Psoas and Paraspinous Muscle Measurements on Computed Tomography Predict Mortality in European Americans with Type 2 Diabetes Mellitus.

BACKGROUND: Appendicular skeletal muscle mass index and muscle attenuation (density) are negatively associated with mortality in European-derived populations. OBJECTIVES: The present analyses assessed association between axial skeletal muscle density and muscle index with mortality in European Americans with type 2 diabetes mellitus (T2D). DESIGN: Single-center observational study. SETTING: Diabetes Heart Study. PARTICIPANTS: 839 European Americans with T2D. METHODS: Computed tomography-measured psoas and paraspinous muscle mass index (cross sectional area/height2) and radiographic density (Hounsfield Units) were assessed in all participants. A Cox proportional hazards model was computed. The fully-adjusted model included covariates age, sex, body mass index, smoking, alcohol use, diabetes duration, insulin use, hormone replacement therapy (women), prevalent cardiovascular disease (CVD), hypertension, and coronary artery calcified atherosclerotic plaque mass score. Deaths were recorded in the National Death Index data through December 31, 2015. RESULTS: Participants included 428 women and 411 men with median (25th, 75th quartile) age 62.8 (56.1, 69.1) years and diabetes duration 8.0 (5.0, 14.0) years. After 11.9 (9.4, 13.3) years of follow-up, 314 (37.4%) of participants were deceased. In the fully-adjusted model, psoas muscle density (hazard ratio [HR] 0.81, p<0.001), psoas muscle index (HR 0.82, p=0.008), and paraspinous muscle density (HR 0.85, p=0.003) were inversely associated with mortality. Paraspinous muscle index was not significantly associated with mortality (HR 0.90, p=0.08). Results did not differ significantly between men and women. CONCLUSIONS: In addition to established risk factors for mortality and CVD, higher psoas muscle index, psoas muscle density, and paraspinous muscle density were significantly associated with lower all-cause mortality in European Americans with T2D.

Volumetric bone mineral density of the spine predicts mortality in African-American men with type 2 diabetes.

The study showed that in African-American men with type 2 diabetes mellitus (T2D), vertebral volumetric bone mineral density (vBMD) predicts all-cause mortality, independent of other risk factors for death. INTRODUCTION: Compared to European Americans, African Americans have lower rates of osteoporosis and higher rates of T2D. The relationships between BMD and fractures with mortality are unknown in this population. The aim of this study was to determine relationships between vertebral fractures and vertebral vBMD and mortality in African Americans with T2D. METHODS: Associations between vertebral fractures and vBMD with all-cause mortality were examined in 675 participants with T2D (391 women and 284 men) in the African American-Diabetes Heart Study (AA-DHS). Lumbar and thoracic vBMD were measured using quantitative computed tomography (QCT). Vertebral fractures were assessed on sagittal CT images. Associations of vertebral fractures and vBMD with all-cause mortality were determined in sex-stratified analyses and in the full sample. Covariates in a minimally adjusted model included age, sex, BMI, smoking, and alcohol use; the full model was adjusted for those variables plus cardiovascular disease, hypertension, coronary artery calcified plaque, hormone replacement therapy (women), African ancestry proportion, and eGFR. RESULTS: After mean 7.6 ± 1.8-year follow-up, 59 (15.1%) of women and 58 (20.4%) of men died. In men, vBMD was inversely associated with mortality in the fully adjusted model: lumbar hazard ratio (HR) per standard deviation (SD) = 0.70 (95% CI 0.52-0.95, p = 0.02) and thoracic HR per SD = 0.71 (95% CI 0.54-0.92, p = 0.01). Only trends toward association between vBMD and mortality were observed in the combined sample of men and women, as significant associations were absent in women. Vertebral fractures were not associated with mortality in either sex. CONCLUSIONS: Lower vBMD was associated with increased all-cause mortality in African-American men with T2D, independent of other risk factors for mortality including subclinical atherosclerosis.

On the mechanism of gas adsorption for pristine, defective and functionalized graphene.

Defects are no longer deemed an adverse aspect of graphene. Contrarily, they can pave ways of extending the applicability of graphene. Herein, we discuss the effects of three types of defects in graphene including carbon deficiency, adatom (single Fe) dopants and the introduction of functional groups (carbonyl, ether group) on the NO2 gas adsorption via density functional theory methods. We have observed that introducing Fe on graphene can enhance the NO2 adsorption process. Adsorption energy calculations suggest that the enhancement in NO2 adsorption is more profound for Fe-doped mono- and tetra-vacant graphene than that for Fe doped bi- and tri-vacant graphene, which is favourable for NO2 gas capture applications. The unsaturated carbons in defected graphene as well as the oxygenated functional groups are very active to attract NO2 molecules. However, though the gas binding strength was not as high as the that found in the Fe-doped graphene structure, the relatively low NO2 gas adsorption energy is suitable for the practical gas sensors both for gas sensitivity and the sensor recovery rate factor. This theoretical study can potentially be useful for developing adsorption-based applications of graphene.

Maternal and neonatal outcomes for pregnancies before and after gastric bypass surgery.

BACKGROUND: Interaction between maternal obesity, intrauterine environment and adverse clinical outcomes of newborns has been described. METHODS: Using statewide birth certificate data, this retrospective, matched-control cohort study compared paired birth weights and complications of infants born to women before and after Roux-en-Y gastric bypass surgery (RYGB) and to matched obese non-operated women in several different groups. Women who had given birth to a child before and after RYGB (group 1; n=295 matches) and women with pregnancies after RYGB (group 2; n=764 matches) were matched to non-operated women based on age, body mass index (BMI) prior to both pregnancy and RYGB, mother's race, year of mother/s birth, date of infant births and birth order. In addition, birth weights of 13 143 live births before and/or after RYGB of their mothers (n=5819) were compared (group 3). RESULTS: Odds ratios (ORs) for having a large-for-gestational-age (LGA) neonate were significantly less after RYGB than for non-surgical mothers: ORs for groups 1 and 2 were 0.19 (0.08-0.38) and 0.33 (0.21-0.51), respectively. In contrast, ORs in all three groups for risk of having a small for gestational age (SGA) neonate were greater for RYGB mothers compared to non-surgical mothers (ORs were 2.16 (1.00-5.04); 2.16 (1.43-3.32); and 2.25 (1.89-2.69), respectively). Neonatal complications were not different for group 1 RYGB and non-surgical women for the first pregnancy following RYGB. Pregnancy-induced hypertension and gestational diabetes were significantly lower for the first pregnancy of mothers following RYGB compared to matched pregnancies of non-surgical mothers. CONCLUSION: Women who had undergone RYGB not only had lower risk for having an LGA neonate compared to BMI-matched mothers, but also had significantly higher risk for delivering an SGA neonate following RYGB. RYGB women were less likely than non-operated women to have pregnancy-related hypertension and diabetes.

The pigeon (Columba livia) model of spontaneous atherosclerosis.

Multiple animal models have been employed to study human atherosclerosis, the principal cause of mortality in the United States. Each model has individual advantages related to specific pathologies. Initiation, the earliest disease phase, is best modeled by the White Carneau (WC-As) pigeon. Atherosclerosis develops spontaneously in the WC-As without either external manipulation or known risk factors. Furthermore, susceptibility is caused by a single gene defect inherited in an autosomal recessive manner. The Show Racer (SR-Ar) pigeon is resistant to atherosclerosis. Breed differences in the biochemistry and metabolism of celiac foci cells have been described. For example, WC-As have lower oxidative metabolism but higher amounts of chondroitin-6-sulfate and nonesterified fatty acids compared with SR-Ar. Gene expression in aortic smooth muscle cells was compared between breeds using representational difference analysis and microarray analysis. Energy metabolism and cellular phenotype were the chief gene expression differences. Glycolysis and synthetic cell types were related to the WC-As but oxidative metabolism and contractile cell types were related to the SR-Ar. Rosiglitazone, a PPARγ agonist, blocked RNA binding motif (RBMS1) expression in WC-As cells. The drug may act through the c-myc oncogene as RBMS1 is a c-myc target. Proteomic tests of aortic smooth muscle cells supported greater glycosylation in the WC-As and a transforming growth factor ß effect in SR-Ar. Unoxidized fatty acids build up in WC-As cells because of their metabolic deficiency, ultimately preventing the contractile phenotype in these cells. The single gene responsible for the disease is likely regulatory in nature.

Rosiglitazone modulates pigeon atherosclerotic lipid accumulation and gene expression in vitro.

Atherosclerosis is a major contributor to the overall United States mortality rate, primarily in the form of heart attacks and stroke. Unlike the human disease, which is believed to be multifactorial, pigeon atherosclerosis is due to a single gene autosomal recessive trait. The White Carneau (WC-As) strain develops atherosclerotic plaques without the presence of known environmental risk factors such as diet and classic predictors such as blood pressure or blood cholesterol levels. With similar parameters, the Show Racer (SR-Ar) is resistant to plaque development. Thiazolidinediones, including rosiglitazone, activate the peroxisome proliferator-activated receptor gamma (PPARγ) raising cellular sensitivity to insulin. The effect of rosiglitazone was evaluated in aortic smooth muscle cells (SMC) from these 2 pigeon breeds. Primary SMC cultures were prepared from WC-As and SR-Ar squabs. Cell monolayers, which achieved confluence in 7 d, were treated with 0 or 4 µM rosiglitazone for 24 h. Cellular lipid accumulation was evaluated by oil red O staining. Control WC-As cells had significantly higher vacuole scores and lipid content than did the SR-Ar control cells. Rosiglitazone treatment decreased WC-As lipid vacuoles significantly compared with the control cells. On the other hand, lipid vacuoles in the treated and untreated SR-Ar cells did not differ significantly. The effect of rosiglitazone on WC-As SMC gene expression was compared with control SMC using representational difference analysis. Significant transcript increases were found for caveolin and RNA binding motif in the control cells compared with the rosiglitazone-treated cells as well as cytochrome p450 family 17 subfamily A polypeptide 1 (CYP171A) in the rosiglitazone-treated cells compared with the control cells. Although rosiglitazone was selected for these experiments because of its role as a PPARγ agonist, it appears that the drug also tempers c-myc expression, as genes related to this second transcription factor were differentially expressed. Both PPARγ and c-myc appear to affect WC-As SMC gene expression, which may relate to disease development, progression, or both.

Effect of cell-surface components and metabolites of lactic acid bacteria and probiotic organisms on cytokine production and induction of CD25 expression in human peripheral mononuclear cells.

In the current study, the relative contribution of cell-surface components (CSC) and cell-free supernatants (CFS) in the immuno-modulatory properties of 17 strains of probiotic and lactic acid bacteria (LAB) was assessed. The production of pro- and antiinflammatory cytokines including IL-2, IL-4, IL-10, IL-12 p70, IFN-γ, tumor necrosis factor-α (TNF-α), and transforming growth factor-ß was measured at different time points after stimulation of buffy coat derived-peripheral blood mononuclear cells (PBMC) from healthy donors with CSC and CFS of probiotic and LAB. Results showed that CSC of probiotic and LAB strains induced production of T helper 1 and 2 type cytokines. Transforming growth factor-ß was stimulated at highest concentrations, followed by IL-10 and TNF-α. The CFS of all tested bacterial strains induced PBMC for significantly high levels of IL-10 secretion compared with unstimulated cells, but the values were less than lipopolysaccharide-stimulated cells. Cytokines due to CFS stimulation showed declined concentration for IL-2, TNF-α, and IL-4, and complete disappearance of IL-12, IFN-γ, and transforming growth factor-ß in the cultured medium at 96 h of incubation. Results of cytokine data demonstrate proinflammatory TNF-α immune responses are mainly directed through cell-surface structures of probiotic and LAB, but antiinflammatory immune responses are mediated both by metabolites and cell-surfaces of these bacteria. The induction of CD4(+)CD25(+) regulatory T cells after stimulation of PBMC with CSC and CFS of probiotic and LAB showed regulatory T cell activity appeared to be influenced both by the CSC and metabolites, but was principally triggered by cell surfaces of probiotic and LAB strains.

Differentially expressed soluble proteins in aortic cells from atherosclerosis-susceptible and resistant pigeons.

Soluble proteins in aortic smooth muscle cells cultured from atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons were extracted and separated on 2-dimensional electrophoresis gels. Spots were analyzed with Phoretix software and compared between the 2 breeds. Proteins differentially expressed were arrayed on a map, plotting molecular weight against isoelectric point. Eight discrete zones were identified, 5 that included only proteins unique to susceptible cells and 3 that included proteins unique to resistant cells. Of the 88 differentially expressed proteins from susceptible cells, 41 were located in unique zones, whereas 29 of 82 differentially expressed proteins from resistant cells were in unique zones. Selected proteins from susceptibility, and resistance zones were annotated by peptide mass fragments, molecular weights, isoelectric points, and correspondence with genes differentially expressed between cells from the 2 breeds. Some of the annotated proteins (such as smooth muscle myosin phosphatase, myosin heavy chain, fatty acid-binding protein, ribophorin, heat shock protein, and tumor necrosis factor alpha-inducing factor) corresponded to the current hypotheses to explain atherogenesis. In addition, the unique electrophoretic migration zones of proteins associated with susceptibility or resistance should prove useful as a diagnostic tool in clinical settings where species or phenotypes, or both, susceptible or resistant to atherosclerosis can be identified.

Expression profiling of Ral-depleted bladder cancer cells identifies RREB-1 as a novel transcriptional Ral effector.

Although the monomeric GTPases RalA and RalB have been shown to regulate a variety of transcription factors, little is known regarding the differences or similarities in transcriptional programs regulated by RalA compared to RalB. Further, the association of these transcriptional pathways to human carcinogenesis and progression remains unclear. Here, we studied the role of RalA and/or RalB in transcriptional regulation by combining short interfering RNA depletion of Ral with gene expression profiling via microarray in the human bladder cancer cell line, UMUC-3. A large number of genes were found to be similarly modulated in cells with RalA and RalB depletion, suggesting that RalA and RalB impinge on overlapping transcriptional signaling pathways. However, smaller sets of genes were modulated by depletion of RalA or RalB, indicating that these closely related proteins also regulate nonoverlapping transcriptional pathways. Computational analysis of upstream sequences of genes modulated by Ral depletion identified Ras-responsive element-binding protein (RREB)-1, as a putative Ral transcriptional target, which we verified experimentally. Importantly, as a group, Ral-regulated probe sets identified here were disproportionally represented among those differentially expressed as a function of human bladder transformation. Taken together, these data strongly suggest that Ral family members mediate both common and specific transcriptional programs that are associated with human cancer and identify RREB-1 as a novel transcriptional effector of Ral.

The development of the Indian vision function questionnaire: field testing and psychometric evaluation.

OBJECTIVE: To develop and evaluate the acceptability, reliability, validity, and responsiveness of the Indian vision function questionnaire (IND-VFQ). METHODS: Problem statements from previous qualitative studies were reduced to a 45 item interviewer administered questionnaire representing three a priori domains (general functioning, psychosocial impact, and visual symptoms) which was evaluated in patients with cataract (n = 420), glaucoma (n = 120), diabetic retinopathy, or age related macular degeneration (n = 120) and normal controls (n = 120). Standard methods were used for item reduction and to evaluate psychometric properties. RESULTS: Psychometric item reduction produced a 33 item questionnaire. Psychometric evaluation showed that two of the three scales (psychosocial impact and visual symptoms) had good acceptability, and that all three scales showed high internal consistency (alpha >0.80; item-total correlations 0.54-0.86) and test-retest reliability (>0.89). All three scales showed moderate evidence of convergent and discriminant validity. Responsiveness, assessed in cataract patients (n = 120) before and after surgery, was good for all three scales (effect sizes >1). CONCLUSIONS: The IND-VFQ33 is a psychometrically sound measure of vision function addressing a gap in patient defined measures of vision function developed in populations living in low income countries.

A study to determine plasma antioxidant concentrations in patients with Barrett's oesophagus.

BACKGROUND: Dietary questionnaire studies have suggested that patients with oesophageal adenocarcinoma are deficient in antioxidants. It is not known whether the same holds true for patients with the precursor lesion, Barrett's oesophagus. AIMS: To evaluate the hypothesis that patients with Barrett's oesophagus are deficient in antioxidants compared with patients without evidence of Barrett's oesophagus. PATIENTS AND METHODS: Plasma antioxidant profiles (copper, selenium, zinc; vitamins A, C, and E; carotenoids) were determined for patients with Barrett's oesophagus (n = 36), patients with erosive oesophagitis (n = 32), and patient controls (n = 35). RESULTS: Patients with Barrett's oesophagus had significantly lower plasma concentrations of selenium, vitamin C, beta cryptoxanthine, and xanthophyll compared with the other groups. CONCLUSIONS: This study confirms the hypothesis that patients with Barrett's oesophagus are deficient in certain antioxidants.

Photodissociation of benzene under collision-free conditions: an ab initio/Rice-Ramsperger-Kassel-Marcus study.

The ab initio/Rice-Ramsperger-Kassel-Marcus (RRKM) approach has been applied to investigate the photodissociation mechanism of benzene at various wavelengths upon absorption of one or two UV photons followed by internal conversion into the ground electronic state. Reaction pathways leading to various decomposition products have been mapped out at the G2M level and then the RRKM and microcanonical variational transition state theories have been applied to compute rate constants for individual reaction steps. Relative product yields (branching ratios) for C(6)H(5)+H, C(6)H(4)+H(2), C(4)H(4)+C(2)H(2), C(4)H(2)+C(2)H(4), C(3)H(3)+C(3)H(3), C(5)H(3)+CH(3), and C(4)H(3)+C(2)H(3) have been calculated subsequently using both numerical integration of kinetic master equations and the steady-state approach. The results show that upon absorption of a 248 nm photon dissociation is too slow to be observable in molecular beam experiments. In photodissociation at 193 nm, the dominant dissociation channel is H atom elimination (99.6%) and the minor reaction channel is H(2) elimination, with the branching ratio of only 0.4%. The calculated lifetime of benzene at 193 nm is about 11 micros, in excellent agreement with the experimental value of 10 micros. At 157 nm, the H loss remains the dominant channel but its branching ratio decreases to 97.5%, while that for H(2) elimination increases to 2.1%. The other channels leading to C(3)H(3)+C(3)H(3), C(5)H(3)+CH(3), C(4)H(4)+C(2)H(2), and C(4)H(3)+C(2)H(3) play insignificant role but might be observed. For photodissociation upon absorption of two UV photons occurring through the neutral "hot" benzene mechanism excluding dissociative ionization, we predict that the C(6)H(5)+H channel should be less dominant, while the contribution of C(6)H(4)+H(2) and the C(3)H(3)+C(3)H(3), CH(3)+C(5)H(3), and C(4)H(3)+C(2)H(3) radical channels should significantly increase.

Sequential changes in plasma selenium concentration after cadaveric renal transplantation.

BACKGROUND: Previous investigations have shown that plasma selenium concentrations are significantly lower in patients with established chronic graft nephropathy (CGN) than in healthy transplant controls. The aims of this study were to determine when in the transplant process low selenium concentrations become apparent and to explore the relationship between selenium levels and risk factors for CGN. METHODS: Plasma selenium concentrations were measured in 40 patients (20 receiving cyclosporin, 20 receiving tacrolimus) undergoing transplantation. Samples were obtained immediately before transplantation and at 3, 6 and 12 months after transplantation. RESULTS: A low plasma selenium concentration was found in 30 patients at the time of transplantation but this had normalized in the majority of patients by 3 months. Plasma selenium concentrations at 3, 6 and 12 months were significantly higher than baseline values for both treatment arms, but were significantly lower at 3 months in patients who experienced either clinical acute rejection (CAR) or cytomegalovirus (CMV) infection during the preceding months. CONCLUSION: Low plasma selenium concentrations are common at the time of transplantation but appear to normalize thereafter. The identification of low selenium levels in patients who experience CAR or CMV (two important risk factors for clinically apparent CGN) suggests that the relationship between selenium and CGN warrants further investigation.

Measurement of thyroglobulin mRNA in peripheral blood as an adjunctive test for monitoring thyroid cancer.

AIMS: Monitoring treated patients with thyroid cancer for recurrent or metastatic disease is currently based upon the serial measurement of circulating plasma thyroglobulin (Tg) concentrations. However, the clinical usefulness of Tg immunoassays is limited by poor sensitivity and interference from anti-Tg antibodies. This study investigated whether the detection of Tg mRNA in peripheral blood, using reverse transcriptase polymerase chain reaction (RT-PCR), is of value in the biochemical surveillance of patients with thyroid cancer. METHODS: RNA was extracted from peripheral blood of five normal controls, six patients with abnormal thyroid function tests, and 28 patients who had undergone thyroidectomy for well differentiated thyroid cancer. From each, an 87 bp product from base pair 262 to 348 in the cDNA sequence of the thyroglobulin gene was amplified by RT-PCR. RESULTS: Tg mRNA was detected in normal individuals and patients with thyroid cancer. In the group of patients studied, identification of metastatic thyroid tissue by radioiodine scanning correlated better with Tg mRNA assay results than with serum Tg concentrations (accuracy 84% v 75%). No interference from circulating Tg antibodies was apparent. In patients studied prospectively over a 12 month period, there was a significant correlation between detectable Tg mRNA in peripheral blood and the presence or absence of metastatic disease, as demonstrated by radioiodine scanning. CONCLUSIONS: These results suggest that detection of Tg mRNA in blood is a more sensitive marker for metastatic thyroid disease than Tg immunoassay, and appears to be unaffected by the presence of circulating anti-Tg antibodies.

Phase II study of anti-gastrin-17 antibodies, raised to G17DT, in advanced pancreatic cancer.

PURPOSE: The prognosis for advanced pancreatic cancer remains poor. Gastrin acts as a growth factor for pancreatic cancer. We describe the first study of the antigastrin immunogen G17DT in pancreatic cancer. Our aims were to determine the antibody response, safety, tolerability, and preliminary evidence of efficacy of G17DT in advanced pancreatic cancer. PATIENTS AND METHODS: Thirty patients with advanced pancreatic cancer were immunized with three doses of either 100 micro g or 250 micro g of G17DT. RESULTS: In the whole group, 20 (67%) of 30 patients produced an antibody response. The 250- micro g dose resulted in a significantly greater response rate of 82% compared with 46% for the 100- micro g group (P =.018). The most significant side effects, seen in three patients, were local abscess and/or fever. The median survival for the whole group from the date of the first immunization was 187 days; median survival was 217 days for the antibody responders and 121 days for the antibody nonresponders. The difference in survival between the antibody responders and nonresponders was significant (P =.0023). CONCLUSION: Patients with advanced pancreatic cancer are able to mount an adequate antibody response to G17DT. The 250- micro g dose is superior to the 100- micro g dose, and it appears to be generally well tolerated. Antibody responders demonstrate significantly greater survival than antibody nonresponders. Phase III studies are currently underway in order to determine efficacy.

Clinical outcomes following percutaneous magnetic resonance image guided laser ablation of symptomatic uterine fibroids.

BACKGROUND: Fibroids are common benign tumours of the uterus. Percutaneous magnetic resonance (MR) image guided laser ablation provides a minimally invasive, day-case alternative to surgery for the treatment of symptomatic fibroids. METHODS: Women with symptomatic fibroids wishing to avoid surgery were treated with laser ablation. MR thermal mapping ensured that maximal safe energy was applied. Fibroid volume was measured at 3 and 12 months, menstrual blood loss was recorded before and after treatment and a menorrhagia outcomes questionnaire (MOQ) was used to assess satisfaction. RESULTS: A total of 66 patients was treated. There was a significant (P < 0.001) reduction in mean fibroid volume of 31%. This was 41% at 1 year follow-up (P < 0.001). Measured menstrual blood loss in eight patients complaining of excessive bleeding was reduced (P = 0.012). The MOQ total outcome score was not as good as that seen in hysterectomy patients (P = 0.02) but the quality of life/satisfaction score was similar (P = 0.06). CONCLUSION: We have used objective and subjective outcome measures to determine the efficacy of MR guided laser ablation for fibroids. Based on this limited study we are encouraged that this procedure may represent a minimally invasive alternative therapy for fibroids.