Characteristics and determinants of the sublingual microcirculation in populations of different ethnicity.

No previous population study assessed sublingual capillary density (CD) or perfused boundary region (PBR). Lower PBR indicates greater glycocalyx width. In 252 Han and 220 She Chinese and 254 Flemish people (mean age, 51.

Weight loss, saline loading, and the natriuretic peptide system.

Background: In epidemiologic studies, obesity has been associated with reduced natriuretic peptide (NP) concentrations. Reduced NP production could impair the ability of obese individuals to respond to salt loads, increasing the risk of hypertension and other disorders. We hypothesized that weight loss enhances NP production before and after salt loading.

Lipid and lipoprotein measurements and the risk of ischemic vascular events: Framingham Study.

Objectives: To examine the relationship between plasma lipid measurements and incident ischemic vascular events (ischemic stroke [IS], and as a positive control, myocardial infarction [MI]) in a community cohort.

Methods: In 6,276 stroke-free Framingham participants (aged 64 ± 10 years, 56% female), we related plasma lipid levels (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], and TC/HDL-C ratio) measured at the original cohort 15th (1977-1979) and 20th examination cycles (1986-1990) and (TC, HDL-C, TC/HDL-C ratio, triglycerides [TG], and low-density lipoprotein cholesterol [LDL-C]) measured at the offspring fourth examination (1995-1998), to 10-year risk of incident IS and MI. Utilizing genome-wide genotyping in the same subjects, we used mendelian randomization methods to assess whether observed associations were incidental or causal.

Tumor necrosis factor: a mechanistic link between angiotensin-II-induced cardiac inflammation and fibrosis.

Background: Continuous angiotensin-II infusion induced the uptake of monocytic fibroblast precursors that initiated the development of cardiac fibrosis; these cells and concurrent fibrosis were absent in mice lacking tumor necrosis factor receptor 1 (TNFR1). We now investigated their cellular origin and temporal uptake and the involvement of TNFR1 in monocyte-to-fibroblast differentiation.

Methods And Results: Within a day, angiotensin-II induced a proinflammatory environment characterized by production of inflammatory chemokines, cytokines, and TH1-interleukins and uptake of bone marrow-derived M1 cells.

Association of sex hormones with sexual function, vitality, and physical function of symptomatic older men with low testosterone levels at baseline in the testosterone trials.

Context: The prevalence of sexual dysfunction, low vitality, and poor physical function increases with aging, as does the prevalence of low total and free testosterone (TT and FT) levels. However, the relationship between sex hormones and age-related alterations in older men is not clear.

Objective: To test the hypotheses that baseline serum TT, FT, estradiol (E2), and sex hormone-binding globulin (SHBG) levels are independently associated with sexual function, vitality, and physical function in older symptomatic men with low testosterone levels participating in the Testosterone Trials (TTrials).

Neurokinin 3 receptor and phosphocholine transferase: missing factors for pathogenesis of C-reactive protein in preeclampsia.

C-reactive protein (CRP), an innate immune mediator, is elevated in the circulation before symptoms in patients with preeclampsia, a severe hypertensive pregnancy disorder with high mortality and morbidity. However, the specific sources underlying increased CRP and the role of elevated CRP in preeclampsia are undefined. Here, we report that circulating CRP levels are significantly increased in a large cohort of normotensive pregnant individuals when compared with nulligravid women and is further increased in patients with preeclampsia.

Role of high-field intraoperative magnetic resonance imaging on a multi-image fusion-guided stereotactic biopsy of the basal ganglia: A case report.

The aim of the present case study was to investigate the advantages of intraoperative magnetic resonance imaging (iMRI) on the real-time guidance and monitoring of a stereotactic biopsy. The study describes a patient with intracranial lesions, which were examined by conventional MRI and diffusion tensor imaging using a 1.5T intraoperative MRI system.

Payments for acute myocardial infarction episodes-of-care initiated at hospitals with and without interventional capabilities.

Background: It is unknown whether hospitals with percutaneous coronary intervention (PCI) capability provide costlier care than hospitals without PCI capability for patients with acute myocardial infarction. The growing number of PCI hospitals and higher rate of PCI use may result in higher costs for episodes-of-care initiated at PCI hospitals. However, higher rates of transfers and postacute care procedures may result in higher costs for episodes-of-care initiated at non-PCI hospitals.

Body mass index and the risk of all-cause mortality among patients with type 2 diabetes mellitus.

Background: Several prospective studies have evaluated the association between body mass index (BMI) and death risk among patients with diabetes mellitus; however, the results have been inconsistent.

Methods And Results: We performed a prospective cohort study of 19 478 black and 15 354 white patients with type 2 diabetes mellitus. Cox proportional hazards regression models were used to estimate the association of different levels of BMI stratification with all-cause mortality.

Motoric cognitive risk syndrome: Multicenter incidence study.

Objective: To report incidence and risk factors for motoric cognitive risk syndrome (MCR), a newly described predementia syndrome characterized by slow gait and cognitive complaints.

Methods: We examined incidence rates of MCR in 3,128 adults aged 60 years and older, MCR- and dementia-free at baseline, participating in 4 US-based cohort studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of modifiable risk factors with risk of MCR were computed using Cox models.

Polygenic overlap between kidney function and large artery atherosclerotic stroke.

Background And Purpose: Epidemiological studies show strong associations between kidney dysfunction and risk of ischemic stroke (IS), the mechanisms of which are incompletely understood. We investigated whether these associations may reflect shared heritability because of a common polygenic basis and whether this differed for IS subtypes.

Methods: Polygenic models were derived using genome-wide association studies meta-analysis results for 3 kidney traits: estimated glomerular filtration rate using serum creatinine (eGFRcrea: n=73 998), eGFR using cystatin C (eGFRcys: n=22 937), and urinary albumin to creatinine ratio (n=31 580).

Germline CARD11 Mutation in a Patient with Severe Congenital B Cell Lymphocytosis.

Purpose: Activating germline mutations in CARD11 have recently been linked to a rare genetic disorder associated with congenital B cell lymphocytosis. We describe a patient with a similar clinical phenotype who had a de novo germline G123D CARD11 mutation.

Methods: Whole exome sequencing was performed on DNA from the patient and his biological parents.

Enhanced methamphetamine metabolism in rhesus macaque as compared with human: an analysis using a novel method of liquid chromatography with tandem mass spectrometry, kinetic study, and substrate docking.

Methamphetamine (MA), which remains one of the widely used drugs of abuse, is metabolized by the cytochrome P450 (P450) family of enzymes in humans. However, metabolism of methamphetamine in macaques is poorly understood. Therefore, we first developed and validated a very sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method using solid phase extraction of rhesus plasma with a lower limit of quantitation at 1.

Ultrasonography versus computed tomography for suspected nephrolithiasis.

Background: There is a lack of consensus about whether the initial imaging method for patients with suspected nephrolithiasis should be computed tomography (CT) or ultrasonography.

Methods: In this multicenter, pragmatic, comparative effectiveness trial, we randomly assigned patients 18 to 76 years of age who presented to the emergency department with suspected nephrolithiasis to undergo initial diagnostic ultrasonography performed by an emergency physician (point-of-care ultrasonography), ultrasonography performed by a radiologist (radiology ultrasonography), or abdominal CT. Subsequent management, including additional imaging, was at the discretion of the physician.

Effect of phosphodiesterase inhibition on insulin resistance in obese individuals.

Background: Obesity is associated with cardiometabolic disease, including insulin resistance (IR) and diabetes. Cyclic guanosine monophosphate (cGMP) signaling affects energy balance, IR, and glucose metabolism in experimental models. We sought to examine effects of phosphodiesterase-5 inhibition with tadalafil on IR in a pilot study of obese nondiabetic individuals.

[Research on parameter optimization of LIBS used for multi-element measurements in water].

The one of the advantages about Laser Induced Breakdown Spectroscopy (LIBS) is multielement detection at the same time. In order to obtain the optimum signal in the multi-element measurements of water with LIBS, the present paper firstly models the numerical relationship between the signal-to-background ratio of characteristic spectral lines and the delay time and gate width time with BP neural network, using DM design experiment data as the checking sample to ensure the generalization ability of the BP neural network model. Based on the above model, genetic algorithm is used to optimize measurement parameters and the fitness function phi is defined.

FGF-21 and skeletal remodeling during and after lactation in C57BL/6J mice.

Lactation is associated with significant alterations in both body composition and bone mass. Systemic and local skeletal factors such as receptor activator of nuclear factor κ-B ligand (RANKL), PTHrP, calcitonin, and estrogen are known to regulate bone remodeling during and after lactation. Fibroblast growth factor 21 (FGF-21) may function as an endocrine factor to regulate body composition changes during lactation by inducing gluconeogenesis and fatty acid oxidation.

AlphaLISA-based high-throughput screening assay to measure levels of soluble amyloid precursor protein α.

Activation of nonamyloidogenic processing of amyloid precursor protein (APP) has been hypothesized to be a viable approach for Alzheimer's disease drug discovery. However, until recently, the lack of HTS-compatible assay technologies precluded large scale screening efforts to discover molecules that potentiate nonamyloidogenic pathways. We have developed an HTS-compatible assay based on AlphaLISA technology that quantitatively detects soluble APPα (sAPPα), a marker of nonamyloidogenic processing of APP, released from live cells in low volume, 384-well plates.

The γ-gliadin-like γ-prolamin genes in the tribe Triticeae.

The γ-prolamins are important components of seed storage proteins in wheat and other Triticeae species. Here, the γ-prolamin genes from the diploid Triticeae species were systemically characterized. Most of the γ-prolamins (except 75 K γ-secalins) characterized were defined as γ-gliadin-like γ-prolamins, since they shared same characteristic model structure with γ-gliadins.

The 19S Deubiquitinase inhibitor b-AP15 is enriched in cells and elicits rapid commitment to cell death.

b-AP15 [(3E,5E)-3,5-bis[(4-nitrophenyl)methylidene]-1-(prop-2-enoyl)piperidin-4-one] is a small molecule inhibitor of the ubiquitin specific peptidase (USP) 14/ubiquitin carboxyl-terminal hydrolase (UCH) L5 deubiquitinases of the 19S proteasome that shows antitumor activity in a number of tumor models, including multiple myeloma. b-AP15 contains an α,β-unsaturated carbonyl unit that is likely to react with intracellular nucleophiles such as cysteine thiolates by Michael addition. We found that binding of b-AP15 to USP14 is partially reversible, and that inhibition of proteasome function is reversible in cells.

Vertical facial height and its correlation with facial width and depth: Three dimensional cone beam computed tomography evaluation based on dry skulls.

Introduction: The aim of the present study was to evaluate how vertical facial height correlates with mandibular plane angle, facial width and depth from a three dimensional (3D) viewing angle.

Methods: In this study 3D cephalometric landmarks were identified and measurements from 43 randomly selected cone beam computed tomography (CBCT) images of dry skulls from the Weisbach collection of Vienna Natural History Museum were analyzed. Pearson correlation coefficients of facial height measurements and mandibular plane angle and the correlation coefficients of height-width and height-depth were calculated, respectively.

Preventable readmissions within 30 days of ischemic stroke among Medicare beneficiaries.

Background And Purpose: The Centers for Medicare and Medicaid Services proposes to use 30-day hospital readmissions after ischemic stroke as part of the Hospital Inpatient Quality Reporting Program for payment determination beginning in 2016. The proportion of poststroke readmissions that is potentially preventable is unknown.

Methods: Thirty-day readmissions for all Medicare fee-for-service beneficiaries aged≥65 years discharged alive with a primary diagnosis of ischemic stroke (International Classification of Diseases, Ninth Revision, Clinical Modification 433, 434, 436) between December 2005 and November 2006 were analyzed.

Usefulness of molecular modeling in characterizing the ligand-binding sites of proteins: experience with human PDI, PDIp and COX.

In this paper, we discussed our recent experience with the use of computational modeling tools in studying the binding interaction of small molecular weight ligands with their protein targets. Specific examples discussed here include the interaction of estrogens with human protein disulfide isomerase (PDI) and its pancreas-specific homolog (PDIp), and the interaction of dietary flavonoids with human cyclooxygenase (COX) I and II. Using human PDIp as an example, biochemical analysis revealed that the estrogen-binding activity is only associated with PDIp's b-b´ domain combination but not associated with the single b or b´ domain or any other domains.

Natural regulatory T cells limit angiotensin II-induced aneurysm formation and rupture in mice.

Objective: Abdominal aortic aneurysm is an inflammatory disease leading to destructive vascular remodeling and ultimately to lethal aortic rupture. Despite its frequent association with atherosclerosis, compelling studies have shown striking differences and potentially opposite roles of T-cell helper responses in aneurysm as compared with atherosclerosis, casting doubt on the relevance and suitability of T-cell-targeted therapies in this context.

Approach And Results: Here, we show that selective depletion of T regulatory (Treg) cells using a CD25-specific monoclonal antibody significantly enhances the susceptibility of C57Bl/6 mice to angiotensin II-induced abdominal aortic aneurysm and promotes aortic rupture (n=25-44 mice/group).

The molecular diversity of α-gliadin genes in the tribe Triticeae.

Many of the unique properties of wheat flour are derived from seed storage proteins such as the α-gliadins. In this study these α-gliadin genes from diploid Triticeae species were systemically characterized, and divided into 3 classes according to the distinct organization of their protein domains. Our analyses indicated that these α-gliadins varied in the number of cysteine residues they contained.