Visceral fat area and cardiometabolic risk: The Kardiovize study

BACKGROUND: Visceral fat is associated with adiposity-based complications. Bioimpedance measurement allows estimation of visceral fat area (VFA) in an easy manner. However, a validated cut-off value for VFA by bioimpedance associated with cardiometabolic risk is lacking in European population. AIM: To determine cut-off values of VFA measured via bioimpedance associated with cardiometabolic risk. METHODS: Random cross-sectional Czech population-based sample of 25-64 years old subjects. Receiver Operating Characteristic (ROC) curves were used and the area under the curve (AUC), sensitivity, and specificity were calculated. The Cardiometabolic Disease Staging System (CMDS) was used to classify cardiometabolic risk: Stage 1 - 1 or 2 metabolic syndrome (MetS) components, without impaired fasting glucose (IFG); Stage 2 - MetS or IFG; Stage 3 - MetS with IFG; Stage 4 - type 2 diabetes and/or cardiovascular disease. RESULTS: 2052 participants (54.5% females, median age 49 years) were included. Median VFA (inter-quartile range) were 82.2 cm2 (54.8) in men and 89.8 cm2 (55.6) in women. The best VFA cut-offs associated with Stage 1 in men and women were 71 cm2 (sensitivity = 0.654; specificity = 0.427) and 83 cm2 (sensitivity = 0.705; specificity = 0.556) ; Stage 2: 84 cm2 (sensitivity = 0.673; specificity = 0.551) and 98 cm2 (sensitivity = 0.702; specificity = 0.628) ; Stage 3: 90 cm2 (sensitivity = 0.886; specificity = 0.605) and 109 cm2 (sensitivity = 0.755; specificity = 0.704); Stage 4: 91 cm2 (sensitivity = 0.625; specificity = 0.611) and 81 cm2 (sensitivity = 0.695; specificity = 0.448), respectively. CONCLUSION: A cut-off value of VFA of 71 cm2 in men and 83 cm2 in women exhibited the earliest stage of cardiometabolic risk, and 90 cm2 in men and 109 cm2 in women showed the best performance to detect risk

Evolution in the Cluster Early-type Galaxy Size-Surface Brightness Relation at z =~ 1

We investigate the evolution in the distribution of surface brightness, as a function of size, for elliptical and S0 galaxies in the two clusters RDCS J1252.9-2927, z=1.237 and RX J0152.7-1357, z=0.837. We use multi-color imaging with the Advanced Camera for Surveys on the Hubble Space Telescope to determine these sizes and surface brightnesses. Using three different estimates of the surface brightnesses, we find that we reliably estimate the surface brightness for the galaxies in our sample with a scatter of < 0.2 mag and with systematic shifts of \lesssim 0.05 mag. We construct samples of galaxies with early-type morphologies in both clusters. For each cluster, we use a magnitude limit in a band which closely corresponds to the rest-frame B, to magnitude limit of M_B = -18.8 at z=0, and select only those galaxies within the color-magnitude sequence of the cluster or by using our spectroscopic redshifts. We measure evolution in the rest-frame B surface brightness, and find -1.41 \+/- 0.14 mag from the Coma cluster of galaxies for RDCS J1252.9-2927 and -0.90 \+/- 0.12 mag of evolution for RX J0152.7-1357, or an average evolution of (-1.13 \+/- 0.15) z mag. Our statistical errors are dominated by the observed scatter in the size-surface brightness relation, sigma = 0.42 \+/- 0.05 mag for RX J0152.7-1357 and sigma = 0.76 \+/- 0.10 mag for RDCS J1252.9-2927. We find no statistically significant evolution in this scatter, though an increase in the scatter could be expected. Overall, the pace of luminosity evolution we measure agrees with that of the Fundamental Plane of early-type galaxies, implying that the majority of massive early-type galaxies observed at z =~ 1 formed at high redshifts.Comment: Accepted in ApJ, 16 pages in emulateapj format with 15 eps figures, 6 in colo

Dysglycemia and Abnormal Adiposity Drivers of Cardiometabolic-Based Chronic Disease in the Czech Population: Biological, Behavioral, and Cultural/Social Determinants of Health

In contrast to the decreasing burden related to cardiovascular disease (CVD), the burden related to dysglycemia and adiposity complications is increasing in Czechia, and local drivers must be identified. A comprehensive literature review was performed to evaluate biological, behavioral, and environmental drivers of dysglycemia and abnormal adiposity in Czechia. Additionally, the structure of the Czech healthcare system was described. The prevalence of obesity in men and diabetes in both sexes has been increasing over the past 30 years. Possible reasons include the Eastern European eating pattern, high prevalence of physical inactivity and health illiteracy, education, and income-related health inequalities. Despite the advanced healthcare system based on the compulsory insurance model with free-for-service healthcare and a wide range of health-promoting initiatives, more effective strategies to tackle the adiposity/dysglycemia are needed. In conclusion, the disease burden related to dysglycemia and adiposity in Czechia remains high but is not translated into greater CVD. This discordant relationship likely depends more on other factors, such as improvements in dyslipidemia and hypertension control. A reconceptualization of abnormal adiposity and dysglycemia into a more actionable cardiometabolic-based chronic disease model is needed to improve the approach to these conditions. This review can serve as a platform to investigate causal mechanisms and secure effective management of cardiometabolic-based chronic disease

Exploiting inflammation for therapeutic gain in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with &#60;5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis

Daycare attendance and risk of childhood acute lymphoblastic leukaemia

The relationship between daycare/preschool (‘daycare’) attendance and the risk of acute lymphoblastic leukaemia was evaluated in the Northern California Childhood Leukaemia Study. Incident cases (age 1–14 years) were rapidly ascertained during 1995–1999. Population-based controls were randomly selected from the California birth registry, individually matched on date of birth, gender, race, Hispanicity, and residence, resulting in a total of 140 case–controls pairs. Fewer cases (n=92, 66%) attended daycare than controls (n=103, 74%). Children who had more total child–hours had a significantly reduced risk of ALL. The odds ratio associated with each thousand child–hours was 0.991 (95% confidence interval (CI): 0.984–0.999), which means that a child with 50 thousand child–hours (who may have, for example, attended a daycare with 15 other children, 25 h per week, for a total duration of 30.65 months) would have an odds ratio of (0.991)50=0.64 (95% CI: 0.45, 0.95), compared to children who never attended daycare. Besides, controls started daycare at a younger age, attended daycare for longer duration, remained in daycare for more hours, and were exposed to more children at each daycare. These findings support the hypothesis that delayed exposure to common infections plays an important role in the aetiology of childhood acute lymphoblastic leukaemia, and suggest that extensive contact with other children in a daycare setting is associated with a reduced risk of acute lymphoblastic leukaemia

Loss of Niemann-Pick C1 or C2 Protein Results in Similar Biochemical Changes Suggesting That These Proteins Function in a Common Lysosomal Pathway

Niemann-Pick Type C (NPC) disease is a lysosomal storage disorder characterized by accumulation of unesterified cholesterol and other lipids in the endolysosomal system. NPC disease results from a defect in either of two distinct cholesterol-binding proteins: a transmembrane protein, NPC1, and a small soluble protein, NPC2. NPC1 and NPC2 are thought to function closely in the export of lysosomal cholesterol with both proteins binding cholesterol in vitro but they may have unrelated lysosomal roles. To investigate this possibility, we compared biochemical consequences of the loss of either protein. Analyses of lysosome-enriched subcellular fractions from brain and liver revealed similar decreases in buoyant densities of lysosomes from NPC1 or NPC2 deficient mice compared to controls. The subcellular distribution of both proteins was similar and paralleled a lysosomal marker. In liver, absence of either NPC1 or NPC2 resulted in similar alterations in the carbohydrate processing of the lysosomal protease, tripeptidyl peptidase I. These results highlight biochemical alterations in the lysosomal system of the NPC-mutant mice that appear secondary to lipid storage. In addition, the similarity in biochemical phenotypes resulting from either NPC1 or NPC2 deficiency supports models in which the function of these two proteins within lysosomes are linked closely

Data sharing: not as simple as it seems

In recent years there has been a major change on the part of funders, particularly in North America, so that data sharing is now considered to be the norm rather than the exception. We believe that data sharing is a good idea. However, we also believe that it is inappropriate to prescribe exactly when or how researchers should preserve and share data, since these issues are highly specific to each study, the nature of the data collected, who is requesting it, and what they intend to do with it. The level of ethical concern will vary according to the nature of the information, and the way in which it is collected - analyses of anonymised hospital admission records may carry a quite different ethical burden than analyses of potentially identifiable health information collected directly from the study participants. It is striking that most discussions about data sharing focus almost exclusively on issues of ownership (by the researchers or the funders) and efficiency (on the part of the funders). There is usually little discussion of the ethical issues involved in data sharing, and its implications for the study participants. Obtaining prior informed consent from the participants does not solve this problem, unless the informed consent process makes it completely clear what is being proposed, in which case most study participants would not agree. Thus, the undoubted benefits of data sharing does not remove the obligations and responsibilities that the original investigators hold for the people they invited to participate in the study

Running Speed in Mammals Increases with Muscle n-6 Polyunsaturated Fatty Acid Content

Polyunsaturated fatty acids (PUFAs) are important dietary components that mammals cannot synthesize de novo. Beneficial effects of PUFAs, in particular of the n-3 class, for certain aspects of animal and human health (e.g., cardiovascular function) are well known. Several observations suggest, however, that PUFAs may also affect the performance of skeletal muscles in vertebrates. For instance, it has been shown that experimentally n-6 PUFA-enriched diets increase the maximum swimming speed in salmon. Also, we recently found that the proportion of PUFAs in the muscle phospholipids of an extremely fast runner, the brown hare (Lepus europaeus), are very high compared to other mammals. Therefore, we predicted that locomotor performance, namely running speed, should be associated with differences in muscle fatty acid profiles. To test this hypothesis, we determined phospholipid fatty acid profiles in skeletal muscles of 36 mammalian species ranging from shrews to elephants. We found that there is indeed a general positive, surprisingly strong relation between the n-6 PUFAs content in muscle phospholipids and maximum running speed of mammals. This finding suggests that muscle fatty acid composition directly affects a highly fitness-relevant trait, which may be decisive for the ability of animals to escape from predators or catch prey