Pulse wave velocity and carotid atherosclerosis in White and Latino patients with hypertension

<p>Abstract</p> <p>Background</p> <p>Preventive cardiology has expanded beyond coronary heart disease towards prevention of a broader spectrum of cardiovascular diseases. Ethnic minorities are at proportionately greater risk for developing extracoronary vascular disease including heart failure and cerebrovascular disease.</p> <p>Methods</p> <p>We performed a cross sectional study of Latino and White hypertension patients in a safety-net healthcare system. Framingham risk factors, markers of inflammation (hsCRP, LPpLA2), arterial stiffness (Pulse wave velocity, augmentation index, and central aortic pressure), and endothelial function (brachial artery flow-mediated dilatation) were measured. Univariate and multivariable associations between these parameters and an index of extracoronary atherosclerosis (carotid intima media thickness) was performed.</p> <p>Results</p> <p>Among 177 subjects, mean age was 62 years, 67% were female, and 67% were Latino. In univariate analysis, markers associated with carotid intima media thickness (IMT) at p < 0.25 included pulse wave velocity (PWV), augmentation index (AIx), central aortic pressure (cAP), and LpPLA₂activity rank. However, AIx, cAP, and LpPLA2 activity were not significantly associated with carotid IMT after adjusting for Framingham risk factors (all p > .10). Only PWV retained a significant association with carotid IMT independent of the Framingham general risk profile parameters (p = .016). No statistically significant interactions between Framingham and other independent variables with ethnicity (all p > .05) were observed.</p> <p>Conclusion</p> <p>In this safety net cohort, PWV is a potentially useful adjunctive atherosclerotic risk marker independent of traditional risk factors and irrespective of ethnicity.</p

Impact of Surgical Timing on Neurological Outcomes for Spinal Arachnoid Cyst: A Single Institution Series

Objective Spinal arachnoid cysts (SACs) are rare lesions that often present with back pain and myelopathy. There is a paucity of literature evaluating the impact of surgical timing on neurological outcomes for primary SAC management. To compare long-term neurological outcomes in patients who were managed differently and to understand natural progression of SAC. Methods We conducted a retrospective analysis of adult patients treated for SAC at our institution from 2010 to 2021, stratified into 3 groups (conservative management only, surgical management, or conservative followed by surgical management). Study outcome measures were neurological outcomes as measured by modified McCormick Neurologic Scale (MNS), postoperative complications, and cyst recurrence. Nonparametric analysis was performed to evaluate differences between groups for selected endpoints. Results Thirty-six patients with SAC were identified. Eighteen patients were managed surgically. The remaining 18 patients were managed conservatively with outpatient serial imaging, 7 of whom (38.9%) ultimately underwent surgical treatment due to neurological decline. Most common presenting symptoms included back pain (50.0%), extremity weakness (36.1%), and numbness/paresthesia (36.1%). Initial/preoperative (p = 0.017) and 1-year postoperative (p = 0.006) MNS were significantly different between the 3 groups, but not at 6 weeks or 6 months postoperatively (p > 0.05). Additionally, at 1 year, there was no difference in MNS between patients managed surgically and those managed conservatively but ultimately underwent surgery (p > 0.99). Conclusion Delayed surgical intervention in minimally symptomatic patients does not seem to result in worse long-term neurofunctional outcomes. At 1 year, postoperative MNS were significantly higher in both surgical groups, when compared to the conservative group highlighting worsening clinical picture regardless of preoperative observational status

Higher D or Li: Probes of Physics beyond the Standard Model

Standard Big Bang Nucleosynthesis at the baryon density determined by the microwave anisotropy spectrum predicts an excess of \li7 compared to observations by a factor of 4-5. In contrast, BBN predictions for D/H are somewhat below (but within ~2 \sigma) of the weighted mean of observationally determined values from quasar absorption systems. Solutions to the \li7 problem which alter the nuclear processes during or subsequent to BBN, often lead to a significant increase in the deuterium abundance consistent with the highest values of D/H seen in absorption systems. Furthermore, the observed D/H abundances show considerable dispersion. Here, we argue that those systems with D/H \simeq 4 \times 10^{-5} may be more representative of the primordial abundance and as a consequence, those systems with lower D/H would necessarily have been subject to local processes of deuterium destruction. This can be accounted for by models of cosmic chemical evolution able to destroy in situ Deuterium due to the fragility of this isotope.Comment: 22 pages, 8 figure

Circulating adiponectin levels are lower in Latino versus non-Latino white patients at risk for cardiovascular disease, independent of adiposity measures

<p>Abstract</p> <p>Background</p> <p>Latinos in the United States have a higher prevalence of type 2 diabetes than non-Latino whites, even after controlling for adiposity. Decreased adiponectin is associated with insulin resistance and predicts T2DM, and therefore may mediate this ethnic difference. We compared total and high-molecular-weight (HMW) adiponectin in Latino versus white individuals, identified factors associated with adiponectin in each ethnic group, and measured the contribution of adiponectin to ethnic differences in insulin resistance.</p> <p>Methods</p> <p>We utilized cross-sectional data from subjects in the Latinos Using Cardio Health Actions to reduce Risk study. Participants were Latino (n = 119) and non-Latino white (n = 60) men and women with hypertension and at least one other risk factor for CVD (age 61 ± 10 yrs, 49% with T2DM), seen at an integrated community health and hospital system in Denver, Colorado. Total and HMW adiponectin was measured by RIA and ELISA respectively. Fasting glucose and insulin were used to calculate the homeostasis model insulin resistance index (HOMA-IR). Variables independently associated with adiponectin levels were identified by linear regression analyses. Adiponectin's contribution to ethnic differences in insulin resistance was assessed in multivariate linear regression models of Latino ethnicity, with logHOMA-IR as a dependent variable, adjusting for possible confounders including age, gender, adiposity, and renal function.</p> <p>Results</p> <p>Mean adiponectin levels were lower in Latino than white patients (beta estimates: -4.5 (-6.4, -2.5), p < 0.001 and -1.6 (-2.7, -0.5), p < 0.005 for total and HMW adiponectin), independent of age, gender, BMI/waist circumference, thiazolidinedione use, diabetes status, and renal function. An expected negative association between adiponectin and waist circumference was seen among women and non-Latino white men, but no relationship between these two variables was observed among Latino men. Ethnic differences in logHOMA-IR were no longer observed after controlling for adiponectin levels.</p> <p>Conclusions</p> <p>Among patients with CVD risk, total and HMW adiponectin is lower in Latinos, independent of adiposity and other known regulators of adiponectin. Ethnic differences in adiponectin regulation may exist and future research in this area is warranted. Adiponectin levels accounted for the observed variability in insulin resistance, suggesting a contribution of decreased adiponectin to insulin resistance in Latino populations.</p

Postsurgical morbidity and mortality favorably informs deep brain stimulation for new indications including schizophrenia and schizoaffective disorder

BackgroundDeep brain stimulation (DBS) shows promise for new indications like treatment-refractory schizophrenia in early clinical trials. In the first DBS clinical trial for treatment refractory schizophrenia, despite promising results in treating psychosis, one of the eight subjects experienced both a symptomatic hemorrhage and an infection requiring device removal. Now, ethical concerns about higher surgical risk in schizophrenia/schizoaffective disorder (SZ/SAD) are impacting clinical trial progress. However, insufficient cases preclude conclusions regarding DBS risk in SZ/SAD. Therefore, we directly compare adverse surgical outcomes for all surgical procedures between SZ/SAD and Parkinson's disease (PD) cases to infer relative surgical risk relevant to gauging DBS risks in subjects with SZ/SAD.DesignIn the primary analysis, we used browser-based statistical analysis software, TriNetX Live (trinetx.com TriNetX LLC, Cambridge, MA), for Measures of Association using the Z-test. Postsurgical morbidity and mortality after matching for ethnicity, over 39 risk factors, and 19 CPT 1003143 coded surgical procedures from over 35,000 electronic medical records, over 19 years, from 48 United States health care organizations (HCOs) through the TriNetX Research Network™. TriNetXis a global, federated, web-based health research network providing access and statistical analysis of aggregate counts of deidentified EMR data. Diagnoses were based on ICD-10 codes. In the final analysis, logistic regression was used to determine relative frequencies of outcomes among 21 diagnostic groups/cohorts being treated with or considered for DBS and 3 control cohorts.ResultsPostsurgical mortality was 1.01–4.11% lower in SZ/SAD compared to the matched PD cohort at 1 month and 1 year after any surgery, while morbidity was 1.91–2.73% higher and associated with postsurgical noncompliance with medical treatment. Hemorrhages and infections were not increased. Across the 21 cohorts compared, PD and SZ/SAD were among eight cohorts with fewer surgeries, nine cohorts with higher postsurgical morbidity, and fifteen cohorts within the control-group range for 1-month postsurgical mortality.ConclusionsGiven that the subjects with SZ or SAD, along with most other diagnostic groups examined, had lower postsurgical mortality than PD subjects, it is reasonable to apply existing ethical and clinical guidelines to identify appropriate surgical candidates for inclusion of these patient populations in DBS clinical trials

An Integrated Microfluidic Device for Monitoring Changes in Nitric Oxide Production in Single T-Lymphocyte (Jurkat) Cells

A considerable amount of attention has been focused on the analysis of single cells in an effort to better understand cell heterogeneity in cancer and neurodegenerative diseases. Although microfluidic devices have several advantages for single cell analysis, few papers have actually demonstrated the ability of these devices to monitor chemical changes in perturbed biological systems. In this paper, a new microfluidic channel manifold is described that integrates cell transport, lysis, injection, electrophoretic separation, and fluorescence detection into a single device, making it possible to analyze individual cells at a rate of 10 cells/min in an automated fashion. The system was employed to measure nitric oxide (NO) production in single T-lymphocytes (Jurkat cells) using a fluorescent marker, 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM DA). The cells were also labeled with 6-carboxyfluorescein diacetate (6-CFDA) as an internal standard. The NO production by control cells was compared to that of cells stimulated using lipopolysaccharide (LPS), which is known to cause the expression of inducible nitric oxide synthase (iNOS) in immune-type cells. Statistical analysis of the resulting electropherograms from a population of cells indicated a twofold increase in NO production in the induced cells. These results compare nicely to a recently published bulk cell analysis of NO

Overview of the massive young star-forming complex study in infrared and X-ray (MYStIX) project

The Massive Young Star-Forming Complex Study in Infrared and X-ray (MYStIX) seeks to characterize 20 OB-dominated young clusters and their environs at distances d ≤ 4 kpc using imaging detectors on the Chandra X-ray Observatory, Spitzer Space Telescope, and the United Kingdom InfraRed Telescope. The observational goals are to construct catalogs of star-forming complex stellar members with well-defined criteria and maps of nebular gas (particularly of hot X-ray-emitting plasma) and dust. A catalog of MYStIX Probable Complex Members with several hundred OB stars and 31,784 low-mass pre-main sequence stars is assembled. This sample and related data products will be used to seek new empirical constraints on theoretical models of cluster formation and dynamics, mass segregation, OB star formation, star formation triggering on the periphery of H II regions, and the survivability of protoplanetary disks in H II regions. This paper gives an introduction and overview of the project, covering the data analysis methodology and application to two star-forming regions: NGC 2264 and the Trifid Nebula

The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile

<p>Abstract</p> <p>Background</p> <p>Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints.</p> <p>Methods</p> <p>Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides) was used for validation.</p> <p>Results</p> <p>By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (<it>p </it>< 0.01). Multimarker clustering showed two distinctive proteomic profiles independent of age and ethnicity. Eighteen of 19 cancer samples clustered together (sensitivity 95%) while 27/36 of non-cancer samples clustered in a second group. Nine non-cancer samples that clustered with cancer samples included 5 pre-malignant lesions (1 adenomatous polyp and 4 intestinal metaplasia). Validation using a second sample set showed the sensitivity and specificity to be 88% and 93%, respectively. Positive predictive value of the combined data was 0.80. Selected peptide sequencing identified pepsinogen C and pepsin A activation peptide as significantly down-regulated and alpha-defensin as significantly up-regulated.</p> <p>Conclusion</p> <p>This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.</p

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe