Aims/hypothesis
Increased inflammation and oxidative stress are associated with insulin resistance (IR) and metabolic disorders. Serum histidine levels are lower and are negatively associated with ...inflammation and oxidative stress in obese women. The objective of this study was to evaluate the efficacy of histidine supplementation on IR, inflammation, oxidative stress and metabolic disorders in obese women with the metabolic syndrome (MetS).
Methods
A total of 100 obese women aged 33–51 years with BMI ≥ 28 kg/m
2
and diagnosed with MetS were included following a health examination in the community hospital in this randomised, double-blinded, placebo-controlled trial. Participants were allocated to interventions by an investigator using sequentially numbered sealed envelopes and received 4 g/day histidine (
n
= 50) or identical placebo (
n
= 50) for 12 weeks. Participants then attended the same clinic every 2 weeks for scheduled interviews and to count tablets returned. Serum histidine, HOMA-IR, BMI, waist circumference, fat mass, serum NEFA, and variables connected to inflammation and oxidative stress were measured at baseline and 12 weeks. Participants, examining physicians and investigators assessing the outcomes were blinded to group assignment. In addition, the inflammatory mechanisms of histidine were also explored in adipocytes.
Results
At 12 weeks, a total of 92 participants completed this trail. Compared with the placebo group (
n
= 47), histidine supplementation significantly decreased HOMA-IR (−1.09 95% CI −1.49, −0.68), BMI (−0.86 kg/m
2
95% CI −1.55, −0.17), waist circumference (−2.86 cm 95% CI −3.86, −1.86), fat mass (−2.71 kg 95% CI −3.69, −1.73), serum NEFA (−173.26 μmol/l 95% CI −208.57, −137.94), serum inflammatory cytokines (TNF-α, −3.96 pg/ml 95% CI −5.29, −2.62; IL-6, −2.15 pg/ml 95% CI −2.52, −1.78), oxidative stress (superoxide dismutase, 17.84 U/ml 95% CI 15.03, 20.65; glutathione peroxidase, 13.71 nmol/ml 95% CI 9.65, 17.78) and increased serum histidine and adiponectin by 18.23 μmol/l 95% CI 11.74, 24.71 and 2.02 ng/ml 95% CI 0.60, 3.44 in histidine supplementation group (
n
= 45), respectively. There were significant correlations between changes in serum histidine and changes of IR and its risk factors. No side effects were observed during the intervention. In vitro study indicated that histidine suppresses
IL6
and
TNF
mRNA expression and nuclear factor kappa-B (NF-κB) protein production in palmitic acid-induced adipocytes in a dose-dependent manner, and these changes were diminished by an inhibitor of NF-κB.
Conclusions/interpretation
Histidine supplementation could improve IR, reduce BMI, fat mass and NEFA and suppress inflammation and oxidative stress in obese women with MetS; histidine could improve IR through suppressed pro-inflammatory cytokine expression, possibly by the NF-κB pathway, in adipocytes.
Trial registration
www.chictr.org/cn/ChiCTR-TRC-11001551
Funding
The study was supported by the National Natural Science Fund of China (No. 81202184, 81130049, 81102112), Heilongjiang Post/doctoral Fund (No. LBN-Z12193) and Key Laboratory of Nutrition and Food Hygiene (Harbin Medical University, Heilongjiang Higher Education Institutions, No. YYKFKT1202).
Room temperature loading of metallic glasses, at stresses below the macroscopic yield stress, raises their enthalpy and causes creep. Thermal cycling of metallic glasses between room temperature and ...77 K also raises their enthalpy. In both cases, the enthalpy increases are comparable to those induced by heavy plastic deformation, but, as we show, the origins must be quite different. For plastic deformation, the enthalpy increase is a fraction (<10%) of the work done (WD) (and, in this sense, the behaviour is similar to that of conventional polycrystalline metals and alloys). In contrast, the room temperature creep and the thermal cycling involve small strains well within the elastic limit; in these cases, the enthalpy increase in the glass exceeds the WD, by as much as three orders of magnitude. We argue that the increased enthalpy can arise only from an endothermic disordering process drawing heat from the surroundings. We examine the mechanisms of this process. The increased enthalpy ('stored energy') is a measure of rejuvenation and appears as an exothermic heat of relaxation on heating the glass. The profile of this heat release (the 'relaxation spectrum') is analysed for several metallic glasses subjected to various treatments. Thus, the effects of the small-strain processing (creep and thermal cycling) can be better understood, and we can explore the potential for improving properties, in particular the plasticity, of metallic glasses. Metallic glasses can exhibit a wide range of enthalpy at a given temperature, and small-strain processing may assist in accessing this for practical purposes.
Context.Our position inside the Galaxy requires 3D-modelling to obtain the distribution of the Galactic magnetic field, cosmic-ray (CR) electrons and thermal electrons. Aims.Our intention is to find ...a Galactic 3D-model which agrees best with available radio observations. Methods.We constrain simulated all-sky maps in total intensity, linear polarization, and rotation measure (RM) by observations. For the simulated maps as a function of frequency we integrate in 15' wide cones the emission along the line of sight calculated from Galactic 3D-models. We test a number of large-scale magnetic field configurations and take the properties of the warm interstellar medium into account. Results.From a comparison of simulated and observed maps we are able to constrain the regular large-scale Galactic magnetic field in the disk and the halo of the Galaxy. The local regular field is 2 μG and the average random field is about 3 μG. The known local excess of synchrotron emission originating either from enhanced CR electrons or random magnetic fields is able to explain the observed high-latitude synchrotron emission. The thermal electron model (NE2001) in conjunction with a proper filling factor accounts for the observed optically thin thermal emission and low frequency absorption by optically thick emission. A coupling factor between thermal electrons and the random magnetic field component is proposed, which in addition to the small filling factor of thermal electrons increases small-scale RM fluctuations and thus accounts for the observed depolarization at 1.4 GHz. Conclusions.We conclude that an axisymmetric magnetic disk field configuration with reversals inside the solar circle fits available observations best. Out of the plane a strong toroidal magnetic field with different signs above and below the plane is needed to account for the observed high-latitude RMs. The large field strength is a consequence of the small thermal electron scale height of 1 kpc, which also limits the CR electron extent up to a height of 1 kpc not to contradict with the observed synchrotron emission out of the plane. Our preferred 3D-model fits the observed Galactic total intensity and polarized emission better than other models over a wide frequency range and also agrees with the observed RM from extragalactic sources.
Although many common diseases occur mostly in old age, the impact of ageing itself on disease risk and expression often goes unevaluated. To consider the impact of ageing requires some useful means ...of measuring variability in health in animals of the same age. In humans, this variability has been quantified by counting age-related health deficits in a frailty index. Here we show the results of extending that approach to mice. Across the life course, many important features of deficit accumulation are present in both species. These include gradual rates of deficit accumulation (slope = 0.029 in humans; 0.036 in mice), a submaximal limit (0.54 in humans; 0.44 in mice), and a strong relationship to mortality (1.05 1.04-1.05 in humans; 1.15 1.12-1.18 in mice). Quantifying deficit accumulation in individual mice provides a powerful new tool that can facilitate translation of research on ageing, including in relation to disease.
The aim of our study was to systematically review studies which had compared self‐concept in left‐behind children with the general population of children in China. Relevant studies about self‐concept ...of left‐behind children in China published from 2004 to 2014 were sought by searching online databases including Chinese Biological Medicine Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, Vip Database, PubMed Database, Google Scholar and Web of Science. The methodological quality of the articles was assessed by using Newcastle‐Ottawa Scale (NOS). Poled effect size and associated 95% confidence interval (CI) were calculated using the random effects model. Cochrane's Q was used to test for heterogeneity and I2 index was used to determine the degree of heterogeneity. Nineteen studies involving 7758 left‐behind children met the inclusion criteria and 15 studies were included in a meta‐analysis. The results indicated that left‐behind group had a lower score of self‐concept and more psychological problems than the control group. The factors associated with self‐concept in left‐behind children were gender, age, grade and the relationships with parents, guardians and teachers. Left‐behind children had lower self‐concept and more mental health problems compared with the general population of children. The development of self‐concept may be an important channel for promoting mental health of left‐behind children.
Excessive alcohol use, a major cause of morbidity and mortality, is less well understood than other addictive disorders. Dopamine release in ventral striatum is a common element of drug reward, but ...alcohol has an unusually complex pharmacology, and humans vary greatly in their alcohol responses. This variation is related to genetic susceptibility for alcoholism, which contributes more than half of alcoholism risk. Here, we report that a functional OPRM1 A118G polymorphism is a major determinant of striatal dopamine responses to alcohol. Social drinkers recruited based on OPRM1 genotype were challenged in separate sessions with alcohol and placebo under pharmacokinetically controlled conditions, and examined for striatal dopamine release using positron emission tomography and (11)C-raclopride displacement. A striatal dopamine response to alcohol was restricted to carriers of the minor 118G allele. To directly establish the causal role of OPRM1 A118G variation, we generated two humanized mouse lines, carrying the respective human sequence variant. Brain microdialysis showed a fourfold greater peak dopamine response to an alcohol challenge in h/mOPRM1-118GG than in h/mOPRM1-118AA mice. OPRM1 A118G variation is a genetic determinant of dopamine responses to alcohol, a mechanism by which it likely modulates alcohol reward.
Cogging torque, inherent in permanent magnet machines, is closely related to the airgap flux density harmonic contents. The third harmonic can be utilized in combination with the fundamental one to ...increase the average torque, whilst its relationship with cogging torque is uncertain. The aim of this paper is to investigate the effect of third harmonic in airgap flux density on cogging torque in surface-mounted permanent magnet (SPM) machines considering different slot/pole (S/P) combinations. First, based on the simplified expressions of cogging torque in machines with sinusoidal plus third harmonic (Sine+3rd) airgap flux density, S/P combinations are classified into four cases for discussion. It is found that when N s /GCD ( N s , N p ) ≥ 4 ( N s : slot number; N p : pole number; GCD: great common divisor), third harmonic in airgap flux density has no effect on cogging torque. Otherwise, cogging torque will be generated. Furthermore, two approaches for obtaining the Sine and Sine+3rd airgap flux density, i.e., Sine/Sine+3rd h m and Sine/Sine+3rd B r , are validated, based on which finite-element analyses are carried out on four machines, i.e., 12-slot/10-pole (12S12P), 12S6P, 12S8P, and 12S10P to verify the conclusion. Finally, the 12S8P and 12S10P Sine+3rd SPM machines are prototyped and tested for validation.
This prospective, randomized, phase III trial shows that prophylactic cranial irradiation prolongs disease-free survival, decreases the rate of cerebral metastases and does not affect quality-of-life ...for patients with fully resected postoperative pathologically confirmed stage IIIA-N2 non-small-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy.
This study compared prophylactic cranial irradiation (PCI) with observation in patients with resected stage IIIA–N2 non-small-cell lung cancer (NSCLC) and high risk of cerebral metastases after adjuvant chemotherapy.
In this open-label, randomized, phase III trial, patients with fully resected postoperative pathologically confirmed stage IIIA–N2 NSCLC and high cerebral metastases risk without recurrence after postoperative adjuvant chemotherapy were randomly assigned to receive PCI (30 Gy in 10 fractions) or observation. The primary end point was disease-free survival (DFS). The secondary end points included the incidence of brain metastases, overall survival (OS), toxicity and quality of life.
This trial was terminated early after the random assignment of 156 patients (81 to PCI group and 75 to control group). The PCI group had significantly lengthened DFS compared with the control group, with a median DFS of 28.5 months versus 21.2 months hazard ratio (HR), 0.67; 95% confidence interval (CI) 0.46–0.98;P = 0.037. PCI was associated with a decrease in risk of brain metastases (the actuarial 5-year brain metastases rate, 20.3% versus 49.9%; HR, 0.28; 95% CI 0.14–0.57;P < 0.001). The median OS was 31.2 months in the PCI group and 27.4 months in the control group (HR, 0.81; 95% CI 0.56–1.16;P = 0.310). While main toxicities were headache, nausea/vomiting and fatigue in the PCI group, they were generally mild.
In patients with fully resected postoperative pathologically confirmed stage IIIA–N2 NSCLC and high risk of cerebral metastases after adjuvant chemotherapy, PCI prolongs DFS and decreases the incidence of brain metastases.
Fatty liver, diagnosed by ultrasound, significantly predicts the 5-year incidence of type 2 diabetes regardless of insulin resistance status in 11,091 healthy Koreans.
Context:
Although fatty liver ...and insulin resistance are known to be associated, the relationship between the two in the development of type 2 diabetes mellitus (T2DM) is unclear.
Objective:
We investigated the 5-yr risk of developing T2DM in individuals diagnosed with fatty liver using ultrasound and stratified by insulin sensitivity using quartiles of fasting insulin concentration.
Design and Methods:
We examined the clinical and laboratory data of 11,091 Koreans who had a medical evaluation including fasting insulin concentration and abdominal ultrasound at baseline and had a follow-up after 5 yr.
Results:
At baseline, 27% of the population had fatty liver. Almost half (47%) of the individuals with fatty liver had baseline insulin concentration in the highest quartile compared with 17% in those without fatty liver (P < 0.001). Regardless of baseline insulin concentration, individuals with fatty liver had significantly (P < 0.001) more baseline clinical and metabolic abnormalities, including higher glucose and triglyceride concentration and lower high-density lipoprotein cholesterol concentration. In addition, regardless of baseline insulin concentration, individuals with fatty liver had a significantly increased risk for incident T2DM compared with those without fatty liver crude odds ratio, 5.05 (95% confidence interval, 2.08–12.29) in the lowest insulin quartile and 6.34 (3.58–11.21) in the highest quartile. In individuals in the highest insulin quartile, the odds ratio for developing T2DM remained significant even after multivariate adjustment including baseline glucose concentration 2.42 (1.23–4.75).
Conclusion:
Although associated with insulin resistance, fatty liver diagnosed by ultrasound appears to independently increase the risk of T2DM.
The present study was conducted to assess rumen bacteria in lactating cows with different milk protein yield, aiming to understand the role of rumen bacteria in this trait. Cows with high milk ...protein yield (high milk yield and high milk protein content, HH; n = 20) and low milk protein yield (low milk yield and low milk protein content, LL; n = 20) were selected from 374 mid-lactation Holstein dairy cows fed a high-grain diet. Measurement of the rumen fermentation products showed that the concentrations of ruminal total volatile fatty acids, propionate, butyrate, and valerate and the proportion of isobutyrate were higher in the HH cows than in the LL cows. Amplicon sequencing analysis of the rumen bacterial community revealed that the richness (Chao 1 index) of rumen microbiota was higher in the LL cows than in the HH cows. Among the 10 predominant bacterial phyla (relative abundance being >0.10%, present in >60% of animals within each group), the relative abundance of Proteobacteria was 1.36-fold higher in the HH cows than in the LL cows. At the genus level, the relative abundance of Succinivibrio was significantly higher and that of Clostridium tended to be higher in the LL cows than in the HH cows. Sharpea was 2.28-fold enriched in the HH cows compared with the LL cows. Different relationships between the relative abundances of rumen microbial taxa and volatile fatty acid concentrations were observed in the HH and the LL animals, respectively. Succinivibrio and Prevotella were positively correlated with acetate, propionate, and valerate in the LL cows, whereas Sharpea was positively correlated with propionate and valerate concentrations in the HH cows. Collectively, our results revealed that rumen bacterial richness and the relative abundances of several bacterial taxa significantly differed between dairy cows with high and low milk protein yields, suggesting the potential roles of rumen microbiota contributing to milk protein yield in dairy cows.
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