Ectopic cardiovascular fat in middle-aged men: effects of race/ethnicity, overall and central adiposity. The ERA JUMP study.

Background/objectivesHigher volumes of ectopic cardiovascular fat (ECF) are associated with greater risk of coronary heart disease (CHD). Identifying factors that are associated with ECF volumes may lead to new preventive efforts to reduce risk of CHD. Significant racial/ethnic differences exist for overall and central adiposity measures, which are known to be associated with ECF volumes. Whether racial/ethnic differences also exist for ECF volumes and their associations with these adiposity measures remain unclear.Subjects/methodsBody mass index (BMI), computerized tomography-measured ECF volumes (epicardial, pericardial and their summation) and visceral adipose tissue (VAT) were examined in a community-based sample of 1199 middle-aged men (24.2% Caucasians, 7.0% African-Americans, 23.6% Japanese-Americans, 22.0% Japanese, 23.2% Koreans).ResultsSignificant racial/ethnic differences existed in ECF volumes and their relationships with BMI and VAT. ECF volumes were the highest among Japanese-Americans and the lowest among African-Americans. The associations of BMI and VAT with ECF differed by racial/ethnic groups. Compared with Caucasians, for each 1-unit increase in BMI, African-Americans had lower, whereas Koreans had higher increases in ECF volumes (P-values<0.05 for both). Meanwhile, compared with Caucasians, for each 1-unit increase in log-transformed VAT, African-Americans, Japanese-Americans and Japanese had similar increases, whereas Koreans had a lower increase in ECF volumes (P-value<0.05).ConclusionsRacial/ethnic groups differed in their propensity to accumulate ECF at increasing level of overall and central adiposity. Future studies should evaluate whether reducing central adiposity or overall weight will decrease ECF volumes more in certain racial/ethnic groups. Evaluating these questions might help in designing race-specific prevention strategy of CHD risk associated with higher ECF

Probing energetic light dark matter with multi-particle tracks signatures at DUNE

The search for relativistic scattering signals of cosmogenic light dark matter at terrestrial detectors has received increasing attention as an alternative approach to probe dark-sector physics. Large-volume neutrino experiments are well motivated for searches of dark matter that interacts very weakly with Standard Model particles and/or that exhibits a small incoming flux. We perform a dedicated signal sensitivity study for a detector similar to the one proposed by the DUNE Collaboration for cosmogenic dark-matter signals resulting from a non-minimal multi-particle dark-sector scenario. The liquid argon time projection chamber technology adopted for the DUNE detectors is particularly suited for searching for complicated signatures owing to good measurement resolution and particle identification, as well as $dE/dx$ measurements to recognize merged tracks. Taking inelastic boosted dark matter as our benchmark scenario that allows for multiple visible particles in the final state, we demonstrate that the DUNE far detectors have a great potential for probing scattering signals induced by relativistic light dark matter. Detector effects and backgrounds have been estimated and taken into account. Model-dependent and model-independent expected sensitivity limits for a DUNE-like detector are presented

Functional consequences of Kir2.1/Kir2.2 subunit heteromerization

Kir2 subunits form channels that underlie classical strongly inwardly rectifying potassium currents. While homomeric Kir2 channels display a number of distinct and physiologically important properties, the functional properties of heteromeric Kir2 assemblies, as well as the stoichiometries and the arrangements of Kir2 subunits in native channels, remain largely unknown. Therefore, we have implemented a concatemeric approach, whereby all four cloned Kir2 subunits were linked in tandem, in order to study the effects of Kir2.1 and Kir2.2 heteromerization on properties of the resulting channels. Kir2.2 subunits contributed stronger to single-channel conductance than Kir2.1 subunits, and channels containing two or more Kir2.2 subunits displayed conductances indistinguishable from that of a Kir2.2 homomeric channel. In contrast, single-channel kinetics was a more discriminating property. The open times were significantly shorter in Kir2.2 channels compared with Kir2.1 channels and decreased nearly proportionally to the number of Kir2.2 subunits in the heteromeric channel. Similarly, the sensitivity to block by barium also depended on the proportions of Kir2.1 to Kir2.2 subunits. Overall, the results showed that Kir2.1 and Kir2.2 subunits exert neither a dominant nor an anomalous effect on any of the properties of heteromeric channels. The data highlight opportunities and challenges of using differential properties of Kir2 channels in deciphering the subunit composition of native inwardly rectifying potassium currents

Relationship of serum bilirubin concentration to kidney function and 24-hour urine protein in Korean adults

<p>Abstract</p> <p>Background</p> <p>The relationships among serum bilirubin concentration, kidney function and proteinuria have yet to be fully elucidated, nor have these relationships been investigated in Korean adults.</p> <p>Method</p> <p>We retrospectively reviewed the medical records of Korean adults who were evaluated at Kosin University Gospel Hospital (Busan, Republic of Korea) during a five-year period from January 2005 to December 2009. We evaluated the relationships among serum bilirubin concentration, estimated glomerular filtration rate (eGFR) and 24-hour urinary protein excretion in a sample of 1363 Korean adults aged 18 years or older.</p> <p>Results</p> <p>The values of eGFR <60 mL/min/1.73 m²and 24-hour urine albumin ≥150 mg/day were observed in 26.1% (n = 356) and 40.5% (n = 553) of subjects, respectively. Fasting glucose levels ≥126 mg/dL were observed in 44.9% (n = 612) of the total sample. After adjustment for potential confounding factors including demographic characteristics, comorbidities and other laboratory measures, total serum bilirubin was positively associated with eGFR and negatively associated with proteinuria both in the whole cohort and in a subgroup of diabetic individuals.</p> <p>Conclusions</p> <p>To our knowledge, this is the first hospital-based study specifically aimed at examining the relationships among serum total bilirubin concentration, 24-hour urine protein and kidney function in Korean adults. We demonstrated that serum total bilirubin concentration was negatively correlated with 24-hour urine protein and positively correlated with eGFR in Korean non-diabetic and diabetic adults.</p

Mitral Cells of the Olfactory Bulb Perform Metabolic Sensing and Are Disrupted by Obesity at the Level of the Kv1.3 Ion Channel

Sixty-five percent of Americans are over-weight. While the neuroendocrine controls of energy homeostasis are well known, how sensory systems respond to and are impacted by obesity is scantily understood. The main accepted function of the olfactory system is to provide an internal depiction of our external chemical environment, starting from the detection of chemosensory cues. We hypothesized that the system additionally functions to encode internal chemistry via the detection of chemicals that are important indicators of metabolic state. We here uncovered that the olfactory bulb (OB) subserves as an internal sensor of metabolism via insulin-induced modulation of the potassium channel Kv1.3. Using an adult slice preparation of the olfactory bulb, we found that evoked neural activity in Kv1.3-expressing mitral cells is enhanced following acute insulin application. Insulin mediated changes in mitral cell excitability are predominantly due to the modulation of Kv1.3 channels as evidenced by the lack of effect in slices from Kv1.3-null mice. Moreover, a selective Kv1.3 peptide blocker (ShK186) inhibits more than 80% of the outward current in parallel voltage-clamp studies, whereby insulin significantly decreases the peak current magnitude without altering the kinetics of inactivation or deactivation. Mice that were chronically administered insulin using intranasal delivery approaches exhibited either an elevation in basal firing frequency or fired a single cluster of action potentials. Following chronic administration of the hormone, mitral cells were inhibited by application of acute insulin rather than excited. Mice made obese through a diet of ∼32% fat exhibited prominent changes in mitral cell action potential shape and clustering behavior, whereby the subsequent response to acute insulin stimulation was either attenuated or completely absent. Our results implicate an inappropriate neural function of olfactory sensors following exposure to chronic levels of the hormone insulin (diabetes) or increased body weight (obesity)

Clustering cliques for graph-based summarization of the biomedical research literature

BACKGROUND: Graph-based notions are increasingly used in biomedical data mining and knowledge discovery tasks. In this paper, we present a clique-clustering method to automatically summarize graphs of semantic predications produced from PubMed citations (titles and abstracts). RESULTS: SemRep is used to extract semantic predications from the citations returned by a PubMed search. Cliques were identified from frequently occurring predications with highly connected arguments filtered by degree centrality. Themes contained in the summary were identified with a hierarchical clustering algorithm based on common arguments shared among cliques. The validity of the clusters in the summaries produced was compared to the Silhouette-generated baseline for cohesion, separation and overall validity. The theme labels were also compared to a reference standard produced with major MeSH headings. CONCLUSIONS: For 11 topics in the testing data set, the overall validity of clusters from the system summary was 10% better than the baseline (43% versus 33%). While compared to the reference standard from MeSH headings, the results for recall, precision and F-score were 0.64, 0.65, and 0.65 respectively

Clinical experience with the Bicarbon heart valve prosthesis

BACGROUND: We have previously reported mid-term results of a study, which ended in January 2000, on the Bicarbon valve. The study concluded that the valve showed excellent clinical results, associated with a low incidence of valve-related complications. In the present study, the same patients were prospectively followed for an additional 5 years. METHODS: Forty-four patients had aortic valve replacement (AVR), 48 had mitral valve replacement (MVR), and 13 had both aortic and mitral valve replacement (DVR). The mean age of the 105 patients was 61.2 ± 11.3 years. The mean follow-up was 6.1 ± 1.9 years with a cumulative follow-up of 616 patient-years. RESULTS: There were 5 early deaths (4.7%: 4 in the AVR group and 1 in the MVR group) and 21 late deaths (3.4%/patient-year: 5 valve related deaths and 16 valve unrelated deaths). Survival at 8 years was 75.2 ± 7.0% in the AVR group, 76.6 ± 6.2% in the MVR group, and 55.4 ± 16.1% in the DVR group. The linearized incidence of thrombo-embolic complications, hemorrhagic complications, and paravalvular leaks in all patients was 0.65 ± 1.48%, 0.81 ± 1.69%, and 0.16 ± 0.54%/patient-year respectively. No other complications were observed. CONCLUSION: The Bicarbon prosthetic heart valve has shown excellent long-term clinical results, associated with a low incidence of valve-related complications

Regional pulse wave velocities and their cardiovascular risk factors among healthy middle-aged men: A cross-sectional population-based study

Background: Both carotid-femoral (cf) pulse wave velocity (PWV) and brachial-ankle (ba) PWV employ arterial sites that are not consistent with the path of blood flow. Few previous studies have reported the differential characteristics between cfPWV and baPWV by simultaneously comparing these with measures of pure central (aorta) and peripheral (leg) arterial stiffness, i.e., heart-femoral (hf) PWV and femoral-ankle (fa) PWV in healthy populations. We aimed to identify the degree to which these commonly used measures of cfPWV and baPWV correlate with hfPWV and faPWV, respectively, and to evaluate whether both cfPWV and baPWV are consistent with either hfPWV or faPWV in their associations with cardiovascular (CV) risk factors.Methods: A population-based sample of healthy 784 men aged 40-49 (202 white Americans, 68 African Americans, 202 Japanese-Americans, and 282 Koreans) was examined in this cross-sectional study. Four regional PWVs were simultaneously measured by an automated tonometry/plethysmography system.Results: cfPWV correlated strongly with hfPWV (r = .81, P < .001), but weakly with faPWV (r = .12, P = .001). baPWV correlated moderately with both hfPWV (r = .47, P < .001) and faPWV (r = .62, P < .001). After stepwise regression analyses with adjustments for race, cfPWV shared common significant correlates with both hfPWV and faPWV: systolic blood pressure (BP) and body mass index (BMI). However, BMI was positively associated with hfPWV and cfPWV, and negatively associated with faPWV. baPWV shared common significant correlates with hfPWV: age and systolic BP. baPWV also shared the following correlates with faPWV: systolic BP, triglycerides, and current smoking.Conclusions: Among healthy men aged 40 - 49, cfPWV correlated strongly with central PWV, and baPWV correlated with both central and peripheral PWVs. Of the CV risk factors, systolic BP was uniformly associated with all the regional PWVs. In the associations with factors other than systolic BP, cfPWV was consistent with central PWV, while baPWV was consistent with both central and peripheral PWVs. © 2014 Choo et al.; licensee BioMed Central Ltd

Dietary preference, physical activity, and cancer risk in men: national health insurance corporation study

<p>Abstract</p> <p>Background</p> <p>The effects of vegetable preference and leisure-time physical activity (LPA) on cancer have been inconsistent. We examined the effects of dietary preference and physical activity, as well as their combined effect on cancer risk.</p> <p>Methods</p> <p>This prospective cohort study included 444,963 men, older than 40 years, who participated in a national health examination program begun in 1996. Based on the answer to the question "What kind of dietary preference do you have?" we categorized dietary preference as (1) vegetables, (2) mixture of vegetables and meat, and (3) meats. We categorized LPA as low (< 4 times/wk, < 30 min/session), moderate (2–4 times/wk, ≥ 30 min/session or ≥ 5 times/wk, < 30 min/session), or high (≥ 5 times/wk, ≥ 30 min/session). We obtained cancer incidence data for 1996 through 2002 from the Korean Central Cancer Registry. We used a standard Poisson regression model with a log link function and person-time offset to estimate incidence and relative risk..</p> <p>Results</p> <p>During the 6-year follow-up period, we identified 14,109 cancer cases. Multivariate analysis revealed that a preference for vegetables or a mixture of vegetables and meat as opposed to a preference for meat played a significant protective role against lung cancer incidence (aRR, 0.81; 95% confidence interval [CI], 0.68–0.98). Compared with the low LPA group, subjects with moderate-high LPA had a significantly lower risk for stomach (aRR, 0.91; 95%CI, 0.86–0.98), lung (aRR, 0.83; 95%CI, 0.75–0.92), and liver (aRR, 0.88; 95%CI, 0.81–0.95) cancer. Among current smokers, the combined moderate-high LPA and vegetable or mixture of vegetables and meat preference group showed a 40% reduced risk of lung cancer (aRR, 0.60; 95%CI, 0.47–0.76) compared with the combined low LPA and meat preference group. Among never/former smokers, subjects with moderate-high LPA and a preference for vegetables or a mixture of vegetables and meat showed reduced stomach cancer risk (aRR, 0.72; 95%CI, 0.54–0.95).</p> <p>Conclusion</p> <p>Our findings add to the evidence of the beneficial effects of vegetable preference on lung cancer risk and of physical activity on lung, stomach, and liver cancer risk. Additionally, vegetable preference combined with LPA might significantly reduce lung and stomach cancer risk.</p

CDK-inhibitor independent cell cycle progression in an experimental haematopoietic stem cell leukaemia despite unaltered Rb-phosphorylation

A CD34-negative haematopoietic progenitor cell line, D064, derived from canine bone marrow stromal cells is able to differentiate into haematopoietic progenitors under the influence of growth factor-mediated signalling. While differentiating, these cells eventually start to express MHC class II molecules (DR homologues) on their surface. The stable transfection of the fibroblast-like wild-type cells with retroviral constructs containing the cDNA for the canine MHC class II DR-genes (DRA and DRB) induces a change in morphology, accelerates cell cycle progression and leads to a loss of anchorage-dependent growth. Transfected cells show features of an immature stem cell leukaemia, such as giant cell formation. In wild-type D064 cells the accumulation of the cyclin-dependent kinase inhibitor (cdki) p27kip-1 induces differentiation, which is dependent upon signalling via the ligand for the tyrosine kinase receptor c-kit (stem cell factor). DR-transfected cells instead apparently grow independently of any growth factor-mediated signals and express high levels of the cdkis p27kip-1 and especially p21waf-1/cip-1, concurrently with accelated cell cycle progression. In contrast to the overexpression of cdkis and despite accelerated cell cycle progression, the expression of the G2/M phase transition kinase p34cdc2 is significantly reduced in DR-transfected and transformed cells as compared to the haematopoietic wild-type cell line D064. This might suggest a possible alternative cell cycle progression pathway in this experimental stem cell leukaemia by by-passing the G0/G1 phase arrest, although retinoblastoma (Rb)-phosphorylation remains unaltered. These results provide evidence that mechanisms normally controlling the cell cycle and early haematopoietic differentiation are disrupted by the constitutive transcription and expression of MHC class II genes (DR) leading to a progression and growth of this experimental stem cell leukaemia independent from cell cycle controlling regulators such as p27 and p21. © 1999 Cancer Research Campaig