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Aim: To determine differences in coronary plaque composition and inflammatory biomarkers between men and women with newly diagnosed Type 2 diabetes without known cardiovascular disease. Methods: A total of 88 people with newly diagnosed (<1 year) Type 2 diabetes underwent contrast‐enhanced coronary computed tomography angiography. Advanced coronary plaque analysis was performed using semi‐automated software. Plasma concentrations of inflammatory biomarkers were determined. Results: There were no significant differences between men (n=60) and women (n=28) regarding age or cardiovascular risk factors (all P>0.05). The median (quartiles) serum levels of fibrinogen [10.9 (9.8–12.6) μmol/l vs 9.7 (8.8–10.9) μmol/l], fibrin d‐dimer [0.3 (0.2–0.4) mg/l vs 0.27 (0.2–0.4) mg/l] and C‐reactive protein [3.1 (1.1–5.2) mg/l vs (0.8–2.6) 1.6 mg/l] were significantly higher in women (all P<0.05). Overall, men more often had multi‐vessel involvement [28 men (47%) vs 4 women (14%)], and higher total plaque burden [median (quartiles) 11.6 (2.3–36.0)% vs 2.0 (0.4–5.4)%; both P<0.05]. The median (quartiles) total plaque volume [269.9 (62.6–641.9) mm3 vs 61.1 (7.6–239.9) mm3] and absolute calcified plaque volume [33.5 (8.3–148.3) mm3 vs 4.7 (0.9–17.3) mm3] were higher in men (both P<0.05). Women had a lower relative proportion of the calcified plaque component [median (quartiles) 7.8 (4.7–15.4)% vs 23.7 (8.4–31.1)%] and a higher relative proportion (median [quartiles]) of the non‐low‐density non‐calfied plaque component [77.6 (66.0–86.0)% vs 63.6 (54.0–72.9)%; both P<0.05]. Conclusions: In people with newly diagnosed Type 2 diabetes, women had lower absolute coronary plaque volumes but a more unfavourable plaque composition and enhanced systemic inflammation compared with men. What's new?: It is known that Type 2 diabetes increases the risk of developing coronary artery disease more markedly in women than in men, but differences in coronary plaque composition between the sexes are poorly elucidated.This study found that women have smaller absolute volumes of coronary plaque components but a more unfavourable coronary plaque structure and enhanced systemic inflammation.The reported difference in plaque composition between men and women with a new diagnosis of Type 2 diabetes might be the basis for larger studies evaluating the impact of sex‐differentiated therapeutic strategies at an early stage of Type 2 diabetes to prevent the development and progression of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Acute trauma is often associated with progressive deterioration of multiple organ systems in humans and is the leading cause of death in trauma care units. Identification of specific organ failure in a non-invasive manner and the contribution of different demographic factors on the casual progression of acute trauma are of supreme interests for successful diagnosis, prognosis or monitoring of trauma status. Recently, electrospray ionization and matrix-assisted laser desorption time-of-flight mass spectrometry have been used to identify biomarkers in both proteomics and metabonomics studies. Data sets generated from mass spectrometers in such studies are generally very large in size and thus require the use of sophisticated statistical techniques to glean useful information. In a recent development, Ghosh et al. ( BMC Bioinformatics 2008; 9:38) suggested a unified semiparametric approach to distinguish urinary metabolic profiles in a group of traumatic subjects from those of a control group consisting of normal individuals. In this study we have extended their approach by combining available covariate information in the development of metabonomic profile of acute trauma. We have shown that age is a statistically significant covariate across trauma and control group, thus pointing out the fact that prognosis of trauma may be acutely linked with subjects' age. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The hypothesis that the introduction of artificial refuges might provide protection for fish and reduce the level of cormorant predation was tested in two, paired-pond, cross-over trials during the winters of 2003 and 2004, using a ‘refuge’ pond and an adjacent equivalently stocked ‘control’ pond. There were 77% fewer cormorant visits to the refuge pond than the control pond, on average. There was also a 67% fall in the mean mass of fish consumed per cormorant visit and 79% less fish mass lost in the refuge pond. The results are discussed in the context of interactions between cormorants and fish and the potential use of the tool in fisheries management. [ABSTRACT FROM AUTHOR]

The efficacy of optimal doses of highly bioavailable (–)-hydroxycitric acid (HCA-SX) alone and in combination with niacin-bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat metabolites. HCA-SX has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels. A randomized, double-blind, placebo-controlled human study was conducted in Elluru, India for 8 weeks in 60 moderately obese subjects (ages 21–50, BMI >26 kg/m2). Subjects were randomly divided into three groups. Group A was administered HCA-SX 4667 mg, group B was administered a combination of HCA-SX 4667 mg, NBC 4 mg and GSE 400 mg, while group C was given placebo daily in three equally divided doses 30–60 min before meals. All subjects received a 2000 kcal diet/day and participated in supervised walking. At the end of 8 weeks, body weight and BMI decreased by 5–6% in both groups A and B. Food intake, total cholesterol, low-density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups, while high-density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non-significant effect was observed in all parameters in group C. The present study shows that optimal doses of HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels. [ABSTRACT FROM AUTHOR]

With the rapid advancements in electronics and in communication infrastructures, the deployment of low‐complexity devices for power system monitoring has become an active area of research. For the large‐scale deployment of monitoring devices, robust and economical remote data acquisition systems for power system monitoring are required. Keeping this in mind, the scheme of a remote leakage current acquisition system for high‐voltage insulators that may be employed for remote monitoring purposes is described. A low‐complexity method is adopted for the extraction of harmonic information from the leakage current signal. Unlike existing remote insulator‐monitoring techniques that employ a dedicated fibre‐optic network and satellite communication, the mobile communication voice channel is used to communicate the data to a central location for analysis. This provides an economical solution for the remote monitoring of insulators that may be used for large‐scale deployment. [ABSTRACT FROM AUTHOR]

Link functions and random effects structures are the two important components in building flexible regression models for dependent ordinal data. The power link functions include the commonly used links as special cases but have an additional skewness parameter, making the probability response curves adaptive to the data structure. It overcomes the arbitrary symmetry assumption imposed by the commonly used logistic or probit links as well as the fixed skewness in the complementary log–log or log–log links. By employing Gaussian processes, the regression model can incorporate various dependence structures in the data, such as temporal and spatial correlations. The full Bayesian estimation of the proposed model is conveniently implemented through RStan. Extensive simulation studies are carried out for discussion in model computation, parameterization, and evaluation in terms of estimation bias and overall model performance. The proposed model is applied to the PM2.5 data in Beijing and the Berberis thunbergii abundance data in New England. The results suggest that the proposed model leads to important improvement in estimation and prediction in modeling dependent ordinal response data. [ABSTRACT FROM AUTHOR]

Presents a reply letter to the editor in response to the correspondence sent by S.B. Heymsfield regarding the author's article on the effects of hydroxycitric acid, chromium and Gymnema sylvestre extract on weight loss. Clarifications to the observations made by S.B. Heymsfield over the failures of the study; Absence of any power analysis as being preliminary feasibility studies; Conduction of comparisons of t-tests using the Boferroni method; Decision to use similar body weight distributions in all three test groups.

Compositional data often result when raw data are normalized or whendata is obtained as proportions of a certain heterogeneous quantity.These conditions are fairly common in geology, economics and biology. The result is, therefore, a vector of such observations per specimen. The usual multivariate procedures are seldom adequate for the analysis of compositional data and there is a relative dearth of alternative techniques suitable for the same. The presence of covariates further adds to complexity of the situation. In this manuscript, a complete Bayesian methodology to model such data is developed and is illustrated on a real data set comprising sand, silt and clay compositions taken at various water depths in an Arctic lake. Alternative methods such as maximum likelihood estimates are compared with the proposed Bayesian estimates. Simulation based approach is adopted to ascertain adequacy of the fit. Several models are finally compared via a posterior predictive loss measure. Copyright (c) 1998 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: The left internal mammary artery (LIMA) is protected from developing atherosclerosis. Perivascular inflammation, which is closely associated with atherosclerosis, can be measured by perivascular adipose tissue attenuation on computed tomography angiography. Whether the absence of atherosclerosis in LIMA is related to the lower level of perivascular inflammation is unknown. This study was performed to compare the level of perivascular inflammation between LIMA in situ and native coronary arteries in patients with coronary artery disease., Methods and Results: A total of 573 patients who underwent both computed tomography angiography and optical coherence tomography imaging were included. The level of perivascular adipose tissue attenuation between LIMA in situ and coronary arteries was compared. Perivascular adipose tissue attenuation around LIMA in situ was significantly lower around the 3 coronary arteries (-82.9 [-87.3 to -78.0] versus -70.8 [-75.9 to -65.9]; P <0.001), irrespective of the level of pericoronary inflammation or the number of vulnerable features on optical coherence tomography. When patients were divided into high and low pericoronary inflammation groups, those in the high inflammation group had more target vessel failure (hazard ratio, 2.97 [95% CI, 1.16-7.59]; P =0.017)., Conclusions: The current study demonstrated that perivascular adipose tissue attenuation was significantly lower around LIMA in situ than around native coronary arteries. The lower level of perivascular inflammation may be related to the low prevalence of atherosclerosis in LIMA., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04523194.

Background: It was recently reported that thin-cap fibroatheroma (TCFA) detected by optical coherence tomography was an independent predictor of future cardiac events in patients with diabetes. However, the clinical usefulness of this finding is limited by the invasive nature of optical coherence tomography. Computed tomography angiography (CTA) characteristics of TCFA have not been systematically studied. The aim of this study was to investigate CTA characteristics of TCFA in patients with diabetes., Methods and Results: Patients with diabetes who underwent preintervention CTA and optical coherence tomography were included. Qualitative and quantitative analyses were performed for plaques on CTA. TCFA was assessed by optical coherence tomography. Among 366 plaques in 145 patients with diabetes, 111 plaques had TCFA. The prevalence of positive remodeling (74.8% versus 50.6%, P <0.001), low attenuation plaque (63.1% versus 33.7%, P <0.001), napkin-ring sign (32.4% versus 11.0%, P <0.001), and spotty calcification (55.0% versus 34.9%, P <0.001) was significantly higher in TCFA than in non-TCFA. Low-density noncalcified plaque volume (25.4 versus 15.7 mm 3 , P <0.001) and remodeling index (1.30 versus 1.20, P =0.002) were higher in TCFA than in non-TCFA. The presence of napkin-ring sign, spotty calcification, high low-density noncalcified plaque volume, and high remodeling index were independent predictors of TCFA. When all 4 predictors were present, the probability of TCFA increased to 82.4%., Conclusions: The combined qualitative and quantitative plaque analysis of CTA may be helpful in identifying TCFA in patients with diabetes., Registration Information: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194.

Background: The Diamond-Forrester model was used extensively to predict obstructive coronary artery disease (CAD) but overestimates probability in current populations. Coronary artery calcium (CAC) is a useful marker of CAD, which is not routinely integrated with other features. We derived simple likelihood tables, integrating CAC with age, sex, and cardiac chest pain to predict obstructive CAD., Methods and Results: The training population included patients from 3 multinational sites (n=2055), with 2 sites for external testing (n=3321). We determined associations between age, sex, cardiac chest pain, and CAC with the presence of obstructive CAD, defined as any stenosis ≥50% on coronary computed tomography angiography. Prediction performance was assessed using area under the receiver-operating characteristic curves (AUCs) and compared with the CAD Consortium models with and without CAC, which require detailed calculations, and the updated Diamond-Forrester model. In external testing, the proposed likelihood tables had higher AUC (0.875 [95% CI, 0.862-0.889]) than the CAD Consortium clinical+CAC score (AUC, 0.868 [95% CI, 0.855-0.881]; P =0.030) and the updated Diamond-Forrester model (AUC, 0.679 [95% CI, 0.658-0.699]; P <0.001). The calibration for the likelihood tables was better than the CAD Consortium model (Brier score, 0.116 versus 0.121; P =0.005)., Conclusions: We have developed and externally validated simple likelihood tables to integrate CAC with age, sex, and cardiac chest pain, demonstrating improved prediction performance compared with other risk models. Our tool affords physicians with the opportunity to rapidly and easily integrate a small number of important features to estimate a patient's likelihood of obstructive CAD as an aid to clinical management.

Direct comparisons of the effectiveness of the numerous novel therapies in the diffuse large B-cell lymphoma (DLBCL) treatment landscape in a range of head-to-head randomized phase 3 trials would be time-consuming and costly. Comparative effectiveness studies using real-world data (RWD) represent a complementary approach. Recently, several studies of relapsed/refractory (R/R) DLBCL have used RWD to create observational cohorts to compare patient outcomes with cohorts derived from single-arm phase 2 trials. Using propensity score methods to balance clinically and prognostically relevant baseline covariates, closely matched patient-level cohorts can be generated. By incorporating appropriate measures to assess covariate balance and address potential bias in comparative effectiveness study designs, robust comparative analyses can be performed. Results from such studies have been used to supplement regulatory approval of therapies assessed in single-arm trials. While RWD studies have a greater susceptibility to bias compared to randomized controlled trials, well-designed and appropriately analyzed studies can provide complementary real-world evidence on treatment effectiveness., (© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Background Inflammation in epicardial adipose tissue (EAT) may contribute to coronary atherosclerosis. Myocardial bridge is a congenital anomaly in which the left anterior descending coronary artery takes a "tunneled" course under a bridge of myocardium: while atherosclerosis develops in the proximal left anterior descending coronary artery, the bridged portion is spared, highlighting the possibility that geographic separation from inflamed EAT is protective. We tested the hypothesis that inflammation in EAT was related to atherosclerosis by comparing EAT from proximal and bridge depots in individuals with myocardial bridge and varying degrees of atherosclerotic plaque. Methods and Results Maximal plaque burden was quantified by intravascular ultrasound, and inflammation was quantified by pericoronary EAT signal attenuation (pericoronary adipose tissue attenuation) from cardiac computed tomography scans. EAT overlying the proximal left anterior descending coronary artery and myocardial bridge was harvested for measurement of mRNA and microRNA (miRNA) using custom chips by Nanostring; inflammatory cytokines were measured in tissue culture supernatants. Pericoronary adipose tissue attenuation was increased, indicating inflammation, in proximal versus bridge EAT, in proportion to atherosclerotic plaque. Individuals with moderate-high versus low plaque burden exhibited greater expression of inflammation and hypoxia genes, and lower expression of adipogenesis genes. Comparison of gene expression in proximal versus bridge depots revealed differences only in participants with moderate-high plaque: inflammation was higher in proximal and adipogenesis lower in bridge EAT. Secreted inflammatory cytokines tended to be higher in proximal EAT. Hypoxia-inducible factor 1a was highly associated with inflammatory gene expression. Seven miRNAs were differentially expressed by depot: 3192-5P, 518D-3P, and 532-5P were upregulated in proximal EAT, whereas miR 630, 575, 16-5P, and 320E were upregulated in bridge EAT. miR 630 correlated directly with plaque burden and inversely with adipogenesis genes. miR 3192-5P, 518D-3P, and 532-5P correlated inversely with hypoxia/oxidative stress, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PCG1a), adipogenesis, and angiogenesis genes. Conclusions Inflammation is specifically elevated in EAT overlying atherosclerotic plaque, suggesting that EAT inflammation is caused by atherogenic molecular signals, including hypoxia-inducible factor 1a and/or miRNAs in an "inside-to-out" relationship. Adipogenesis was suppressed in the bridge EAT, but only in the presence of atherosclerotic plaque, supporting cross talk between the vasculature and EAT. miR 630 in EAT, expressed differentially according to burden of atherosclerotic plaque, and 3 other miRNAs appear to inhibit key genes related to adipogenesis, angiogenesis, hypoxia/oxidative stress, and thermogenesis in EAT, highlighting a role for miRNA in mediating cross talk between the coronary vasculature and EAT.

Background: CD4 + regulatory T-cells (Tregs) expand during chronic hepatitis B virus (HBV) infection and inhibit antiviral immunity, although the underlying mechanism remains largely elusive. Myeloid-derived suppressor cells (MDSC) have been linked with T-cell dysfunction but questions remain regarding their persistence/profile/function in chronically HBV infected patients., Aim: To characterise MDSC in different phases of chronic HBV infection namely, immune-tolerant (IT), hepatitis B e-antigen-positive chronic hepatitis B (EP-CHB), inactive carriers (IC) and hepatitis B e-antigen-negative chronic hepatitis B (EN-CHB), to investigate their role in Treg induction and evaluate the effect of anti-viral therapy on these cells., Methods: Multiparametric flow cytometry, cell-sorting and co-culture assays were performed along with longitudinal immune monitoring of CHB patients receiving tenofovir., Results: HLA-DR - CD11b + CD33 hi -Monocytic-MDSC (M-MDSC) were enhanced in IT, EP-CHB and EN-CHB compared with IC, and this was related to increasing hepatitis B surface antigen (HBsAg) concentration. IT and EP-/EN-CHB displayed elevated frequency of CD4 + CD25 + FOXP3 + Treg that positively correlated with that of M-MDSC. However, both M-MDSC and HLA-DR - CD11b + CD33 low -granulocytic-MDSC from IT and EP-/EN-CHB expressed high transforming growth factor beta (TGF-β) and interleukin-10 (IL-10). Co-culture of sorted HLA-DR - CD33 + -MDSC with autologous MDSC depleted-PBMC from IT and CHB but not from IC, increased CD4 + CD25 + FOXP3 + -iTreg and CD4 + FOXP3 - IL-10 + -Tr1-cells through a cell-contact independent mechanism. While MDSC-derived TGF-β and IL-10 promoted development of iTreg, only IL-10 appeared to be crucial for Tr1 induction. One year of tenofovir treatment failed to normalise MDSC frequency/function or reduce Treg percentage and serum HBsAg levels, despite reduction in viral load., Conclusions: We established a previously unrecognised role of MDSC in Treg development in IT and EP-/EN-CHB via TGF-β/IL-10-dependent pathways and both cell-types persisted after anti-viral therapy. Hence, therapeutic targeting of MDSC or reducing circulating HBsAg level together with tenofovir-therapy might be more effective in restricting HBV persistence and disease progression., (© 2019 John Wiley & Sons Ltd.)

The cooperative roles of various structural motifs associated with the presence of different intermolecular interactions in the formation of molecular crystals are investigated in a series of trifluoromethylated phenylhydrazones. Out of the six compounds analysed, two exhibit three-dimensional structural similarities with geometrically equivalent building blocks, while a third exists as two polymorphic forms crystallized from ethanol solutions at low temperature (277 K) and room temperature (298 K), respectively. The compounds were characterized via single-crystal and powder X-ray diffraction techniques and differential scanning calorimetry. In the absence of any strong hydrogen bonding, the supramolecular constructs are primarily stabilized via molecular pairs with a high dispersion-energy contribution, due to the presence of molecular stacking along the molecular backbone along with C-H...π interactions in the solid state, in preference to an electrostatic contribution. The interaction energies for the most stabilizing molecular building blocks are in the range -29 to -43 kJ mol -1 . In addition, weak N-H...F, C-H...F and N-H...C interactions and F...F, F...C, F...N and C...N contacts act as secondary motifs, providing additional stability to the crystal packing. The overall molecular arrangements are carefully analysed in terms of their nature and energetics, and the roles of different molecular pairs towards the crystal structure are delineated. A topological study using the quantum theory of atoms in molecules was used to characterize all the atomic interactions in the solid state. It established the presence of (3, -1) bond critical points and the closed-shell nature of all the interactions.

In the current study, the crystal structure of 1-(3-nitrophenyl)-2,2,2-trifluoroethanone (A1) and (E)-4-((4-fluorophenyl) diazenyl)phenol (A2) has been analyzed for the characterization of the presence of a `unique' and `rare' intermolecular C(sp 3 /sp 2 )-F...O contact, which has been observed to play a significant role in the crystal packing. Theoretical charge-density calculations have been performed to study the nature and strength associated with the existence of this intermolecular F...O contact, wherein the F atom is attached to an sp 3 -hybridized C atom in the case of A1 and to an sp 2 hybridized carbon in the case of A2. The crystal packing of the former contains two `electronically different' Csp 3 -F...O contacts which are present across and in between the layers of molecules. In the latter case, it is characterized by the presence of a very `short' (2.708 Å) and `highly directional' (168° at ∠C4-F1...O1 and 174° at ∠C10-O1...F1) Csp 2 -F...O contact. According to the Cambridge Structural Database (CSD) study, it is a rare example in molecular crystals. Topological features of F...O contacts in the solid state were compared with the gas-phase models. The two-dimensional and three-dimensional static deformation density obtained from theoretical multipole modeling confirm the presence of a charge depleted region on the F atoms. Minimization of the electrostatic repulsion between like charges are observed through subtle arrangements in the electronic environment in two of the short intermolecular F...O contacts. These contacts were investigated using inputs from pair energy decomposition analysis, Bader's quantum theory of atoms in molecules (QTAIM), Hirshfeld surface analysis, delocalization index, reduced density gradient (RDG) plot, electrostatic potential surface and distributed atomic polarizability. The intermolecular energy decomposition (PIXEL) and RDG-NCI (non-covalent interaction) analysis of the F...O contacts establish the interaction to be dispersive in nature. The mutual polarization of an O atom by fluorine and vice versa provides real physical insights into the role of atomic polarizability in interacting atoms in molecules in crystals.

Aim: The efficacy of optimal doses of highly bioavailable (-)-hydroxycitric acid (HCA-SX) alone and in combination with niacin-bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat metabolites. HCA-SX has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels., Methods: A randomized, double-blind, placebo-controlled human study was conducted in Elluru, India for 8 weeks in 60 moderately obese subjects (ages 21-50, BMI >26 kg/m(2)). Subjects were randomly divided into three groups. Group A was administered HCA-SX 4667 mg, group B was administered a combination of HCA-SX 4667 mg, NBC 4 mg and GSE 400 mg, while group C was given placebo daily in three equally divided doses 30-60 min before meals. All subjects received a 2000 kcal diet/day and participated in supervised walking., Results: At the end of 8 weeks, body weight and BMI decreased by 5-6% in both groups A and B. Food intake, total cholesterol, low-density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups, while high-density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non-significant effect was observed in all parameters in group C., Conclusion: The present study shows that optimal doses of HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels.