Soluble gC1qR is an autocrine signal that induces B1R expression on endothelial cells

Bradykinin (BK) is one of the most potent vasodilator agonists known and belongs to the kinin family of proinflammatory peptides. BK induces its activity via two G protein-coupled receptors: BK receptor 1 (B1R) and BK receptor 2. Although BK receptor 2 is constitutively expressed on endothelial cells (ECs), B1R is induced by IL-1β. The C1q receptor, receptor for the globular heads of C1q (gC1qR), which plays a role in BK generation, is expressed on activated ECs and is also secreted as soluble gC1qR (sgC1qR). Because sgC1qR can bind to ECs, we hypothesized that it may also serve as an autocrine/paracrine signal for the induction of B1R expression. In this study, we show that gC1qR binds to ECs via a highly conserved domain consisting of residues 174-180, as assessed by solid-phase binding assay and deconvolution fluorescence microscopy. Incubation of ECs (24 h, 37°C) with sgC1qR resulted in enhancement of B1R expression, whereas incubation with gC1qR lacking aa 174-180 and 154-162 had a diminished effect. Binding of sgC1qR to ECs was through surface-bound fibrinogen and was inhibited by anti-fibrinogen. In summary, our data suggest that, at sites of inflammation, sgC1qR can enhance vascular permeability by upregulation of B1R expression through de novo synthesis, as well as rapid translocation of preformed B1R

Circulating complexes of the vitamin D binding protein with G-actin induce lung inflammation by targeting endothelial cells

This study investigated the actin scavenger function of the vitamin D binding protein (DBP) in vivo using DBP null (-/-) mice. Intravenous injection of G-actin into wild-type (DBP+/+) and DBP-/- mice showed that contrary to expectations, DBP+/+ mice developed more severe acute lung inflammation. Inflammation was restricted to the lung and pathological changes were clearly evident at 1.5 and 4 h post-injection but were largely resolved by 24 h. Histology of DBP+/+ lungs revealed noticeably more vascular leakage, hemorrhage and thickening of the alveolar wall. Flow cytometry analysis of whole lung homogenates showed significantly increased neutrophil infiltration into DBP+/+ mouse lungs at 1.5 and 4h. Increased amounts of protein and leukocytes were also noted in bronchoalveolar lavage fluid from DBP+/+. mice 4 h after actin injection. In vitro, purified DBP-actin complexes did not activate complement or neutrophils but induced injury and death of cultured human lung microvascular endothelial cells (HLMVEC) and human umbilical vein endothelial cells (HUVEC). Cells treated with DBP-actin showed a significant reduction in viability at 4 h, this effect was reversible if cells were cultured in fresh media for another 24 h. However, a 24-h treatment with DBP-actin complexes showed a significant increase in cell death (95% for HLMVEC, 45% for HUVEC). The mechanism of endothelial cell death was via both caspase-3 dependent (HUVEC) and independent (HLMVEC) pathways. These results demonstrate that elevated levels and/or prolonged exposure to DBP-actin complexes may induce endothelial cell injury and death, particularly in the lung microvasculature. (C) 2013 Elsevier GmbH. All rights reserved

c-erbB-4 protein expression in human breast cancer

The Type 1 family of growth factor receptors includes epidermal growth factor receptor (EGFR), c- erb B-2, c- erb B-3 and c- erb B-4. Overexpression of the first two members is associated with poorer prognosis in patients with breast carcinoma. In this study we examined the expression of c- erb B-4 protein using the monoclonal antibody HFR-1. A total of 127 consecutive cases of primary operable invasive breast carcinoma presenting between 1975 and 1977 were studied. All patients were managed by simple mastectomy or conservation surgery with radiotherapy and no adjuvant therapy given. Long-term follow-up was maintained. Routine, formalin-fixed, paraffin-embedded tumour samples were used and sections were stained immunohistochemically using the Duet StreptABC method. Immunoreactivity was classified using a simple semi-quantitative scoring method. Protein expression was generally low but definite positive cytoplasmic, membranous and nuclear reactivity was identified in 58%, 41% and 25% of cases respectively. Expression at all three sites demonstrated significant inverse associations were histological grade. In addition, membrane accentuation correlated inversely with the Nottingham Prognostic Index (NPI), while cytoplasmic reactivity showed a positive association with c- erb B-3 expression. No significant associations were found with disease-free interval or survival. The results of this study demonstrate that higher levels of c- erb B-4 protein expression are associated with a more differentiated histological phenotype in contrast to the other members of the Type 1 family. Larger series with extended follow-up will be required to ascertain definitively the prognostic value of c- erb B-4 expression in breast carcinoma. © 2000 Cancer Research Campaig

Risk factors for exacerbations and pneumonia in patients with chronic obstructive pulmonary disease: a pooled analysis.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear. METHODS: This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo. Backward elimination via Cox's proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation. RESULTS: Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216. Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk. BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2. The modelled probability of pneumonia varied between 3 and 12% during the first year. Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment. The influence of the other exacerbation risk factors was not modified by ICS treatment. Modelled probabilities of an exacerbation varied between 31 and 82% during the first year. CONCLUSIONS: The probability of an exacerbation was considerably higher than for pneumonia. ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex. The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2. Analyses of this type may help the development of COPD risk equations

Human influence on growing-period frosts like the early April 2021 in Central France

International audienceAbstract. In early April 2021 several days of harsh frost affected central Europe. This led to very severe damage in grapevine and fruit trees in France, in regions where young leaves had already unfolded due to unusually warm temperatures in the preceding month (March 2021). We analysed with observations and 172 climate model simulations how human-induced climate change affected this event over central France, where many vineyards are located. We found that, without human-caused climate change, such temperatures in April or later in spring would have been even lower by 1.2 ∘C (0.75 to 1.7 ∘C). However, climate change also caused an earlier occurrence of bud burst that we characterized in this study by a growing degree day index value. This shift leaves young leaves exposed to more winter-like conditions with lower minimum temperatures and longer nights, an effect that overcompensates the warming effect. Extreme cold temperatures occurring after the start of the growing season such as those of April 2021 are now 2 ∘C colder (0.5 to 3.3 ∘C) than in preindustrial conditions, according to observations. This observed intensification of growing-period frosts is attributable, at least in part, to human-caused climate change with each of the five climate model ensembles used here simulating a cooling of growing-period annual temperature minima of 0.41 ∘C (0.22 to 0.60 ∘C) since preindustrial conditions. The 2021 growing-period frost event has become 50 % more likely (10 %–110 %). Models accurately simulate the observed warming in extreme lowest spring temperatures but underestimate the observed trends in growing-period frost intensities, a fact that yet remains to be explained. Model ensembles all simulate a further intensification of yearly minimum temperatures occurring in the growing period for future decades and a significant probability increase for such events of about 30 % (20 %–40 %) in a climate with global warming of 2 ∘C

Dual-Band Metamaterial Microwave Absorber using Ring and Circular Patch with Slits

This paper proposes a dual-band metamaterial microwave absorber operating at 2.5 GHz and 5.8 GHz. The absorber consists of a ring and a circular patch with slits resonator structures printed on a FR4 dielectric substrate backed by a ground layer. The main advantage of the absorber lies in its design flexibility in which each absorption band is independent and can be individually tuned by changing the dimensions of each resonator structure. The absorber unit cell is simulated and parametrically optimized using Computer Simulation Technology (CST) software. The absorption mechanism is analyzed through surface current analysis.  The absorber prototype, with dimensions of 200 × 200 × 1.6 mm3 and consisting of an array of 7 × 7 unit cells, is fabricated and experimentally investigated using antennas in free-space measurement. The absorber exhibits over 97% absorption at both resonance frequencies. Furthermore, the absorber is demonstrated to be applicable in sensing applications for dielectric constant determination. With its design simplicity, wide-angle receptive, and polarization insensitive behavior, it is envisaged that the proposed absorber will find practical use in absorbing and sensing applications

Giant pedunculated hepatocellular carcinoma with hemangioma mimicking intestinal obstruction

<p>Abstract</p> <p>Background</p> <p>Pedunculated hepatocellular carcinoma (P-HCC) has rarely been reported and is characteristically large and encapsulated. Only sporadic cases have been published, in which P-HCC was combined with other liver tumors (mostly benign), making the diagnosis difficult.</p> <p>Case presentation</p> <p>We report a patient who was admitted to our hospital with clinical features of intestinal obstruction and a palpable mass in the right iliac fossa. Ultrasound, computed tomography and magnetic resonance imaging demonstrated an encapsulated mass of unclear origin and characteristics of liver hemangioma. Laboratory tests revealed elevated α-fetoprotein (> 800 ng/ml) and cancer antigen 125 (> 51.2 U/ml). With a possible diagnosis of giant liver hemangioma, we proceeded to surgery. During surgery, a giant pedunculated tumor was discovered on the inferior surface of the right lobe of the liver, hanging free in the right abdominal cavity towards the right iliac fossa. The macroscopic appearance of the tumor was compatible with liver hemangioma. Tumor resection was performed at a safe distance, including the pedicle. The rest of the liver appeared normal. Histopathological examination revealed grade II and III HCC (according to Edmondson-Steiner's classification) with nodular configuration, central necrosis, and infiltration of the capsule. Underneath the tumor capsule, residual tissue of a cavernous hemangioma was recognized. The resection margins were free of neoplastic tissue.</p> <p>Conclusion</p> <p>This rare presentation of a giant P-HCC combined with a hemangioma with features of intestinal obstruction confirmed the diagnostic difficulties of similar cases, and required prompt surgical treatment. Therefore, patients benefit from surgical resection because both the capsule and the pedicle prevent vascular invasion, therefore improving prognosis.</p

Estimating the Extent of Vaccine-Derived Poliovirus Infection

BACKGROUND: Eight outbreaks of paralytic polio attributable to circulating vaccine-derived poliovirus (cVDPV) have highlighted the risks associated with oral poliovirus vaccine (OPV) use in areas of low vaccination coverage and poor hygiene. As the Polio Eradication Initiative enters its final stages, it is important to consider the extent to which these viruses spread under different conditions, so that appropriate strategies can be devised to prevent or respond to future cVDPV outbreaks. METHODS AND FINDINGS: This paper examines epidemiological (temporal, geographic, age, vaccine history, social group, ascertainment), and virological (type, genetic diversity, virulence) parameters in order to infer the numbers of individuals likely to have been infected in each of these cVDPV outbreaks, and in association with single acute flaccid paralysis (AFP) cases attributable to VDPVs. Although only 114 virologically-confirmed paralytic cases were identified in the eight cVDPV outbreaks, it is likely that a minimum of hundreds of thousands, and more likely several million individuals were infected during these events, and that many thousands more have been infected by VDPV lineages within outbreaks which have escaped detection. CONCLUSIONS: Our estimates of the extent of cVDPV circulation suggest widespread transmission in some countries, as might be expected from endemic wild poliovirus transmission in these same settings. These methods for inferring extent of infection will be useful in the context of identifying future surveillance needs, planning for OPV cessation and preparing outbreak response plans