Adipokine secretion and lipolysis following gender-affirming treatment in transgender individuals.

BACKGROUND: The organ-specific effects of gender-affirming sex hormone treatment (GAHT) in transgender women (TW) and transgender men (TM) are insufficiently explored. This study investigated the effects of GAHT on adipose tissue function. METHODS: In a single-center interventional prospective study, 32 adults undergoing GAHT, 15 TW and 17 TM, were examined with anthropometry and abdominal subcutaneous adipose tissue biopsies obtained before initiation of treatment, 1 month after endogenous sex hormone inhibition and three and 11 months after initiated GAHT. Fat cell size, basal/stimulated lipolysis and cytokine secretion in adipose tissue were analyzed. RESULTS: TW displayed an increase in complement component 3a and retinol-binding protein 4 (RBP4) secretion after sex hormone inhibition, which returned to baseline following estradiol treatment. No changes in lipolysis were seen in TW. TM showed downregulation of RBP4 after treatment, but no changes in basal lipolysis. In TM, the estrogen suppression led to higher noradrenaline stimulated (NA) lipolysis that was normalized following testosterone treatment. At 11 months, the ratio of NA/basal lipolysis was lower compared to baseline. There were no significant changes in fat cell size in either TW or TM. CONCLUSION: In TW, gonadal hormone suppression results in transient changes in cytokines and in TM there are some changes in NA-stimulated lipolysis following testosterone treatment. However, despite the known metabolic effects of sex hormones, the overall effects of GAHT on adipose tissue function are small and likely have limited clinical relevance, but larger studies with longer follow-up are needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02518009, Retrospectively registered 7 August 2015.

Preferences regarding antibiotic treatment and the role of antibiotic resistance: A discrete choice experiment.

OBJECTIVES: To identify preferences of the Swedish public regarding antibiotic treatment characteristics and the relative weight of antibiotic resistance in their treatment choices. METHODS: A questionnaire including a discrete choice experiment questionnaire was answered by 378 Swedish participants. Preferences of the general public regarding five treatment characteristics (attributes) were measured: contribution to antibiotic resistance, cost, side effects, failure rate and treatment duration. Latent class analysis models were used to determine attribute-level estimates and heterogeneity in preferences. Relative importance of the attributes and willingness to pay for antibiotics with a lower contribution to antibiotic resistance were calculated from the estimates. RESULTS: All attributes influenced participants' preferences for antibiotic treatment. For the majority of participants, contribution to antibiotic resistance was the most important attribute. Younger respondents found contribution to antibiotic resistance more important in their choice of antibiotic treatments. Choices of respondents with lower numeracy, higher health literacy and higher financial vulnerability were influenced more by the cost of the antibiotic treatment. Older respondents with lower financial vulnerability and health literacy, and higher numeracy found side effects to be most important. CONCLUSIONS: All attributes can be considered as potential drivers of antibiotic use by lay people. Findings also suggest that the behaviour of lay people may be influenced by concerns over the rise of antibiotic resistance. Therefore, stressing individual responsibility for antibiotic resistance in clinical and societal communication has the potential to affect personal decision making.

Long-term changes in adipose tissue gene expression following bariatric surgery.

OBJECTIVE: Patients undergoing bariatric surgery present long-term metabolic improvements and reduced type 2 diabetes risk, despite long-term weight regain. We hypothesized that part of these protective effects could be linked to altered gene expression in white adipose tissue (WAT). METHODS: Transcriptomic profiling by gene microarray was performed in abdominal subcutaneous WAT from women before (n = 50) and two (n = 49) and five (n = 38) years after Roux-en-Y gastric bypass (RYGB) surgery as well as in 28 age-matched nonoperated women. RESULTS: In the obese women, the average body weight decrease was 38 kg 2 years postsurgery followed by an 8 kg weight regain between 2 and 5 years. Most of the long-term changes in WAT gene expression occurred during the first 2 years. However, a subset of genes encoding proteins involved in inflammation displayed a continued decrease between baseline, 2 and 5 years, respectively; that is an expression pattern independent of body weight regain. Expression of 71 of these genes correlated with measurements of adipocyte morphology or serum adipokine levels. CONCLUSION: The continuous improvement in WAT inflammatory gene expression, despite body weight relapse, may contribute to the sustained effects on adipose morphology after bariatric surgery.

Kynurenine aminotransferase isoforms display fiber-type specific expression in young and old human skeletal muscle.

Conversion of kynurenine (KYN) to kynurenic acid (KYNA) is the main pathway for free tryptophan degradation in skeletal muscle and has emerged as an important mechanism of how exercise is linked to promotion of mental health. Metabolism of KYN to KYNA mainly depends on the expression of kynurenine aminotransferases (KATs) that is under control of the mitochondria biogenesis regulator PGC-1α. We therefore hypothesized that expression of KATs would vary between muscle fibers that differ in mitochondrial content, i.e. oxidative type I vs more glycolytic type II muscle fibers. Moreover, we tested the hypothesis that KAT expression differs with age. Single muscle fibers were isolated from biopsies taken from the vastus lateralis muscle in young and old healthy subjects. In young and old subjects the abundance of KAT I, KAT III and KAT IV was greater in Type I than Type II fibers without age-dependent difference in the KAT isoform expressions. The link to mitochondrial content was further seen as the expression of KAT IV correlated to mitochondrial cytochrome c oxidase IV (COX IV) abundance in both fiber types. In conclusion, we describe for the first time the expression pattern of KAT isoforms with respect to specific fiber types and age in human skeletal muscle.

Adipose lipid turnover and long-term changes in body weight.

The worldwide obesity epidemic1 makes it important to understand how lipid turnover (the capacity to store and remove lipids) regulates adipose tissue mass. Cross-sectional studies have shown that excess body fat is associated with decreased adipose lipid removal rates2,3. Whether lipid turnover is constant over the life span or changes during long-term weight increase or loss is unknown. We determined the turnover of fat cell lipids in adults followed for up to 16 years, by measuring the incorporation of nuclear bomb test-derived 14C in adipose tissue triglycerides. Lipid removal rate decreases during aging, with a failure to reciprocally adjust the rate of lipid uptake resulting in weight gain. Substantial weight loss is not driven by changes in lipid removal but by the rate of lipid uptake in adipose tissue. Furthermore, individuals with a low baseline lipid removal rate are more likely to remain weight-stable after weight loss. Therefore, lipid turnover adaptation might be important for maintaining pronounced weight loss. Together these findings identify adipose lipid turnover as an important factor for the long-term development of overweight/obesity and weight loss maintenance in humans.

Insulin action is severely impaired in adipocytes of apparently healthy overweight and obese subjects.

OBJECTIVE: Many overweight/obese subjects appear metabolically healthy with normal in vivo insulin sensitivity. Still, they have increased long-term risk of developing type 2 diabetes. We hypothesized that adipose tissue dysfunction involving decreased insulin action in adipocytes is present in apparently healthy overweight/obese subjects. DESIGN/METHODS: Subjects with normal metabolic health according to Adult Treatment Panel-III or Framingham risk score criteria were subdivided into 67 lean, 32 overweight and 37 obese according to body mass index. They were compared with 200 obese individuals with metabolic syndrome. Insulin sensitivity and maximum action on inhibition of lipolysis and stimulation of lipogenesis was determined in subcutaneous adipocytes. Gene expression was determined by micro-array and qPCR. DNA methylation was assessed by array, pyrosequencing and reporter assays. RESULTS: Compared with lean, adipocytes in overweight/obese displayed marked reductions in insulin sensitivity in both antilipolysis and lipogenesis as well as an attenuated maximum lipogenic response. Among these, only antilipolysis sensitivity correlated with whole-body insulin sensitivity. These differences were already evident in the overweight state, were only slightly worse in the unhealthy obese state and were not related to fat cell size. Adipose tissue analyses linked this to reduced expression of the insulin signalling protein AKT2, which associated with increased methylation at regulatory sites in the AKT2 promoter. CONCLUSIONS: Apparently healthy subjects have severely disturbed adipocyte insulin signalling already in the overweight state which involves epigenetic dysregulation of AKT2. This may constitute an early defect in insulin action that appears even upon modest increases in fat mass.

Improved metabolism and body composition beyond normal levels following gastric bypass surgery: a longitudinal study.

BACKGROUND: The cardiometabolic risk profile improves following bariatric surgery. However, the degree of improvement in relation to weight-stable control subjects is unknown. OBJECTIVES: To study the differences in cardiometabolic risk profile between formerly obese patients following Roux-en-Y gastric bypass (RYGB) surgery and control subjects. METHODS: Subjects undergoing RYGB and reaching a BMI <30 kg m-2 2 years postsurgery were matched with control subjects regarding age, sex and BMI. The following examinations were performed: insulin sensitivity measured by hyperinsulinaemic-euglycaemic clamp, insulin clearance, homeostatic model assessment of insulin resistance (HOMA-IR), lipid profile, inflammatory marker levels, dual-energy X-ray absorptiometry and subcutaneous adipose tissue cellularity (fat cell size and number). RESULTS: Sixty-nine subjects undergoing RYGB were matched to a control subject. Insulin sensitivity measured by hyperinsulinaemic-euglycaemic clamp, blood pressure, inflammatory status and glucose, triglyceride and HDL cholesterol levels were comparable to values of control subjects. However, HOMA-IR (1.0 ± 0.5 vs. 1.3 ± 0.7, P = 0.005), insulin clearance (0.38 ± 0.08 vs. 0.34 ± 0.08 µL m-2  min-1 , P < 0.0001) and circulating levels of insulin (31 ± 15 vs. 37 ± 17 pmol L-1 , P = 0.008), total cholesterol (4.1 ± 0.7 vs. 4.8 ± 0.9 mmol L-1 , P < 0.0001) and LDL cholesterol (2.1 ± 0.6 vs. 2.9 ± 0.8 mmol L-1 , P < 0.0001) were improved beyond the levels in matched control subjects. Furthermore, formerly obese subjects had higher lean and lower fat mass as well as a more benign type of adipose cellularity (hyperplasia with many small fat cells) compared to control subjects. CONCLUSIONS: Subjects who underwent RYGB and reached a postobese state demonstrated a beneficial body composition, slightly increased insulin sensitivity as indirectly measured by HOMA-IR and higher insulin clearance, lower atherogenic lipid/lipoprotein levels and benign adipocyte morphology compared with control subjects who had never been obese. In line with previous results, our findings may in part explain why RYGB confers long-term protection against metabolic complications.

Predictable Phenotypes of Antibiotic Resistance Mutations.

Antibiotic-resistant bacteria represent a major threat to our ability to treat bacterial infections. Two factors that determine the evolutionary success of antibiotic resistance mutations are their impact on resistance level and the fitness cost. Recent studies suggest that resistance mutations commonly show epistatic interactions, which would complicate predictions of their stability in bacterial populations. We analyzed 13 different chromosomal resistance mutations and 10 host strains of Salmonella enterica and Escherichia coli to address two main questions. (i) Are there epistatic interactions between different chromosomal resistance mutations? (ii) How does the strain background and genetic distance influence the effect of chromosomal resistance mutations on resistance and fitness? Our results show that the effects of combined resistance mutations on resistance and fitness are largely predictable and that epistasis remains rare even when up to four mutations were combined. Furthermore, a majority of the mutations, especially target alteration mutations, demonstrate strain-independent phenotypes across different species. This study extends our understanding of epistasis among resistance mutations and shows that interactions between different resistance mutations are often predictable from the characteristics of the individual mutations.IMPORTANCE The spread of antibiotic-resistant bacteria imposes an urgent threat to public health. The ability to forecast the evolutionary success of resistant mutants would help to combat dissemination of antibiotic resistance. Previous studies have shown that the phenotypic effects (fitness and resistance level) of resistance mutations can vary substantially depending on the genetic context in which they occur. We conducted a broad screen using many different resistance mutations and host strains to identify potential epistatic interactions between various types of resistance mutations and to determine the effect of strain background on resistance phenotypes. Combinations of several different mutations showed a large amount of phenotypic predictability, and the majority of the mutations displayed strain-independent phenotypes. However, we also identified a few outliers from these patterns, illustrating that the choice of host organism can be critically important when studying antibiotic resistance mutations.

Piezomagnetism and magnetoelastic memory in uranium dioxide.

The thermal and magnetic properties of uranium dioxide, a prime nuclear fuel and thoroughly studied actinide material, remain a long standing puzzle, a result of strong coupling between magnetism and lattice vibrations. The magnetic state of this cubic material is characterized by a 3-k non-collinear antiferromagnetic structure and multidomain Jahn-Teller distortions, likely related to its anisotropic thermal properties. Here we show that single crystals of uranium dioxide subjected to strong magnetic fields along threefold axes in the magnetic state exhibit the abrupt appearance of positive linear magnetostriction, leading to a trigonal distortion. Upon reversal of the field the linear term also reverses sign, a hallmark of piezomagnetism. A switching phenomenon occurs at ±18 T, which persists during subsequent field reversals, demonstrating a robust magneto-elastic memory that makes uranium dioxide the hardest piezomagnet known. A model including a strong magnetic anisotropy, elastic, Zeeman, Heisenberg exchange, and magnetoelastic contributions to the total energy is proposed.The nuclear fuel uranium dioxide is of intrinsic interest due to its industrial applications but it also exhibits intriguing electronic and magnetic properties. Here, the authors demonstrate how its complex magnetic structure and interactions give rise to a strong piezomagnetic effect.

Abdominal subcutaneous adipose tissue cellularity in men and women.

BACKGROUND/OBJECTIVE: Differences in subcutaneous abdominal adipose tissue (SAT) fat cell size and number (cellularity) are linked to insulin resistance. Men are generally more insulin resistant than women but it is unknown whether there is a gender dimorphism in SAT cellularity. The objective was to determine SAT cellularity and its relationship to insulin sensitivity in men and women. METHODS: In a cohort study performed at an outpatient academic clinic in Sweden, 798 women and 306 men were included. Estimated SAT mass (ESAT) was derived from measures of dual-energy X-ray absorptiometry and a formula. SAT biopsies were obtained to measure mean fat cell size; SAT adipocyte number was obtained by dividing ESAT with mean fat cell weight. Fat cell size was also compared with level of insulin sensitivity in vivo. RESULTS: Over the entire range of body mass index (BMI) both fat cell size and number correlated positively with ESAT in either sex. On average, fat cell size was larger in men than in women, which was driven by significantly larger fat cells in non-obese men compared with non-obese women; no gender effect on fat cell size was seen in obese subjects. For all subjects fat cell number was larger in women than men, which was driven by a gender effect among non-obese individuals (P<0.0001). The relationship between fat cell size and insulin resistance was significant in both genders (P<0.0001) but steeper in men than in women (F=19, P<0.0001). CONCLUSIONS: Although both fat cell size and number determine SAT mass, adipocyte number contributes more and size less in women than in men and this is most evident in non-obese subjects. Over the entire BMI range, fat cell size contributes stronger to insulin resistance in men.

Pipe and grain boundary diffusion of He in UO2.

Molecular dynamics simulations have been conducted to study the effects of dislocations and grain boundaries on He diffusion in [Formula: see text]. Calculations were carried out for the {1 0 0}, {1 1 0} and {1 1 1} [Formula: see text] edge dislocations, the screw [Formula: see text] dislocation and Σ5, Σ13, Σ19 and Σ25 tilt grain boundaries. He diffusivity as a function of distance from the dislocation core and grain boundaries was investigated for the temperature range 2300-3000 K. An enhancement in diffusivity was predicted within 20 Å of the dislocations or grain boundaries. Further investigation showed that He diffusion in the edge dislocations follows anisotropic behaviour along the dislocation core, suggesting that pipe diffusion occurs. An Arrhenius plot of He diffusivity against the inverse of temperature was also presented and the activation energy calculated for each structure, as a function of distance from the dislocation or grain boundary.

Development of Xe and Kr empirical potentials for CeO2, ThO2, UO2 and PuO2, combining DFT with high temperature MD.

The development of embedded atom method (EAM) many-body potentials for actinide oxides and associated mixed oxide (MOX) systems has motivated the development of a complementary parameter set for gas-actinide and gas-oxygen interactions. A comprehensive set of density functional theory (DFT) calculations were used to study Xe and Kr incorporation at a number of sites in CeO2, ThO2, UO2 and PuO2. These structures were used to fit a potential, which was used to generate molecular dynamics (MD) configurations incorporating Xe and Kr at 300 K, 1500 K, 3000 K and 5000 K. Subsequent matching to the forces predicted by DFT for these MD configurations was used to refine the potential set. This fitting approach ensured weighted fitting to configurations that are thermodynamically significant over a broad temperature range, while avoiding computationally expensive DFT-MD calculations. The resultant gas potentials were validated against DFT trapping energies and are suitable for simulating combinations of Xe and Kr in solid solutions of CeO2, ThO2, UO2 and PuO2, providing a powerful tool for the atomistic simulation of conventional nuclear reactor fuel UO2 as well as advanced MOX fuels.

Mechanisms and consequences of bacterial resistance to antimicrobial peptides.

Cationic antimicrobial peptides (AMPs) are an intrinsic part of the human innate immune system. Over 100 different human AMPs are known to exhibit broad-spectrum antibacterial activity. Because of the increased frequency of resistance to conventional antibiotics there is an interest in developing AMPs as an alternative antibacterial therapy. Several cationic peptides that are derivatives of AMPs from the human innate immune system are currently in clinical development. There are also ongoing clinical studies aimed at modulating the expression of AMPs to boost the human innate immune response. In this review we discuss the potential problems associated with these therapeutic approaches. There is considerable experimental data describing mechanisms by which bacteria can develop resistance to AMPs. As for any type of drug resistance, the rate by which AMP resistance would emerge and spread in a population of bacteria in a natural setting will be determined by a complex interplay of several different factors, including the mutation supply rate, the fitness of the resistant mutant at different AMP concentrations, and the strength of the selective pressure. Several studies have already shown that AMP-resistant bacterial mutants display broad cross-resistance to a variety of AMPs with different structures and modes of action. Therefore, routine clinical administration of AMPs to treat bacterial infections may select for resistant bacterial pathogens capable of better evading the innate immune system. The ramifications of therapeutic levels of exposure on the development of AMP resistance and bacterial pathogenesis are not yet understood. This is something that needs to be carefully studied and monitored if AMPs are used in clinical settings.

Mortality and cardiovascular disease outcomes among 740 patients with new-onset Type 2 diabetes detected by screening or clinically diagnosed in general practice.

AIM: Screening for Type 2 diabetes among people at high risk is recommended by many organizations. The aim of this study was to analyse all-cause mortality and cardiovascular disease (CVD) outcomes in patients with Type 2 diabetes detected by screening or diagnosed clinically. METHODS: A diabetes register was established at the primary healthcare centre in Laxå, Sweden beginning in 1972. The register was based on data from clinical records with information on medical treatment and laboratory data, as well as all-cause mortality, CVD, myocardial infarction and stroke events from national registers until 31 December 2013. A total of 740 patients with new-onset Type 2 diabetes were registered between 1972 and 2001. In addition, an opportunistic diabetes-screening programme involving people aged 35-79 years started in 1983 and was repeated onwards in 5-year cycles. RESULTS: Baseline characteristics showed a significantly higher CVD risk, mainly depending on more prevalent CVD events in the screened compared with the clinically detected group (propensity score 0.59 vs. 0.46, P < 0.0001). After mean follow-up periods of 12.9 and 13.6 years for screening detected vs. clinically detected patients, respectively, hazard ratios were as follows: all-cause mortality, 0.99 (P = 0.89); CVD, 1.17 (P = 0.10); myocardial infarction, 1.08 (P = 0.49); and stroke, 1.03 (P = 0.83). CONCLUSIONS: No reduction in total mortality or CVD outcomes was found in patients with Type 2 diabetes that was detected by screening compared with those diagnosed clinically.

Improving predictions of the risk of resistance development against new and old antibiotics.

The methods used today by academic researchers and the pharmaceutical industry to assess the risk of emergence of resistance, for example during development of new antibiotics or when assessing an old antibiotic, are sub-optimal. Even though easy to perform, the presently used serial passage procedures, minimal prevention concentration measurements and determination of mutation rates in vitro are generally providing inadequate knowledge for risk assessment and making decisions to continue/discontinue drug development. These methods need to be complemented and replaced with more relevant methods such as determination of whether resistance genes already pre-exist in various metagenomes, and the likelihood that these genes can transfer into the relevant pathogens and be stably maintained. Furthermore, to determine the risk of emergence of mutationally conferred resistance the fitness effect of the resistance mechanism is key, as this parameter will determine the ability of the resistant mutants to be maintained and enriched in the host after they have emerged. This information combined with knowledge of bacterial population sizes and growth and killing dynamics at relevant infection sites should allow for better forecasting of the risk of resistance emerging in clinical settings.

The fat cell epigenetic signature in post-obese women is characterized by global hypomethylation and differential DNA methylation of adipogenesis genes.

BACKGROUND/OBJECTIVES: Obese subjects have increased number of enlarged fat cells that are reduced in size but not in number in post-obesity. We performed DNA methylation profiling in fat cells with the aim of identifying differentially methylated DNA sites (DMS) linked to adipose hyperplasia (many small fat cells) in post-obesity. SUBJECTS/METHODS: Genome-wide DNA methylation was analyzed in abdominal subcutaneous fat cells from 16 women examined 2 years after gastric bypass surgery at a post-obese state (body mass index (BMI) 26±2 kg m(-2), mean±s.d.) and from 14 never-obese women (BMI 25±2 kg m(-2)). Gene expression was analyzed in subcutaneous adipose tissue from nine women in each group. In a secondary analysis, we examined DNA methylation and expression of adipogenesis genes in 15 and 11 obese women, respectively. RESULTS: The average degree of DNA methylation of all analyzed CpG sites was lower in fat cells from post-obese as compared with never-obese women (P=0.014). A total of 8504 CpG sites were differentially methylated in fat cells from post-obese versus never-obese women (false discovery rate 1%). DMS were under-represented in CpG islands and surrounding shores. The 8504 DMS mapped to 3717 unique genes; these genes were over-represented in cell differentiation pathways. Notably, 27% of the genes linked to adipogenesis (that is, 35 of 130) displayed DMS (adjusted P=10(-8)) in post-obese versus never-obese women. Next, we explored DNA methylation and expression of genes linked to adipogenesis in more detail in adipose tissue samples. DMS annotated to adipogenesis genes were not accompanied by differential gene expression in post-obese compared with never-obese women. In contrast, adipogenesis genes displayed differential DNA methylation accompanied by altered expression in obese women. CONCLUSIONS: Global CpG hypomethylation and over-representation of DMS in adipogenesis genes in fat cells may contribute to adipose hyperplasia in post-obese women.

Adipose tissue morphology predicts improved insulin sensitivity following moderate or pronounced weight loss.

BACKGROUND: Cross-sectional studies show that white adipose tissue hypertrophy (few, large adipocytes), in contrast to hyperplasia (many, small adipocytes), associates with insulin resistance and increased risk of developing type 2 diabetes. We investigated if baseline adipose cellularity could predict improvements in insulin sensitivity following weight loss. METHODS: Plasma samples and subcutaneous abdominal adipose biopsies were examined in 100 overweight or obese individuals before and 10 weeks after a hypocaloric diet (7±3% weight loss) and in 61 obese subjects before and 2 years after gastric by-pass surgery (33±9% weight loss). The degree of adipose tissue hypertrophy or hyperplasia (termed the morphology value) in each individual was calculated on the basis of the relationship between fat cell volume and total fat mass. Insulin sensitivity was determined by homeostasis model assessment-estimated insulin resistance (HOMAIR). RESULTS: In both cohorts at baseline, subjects with hypertrophy displayed significantly higher fasting plasma insulin and HOMAIR values than subjects with hyperplasia (P<0.0001), despite similar total fat mass. Plasma insulin and HOMAIR were normalized in both cohorts following weight loss. The improvement (delta insulin or delta HOMAIR) was more pronounced in individuals with hypertrophy, irrespective of whether adipose morphology was used as a continuous (P=0.0002-0.027) or nominal variable (P=0.002-0.047). Absolute adipocyte size associated (although weaker than morphology) with HOMAIR improvement only in the surgery cohort. Anthropometric measures at baseline (fat mass, body mass index, waist-to-hip ratio or waist circumference) showed no significant association with delta insulin or delta HOMAIR. CONCLUSIONS: In contrast to anthropometric variables or fat cell size, subcutaneous adipose morphology predicts improvement in insulin sensitivity following both moderate and pronounced weight loss in overweight/obese subjects.

Regional variations in the relationship between arterial stiffness and adipocyte volume or number in obese subjects.

BACKGROUND: Cardiovascular disease is associated with multiple risk factors including stiff arteries and large adipocytes. Whether the latter two are interrelated is unknown. We aimed to determine whether arterial stiffness is associated with fat cell size and number in subcutaneous or visceral white adipose tissue (WAT). METHODS: A cross-sectional study of 120 obese subjects scheduled for bariatric surgery in whom WAT mass and distribution was assessed by dual-X-ray absorptiometry. Biopsies from visceral (greater omentum) and subcutaneous (abdominal) WAT were obtained to calculate fat cell volume and number. Arterial stiffness was determined as aortic pulse wave velocity (PWV). RESULTS: Visceral adipocyte volume, but not number, was strongly (P<0.0001) and positively correlated with PWV, explaining 20% of the inter-individual variations in this parameter. This relationship remained significant after correction for clinical confounders. PWV correlated positively (r=0.38, P<0.0001) with visceral (but not subcutaneous) WAT mass. Furthermore, PWV was also positively associated with subcutaneous adipocyte volume (r=0.20, P=0.031) and negatively with fat cell number (r=-0.26, P=0.006). However, the relationships between PWV and visceral WAT mass or subcutaneous fat cell size/number became non-significant when controlling for visceral fat cell volume. In a multiple regression analysis to determine the factors that explain variations in PWV, only visceral fat cell volume, age, pulse rate and diastolic blood pressure entered the model, together explaining 42% of the variation in PWV. CONCLUSIONS: Visceral fat cell volume was the only WAT parameter that constituted an independent and significant, positive regressor for arterial stiffness determined by PWV. Although a causal relationship is not established, visceral fat cell volume may explain the well-known correlation between central fat mass, arterial stiffness and cardiovascular risk, at least in severely/morbidly obese subjects.

Anisotropic thermal conductivity in uranium dioxide.

The thermal conductivity of uranium dioxide has been studied for over half a century, as uranium dioxide is the fuel used in a majority of operating nuclear reactors and thermal conductivity controls the conversion of heat produced by fission events to electricity. Because uranium dioxide is a cubic compound and thermal conductivity is a second-rank tensor, it has always been assumed to be isotropic. We report thermal conductivity measurements on oriented uranium dioxide single crystals that show anisotropy from 4 K to above 300 K. Our results indicate that phonon-spin scattering is important for understanding the general thermal conductivity behaviour, and also explains the anisotropy by coupling to the applied temperature gradient and breaking cubic symmetry.

Short general anaesthesia induces prolonged changes in gene expression in the mouse hippocampus.

BACKGROUND: The long-term molecular changes in the central nervous system constitute an important aspect of general anaesthesia, but little is known about to what extent these molecular changes are affected by anaesthesia duration. The aim of the present study was to evaluate the effects of short duration (20 min) general anaesthesia with isoflurane or avertin on the expression of 20 selected genes in the mouse hippocampus at 1 and 4 days after anaesthesia. METHODS: Nine to eleven-weeks-old male mice received one of the following treatments: 20 min of avertin-induced anaesthesia (n=11), 20 min of isoflurane-induced anaesthesia (n=10) and no anaesthesia (n=5). One and four days after anaesthesia, gene expression in the hippocampus was determined with reverse transcription quantitative real-time polymerase chain reaction. RESULTS: We found that anaesthesia led to the upregulation of six genes: Hspd1 (heat shock protein 1), Plat (tissue plasminogen activator) and Npr3 (natriuretic peptide receptor 3) were upregulated only 1 day after anaesthesia, whereas Thbs4 (thrombospondin 4) was upregulated only 4 days after anaesthesia. Syp (synaptophysin) and Mgst1 (microsomal glutathione S-transferase 1) were upregulated at both time points. Hspd1, Mgst1 and Syp expression was increased regardless of the anaesthetic used, Npr3 and Plat were increased only in mice exposed to avertin, and Thbs4 was upregulated only after isoflurane-induced anaesthesia. CONCLUSIONS: This study shows that some of the effects of short general anaesthesia on gene expression in the mouse hippocampus persist for at least 4 days.