We previously demonstrated that when platelets are in motion and in proximity to endothelial cells, they become unresponsive to agonists (Marcus, A.J., L.B. Safier, K.A. Hajjar, H.L. Ullman, N. ...Islam, M.J. Broekman, and A.M. Eiroa. 1991. J. Clin. Invest. 88:1690-1696). This inhibition is due to an ecto-ADPase on the surface of endothelial cells which metabolizes ADP released from activated platelets, resulting in blockade of the aggregation response. Human umbilical vein endothelial cells (HUVEC) ADPase was biochemically classified as an E-type ATP-diphosphohydrolase. The endothelial ecto-ADPase is herein identified as CD39, a molecule originally characterized as a lymphoid surface antigen. All HUVEC ecto-ADPase activity was immunoprecipitated by monoclonal antibodies to CD39. Surface localization of HUVEC CD39 was established by confocal microscopy and flow cytometric analyses. Transfection of COS cells with human CD39 resulted in both ecto-ADPase activity as well as surface expression of CD39. PCR analyses of cDNA obtained from HUVEC mRNA and recombinant human CD39 revealed products of the same size, and of identical sequence. Northern blot analyses demonstrated that HUVEC express the same sized transcripts for CD39 as MP-1 cells (from which CD39 was originally cloned). We established the role of CD39 as a prime endothelial thromboregulator by demonstrating that CD39-transfected COS cells acquired the ability to inhibit ADP-induced aggregation in platelet-rich plasma. The identification of HUVEC ADPase/CD39 as a constitutively expressed potent inhibitor of platelet reactivity offers new prospects for antithrombotic therapeusis.
The 2xxx Al series (Al-Cu-Mg) is widely used for the aircraft and aerospace industry, it has low density and presents excellent mechanical properties such as high fracture toughness, high tensile ...strength, and good damage tolerance. Identifying and understanding the strengthening mechanisms of these alloys to improve their strength, is the aim of several research works. At present study is analyzed the microstructure and the microhardness of a 2xxx modified Al alloy to identify the strengthening mechanisms involved.
In this article, Conley’s connection matrix theory and a spectral sequence analysis of a filtered Morse chain complex
$(C,{\rm\Delta})$
are used to study global continuation results for flows on ...surfaces. The briefly described unfoldings of Lyapunov graphs have been proved to be a well-suited combinatorial tool to keep track of continuations. The novelty herein is a global dynamical cancellation theorem inferred from the differentials of the spectral sequence
$(E^{r},d^{r})$
. The local version of this theorem relates differentials
$d^{r}$
of the
$r$
th page
$E^{r}$
to Smale’s theorem on cancellation of critical points.
Radiofrequency ablation of the atrioventricular node and permanent pacing are used for symptomatic relief in patients with medically refractory atrial fibrillation. In this study, meta-analysis was ...used to clarify clinical outcomes and survival after ablation and pacing therapy using data from the published literature.
We used 21 studies with a total of 1181 patients in the meta-analysis. All patients had medically refractory atrial tachyarrhythmias, primarily atrial fibrillation (97%). Nineteen measures of clinical outcome, encompassing quality of life, ventricular function, exercise duration, and healthcare use, were derived from the studies. The meta-analysis demonstrated significant improvement after ablation and pacing therapy in all outcome measures except fractional shortening, which demonstrated a trend toward improvement (P=0.08). Ejection fraction did show significant improvement (P<0.001). The calculated 1-year total and sudden death mortality rates after ablation and pacing therapy were 6.3% and 2.0%, respectively.
Ablation and pacing therapy improves a broad range of clinical outcomes for patients with medically refractory atrial fibrillation. The calculated 1-year mortality rates after this therapy are low and comparable with medical therapy.
Hundreds of laws have been implemented in the United States over the past few decades designed to reduce alcohol-impaired driving and the crashes that often result. One approach has been to lower the ...legally allowable alcohol concentration for drivers. We examined the effects of changes in legal BAC limit in 28 U.S. states from January, 1976 to December, 2002.
An interrupted time-series quasi-experimental design was used, incorporating non-alcohol-related crashes as comparisons. Four outcome measures of alcohol-related crash involvement were examined: single-vehicle nighttime, BAC
=
0.01–0.07, BAC
=
0.08–0.14, and BAC
≥
0.15. Missing BAC test result data were handled by using multiple imputations. Analyses involved estimation of state-specific ARIMA models, controlling for other factors affecting overall crash rates and other major DUI policy changes. Inverse variance weighting methods were used to pool results across states for the most precise underlying estimate of effect of legal BAC limits.
Considerable state by state variability in estimated effects was observed, but results from the pooled analyses were clear and consistent. Changes in legal BAC limits significantly affected alcohol-related fatal crash involvement for both the SVN and BAC test result measures, and the laws affected drivers at all drinking levels.
An estimated 360 deaths are prevented each year in the United States as a result of the move from a 0.10 to 0.08 legal limit in recent years, and an additional 538 lives could be saved each year if the United States reduced the limit to 0.05, consistent with limits in most countries worldwide.
Given the significant effects of lower legal BAC limits on fatal crash involvement, businesses should support implementation of laws that further reduce the legal BAC limit for all drivers. Furthermore, all companies should set higher standards for employees, such as a zero allowable BAC limit for driving during work time.
Recent microarray studies have identified distinct subtypes of breast tumors that arise from different cell types and that show statistically significant differences in patient outcome. To gain ...insight into these differences, we identified in vitro and in vivo changes in gene expression induced by chemotherapeutics. We treated two cell lines derived from basal epithelium (immortalized human mammary epithelial cells) and two lines derived from luminal epithelium (MCF-7 and ZR-75-1) with chemotherapeutics used in the treatment of breast cancer and assayed for changes in gene expression using DNA microarrays. Treatment doses for doxorubicin and 5-fluorouracil were selected to cause comparable cytotoxicity across all four cell lines. The dominant expression response in each of the cell lines was a general stress response; however, distinct expression patterns were observed. Both cell types induced DNA damage-response genes such as p21(waf1), but the response in the luminal cells showed higher fold changes and included more p53-regulated genes. Luminal cell lines repressed a large number of cell cycle-regulated genes and other genes involved in cellular proliferation, whereas the basal cell lines did not. Instead, the basal cell lines repressed genes that were involved in differentiation. These in vitro responses were compared with expression responses in breast tumors sampled before and after treatment with doxorubicin or 5-fluorouracil/mitomycin C. The in vivo data corroborated the cell-type-specific responses to chemotherapeutics observed in vitro, including the induction of p21(waf1). Similarities between in vivo and in vitro responses help to identify important response mechanisms to chemotherapeutics.
Diabetes mellitus (DM) is a worldwide health threat affecting millions of people, which is associated with different micro- and macro-vascular complications. Type 2 diabetes mellitus (T2DM) is one of ...the different types of DM caused by insulin resistance and/or reduced secretion of insulin from the pancreas. A validated novel biomarker is required to enhance the accuracy of disease prediction, provide novel insights into pathophysiology and contribute to future prevention of T2DM. Various newer diagnostic methods have been developed by targeting endogenous proteins among which Adipsin is one of the promising target. Therefore, this review discusses Adipsin as a potential biomarker and its implication in T2DM. Adipsin is one of the adipokines secreted by adipose tissues which is involved in maintaining adipose tissue homeostasis and increasing insulin secretion in response to glucose. According to different experimental and clinical studies, plasma Adipsin concentrations are low in animals and patients with DM which support its use as a biomarker in combination to the other diagnostic modalities for DM. Additionally, the existence of Adipsin could be important in improving hyperglycemia by preserving (beta-cell mass through improving (beta-cell survival and maintaining their transcriptional identity. Keywords: adipsin, type 2 diabetes mellitus, biomarker
Flourishing is related to positive outcomes for physical and mental health, as well as overall wellbeing. The aim of the present study was to determine the validity and reliability of the Flourishing ...Scale (FS) among a sample of older participants in Iran.
In this validation study, 300 older people were selected by cluster sampling method. Data were collected using a checklist for demographic characteristics, the FS, and the Oxford happiness questionnaire. The validity (face, content, convergent, and construct) and reliability (Cronbach's alpha, test-retest) of the FS was evaluated in this cross-sectional study.
The exploratory factor analysis demonstrated a one-dimensional structure consisting of 8 items with an eigenvalue of 3.583. The model had a good fit χ
= 52.983, p < 0.001, χ
/df = 2.944, GFI = 0.958, CFI = 0.915, IFI = 0.949, TLI = 0.919, AGFI = 0.948, and RMSEA = 0.081, SRMR = 0.086 with all factor loadings greater than 0.5 and statistically significant. A test of concurrent validity showed a direct and significant association between the FS and the Oxford happiness questionnaire (
= 0.647,
< 0.001). The results of the reliability tests confirmed that the values of Cronbach's alpha coefficient (0.819) and test-retest (0.821) were acceptable.
The Persian version of the FS demonstrated suitable validity and reliability among a sample of older participants.
Friction stir welding was investigated for joining specimens of the ODS 14YWT ferritic alloy together and to an F82H tempered martensitic steel plate. The FSW run was performed using a ...polycrystalline boron nitride tool and resulted in good bonding between 14YWT/14YWT and 14YWT/F82H. Joints and interfaces were observed by light microscopy and SEM analysis to be narrow in width. The ultra-small grain size of 14YWT increased by a factor up to 4 while that of F82H decreased by a considerable amount in the weld zones. The TEM analysis showed no significant changes in the size of the oxygen-enriched nanoclusters in the weld zone of 14YWT. However, defects such as a wormhole on the advancing side of the weld zone in 14YWT and small pores associated with joints and interfaces were observed in the FSW sample. The hardness measurements from unaffected zone into weld zones showed ∼20% decrease in hardness for 14YWT (from ∼500VH to ∼380VH) and ∼100% increase in hardness of F82H (from ∼220VH to ∼440VH).
To investigate the cause(s) of an increased incidence of clinical cultures growing Mycobacterium abscessus at a hospital in Florida.
Outbreak investigation.
University-affiliated, tertiary-care ...hospital.
A site visit was done during the first week of September 2006. We reviewed the medical records of patients from whom M. abscessus was recovered during the period from January 1, 2003, through June 30, 2006. We collected environmental samples from various sites and evaluated specimen processing procedures in the microbiology laboratory. Isolates of M. abscessus recovered from the environment and from 12 randomly selected patients who sought medical care in 2006 were compared by pulsed-field gel electrophoresis (PFGE). Follow-up case surveillance was continued through March 31, 2007.
Specimens from 143 patients obtained from various anatomical sites grew M. abscessus on culture in 2005-2006, compared with specimens from 21 patients in 2003-2004. The 12 isolates from patients that were selected for molecular typing had indistinguishable PFGE patterns. Observations revealed no major breaches in the processing of mycobacterial specimens in the laboratory. Isolates grew only after prolonged incubation (mean +/- SD, 45 +/- 15 days) in test tubes containing diagonally oriented Middlebrook and Cohn 7H10 agar or Lowenstein-Jensen medium. Environmental samples obtained from the inside of the specimen incubator grew M. abscessus on culture. A test tube containing diagonally oriented, uninoculated Middlebrook and Cohn 7H10 agar that was incubated in the same incubator as clinical specimens grew M. abscessus with a PFGE pattern that matched the pattern of the patient isolates. Cases of M. abscessus infection decreased to baseline after the hospital changed suppliers of mycobacterial media and cleaned the incubator.
Although the source was never confirmed, our investigation suggests that this was a pseudo-outbreak of M. abscessus infection that resulted from contamination of mycobacterial cultures during incubation. Our findings emphasize the need for guidance on the disinfection of specimen incubators.
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