OCP acquires FTTH player

PURPOSE OF REVIEW: In this review, we highlight the most important cellular and molecular mechanisms that contribute to cardiac inflammation and fibrosis. We also discuss the interplay between inflammation and fibrosis in various precursors of heart failure (HF) and how such mechanisms can contribute to myocardial tissue remodelling and development of HF. RECENT FINDINGS: Recently, many research articles attempt to elucidate different aspects of the interplay between inflammation and fibrosis. Cardiac inflammation and fibrosis are major pathophysiological mechanisms operating in the failing heart, regardless of HF aetiology. Currently, novel therapeutic options are available or are being developed to treat HF and these are discussed in this review. A progressive disease needs an aggressive management; however, existing therapies against HF are insufficient. There is a dynamic interplay between inflammation and fibrosis in various precursors of HF such as myocardial infarction (MI), myocarditis and hypertension, and also in HF itself. There is an urgent need to identify novel therapeutic targets and develop advanced therapeutic strategies to combat the syndrome of HF. Understanding and describing the elements of the inflammatory and fibrotic pathways are essential, and specific drugs that target these pathways need to be evaluated

Vascular Endothelial Growth Factor in the Circulation in Cancer Patients May Not Be a Relevant Biomarker

Levels of circulating vascular endothelial growth factor (VEGF) have widely been used as biomarker for angiogenic activity in cancer. For this purpose, non-standardized measurements in plasma and serum were used, without correction for artificial VEGF release by platelets activated ex vivo. We hypothesize that "true" circulating (c)VEGF levels in most cancer patients are low and unrelated to cancer load or tumour angiogenesis. We determined VEGF levels in PECT, a medium that contains platelet activation inhibitors, in citrate plasma, and in isolated platelets in 16 healthy subjects, 18 patients with metastatic non-renal cancer (non-RCC) and 12 patients with renal cell carcinoma (RCC). In non-RCC patients, circulating plasma VEGF levels were low and similar to VEGF levels in controls if platelet activation was minimized during the harvest procedure by PECT medium. In citrate plasma, VEGF levels were elevated in non-RCC patients, but this could be explained by a combination of increased platelet activation during blood harvesting, and by a two-fold increase in VEGF content of individual platelets (controls: 3.4 IU/10(6), non-RCC: 6.2 IU/10(6) platelets, p = 0.001). In contrast, cVEGF levels in RCC patients were elevated (PECT plasma: 64 pg/ml vs. 21 pg/ml, RCC vs. non-RCC, p<0.0001), and not related to platelet VEGF concentration. Our findings suggest that "true" freely cVEGF levels are not elevated in the majority of cancer patients. Previously reported elevated plasma VEGF levels in cancer appear to be due to artificial release from activated platelets, which in cancer have an increased VEGF content, during the blood harvest procedure. Only in patients with RCC, which is characterized by excessive VEGF production due to a specific genetic defect, were cVEGF levels elevated. This observation may be related to limited and selective success of anti-VEGF agents, such as bevacizumab and sorafenib, as monotherapy in RCC compared to other forms of cance

Addressing climate change with behavioral science:A global intervention tournament in 63 countries

Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions’ effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior—several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people’s initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors

p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease

Background. Indoxyl sulphate (IS) and p-cresyl sulphate (PCS) are uraemic toxins that have similar protein binding, dialytic clearance and proinflammatory features. However, only a few prospective studies have evaluated possible associations between these two retained solutes and renal disease progression in chronic kidney disease (CKD) patients

HE4 Serum Levels Are Associated with Heart Failure Severity in Patients With Chronic Heart Failure

AbstractBackgroundThe novel biomarker human epididymis protein 4 (HE4) shows prognostic value in acute heart failure (HF) patients. We measured HE4 levels in patients with chronic heart failure (CHF) and correlated them to HF severity, kidney function, and HF biomarkers, and determined its predictive value.MethodsSerum HE4 levels in patients (n = 101) with stable CHF with reduced left ventricular ejection fraction (LVEF <45%) from the Vitamin D CHF (VitD-CHF) study (NCT01092130) were compared with those in age- and sex-matched healthy control subjects (n = 58) from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study.ResultsHE4 levels were higher in CHF compared with control subjects (69.2 pmol/L [interquartile range 55.6-93.8] vs 56.1 pmol/L [46.6-69.0]; P < .001) and were higher with increasing New York Heart Association functional class. Levels were associated with HF risk factors, including age, gender, diabetes, smoking and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP). HE4 demonstrated strong associations with kidney function and HF fibrosis biomarkers. In a multivariable model, we identified creatinine, NT-proBNP, galectin-3, high-sensitive troponin T, and smoking as factors associated with HE4. Independently from these factors, HE4 levels predicted death and HF rehospitalization (5-year follow-up, hazard ratio 3.8; confidence interval 1.31–11.1; P = .014).ConclusionsHE4 levels are increased in CHF, correlate with HF severity and kidney function, and predict HF outcome

Galectin-3 Activation and Inhibition in Heart Failure and Cardiovascular Disease:An Update

Galectin-3 is a versatile protein orchestrating several physiological and pathophysiological processes in the human body. In the last decade, considerable interest in galectin-3 has emerged because of its potential role as a biotarget. Galectin-3 is differentially expressed depending on the tissue type, however its expression can be induced under conditions of tissue injury or stress. Galectin-3 overexpression and secretion is associated with several diseases and is extensively studied in the context of fibrosis, heart failure, atherosclerosis and diabetes mellitus. Monomeric (extracellular) galectin-3 usually undergoes further "activation" which significantly broadens the spectrum of biological activity mainly by modifying its carbohydrate-binding properties. Self-interactions of this protein appear to play a crucial role in regulating the extracellular activities of this protein, however there is limited and controversial data on the mechanisms involved. We therefore summarize (recent) literature in this area and describe galectin-3 from a binding perspective providing novel insights into mechanisms by which galectin-3 is known to be "activated" and how such activation may be regulated in pathophysiological scenarios

Coagulopathy in Zellweger spectrum disorders: a role for vitamin K

Introduction: Zellweger spectrum disorders (ZSDs) are caused by an impairment of peroxisome biogenesis, resulting in multiple metabolic abnormalities. This leads to a range of symptoms, including hepatic dysfunction and coagulopathy. This study evaluated the incidence and severity of coagulopathy and the effect of vitamin K supplementation orally and IV in ZSD. Methods: Data were retrospectively retrieved from the medical records of 30 ZSD patients to study coagulopathy and the effect of vitamin K orally on proteins induced by vitamin K absence (PIVKA-II) levels. Five patients from the cohort with a prolonged prothrombin time, low factor VII, and elevated PIVKA-II levels received 10 mg of vitamin K IV. Laboratory results, including thrombin generation, at baseline and 72 h after vitamin K administration were examined. Results: In the retrospective cohort, four patients (13.3%) experienced intracranial bleedings and 14 (46.7%) reported minor bleeding. No thrombotic events occurred. PIVKA-II levels decreased 38% after start of vitamin K therapy orally. In the five patients with a coagulopathy, despite treatment with oral administration of vitamin K, vitamin K IV caused an additional decrease (23%) of PIVKA-II levels and increased thrombin generation. Conclusion: Bleeding complications frequently occur in ZSD patients due to liver disease and vitamin K deficiency. Vitamin K deficiency is partly corrected by vitamin K supplementation orally, and vitamin K administered IV additionally improves vitamin K status, as shown by further decrease of PIVKA-II and improved thrombin generation

Nonequilibrium spectral diffusion due to laser heating in stimulated photon echo spectroscopy of low temperature glasses

A quantitative theory is developed, which accounts for heating artifacts in three-pulse photon echo (3PE) experiments. The heat diffusion equation is solved and the average value of the temperature in the focal volume of the laser is determined as a function of the 3PE waiting time. This temperature is used in the framework of nonequilibrium spectral diffusion theory to calculate the effective homogeneous linewidth of an ensemble of probe molecules embedded in an amorphous host. The theory fits recently observed plateaus and bumps without introducing a gap in the distribution function of flip rates of the two-level systems or any other major modification of the standard tunneling model.Comment: 10 pages, Revtex, 6 eps-figures, accepted for publication in Phys. Rev.