Ke; Zhu, Tracy Y; Zheng, Li-Zhen; Huang, Xiao-Ru; Chen, Hai-Yong; Yao, Dong; Lan, Hui-Yao; Qin, Ling

2016-06-10

This study aimed to evaluate the validation of the leptin receptor-deficient mice model for secondary osteoporosis associated with type 2 diabetes mellitus (T2DM) at bone micro-architectural level. Thirty three 36-week old male mice were divided into four groups: normal control (db/m) (n = 7), leptin receptor-deficient T2DM (db/db) (n = 8), human C-reactive protein (CRP) transgenic normal control (crp/db/m) (n = 7), and human CRP transgenic T2DM (crp/db/db) (n = 11). Lumber vertebrae (L5) and bilateral lower limbs were scanned by micro-CT to analyze trabecular and cortical bone quality. Right femora were used for three-point bending to analyze the mechanical properties. Trabecular bone quality at L5 was better in db/db or crp/db/db group in terms of bone mineral density (BMD), bone volume fraction, connectivity density, trabecular number and separation (all p < 0.05). However the indices measured at proximal tibia showed comparable trabecular BMD and microarchitecture among the four groups. Femur length in crp/db/db group was significantly shorter than db/m group (p < 0.05) and cortices were thinner in db/db and crp/db/db groups (p > 0.05). Maximum loading and energy yield in mechanical test were similar among groups while the elastic modulus in db/db and crp/db/db significantly lower than db/m. The leptin-receptor mice is not a proper model for secondary osteoporosis associated with T2DM.

Association of Dental Care with Adherence to HEDIS Measures

PubMed Central

Mosen, David; Pihlstrom, Dan; Snyder, John; Smith, Ning; Shuster, Elizabeth; Rust, Kristal

2016-01-01

Context: The dental setting represents an unrealized opportunity to increase adherence to preventive services and improve health outcomes. Objective: To compare adherence to a subset of Healthcare Effectiveness Data and Information Set (HEDIS) measures among a population that received dental care with a population that did not receive dental care. Design: Using a retrospective cohort design, we identified 5216 adults who received regular dental care and 5216 persons who did not. The groups were matched on propensity scores, were followed for 3 years, and retained medical and dental benefits. Receipt of dental care was defined as 1 or more dental visits in each 12-month period. Main Outcome Measures: Outcome measures were assessed in a subpopulation that qualified for 1 of 5 HEDIS denominator groups (dental = 4184 patients; nondental = 3871 patients). They included 3 preventive measures (cervical, colorectal, and breast cancer screening), 4 chronic disease management services (hemoglobin A1c and low-density lipoprotein cholesterol testing, and nephropathy and retinopathy screening among the diabetes mellitus [DM] population), and 4 health outcome measures (poor glycemic control, low-density lipoprotein cholesterol control, blood pressure control in the DM population, and blood pressure control in the hypertensive population). Results: Dental care was associated with higher adherence to all three cancer screening measures, one of four disease management services (higher retinopathy screening), and three of four health outcomes (better glycemic control in the DM population and better blood pressure control in the DM and hypertensive populations). Conclusions: Dental care was associated with improved adherence to 7 of 11 HEDIS measures. PMID:26580145

Validity of leptin receptor-deficiency (db/db) type 2 diabetes mellitus mice as a model of secondary osteoporosis

NASA Astrophysics Data System (ADS)

Huang, Le; You, Yong-Ke; Zhu, Tracy Y.; Zheng, Li-Zhen; Huang, Xiao-Ru; Chen, Hai-Yong; Yao, Dong; Lan, Hui-Yao; Qin, Ling

2016-06-01

This study aimed to evaluate the validation of the leptin receptor-deficient mice model for secondary osteoporosis associated with type 2 diabetes mellitus (T2DM) at bone micro-architectural level. Thirty three 36-week old male mice were divided into four groups: normal control (db/m) (n = 7), leptin receptor-deficient T2DM (db/db) (n = 8), human C-reactive protein (CRP) transgenic normal control (crp/db/m) (n = 7), and human CRP transgenic T2DM (crp/db/db) (n = 11). Lumber vertebrae (L5) and bilateral lower limbs were scanned by micro-CT to analyze trabecular and cortical bone quality. Right femora were used for three-point bending to analyze the mechanical properties. Trabecular bone quality at L5 was better in db/db or crp/db/db group in terms of bone mineral density (BMD), bone volume fraction, connectivity density, trabecular number and separation (all p < 0.05). However the indices measured at proximal tibia showed comparable trabecular BMD and microarchitecture among the four groups. Femur length in crp/db/db group was significantly shorter than db/m group (p < 0.05) and cortices were thinner in db/db and crp/db/db groups (p > 0.05). Maximum loading and energy yield in mechanical test were similar among groups while the elastic modulus in db/db and crp/db/db significantly lower than db/m. The leptin-receptor mice is not a proper model for secondary osteoporosis associated with T2DM.

Precise small molecule recognition of a toxic CUG RNA repeat expansion

PubMed Central

Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

2017-01-01

Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG)exp) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG)exp. In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG)exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG)exp in its natural context. PMID:27941760

Precise small-molecule recognition of a toxic CUG RNA repeat expansion.

PubMed

Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

2017-02-01

Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG) exp ) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG) exp . In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG) exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG) exp in its natural context.

Epigenetics of the myotonic dystrophy-associated DMPK gene neighborhood

PubMed Central

Buckley, Lauren; Lacey, Michelle; Ehrlich, Melanie

2016-01-01

Aim: Identify epigenetic marks in the vicinity of DMPK (linked to myotonic dystrophy, DM1) that help explain tissue-specific differences in its expression. Materials & methods: At DMPK and its flanking genes (DMWD, SIX5, BHMG1 and RSPH6A), we analyzed many epigenetic and transcription profiles from myoblasts, myotubes, skeletal muscle, heart and 30 nonmuscle samples. Results: In the DMPK gene neighborhood, muscle-associated DNA hypermethylation and hypomethylation, enhancer chromatin, and CTCF binding were seen. Myogenic DMPK hypermethylation correlated with high expression and decreased alternative promoter usage. Testis/sperm hypomethylation of BHMG1 and RSPH6A was associated with testis-specific expression. G-quadruplex (G4) motifs and sperm-specific hypomethylation were found near the DM1-linked CTG repeats within DMPK. Conclusion: Tissue-specific epigenetic features in DMPK and neighboring genes help regulate its expression. G4 motifs in DMPK DNA and RNA might contribute to DM1 pathology. PMID:26756355

[The profile of plasma non-esterified fatty acids in children with different terms of type 1 diabetes mellitus].

PubMed

Akmurzina, V A; Petryairina, E E; Saveliev, S V; Selishcheva, A A

2016-01-01

Composition and quantitative content of non-esterified fatty acids (NEFA) were investigated in plasma samples of healthy children (12) and children with type 1 diabetes mellitus (DM1) (31) by gas chromatography (GC) after preliminary NEFA solid-phase extraction from plasma lipids. There was a significant (p<0.001) 1.6-fold increase in the total level of NEFA regardless of the disease duration. In the group of DM1 children with the disease period less than 1 year there was an increase in the arachidonic acid (20:4) content (30%) and the oleic acid trans-isomer (18:1) content (82%), and also a decrease in the docosahexaenoic acid (22:6 n3) content (26% ) and the docosapentaenoic acids (22:5 n-6) content (60%). In the group of DM1 children with prolonged course of this disease the altered NEFA levels returned to the normal level.

Cross-sectional study of patients with type 2 diabetes in OR Tambo district, South Africa

PubMed Central

Yogeswaran, Parimalaranie; Longo-Mbenza, Benjamin; Ter Goon, Daniel; Ajayi, Anthony Idowu

2016-01-01

Objectives South Africa has pledged to the sustainable development goal of promoting good health and well-being to all residents. While this is laudable, paucity of reliable epidemiological data for different regions on diabetes and treatment outcomes may further widen the inequalities of access and quality of healthcare services across the country. This study examines the sociodemographic and clinical determinants of uncontrolled type 2 diabetes mellitus (T2DM) in individuals attending primary healthcare in OR Tambo district, South Africa. Design A cross-sectional analytical study. Setting Primary healthcare setting in OR Tambo district, South Africa. Participants Patients treated for T2DM for 1 or more years (n=327). Primary outcome measure Prevalence of uncontrolled T2DM. Secondary outcome measure Determinants of uncontrolled T2DM (glycosylated haemoglobin (HbA1c) ≥7%). Results Out of the 327 participants, 274 had HbA1c≥7% (83.8%). Female sex (95% CI 1.3 to 4.2), overweight/obesity (95% CI 1.9 to 261.2), elevated low-density lipoprotein cholesterol (95% CI 4.4 to 23.8), sedentary habits (95% CI 7.2 to 61.3), lower monthly income (95% CI 1.3 to 6.5), longer duration of T2DM (95% CI 4.4 to 294.2) and diabetes information from non-health workers (95% CI 1.4 to 7.0) were the significant determinants of uncontrolled T2DM. There was a significant positive correlation of uncontrolled T2DM with increasing duration of T2DM, estimated glomerular filtration rate and body mass index. However, a significant negative correlation exists between monthly income and increasing HbA1c. Conclusions We found a significantly high prevalence (83.8%) of uncontrolled T2DM among the patients, possibly attributable to overweight/obesity, sedentary living, lower income and lack of information on diabetes. Addressing these determinants will require re-engineering of primary healthcare in the district. PMID:27473948

Prevalence of unrecognized diabetes, prediabetes and metabolic syndrome in patients undergoing elective percutaneous coronary intervention.

PubMed

Balakrishnan, Revathi; Berger, Jeffrey S; Tully, Lisa; Vani, Anish; Shah, Binita; Burdowski, Joseph; Fisher, Edward; Schwartzbard, Arthur; Sedlis, Steven; Weintraub, Howard; Underberg, James A; Danoff, Ann; Slater, James A; Gianos, Eugenia

2015-09-01

Diabetes mellitus (DM) and metabolic syndrome are important targets for secondary prevention in cardiovascular disease. However, the prevalence in patients undergoing elective percutaneous coronary intervention is not well defined. We aimed to analyse the prevalence and characteristics of patients undergoing percutaneous coronary intervention with previously unrecognized prediabetes, diabetes and metabolic syndrome. Data were collected from 740 patients undergoing elective percutaneous coronary intervention between November 2010 and March 2013 at a tertiary referral center. Prevalence of DM and prediabetes was evaluated using Haemoglobin A1c (A1c ≥ 6.5% for DM, A1c 5.7-6.4% for prediabetes). A modified definition was used for metabolic syndrome [three or more of the following criteria: body mass index ≥30 kg/m2; triglycerides ≥ 150 mg/dL; high density lipoprotein <40 mg/dL in men and <50 mg/dL in women; systolic blood pressure ≥ 130 mmHg and/or diastolic ≥ 85 mmHg; and A1c ≥ 5.7% or on therapy]. Mean age was 67 years, median body mass index was 28.2 kg/m(2) and 39% had known DM. Of those without known DM, 8.3% and 58.5% met A1c criteria for DM and for prediabetes at time of percutaneous coronary intervention. Overall, 54.9% met criteria for metabolic syndrome (69.2% of patients with DM and 45.8% of patients without DM). Among patients undergoing elective percutaneous coronary intervention, a substantial number were identified with a new DM, prediabetes, and/or metabolic syndrome. Routine screening for an abnormal glucometabolic state at the time of revascularization may be useful for identifying patients who may benefit from additional targeting of modifiable risk factors. Copyright © 2015 John Wiley & Sons, Ltd.

P2Y12 shRNA treatment decreases SGC activation to relieve diabetic neuropathic pain in type 2 diabetes mellitus rats.

PubMed

Wang, Shouyu; Wang, Zilin; Li, Lin; Zou, Lifang; Gong, Yingxin; Jia, Tianyu; Zhao, Shanhong; Yuan, Huilong; Shi, Liran; Liu, Shuangmei; Wu, Bing; Yi, Zhihua; Liu, Hui; Gao, Yun; Li, Guilin; Deussing, Jan M; Li, Man; Zhang, Chunping; Liang, Shangdong

2018-06-26

Diabetic neuropathic pain is a common complication of type 2 diabetes mellitus (DM). Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in neuropathic pain through the release of proinflammatory cytokines. The P2Y12 receptor is expressed in SGCs of the DRG. In this study, our aim was to investigate the role of the P2Y12 receptor on the pathological changes in diabetic neuropathic pain. The present study showed that diabetic neuropathic pain increased mechanical and thermal hyperalgesia in type 2 DM model rats. The results showed that the expression levels of P2Y12 messenger RNA (mRNA) and protein in DRG SGCs were increased in DM model rats compared with control rats. Glial fibrillary acidic protein (GFAP) and interleukin-1β (IL-1β) expression levels in the DRG were increased in DM rats. Upregulation of GFAP is a marker of SGC activation. Targeting the P2Y12 receptor by short hairpin RNA (shRNA) decreased the upregulated expression of P2Y12 mRNA and protein, coexpression of P2Y12 and GFAP, the expression of GFAP, IL-1β, and tumor necrosis factor-receptor 1 in the DRG of DM rats, and relieved mechanical and thermal hyperalgesia in DM rats. After treatment with the P2Y12 receptor shRNA, the enhancing integrated OPTICAL density (IOD) ratios of p-P38 MAPK to P38 mitogen activated protein kinase (MAPK) in the DM rats treated with P2Y12 shRNA were significantly lower than that in the untreated DM rats. Therefore, P2Y12 shRNA treatment decreased SGC activation to relieve mechanical and thermal hyperalgesia in DM rats. © 2018 Wiley Periodicals, Inc.

Validation of Type 2 Diabetes Risk Variants Identified by Genome-Wide Association Studies in Northern Han Chinese

PubMed Central

Rao, Ping; Zhou, Yong; Ge, Si-Qi; Wang, An-Xin; Yu, Xin-Wei; Alzain, Mohamed Ali; Veronica, Andrea Katherine; Qiu, Jing; Song, Man-Shu; Zhang, Jie; Wang, Hao; Fang, Hong-Hong; Gao, Qing; Wang, You-Xin; Wang, Wei

2016-01-01

Background: More than 60 genetic susceptibility loci associated with type 2 diabetes mellitus (T2DM) have been established in populations of Asian and European ancestry. Given ethnic differences and environmental factors, validation of the effects of genetic risk variants with reported associations identified by Genome-Wide Association Studies (GWASs) is essential. The study aims at evaluating the associations of T2DM with 29 single nucleotide polymorphisms (SNPs) from 19 candidate genes derived from GWASs in a northern Han Chinese population. Method: In this case-control study, 461 T2DM-diagnosed patients and 434 controls were recruited at the Jidong oil field hospital (Hebei, China) from January 2009 to October 2013. A cumulative genetic risk score (cGRS) was calculated by summation of the number of risk alleles, and a weight GRS (wGRS) was calculated as the sum of risk alleles at each locus multiplied by their effect sizes for T2DM, using the independent variants selected. Result: The allelic frequency of the “A” allele at rs17106184 (Fas-associated factor 1, FAF1) was significantly higher in the T2DM patients than that of the healthy controls (11.7% vs. 6.4%, p < 0.001). Individuals in the highestquartile of wGRS had an over three-fold increased risk for developing T2DM compared with those in the lowest quartile (odds ratio = 3.06, 95% CI = 1.92–4.88, p < 0.001) adjusted for age, sex, BMI, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP). The results were similar when analyzed with the cGRS. Conclusions: We confirmed the association between rs17106184 (FAF1) and T2DM in a northern Han Chinese population. The GRS calculated based on T2DM susceptibility variants may be a useful tool for predicting the T2DM susceptibility. PMID:27589775

Correlation between reactive oxygen metabolites & atherosclerotic risk factors in patients with type 2 diabetes mellitus

PubMed Central

Kotani, Kazuhiko; Tsuzaki, Kokoro; Taniguchi, Nobuyuki; Sakane, Naoki

2013-01-01

Background & objectives: Oxidative stress plays important roles in the pathophysiology of type 2 diabetes mellitus (T2DM). The diacron reactive oxygen metabolites (d-ROMs) test has been used in the clinics. The present study was aimed to investigate the correlation of the oxidative stress status, as evaluated by the d-ROMs, with atherosclerotic risk factors in T2DM patients, in comparison to controls. Methods: The study included 200 subjects (100 patients with T2DM and 100 controls; 86 males/114 females; mean age 59.0 yr). Clinical variables including the body mass index, blood pressure (BP), glucose and lipid panels, in addition to the d-ROMs, were measured. Results: Patients with T2DM showed significantly higher d-ROMs levels than controls (322 ± 60 vs. 345 ± 64 U. Carr., P<0.05). A multiple linear regression analysis revealed that systolic BP (β=0.26, P<0.05) and high-density lipoprotein cholesterol (HDL-C: β= -0.30, P<0.05) were independently and significantly correlated with the d-ROMs levels in patients with T2DM, although these correlations were not significant in the controls. The gender-based analysis showed that systolic BP (β = 0.44, P<0.05) and HDL-C (β = -0.36, P<0.05) were independently and significantly correlated with the d-ROMs levels in females with T2DM, while there was a marginally significant correlation between HDL-C and the d-ROMs levels (β = -0.36, P=0.06) in males with T2DM. Interpretation & conclusions: The present findings may reinforce the importance of BP control in female patients with T2DM, as well as the management of HDL-C in male and female patients with T2DM, under the linkage between oxidative stress and atherosclerosis. PMID:23703342

Commercially available avian and mammalian whole prey diet items targeted for consumption by managed exotic and domestic pet felines: true metabolizable energy and amino acid digestibility using the precision-fed cecectomized rooster assay.

PubMed

Kerr, K R; Kappen, K L; Garner, L M; Utterback, P L; Parsons, C M; Swanson, K S

2014-10-01

Whole prey diets are commonly used in the zoo and home setting for captive exotic and domestic cats, respectively. Despite their increase in popularity, nutrient digestibility of such diets has been poorly studied. In this study, the precision-fed cecectomized rooster assay was used to determine the protein quality and nitrogen-corrected true ME (TMEn) of 17 whole prey samples (mice [1 to 2 , 10 to 13 , 21 to 25 , 30 to 40 , and 150 to 180 d old], rats [1 to 4, 10 to 13, 21 to 25, 32 to 42, and >60 d old], rabbits [stillborn, 30 to 45 d old, and >65 d old], chicken [1 to 3 d old], and quail [1 to 3, 21 to 40, and >60 d old]) and 2 ground poultry-based products (chicken and duck). Amino acid score (AAS) and protein digestibility corrected AAS (PDCAAS) were calculated using the nutrient profile recommendations for domestic cat food as a reference value (AAFCO, 2012). Average individual indispensable AA (IAA) and total IAA (TIAA) digestibility coefficients were variable anddepended on AA (84 to 94% TIAA, 85 to 95% Arg, 87 to 96% His, 82 to 92% Ile, 84 to 94% Leu, 85 to 93% Lys, 89 to 97% Met, 83 to 94% Phe, 80 to 95% Thr, 84 to 94% Trp, and 80 to 93% Val) and sample. For a majority of the whole prey items, AA concentrations were greater than the Association of American Feed Control Officials ( AAFCO: , 2012) domestic cat nutrient profile recommendations for growth and reproduction and adult maintenance; however, some whole prey had AA concentrations below the AAFCO (2012) recommendations: Met + Cys (1.10% DM) in ground duck (1.06% DM) and taurine (Tau; 0.20% DM) in 30-to-45- and >65-d-old rabbits (0.01 and 0.10% DM, respectively), 150-to-180-d-old mice (0.18% DM), and ground duck (0.15% DM). The TMEn (3.76 to 6.44 kcal/g DM) expressed as the percent of GE (i.e., TMEn/GE) ranged from 66 to 85%, demonstrating how variable the digestibility of these items may be and justifying more research in this area. Both Met and Tau are commonly added to commercial pet foods, so supplements are readily available to address potential deficiencies and improve protein quality. A direct comparison of the ME of whole prey items by in vivo feline and rooster experiments is needed.

Practical Focus on American Diabetes Association/European Association for the Study of Diabetes Consensus Algorithm in Patients with Type 2 Diabetes Mellitus: Timely Insulin Initiation and Titration (Iran-AFECT).

PubMed

Khamseh, Mohammad Ebrahim; Yousefzadeh, Gholamreza; Banazadeh, Zahra; Ghareh, Sahar

2017-02-01

The aim of this study was to evaluate the safety and effectiveness of insulin glargine in a large population from a variety of clinical care in Iranian people with type 2 diabetes mellitus (T2DM) and to measure the percentage of patients achieving glycosylated hemoglobin (HbA1c) <7% by the end of 24 weeks of treatment in routine clinical practice. This study was a 24 week, observational study of patients with T2DM, for whom the physician had decided to initiate or to switch to insulin glargine. The safety and efficacy of glargine were assessed at baseline and at week 24. Seven hundred and twenty-five people with T2DM (63% female) including both insulin naïve and prior insulin users were recruited in this study. The mean age of the participants was 54.2±11.2 years, and the mean HbA1c level was 8.88%±0.93% at baseline. By the end of the study, 27% of the entire participants reached to HbA1c target of less than 7% and 52% had HbA1c ≤7.5%. No serious adverse event was reported in this study. Furthermore, overall hypoglycemia did not increase in prior insulin users and the entire cohort. In addition, body weight did not change in participants while lipid profile improved significantly. Treatment with insulin glargine could improve glycemic control without increasing the risk of hypoglycemic events in people with T2DM. In addition, a significant clinical improvement was observed in lipid profile. Copyright © 2017 Korean Diabetes Association

Investigation of serotonin transporter gene (SLC6A4) by child abuse history interaction with body mass index and diabetes mellitus of White female depressed psychiatric inpatients.

PubMed

Shinozaki, Gen; Romanowicz, Magdalena; Kung, Simon; Rundell, James; Mrazek, David

2012-06-01

The serotonin transporter gene promoter polymorphism (5HTTLPR) and child abuse have been associated with an increased risk for depression. We previously reported the long/long (l/l) genotype of 5HTTLPR being associated with higher heart rate among patients with a history of child abuse compared with those without a history of child abuse, whereas the short allele carriers did not have heart rate differences dependent on child abuse history. This time, we extended our investigation to other outcomes with body mass index (BMI), and diabetes mellitus (DM) diagnosis. A retrospective chart review identified 185 White female depressed inpatients who were genotyped for 5HTTLPR. Child abuse history, BMI, and DM diagnosis were recorded. The relationship between 5HTTLPR, child abuse, and BMI, as well as a prevalence of DM were analyzed. Among the l/l genotype group, patients with a history of child abuse had a higher prevalence of DM (14.3 vs. 0%, P=0.06), and higher BMI (32.3 vs. 27.3 kg/m, P=0.03) compared with those without. Patients with the short allele (s/s or s/l) had fewer differences on the basis of abuse history. A potential interaction between 5HTTLPR and child abuse influenced metabolic profiles of White female depressed inpatients. In contrast with the widely recognized 'reactivity' associated with the short allele of 5HTTLPR, our White female depressed psychiatric inpatients with the l/l genotype showed relatively greater clinical pathology in metabolic profiles if they have a history of child abuse than inpatients with at least one short allele who had a history of child abuse.

Replacement of grass and maize silages with lucerne silage: effects on performance, milk fatty acid profile and digestibility in Holstein-Friesian dairy cows.

PubMed

Sinclair, L A; Edwards, R; Errington, K A; Holdcroft, A M; Wright, M

2015-12-01

In total, 20 multiparous Holstein-Friesian dairy cows received one of four diets in each of four periods of 28-day duration in a Latin square design to test the hypothesis that the inclusion of lucerne in the ration of high-yielding dairy cows would improve animal performance and milk fatty acid (FA) composition. All dietary treatments contained 0.55 : 0.45 forage to concentrates (dry matter (DM) basis), and within the forage component the proportion of lucerne (Medicago sativa), grass (Lolium perenne) and maize silage (Zea mays) was varied (DM basis): control (C)=0.4 : 0.6 grass : maize silage; L20=0.2 : 0.2 : 0.6 lucerne : grass : maize silage; L40=0.4 : 0.6 lucerne : maize silage; and L60=0.6 : 0.4 lucerne : maize silage. Diets were formulated to contain a similar CP and metabolisable protein content, with the reduction of soya bean meal and feed grade urea with increasing content of lucerne. Intake averaged 24.3 kg DM/day and was lowest in cows when fed L60 (P0.05) by dietary treatment. Digestibility of DM, organic matter, CP and fibre decreased (P<0.01) with increasing content of lucerne in the diet, although fibre digestibility was similar in L40 and L60. It is concluded that first cut grass silage can be replaced with first cut lucerne silage without any detrimental effect on performance and an improvement in the milk FA profile, although intake and digestibility was lowest and plasma urea concentrations highest in cows when fed the highest level of inclusion of lucerne.

Triglyceride-to-high-density-lipoprotein-cholesterol ratio is an index of heart disease mortality and of incidence of type 2 diabetes mellitus in men.

PubMed

Vega, Gloria Lena; Barlow, Carolyn E; Grundy, Scott M; Leonard, David; DeFina, Laura F

2014-02-01

High triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) impart risk for heart disease. This study examines the relationships of TG/HDL-C ratio to mortality from all causes, coronary heart disease (CHD), or cardiovascular disease (CVD). Survival analysis was done in 39,447 men grouped by TG/HDL-C ratio cut point of 3.5 and for metabolic syndrome. National Death Index International Classification of Diseases (ICD-9 and ICD-10) codes were used for CVD and CHD deaths occurring from 1970 to 2008. Incidence of type 2 diabetes mellitus (DM) according to ratio was estimated in 22,215 men. Triglyceride/HDL-C ratio and cross-product of TG and fasting blood glucose (TyG index) were used in analysis. Men were followed up for 581,194 person-years. Triglyceride/HDL-C ratio predicted CHD, CVD, and all-cause mortality after adjustment for established risk factors and non-HDL-C. Mortality rates were higher in individuals with a high ratio than in those with a low ratio. Fifty-five percent of men had metabolic syndrome that was also predictive of CHD, CVD, and all-cause mortality. Annual incidence of DM was 2 times higher in men with high TG/HDL-C ratio than in those with a low ratio. Individuals with high TG/HDL-C ratio had a higher incidence of DM than those with a low ratio. The TyG index was not equally predictive of causes of mortality to TG/HDL-C, but both were equally predictive of diabetes incidence. Triglyceride/HDL-C ratio predicts CHD and CVD mortality as well as or better than do metabolic syndrome in men. Also, a high ratio predisposes to DM. The TyG index does not predict CHD, CVD, or all-cause mortality equally well, but like TG/HDL-C ratio, it predicts DM incidence.

Effect of bile acid sequestrants on glycaemic control: protocol for a systematic review with meta-analysis of randomised controlled trials.

PubMed

Hansen, Morten; Sonne, David Peick; Mikkelsen, Kristian Hallundbæk; Gluud, Lise Lotte; Vilsbøll, Tina; Knop, Filip Krag

2012-01-01

In addition to the lipid-lowering effect of bile acid sequestrants (BASs), they also lower blood glucose and, therefore, could be beneficial in the treatment of patients with type 2 diabetes mellitus (T2DM). Three oral BASs are approved by the US Food and Drug Administration (FDA) for the treatment of hypercholesterolaemia: colestipol, cholestyramine and colesevelam. The BAS colestimide/colestilan is used in Japan. Colesevelam was recently approved by the FDA for the treatment of T2DM. We plan to provide a systematic review with meta-analysis of the glucose-lowering effect of BASs with the aim to evaluate their potential as glucose-lowering agents in patients with T2DM. In accordance with the preferred reporting items for systematic reviews and meta-analyses statement, a systematic review with meta-analysis of randomised clinical trials of BASs (vs placebo, oral antidiabetes drugs or insulin), reporting measures of glycaemic control in adult patients with T2DM, will be performed. Change in glycated haemoglobin constitutes the primary endpoint, and secondary endpoints include changes in fasting plasma glucose, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, triglycerides, body weight and body mass index and adverse events. Electronic searches will be performed in The Cochrane Library, MEDLINE and EMBASE, along with manual searches in the reference lists of relevant papers. The analyses will be performed based on individual patient data and summarised data. The primary meta-analysis will be performed using random effects models owing to expected intertrial heterogeneity. Dichotomous data will be analysed using risk difference and continuous data using weighted mean differences, both with 95% CIs. The study will evaluate the potential of BASs as glucose-lowering agents and possibly contribute to the clinical management of patients with T2DM. The study will be disseminated by peer-review publication and conference presentation. PROSPERO CRD42012002552.

A generalized model for estimating the energy density of invertebrates

USGS Publications Warehouse

James, Daniel A.; Csargo, Isak J.; Von Eschen, Aaron; Thul, Megan D.; Baker, James M.; Hayer, Cari-Ann; Howell, Jessica; Krause, Jacob; Letvin, Alex; Chipps, Steven R.

2012-01-01

Invertebrate energy density (ED) values are traditionally measured using bomb calorimetry. However, many researchers rely on a few published literature sources to obtain ED values because of time and sampling constraints on measuring ED with bomb calorimetry. Literature values often do not account for spatial or temporal variability associated with invertebrate ED. Thus, these values can be unreliable for use in models and other ecological applications. We evaluated the generality of the relationship between invertebrate ED and proportion of dry-to-wet mass (pDM). We then developed and tested a regression model to predict ED from pDM based on a taxonomically, spatially, and temporally diverse sample of invertebrates representing 28 orders in aquatic (freshwater, estuarine, and marine) and terrestrial (temperate and arid) habitats from 4 continents and 2 oceans. Samples included invertebrates collected in all seasons over the last 19 y. Evaluation of these data revealed a significant relationship between ED and pDM (r2  =  0.96, p < 0.0001), where ED (as J/g wet mass) was estimated from pDM as ED  =  22,960pDM − 174.2. Model evaluation showed that nearly all (98.8%) of the variability between observed and predicted values for invertebrate ED could be attributed to residual error in the model. Regression of observed on predicted values revealed that the 97.5% joint confidence region included the intercept of 0 (−103.0 ± 707.9) and slope of 1 (1.01 ± 0.12). Use of this model requires that only dry and wet mass measurements be obtained, resulting in significant time, sample size, and cost savings compared to traditional bomb calorimetry approaches. This model should prove useful for a wide range of ecological studies because it is unaffected by taxonomic, seasonal, or spatial variability.

Bioactive Androgens and Glucuronidated Androgen Metabolites are Associated with Subcutaneous and Ectopic Skeletal Muscle Adiposity among Older Black Men

PubMed Central

Miljkovic, Iva; Cauley, Jane A; Dressen, Amy S; Gordon, Christopher L; Goodpaster, Bret H; Kuller, Lewis H; Bunker, Clareann H; Patrick, Alan L; Wheeler, Victor W; Orwoll, Eric S; Zmuda, Joseph M

2011-01-01

Aging is associated with declining serum levels of androgenic hormones and with increased skeletal muscle fat infiltration, an emerging risk factor for type 2 diabetes mellitus (T2DM). Androgens regulate fat mass and glucose homeostasis, but the effect of androgenic hormones on skeletal muscle fat infiltration is largely unknown. Thus, the aim of the current study was to examine the association of serum androgens and their precursors and metabolites with skeletal muscle fat infiltration and T2DM in a black male population group at high risk of T2DM. Serum androgens, estrogens, and androgen precursors and metabolites were measured using mass spectrometry, and calf skeletal muscle fat distribution [subcutaneous and intermuscular fat; skeletal muscle density] were measured using quantitative computed tomography in 472 Afro-Caribbean men aged 65 and older. Bioactive androgens, testosterone, free testosterone and dihydrotestosterone, were associated with less skeletal muscle fat infiltration (r=−0.14 to −0.18, P<0.05) and increased skeletal muscle density (r=0.10 to 0.14, P<0.05), independent of total adiposity. Additionally, glucuronidated androgen metabolites were associated with less subcutaneous fat (r=−0.11 to −0.15, P<0.05). Multivariate logistic regression analysis identified an increased level of 3α-diol-3 glucuronide (OR=1.38, P<0.01) and a decreased level of dihydrotestosterone (OR=0.66, P<0.01) to be significantly associated with T2DM. Our findings suggest that in elderly black men, independent of total adiposity, bioactive androgens and glucuronidated androgen metabolites may play previously unrecognized role in skeletal muscle fat distribution. Longitudinal studies are needed to further evaluate the relationship between androgens and androgen metabolites with changes in skeletal muscle fat distribution with aging and the incidence of T2DM. PMID:21353258

NAMPT -3186C/T polymorphism affects repaglinide response in Chinese patients with Type 2 diabetes mellitus.

PubMed

Sheng, Fei-Feng; Dai, Xing-Ping; Qu, Jian; Lei, Guang-Hua; Lu, Hong-Bin; Wu, Jing; Xu, Xiao-Jing; Pei, Qi; Dong, Min; Liu, Ying-Zi; Zhou, Hong-Hao; Liu, Zhao-Qian

2011-08-01

1. In the present study, we investigated the associations of nicotinamide phosphoribosyltransferase (NAMPT)-3186 C/T and -948G/T polymorphisms with the risk of Type 2 diabetes mellitus (T2DM) and their impact on the efficacy of repaglinide in Chinese Han T2DM patients. 2. In all, 170 patients with T2DM and 129 healthy controls were genotyped for NAMPT-948G>T and -3186C>T polymorphisms. Thirty-five patients with different NAMPT -3186 C/T genotypes and the same organic anion-transporting polypeptide 1B1 (OATP1B1521) T/C genotype were randomly selected to undergo 8 weeks preprandial repaglinide treatment (1 mg, three times daily). Serum fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), glycated haemoglobin (HbAlc), fasting serum insulin (FINS), post-prandial serum insulin (PINS), triglyceride (TG), total cholesterol (CHO), homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were determined before and after repaglinide treatment. 3. After repaglinide treatment for 8 consecutive weeks, there were significantly decreases in PFG, PPG, HbAlc, CHO and LDL-C, and increases in FINS, HDL-C and the HDL-C : LDL-C ratio, in T2DM patients. The elevated PINS value in patients with CT genotypes was significantly lower than that in patients with the CC and TT genotypes (P < 0.05) and there were significant differences in CHO between patients with the CT genotype and the CC or TT genotype (P < 0.05). 4. The data suggest that the NAMPT -3186C>T polymorphism is significantly associated with plasma levels of PINS and CHO in Chinese T2DM patients with repaglinide monotherapy. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

Control of risk factors for cardiovascular disease among adults with previously diagnosed type 2 diabetes mellitus: a descriptive study from a middle eastern arab population.

PubMed

Al-Lawati, Jawad A; N Barakat, Mohammed; Al-Zakwani, Ibrahim; Elsayed, Medhat K; Al-Maskari, Masoud; M Al-Lawati, Nawar; Mohammed, Ali Jaffer

2012-01-01

Despite the high burden of type 2 diabetes mellitus (T2DM) in Oman, there are scarce data from a nationally representative sample on the level of glycaemia and other cardiovascular (CVD) risk factor control. To estimate the proportion of patients with T2DM at goal for glycaemia and CVD risk factors using the National Diabetes Guidelines (NDG) and the American Diabetes Association (ADA) clinical care guidelines; and to assess the quality of selected services provided to patients with T2DM. A sample of 2,551 patients (47% men) aged ≥20 years with T2DM treated at primary health care centers was selected. Patient characteristics, medical history and treatment were collected from case notes, Diabetes Registers and computer frameworks including the use of the last 3 laboratory investigations results and blood pressure (BP) readings recorded in 2007. The overall mean age of the cohort was 54±13 years with an average median duration of diabetes of 4 (range 2 to 6) years. Over 80% of patients were overweight or obese (body mass index (BMI) of ≥25 Kg/m(2)). Sixty-nine percent were on oral anti-diabetic medication, 52% on anti-hypertensives and 40% on lipid lowering drugs. Thirty percent of patients were at goal for glycosylated haemoglobin level (<7%), 26% for BP (systolic/diastolic <130/80 mmHg), 55% for total cholesterol (<5.2 mmol/l), 4.5% for low-density lipoprotein cholesterol (<1.8 mmol/l), 52% for high-density lipoprotein cholesterol (>1 mmol/l for men, >1.3 mmol/l for women), and 61% for triglycerides (<1.7 mmol/l). Over 37% had micro-albuminuria and 5% had diabetic nephropathy. Control of hyperglycaemia and other CVD risk factor appears to be suboptimal in Omani patients with T2DM and need to be addressed in the triad of patient, physician and health system.

Partial characterization, antioxidative properties and hypolipidemic effects of oilseed cake of Allanblackia floribunda and Jatropha curcas.

PubMed

Boudjeko, Thaddée; Ngomoyogoli, Judith Emery Kanemoto; Woguia, Alice Louise; Yanou, Nicolas Njintang

2013-12-11

High fat diet is known to induce oxidative stress and abnormal changes in lipid metabolism. Many traditional plants have been shown to possess antioxidant and lipid-lowering activities, improving on oxidative status and lipid profile. In this paper, we characterized and examined the antioxidative properties of the oilseed cake of A. floribunda and J. curcas. We also evaluated their effect on lipid profile in the plasma and liver of experimental rats placed on a high fat diet. For a partial characterization, the qualitative and quantitative analyses of storage proteins, dietary fibre and polyphenol content were evaluated. Four extracts (aqueous, ethanolic, methanolic and 0.1 N HCl) were evaluated for their antioxidant properties and scavenging activities. The effect on lipid profile was evaluated after the administration of the crude extracts to albino rats placed on a high fat diet. Our results showed that J. curcas contains 10 times more storage proteins than A. floribunda while A. floribunda contains twice as much total dietary fibre than J. curcas. An evaluation of the different families of storage proteins showed that J. curcas has glutelins as the major storage proteins in its seeds (61.65 mg/g d.m), followed by globulins (25.30 mg/g d.m) and albumins (18.30 mg/g d.m). The electrophoretic analyses revealed a diversity of bands at the level of the different families and for both species. The evaluation of the in vitro antioxidant activities showed that A. floribunda extracts had higher antioxidant properties. Although the composition of A. floribunda and J. curcas oilseed cake are different, they lowered serum triglycerides (TG), total cholesterol (TC) and blood glucose level. These results show that the oilseed cake of A. floribunda and J. curcas possess antioxidant properties with an effect on blood glucose level and lipid profile.

Partial characterization, antioxidative properties and hypolipidemic effects of oilseed cake of Allanblackia floribunda and Jatropha curcas

PubMed Central

2013-01-01

Background High fat diet is known to induce oxidative stress and abnormal changes in lipid metabolism. Many traditional plants have been shown to possess antioxidant and lipid-lowering activities, improving on oxidative status and lipid profile. In this paper, we characterized and examined the antioxidative properties of the oilseed cake of A. floribunda and J. curcas. We also evaluated their effect on lipid profile in the plasma and liver of experimental rats placed on a high fat diet. Methods For a partial characterization, the qualitative and quantitative analyses of storage proteins, dietary fibre and polyphenol content were evaluated. Four extracts (aqueous, ethanolic, methanolic and 0.1 N HCl) were evaluated for their antioxidant properties and scavenging activities. The effect on lipid profile was evaluated after the administration of the crude extracts to albino rats placed on a high fat diet. Results Our results showed that J. curcas contains 10 times more storage proteins than A. floribunda while A. floribunda contains twice as much total dietary fibre than J. curcas. An evaluation of the different families of storage proteins showed that J. curcas has glutelins as the major storage proteins in its seeds (61.65 mg/g d.m), followed by globulins (25.30 mg/g d.m) and albumins (18.30 mg/g d.m). The electrophoretic analyses revealed a diversity of bands at the level of the different families and for both species. The evaluation of the in vitro antioxidant activities showed that A. floribunda extracts had higher antioxidant properties. Although the composition of A. floribunda and J. curcas oilseed cake are different, they lowered serum triglycerides (TG), total cholesterol (TC) and blood glucose level. Conclusion These results show that the oilseed cake of A. floribunda and J. curcas possess antioxidant properties with an effect on blood glucose level and lipid profile. PMID:24330337

Impact of post-meal and one-time daily exercise in patient with type 2 diabetes mellitus: a randomized crossover study.

PubMed

Pahra, Daizy; Sharma, Nitasha; Ghai, Sandhya; Hajela, Abhishek; Bhansali, Shobhit; Bhansali, Anil

2017-01-01

To evaluate the effectiveness of short-timed post-meal and one-time daily exercise on glycemic control in patients with T2DM. Sixty-four T2DM patients were randomised into crossover design. Group A (n = 32) underwent post-meal exercise (moderate-intensity brisk walking covering 1500-1600 steps for 15 min, starting 15 min after each meal) from d1 to d60 followed by one-time daily exercise (45 min pre-breakfast brisk walking at stretch covering 4500-4800 steps) from d61 to d120, while it was vice versa for the group B (n = 32). The five-point blood glucose profile was performed on d1, d30, d60, d90 and d120, and HbA1c on d1, d60 and d120. Fitness wrist band was used for step-counting to ensure the intensity of exercise and compliance to exercise protocol. Group A patients showed a significant improvement in five point blood glucose profile and HbA1c after performing post-meal exercise (p < 0.001), which was mitigated after switchover to one-time daily exercise (p < 0.001). While, group B patients showed improvement in glucose profile and HbA1c (p < 0.001) after performing post-meal exercise, as compared to one-time daily exercise. Further, on pooled analysis (post-meal versus one-time daily exercise group) the beneficial effect of post-meal exercise on glucose profile and HbA1c was consistent as compared to one time daily exercise and the significance persisted on comparison between the two groups. No hypoglycemic events were noted between the groups during the study period. Post-meal exercise is more effective than routine one-time daily exercise for glycemic control in T2DM patients.

Association of Parental Obesity and Diabetes Mellitus With Circulating Adipokines in Nonobese Nondiabetic Offspring.

PubMed

Zachariah, Justin P; Quiroz, Rene; Enserro, Danielle; Andersson, Charlotte; Keaney, John F; Sullivan, Lisa M; Vasan, Ramachandran S

2017-07-16

Adipokines are implicated in the development of obesity-related traits. We hypothesized that nonobese participants without diabetes mellitus (DM) whose parents were obese or had DM would have altered circulating adipokines compared with those without parental history of these conditions. Participants in the community-based Framingham Third Generation cohort who were not obese (body mass index <30) and not diabetic with both parents in the Framingham Offspring cohort were included in this analysis (n=2034, mean age 40 years, 54% women). Circulating concentrations of fetuin A, RBP4 (retinol binding protein 4), FABP4 (fatty acid binding protein 4), leptin, LEP-R (leptin receptor), and adiponectin were assayed. Parental DM was defined as occurring before age 60 years, and obesity was defined as body mass index ≥30 before age 60 years. General estimating equations were used to compare concentrations of adipokines among participants with 0, 1, or 2 parents affected by obesity or DM (separate analyses for each), adjusting for known correlates of adipokines. Overall, 44% had at least 1 parent who was obese and 15% had parents with DM. Parental obesity was associated with higher serum levels of FABP4 and LEP-R in their offspring ( P =0.02 for both). Parental DM was associated with lower adiponectin but higher RBP4 concentrations in offspring ( P ≤0.02 for both). In our community-based sample, a parental history of DM or obesity was associated with an altered adipokine profile in nonobese nondiabetic offspring. Additional studies are warranted to evaluate whether such preclinical biomarker alterations presage future risk of disease. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Progression from impaired glucose tolerance to type 2 diabetes in obese children and adolescents: a 3-6-year cohort study in southern Thailand.

PubMed

Jaruratanasirikul, Somchit; Thammaratchuchai, Sudarat; Puwanant, Maneerat; Mo-Suwan, Ladda; Sriplung, Hutcha

2016-11-01

Childhood obesity is associated with abnormal glucose metabolism and type 2 diabetes mellitus (T2DM). This study evaluated the prevalence of abnormal glucose metabolism in asymptomatic obese children and adolescents, and determined the percentage of T2DM development after 3-6 years of follow-up. During 2007-2013, 177 obese children and adolescents who had normal fasting plasma glucose (FPG<100 mg/dL) were given an oral glucose tolerance test (OGTT). The participants were classified into four groups: normal glucose tolerance (NGT), NGT-hyperinsulinemia (NGT-HI), impaired glucose tolerance (IGT), and diabetes mellitus (DM). Blood chemistries, including FPG, glycated hemoglobin, and lipid profiles, and liver function test were performed every 6-12 months or when the patient developed any symptom or sign indicative of diabetes. Glucose metabolism alterations were detected in 81.4% of the participants: 63.8% with NGT-HI, 15.3% with IGT, and 2.3% with T2DM. The median levels of homeostasis model assessment-insulin resistance (HOMA-IR) in patients with IGT (8.63) were significantly greater than those in the patients with NGT (4.04) (p<0.01). During the follow-up, 22 patients (14.4%) developed T2DM significantly more from the IGT group (nine of 33 cases, 27.3%) than the NGT-HI group (12 of 108 cases, 11.1%) (p=0.022). The predicting parameters for T2DM conversion were weight status, body mass index (BMI), FBG, fasting insulin, alanine transaminase (ALT) levels, and HOMA-IR. Glucose metabolism alteration was commonly found among obese adolescents. Factors associated with T2DM development were greater weight status and the severity of insulin resistance as shown by higher HOMA-IR levels.

Association of polymorphism in adiponectin (+45 T/G) and leptin (–2548 G/A) genes with type 2 diabetes mellitus in male Egyptians

PubMed Central

Motawi, Tarek; Salman, Tarek; Shaker, Olfat

2015-01-01

Introduction Adiponectin is an adipose tissue-specific protein with insulin-sensitizing properties. Many investigators have explored the association between adiponectin single nucleotide polymorphisms (SNPs) and type 2 diabetes mellitus (T2DM) in different ethnic populations from different regions. Leptin is a protein hormone constituting an important signal in the regulation of adipose tissue mass and body weight. The aim of this study was to explore potential associations between SNP +45 T>G of the adiponectin gene and SNP 2548G/A of leptin with T2DM and the effect of SNPs on serum adiponectin and leptin levels. Material and methods From the Egyptian population, we enrolled 110 T2DM patients and 90 non-diabetic controls. Serum lipid profile, blood glucose, serum adiponectin, and leptin were measured. Genotyping for two common SNPs of the adiponectin and leptin genes was performed by polymerase chain reaction–restriction fragment length polymorphism. Results The G allele and TG/GG genotype of SNP 45 occurred more frequently than the T allele and TT genotype in T2DM patients compares to the controls. Subjects with the GG + TG genotype of SNP 45 were at increased risk for T2DM (OR = 6.476; 95% CI: 3.401–12.33) and associated with a low serum adiponectin level compared with the TT genotype. The serum leptin concentration of GA + AA genotype carriers was not significantly different from that of the GG genotype in the diabetic group. Conclusions The G allele carriers who have reduced plasma concentrations of adiponectin may have an association with T2DM, while leptin SNP 2548 G/A is not associated with the risk of development of T2DM in the Egyptian population. PMID:26528333

Impact of clinical status and salivary conditions on xerostomia and oral health-related quality of life of adolescents with type 1 diabetes mellitus.

PubMed

Busato, Ivana Maria Saes; Ignácio, Sérgio Aparecido; Brancher, João Armando; Moysés, Simone Tetu; Azevedo-Alanis, Luciana Reis

2012-02-01

To investigate the influence of clinical status and salivary conditions on the presence of xerostomia on adolescents with and without type 1 diabetes mellitus (DM1), and further to investigate the influence of clinical status, salivary conditions and xerostomia on oral health-related quality of life (OHQoL) of those with DM1. A cross-sectional study was performed on 102 adolescents, 51 with DM1 and 51 nondiabetics. Xerostomia was detected by asking a question about the sensation of having 'dry mouth', and Oral Health Impact Profile-14 was used to measure the impact of xerostomia on OHQoL. The clinical status was assessed by using decayed, missing or filled and Community Periodontal indices, and by evaluating oral manifestations; and the following salivary conditions were evaluated: stimulated salivary flow, pH, buffer capacity, total protein, amylase, urea, calcium, and glucose salivary concentrations. Multiple logistic regression analysis was used to evaluate the influence of clinical status and salivary conditions on xerostomia and the impact of xerostomia on the OHQoL of adolescents with DM1. Clinical status and salivary conditions was shown to have no influence on the presence of xerostomia. Bivariate (P = 0.00) and logistic regression (P = 0.01) analysis showed a significant association between DM1 and xerostomia. Logistic regression analysis showed association between xerostomia (P = 0.00) and OHQoL, and caries experience (P = 0.03) and OHQoL. DM1 showed to be predictive of a high prevalence of xerostomia in adolescents. Caries experience and xerostomia showed to have a negative impact on the OHQoL of adolescents with DM1. © 2011 John Wiley & Sons A/S.

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial.

PubMed

Maggioni, Aldo P; Greene, Stephen J; Fonarow, Gregg C; Böhm, Michael; Zannad, Faiez; Solomon, Scott D; Lewis, Eldrin F; Baschiera, Fabio; Hua, Tsushung A; Gimpelewicz, Claudio R; Lesogor, Anastasia; Gheorghiade, Mihai

2013-10-01

The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without DM.

Clinical characteristics of patients with type 2 diabetes mellitus at the time of insulin initiation: INSTIGATE observational study in Spain

PubMed Central

Dilla, Tatiana; Reviriego, Jesús; Castell, Conxa; Goday, Albert

2009-01-01

Little information is available on the management of patients with type 2 diabetes mellitus (DM2) in regular clinical practice, prior to and at the point of initiating treatment with insulin. The INSTIGATE study provides a description of the clinical profile of the patient with DM2 who begins treatment with insulin in both primary and secondary care. A total of 224 patients who had been diagnosed with DM2, were not responding to oral treatment, and began receiving insulin were included in the INSTIGATE study in Spain. Demographic data were collected, as well as data on macro- and microvascular complications of diabetes and comorbidities, past medical history of diabetes and oral treatment administered, the clinical severity of diabetes (HbA1c concentration) and insulin treatment initiated. Mean age of the sample was 65.4 years and 56.7% were men. There were 87% of patients who had a diagnosis of at least one significant comorbidity, notably hypertension and hyperlipidemia. The patient profile for metabolic syndrome was met by 75.1% of the patients. There was a higher incidence of macrovascular complications (38.4%) than microvascular complications (16.1%). Prior to insulin initiation, the most recent mean HbA1c was 9.2%. The majority of patients had been treated in the last 12 months with sulfonylureas and/or metformin (69.6 and 57.6%). The most common treatment prior to insulinization was the co-administration of two oral antidiabetics (OADs) (37.5%). Patients with DM2 observed in the study presented with elevated mean HbA1c and body mass index levels, comorbidities and complications related to diabetes at the time of insulin initiation. Changes and adjustments in treatment from diagnosis of diabetes occur when HbA1c levels are far above those recommended by the IDF (International Diabetes Federation), a factor which could be contributing to the development of both macrovascular and microvascular complications in the patient profile described in the study. PMID:19855919

Gravitational waves with dark matter minispikes: The combined effect

NASA Astrophysics Data System (ADS)

Yue, Xiao-Jun; Han, Wen-Biao

2018-03-01

It was shown that the dark matter (DM) minihalo around an intermediate mass black hole (IMBH) can be redistributed into a cusp, called the DM minispike. We consider an intermediate-mass-ratio inspiral consisting of an IMBH harbored in a DM minispike with nonannihilating DM particles and a small black hole (BH) orbiting around it. We investigate gravitational waves (GWs) produced by this system and analyze the waveforms with the comprehensive consideration of gravitational pull, dynamical friction and accretion of the minispike and calculate the time difference and phase difference caused by it. We find that for a certain range of frequency, the inspiralling time of the system is dramatically reduced for smaller central IMBH and large density of DM. For the central IMBH with 105 M⊙ , the time of merger is ahead, which can be distinguished by LISA, Taiji and Tianqin. We focus on the effect of accretion and compare it with that of gravitational pull and friction. We find that the accretion mass is a small quantity compared to the initial mass of the small BH and the accretion effect is inconspicuous compared with friction. However, the accumulated phase shift caused by accretion is large enough to be detected by LISA, Taiji, and Tianqin, which indicate that the accretion effect can not be ignored in the detection of GWs.

Fermionic dark matter with pseudo-scalar Yukawa interaction

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

Ghorbani, Karim, E-mail: k-ghorbani@araku.ac.ir

2015-01-01

We consider a renormalizable extension of the standard model whose fermionic dark matter (DM) candidate interacts with a real singlet pseudo-scalar via a pseudo-scalar Yukawa term while we assume that the full Lagrangian is CP-conserved in the classical level. When the pseudo-scalar boson develops a non-zero vacuum expectation value, spontaneous CP-violation occurs and this provides a CP-violated interaction of the dark sector with the SM particles through mixing between the Higgs-like boson and the SM-like Higgs boson. This scenario suggests a minimal number of free parameters. Focusing mainly on the indirect detection observables, we calculate the dark matter annihilation crossmore » section and then compute the DM relic density in the range up to m{sub DM} = 300 GeV.We then find viable regions in the parameter space constrained by the observed DM relic abundance as well as invisible Higgs decay width in the light of 125 GeV Higgs discovery at the LHC. We find that within the constrained region of the parameter space, there exists a model with dark matter mass m{sub DM} ∼ 38 GeV annihilating predominantly into b quarks, which can explain the Fermi-LAT galactic gamma-ray excess.« less

Genome-wide association study identifies three key loci for high mesocarp oil content in perennial crop oil palm

PubMed Central

Teh, Chee-Keng; Ong, Ai-Ling; Kwong, Qi-Bin; Apparow, Sukganah; Chew, Fook-Tim; Mayes, Sean; Mohamed, Mohaimi; Appleton, David; Kulaveerasingam, Harikrishna

2016-01-01

GWAS in out-crossing perennial crops is typically limited by insufficient marker density to account for population diversity and effects of population structure resulting in high false positive rates. The perennial crop oil palm is the most productive oil crop. We performed GWAS for oil-to-dry-mesocarp content (O/DM) on 2,045 genotyped tenera palms using 200K SNPs that were selected based on the short-range linkage disequilibrium distance, which is inherent with long breeding cycles and heterogeneous breeding populations. Eighty loci were significantly associated with O/DM (p ≤ 10−4) and three key signals were found. We then evaluated the progeny of a Deli x AVROS breeding trial and a 4% higher O/DM was observed amongst those having the beneficial genotypes at two of the three key loci (p < 0.05). We have initiated MAS and large-scale planting of elite dura and pisifera parents to generate the new commercial tenera palms with higher O/DM potential. PMID:26743827

Sustained Exendin-4 Secretion through Gene Therapy Targeting Salivary Glands in Two Different Rodent Models of Obesity/Type 2 Diabetes

PubMed Central

Raimondi, Laura; Pagano, Claudio; Egan, Josephine M.; Cozzi, Andrea; Cinci, Lorenzo; Loreto, Andrea; Manni, Maria E.; Berretti, Silvia; Morelli, Annamaria; Zheng, Changyu; Michael, Drew G.; Maggi, Mario; Vettor, Roberto; Chiorini, John A.; Mannucci, Edoardo; Rotella, Carlo M.

2012-01-01

Exendin-4 (Ex-4) is a Glucagon-like peptide 1 (GLP-1) receptor agonist approved for the treatment of Type 2 Diabetes (T2DM), which requires daily subcutaneous administration. In T2DM patients, GLP-1 administration is reported to reduce glycaemia and HbA1c in association with a modest, but significant weight loss. The aim of present study was to characterize the site-specific profile and metabolic effects of Ex-4 levels expressed from salivary glands (SG) in vivo, following adeno-associated virus-mediated (AAV) gene therapy in two different animal models of obesity prone to impaired glucose tolerance and T2DM, specifically, Zucker fa/fa rats and high fed diet (HFD) mice. Following percutaneous injection of AAV5 into the salivary glands, biologically active Ex-4 was detected in the blood of both animal models and expression persisted in salivary gland ductal cell until the end of the study. In treated mice, Ex-4 levels averaged 138.9±42.3 pmol/L on week 6 and in treated rats, mean circulating Ex-4 levels were 238.2±72 pmol/L on week 4 and continued to increase through week 8. Expression of Ex-4 resulted in a significant decreased weight gain in both mice and rats, significant improvement in glycemic control and/or insulin sensitivity as well as visceral adipose tissue adipokine profile. In conclusion, these results suggest that sustained site-specific expression of Ex-4 following AAV5-mediated gene therapy is feasible and may be useful in the treatment of obesity as well as trigger improved metabolic profile. PMID:22808093