Human blood monocytes play a central role in dengue infections and form the majority of virus infected cells in the blood. Human blood monocytes are heterogeneous and divided into CD16(-) and CD16(+) subsets. Monocyte subsets play distinct roles during disease, but it is not currently known if monocyte subsets differentially contribute to dengue protection and pathogenesis. Here, we compared the susceptibility and response of the human CD16(-) and CD16(+) blood monocyte subsets to primary dengue virus in vitro. We found that both monocyte subsets were equally susceptible to dengue virus (DENV2 NGC), and capable of supporting the initial production of new infective virus particles. Both monocyte subsets produced anti-viral factors, including IFN-α, CXCL10 and TRAIL. However, CD16(+) monocytes were the major producers of inflammatory cytokines and chemokines in response to dengue virus, including IL-1β, TNF-α, IL-6, CCL2, 3 and 4. The susceptibility of both monocyte subsets to infection was increased after IL-4 treatment, but this increase was more profound for the CD16(+) monocyte subset, particularly at early time points after virus exposure. These findings reveal the differential role that monocyte subsets might play during dengue disease.

The work of adhesion at the interface of electrospun membrane and rigid substrate is measured by a shaft-loaded blister test (SLBT). Poly(vinylidene fluoride)(PVDF) were electrospun with an average fiber diameter of 333±59 nm. Commercial cardboard with inorganic coating was used to provide a model substrate for adhesion tests. In SLBT, the elastic response PVDF was analyzed and its adhesion energy measured. The average value of the adhesion work is 206 ± 26 mJ/m2. Elastic modulus of electrospun membrane obtained by SLBT is found to be 23.42 ± 2.69 MPa, which is consistent with the value obtained from standard tensile tests. The results show SLBT presented a viable methodology for evaluating the adhesion energy of electrospun polymer fabrics.

This paper proposes a cellular automata model of pedestrian flow that defines a cost potential field, which takes into account the costs of travel time and discomfort, for a pedestrian to move to an empty neighboring cell. The formulation is based on a reconstruction of the density distribution and the underlying physics, including the rule for resolving conflicts, which is comparable to that in the floor field cellular automaton model. However, we assume that each pedestrian is familiar with the surroundings, thereby minimizing his or her instantaneous cost. This, in turn, helps reduce the randomness in selecting a target cell, which improves the existing cellular automata modelings, together with the computational efficiency. In the presence of two pedestrian groups, which are distinguished by their destinations, the cost distribution for each group is magnified due to the strong interaction between the two groups. As a typical phenomenon, the formation of lanes in the counter flow is reproduced.

Human blood monocytes are heterogeneous and conventionally subdivided into two subsets based on CD16 expression. Recently, the official nomenclature subdivides monocytes into three subsets, the additional subset arising from the segregation of the CD16+ monocytes into two based on relative expression of CD14. Recent whole genome analysis reveal that specialized functions and phenotypes can be attributed to these newly defined monocyte subsets. In this review, we discuss these recent results, and also the description and utility of this new segregation in several disease conditions. We also discuss alternative markers for segregating the monocyte subsets, for example using Tie-2 and slan, which do not necessarily follow the official method of segregating monocyte subsets based on relative CD14 and CD16 expressions.

Blood monocytes recognize Gram-negative bacteria through the TLR4, which signal via MyD88- and TRIF-dependent pathway to trigger an immune-inflammatory response. However, a dysregulated inflammatory response by these cells often leads to severe pathologies such as sepsis. We investigated the role of CD16 in the regulation of human monocyte response to Gram-negative endotoxin and sepsis. Blood monocytes from sepsis patients demonstrated an upregulation of several TRIF-dependent genes as well as a selective expansion of CD16-expressing (CD16(+)) monocytes. Gene expression and biochemical studies revealed CD16 to regulate the TRIF-dependent TLR4 pathway in monocytes by activating Syk, IFN regulatory factor 3, and STAT1, which resulted in enhanced expression of IFNB, CCL5, and CXCL10. CD16 also upregulated the expression of IL-1R-associated kinase M and IL-1 receptor antagonist, which are negative regulators of the MyD88-dependent pathway. CD16 overexpression or small interfering RNA knockdown in monocytes confirmed the above findings. Interestingly, these results were mirrored in the CD16(+) monocyte subset isolated from sepsis patients, providing an in vivo confirmation to our findings. Collectively, the results from the current study demonstrate CD16 as a key regulator of the TRIF-dependent TLR4 pathway in human monocytes and their CD16-expressing subset, with implications in sepsis.

OBJECTIVES The aim of this study was to describe differences in treatment and in-hospital mortality of early, late, and very late stent thrombosis (ST). BACKGROUND Early, late, and very late ST may differ in clinical presentation, management, and in-hospital outcomes. METHODS We analyzed definite (angiographically documented) ST cases identified from February 2009 to June 2010 in the CathPCI Registry. We stratified events by timing of presentation: early (≤1 month), late (1 to 12 months), or very late (≥12 months) following stent implantation. Multivariable logistic regression modeling was performed to compare in-hospital mortality for each type of ST after adjusting for baseline comorbidities. RESULTS During the study period, 7,315 ST events were identified in 7,079 of 401,662 patients (1.8%) presenting with acute coronary syndromes. This ST cohort consisted of 1,391 patients with early ST (19.6%), 1,370 with late ST (19.4%), and 4,318 with very late ST (61.0%). Subjects with early ST had a higher prevalence of black race and diabetes, whereas subjects with very late ST had a higher prevalence of white race and a lower prevalence of prior myocardial infarction or diabetes. In-hospital mortality was significantly higher in early ST (7.9%) compared with late (3.8%) and very late ST (3.6%, p < 0.001). This lower mortality for late and very late ST persisted after multivariable adjustment (odds ratio: 0.53 [95% confidence interval (CI): 0.36 to 0.79] and 0.58 [95% CI: 0.43 to 0.79], respectively). CONCLUSIONS Significant differences exist in the presentation and outcomes of early, late, and very late ST. Among patients with acute coronary syndromes who are undergoing percutaneous coronary intervention for angiographically documented ST, early ST is associated with the highest in-hospital mortality.

Adhesive force exists between polymer nano/microfibers. An elaborate experiment was performed to investigate the adhesion between polymer nano/microfibers using a nano force tensile tester. Electrospun polycaprolactone (PCL) fibers with radii ranging from 0.2 - 1.1 μm were studied. The response of surface property of electrospun fiber to the environmental conditions was tracked by Fourier Transform Infrared Spectroscopy (FTIR) and Atomic Force Microscopy (AFM) measurements. The effect of temperature on molecular orientation was examined by Wide Angle X-ray diffraction (WAXD). The adhesive force was found to increase with temperature and pull-off speed, but insensitive to the change of relative humidity. And the abrupt increase of adhesion energy with temperature accompanied by a reduced molecular orientation in the amorphous part of fiber was observed. Results show that adhesion is mainly driven by van der Waals interactions between inter-diffusion chain segments across the interface.

BACKGROUND Within 1 year after percutaneous coronary intervention, more than 20% of patients experience new adverse events. Physical activity confers a 25% reduction in mortality; however, physical activity is widely underused. Thus, there is a need for more powerful behavioral interventions to promote physical activity. Our objective was to motivate patients to achieve an increase in expenditure of 336 kcal/wk or more at 12 months as assessed by the Paffenbarger Physical Activity and Exercise Index. METHODS Two hundred forty-two patients were recruited immediately after percutaneous coronary intervention between October 2004 and October 2006. Patients were randomized to 1 of 2 groups. The patient education (PE) control group (n = 118)(1) received an educational workbook,(2) received a pedometer, and (3) set a behavioral contract for a physical activity goal. The positive-affect/self-affirmation (PA) intervention group (n = 124) received the 3 PE control components plus (1) a PA workbook chapter,(2) bimonthly induction of PA by telephone, and (3) small mailed gifts. All patients were contacted with standardized bimonthly telephone follow-up for 12 months. RESULTS Attrition was 4.5%, and 2.1% of patients died. Significantly more patients in the PA intervention group increased expenditure by 336 kcal/wk or more at 12 months, our main outcome, compared with the PE control group (54.9% vs 37.4%, P =.007). The PA intervention patients were 1.7 times more likely to reach the goal of a 336-kcal/wk or more increase by 12 months, controlling for demographic and psychosocial measures. In multivariate analysis, the PA intervention patients had nearly double the improvement in kilocalories per week at 12 months compared with the PE control patients (602 vs 328, P =.03). CONCLUSION Patients who receive PA intervention after percutaneous coronary intervention are able to achieve a sustained and clinically significant increase in physical activity by 12 months. Trial Registration clinicaltrials.gov Identifier: NCT00248846.

High macrophage infiltration into tumours often correlates with poor prognoses; in colorectal, stomach and skin cancers however, the opposite is observed but the mechanisms behind this phenomenon remain unclear. Here, we sought to understand how tumour-associated macrophages (TAMs) in colorectal cancer execute tumour-suppressive roles. We found that TAMs in a colorectal cancer model were pro-inflammatory and inhibited the proliferation of tumour cells. TAMs also produced chemokines that attract T cells, stimulated proliferation of allogeneic T cells and activated type-1 T cells associated with anti-tumour immune responses. Using colorectal tumour tissues, we verified that TAMs in vivo were indeed pro-inflammatory. Furthermore, the number of tumour-infiltrating T cells correlated with the number of TAMs, suggesting that TAMs could attract T cells; and indeed, type-1 T cells were present in the tumour tissues. Patient clinical data suggested that TAMs exerted tumour-suppressive effects with the help of T cells. Hence, the tumour-suppressive mechanisms of TAMs in colorectal cancer involve the inhibition of tumour cell proliferation alongside the production of pro-inflammatory cytokines, chemokines and promoting type-1 T-cell responses. These new findings would contribute to the development of future cancer immunotherapies based on enhancing the tumour-suppressive properties of TAMs to boost anti-tumour immune responses.

OBJECTIVES The purpose of this study was to compare a one-time primary percutaneous coronary intervention (PCI) of the culprit and nonculprit lesions with PCI of only the culprit lesion and staged nonculprit PCI at a later date in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. BACKGROUND In patients with STEMI and multivessel disease, it is unknown whether it is safe or even desirable to also treat the nonculprit vessel during the primary PCI procedure. METHODS In the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial, 668 of the 3,602 STEMI patients enrolled (18.5%) underwent PCI of culprit and nonculprit lesions for multivessel disease. Patients were categorized into a single PCI strategy (n = 275) versus staged PCI (n = 393). The endpoints analyzed included the 1-year rates of major adverse cardiovascular events and its components, death, reinfarction, target-vessel revascularization for ischemia, and stroke. RESULTS Single versus staged PCI was associated with higher 1-year mortality (9.2% vs. 2.3%; hazard ratio [HR]: 4.1, 95% confidence interval [CI]: 1.93 to 8.86, p < 0.0001), cardiac mortality (6.2% vs. 2.0%; HR: 3.14, 95% CI: 1.35 to 7.27, p = 0.005), definite/probable stent thrombosis (5.7% vs. 2.3%; HR: 2.49, 95% CI: 1.09 to 5.70, p = 0.02), and a trend toward greater major adverse cardiovascular events (18.1% vs. 13.4%; HR: 1.42, 95% CI: 0.96 to 2.1, p = 0.08). The mortality advantage favoring staged PCI was maintained in a subgroup of patients undergoing truly elective multivessel PCI. Also, the staged PCI strategy was independently associated with lower all-cause mortality at 30 days and at 1 year. CONCLUSIONS A deferred angioplasty strategy of nonculprit lesions should remain the standard approach in patients with STEMI undergoing primary PCI, as multivessel PCI may be associated with a greater hazard for mortality and stent thrombosis.(Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966).