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Polymethoxyflavones (PMFs) occur naturally in citrus peels and citrus-derived foods as well as in other plants. Many in vitro and some in vivo studies have shown potentially relevant biological effects of PMFs, including anticancer, anti-inflammatory, anti-atherosclerosis, and neuroprotective activities. These promising biological effects still require further research to establish their impact on human health. This review updates the current clinical trials data. It highlights the limited information available on the bioavailability and metabolism of PMFs (pharmacokinetics, human phase I and II metabolites in biological fluids and tissues, and gut microbiota metabolism). [ABSTRACT FROM AUTHOR]

Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory condition resulting from monoallelic NLRP3 variants that facilitate IL-1β production. Although these are gain-of-function variants characterized by hypersensitivity to cell priming, patients with CAPS and animal models of the disease may present inflammatory flares without identifiable external triggers. Here we find that CAPS-associated NLRP3 variants are forming constitutively active inflammasome, which induce increased basal cleavage of gasdermin D, IL-18 release and pyroptosis, with a concurrent basal pro-inflammatory gene expression signature, including the induction of nuclear receptors 4 A. The constitutively active NLRP3-inflammasome of CAPS is responsive to the selective NLRP3 inhibitor MCC950 and its activation is regulated by deubiquitination. Despite their preactivated state, the CAPS inflammasomes are responsive to activation of the NF-κB pathway. NLRP3-inflammasomes with CAPS-associated variants affect the immunometabolism of the myeloid compartment, leading to disruptions in lipids and amino acid pathways and impaired glycolysis, limiting IL-1β production. In summary, NLRP3 variants causing CAPS form a constitutively active inflammasome inducing pyroptosis and IL-18 release without cell priming, which enables the host's innate defence against pathogens while also limiting IL-1β–dependent inflammatory episodes through immunometabolism modulation. Gain-of-function mutations in NLRP3 result in Cryopyrin-Associated Periodic Syndrome in human patients. Here authors show that although these NLRP3 variants are constitutively active, they preserve their responsiveness to external pro-inflammatory stimuli, and they interfere with the immune-metabolic inflammatory pathways in monocytes. [ABSTRACT FROM AUTHOR]

In this article, we analyse the relationship between union instability and cumulated fertility among ever-partnered women in several regions across Europe and the Americas with different patterns of demographic behaviour in terms of fertility levels, union instability and fertility across partnerships. We hypothesise that the relationship between union dissolution and fertility might be less negative in contexts where repartnering is more prevalent. The analysis is performed on a large dataset of 25 countries, combining information from the Harmonised Histories of the Generation and Gender Programme with our own harmonisation of survey data from three Latin American countries. This allows for the inclusion of countries with differing prevalence of union instability as measured by (a) the proportion of women who separated by age 40, and (b) the proportion who repartnered by age 40. We first examine the prevalence of separation and repartnering during reproductive ages across regions, and we estimate the proportion of cumulated fertility attributable to unions of different ranks using a decomposition method. We then analyse the links between union instability and the number of children born by age 40 among ever-partnered and ever-repartnered women, using Poisson regression. Despite observing a high degree of heterogeneity in the proportions of births occurring in the context of repartnering both within and between regions, we find a pattern where a greater prevalence of repartnering by age 40 is accompanied by higher cumulated fertility in second or subsequent unions. Our multivariate findings reveal a negative statistical relationship between separation and cumulated fertility that is partially offset by repartnering in some contexts, and that the time spent in a union during the reproductive lifespan is a key determinant of cumulated fertility, regardless of national context and independently from age at union formation and union rank. [ABSTRACT FROM AUTHOR]

The objective of this study is to ascertain whether income inequality and per capita income of area of residence show a relationship with mortality in Spain. Data are from a nation-wide prospective study with a 7-year mortality follow-up covering all persons living in Spain's 50 provinces in 2001. In total 28,944,854 subjects aged 25 years or over at baseline were studied. Rate ratio for total mortality and cause-specific mortality, according to provincial income inequality and per capita income in two age groups, 25-64 years (adult population) and 65 years and over (elderly population). Provincial income inequality was not related to total mortality or cause-specific mortality. Total mortality rate ratios among residents of the poorest versus the richest provinces were 0.89 (95 % CI 0.95-0.93) in men and 0.91 (0.87-0.96) in women, among the adult population; and 1.02 (0.97-1.08) in men and 1.08 (1.02-1.16) in women, among the elderly population. With the exception of cardiovascular-disease mortality for which no association with per capita income was observed, adult residents of the poorest provinces registered the lowest mortality rate ratio for other causes of death. Elderly residents of the poorest provinces registered the highest mortality rate ratio for cardiovascular disease and the lowest mortality rate ratio for cancer and external causes. Aside from cardiovascular-disease mortality, the lowest mortality for most causes of death was registered by residents of the poorest provinces. Nevertheless, these findings need to be confirmed by similar studies using smaller areas as the unit of analysis. [ABSTRACT FROM AUTHOR]

Pepper (Capsicum annuum L.) fruits are highly appreciated by producers and consumers for their economical and nutritional value. Four different cultivars of coloured peppers in immature and mature stages were harvested throughout the spring and examined for their content of phenolic compounds, ascorbic acid and total antioxidant capacity (TAA) as well as for lipid peroxidation and carbonyl proteins as index of oxidative stress. Ripening and harvest period influenced the antioxidants and the development of oxidative processes in the cultivars differently: lipid peroxidation increased in mature peppers except in one cultivar (Y1075), while no changes in protein oxidation or in TAA were produced, except in Y1075 in which both parameters increased. Each cultivar presented differences in antioxidant compounds depending on the harvest period, but we could recommend May as the optimal if all cultivars have to be harvested at the same time, when levels of ascorbate, phenols and TAA were not decreased, fresh weight and proteins were elevated, and levels of oxidation were not as high as in June (except for Y1075). A previous study of the response of each cultivar to different environmental conditions results essential to establish a good program of selection of cultivars with high quality and productivity. [ABSTRACT FROM AUTHOR]

Transactional Memory (TM) intends to simplify the design and implementation of the shared-memory data structures used in parallel software. Many Software TM systems are based on writer-locks to protect the data being modified. Such implementations can suffer from the 'privatization' problem, in which transactional and non-transactional accesses to the same location can lead to inconsistent results. One solution is the use of Pessimistic Concurrency Control, but it entails an important performance penalty due to the need of reader-writer locking. In this paper a hybrid TM design is proposed to reduce the performance overheads caused by the use of these locks while combining three desirable features: (i) full TM functionality whether or not the architectural support is present; (ii) execution of a single common code path in software or hardware; and, (iii) immunity from the privatization problem. The analysis shows how a Hybrid TM can lose important properties, such as starvation freedom. To overcome this issue, Directory Reservations is presented, a low-cost mechanism improving existent solutions designed for Hardware TM. [ABSTRACT FROM AUTHOR]

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a clonal disease of blood cells caused by the lack of glycosyl phosphatidyl inositol anchored proteins bound to the cell membrane. In consequence, erythrocytes lead to intravascular hemolysis upon complement activation, which promotes high risk of thrombosis, intravascular hemolytic anemia, and bone marrow failure in patients. The mechanisms of thrombosis in PNH are still poorly understood. Treatment with eculizumab reduces intravascular hemolysis and thrombotic risk, but not in all cases. Exosomes are extracellular vesicles released by cells and whose secretion is closely related to the inflammatory status. They participate in cell communication by activating signaling pathways and transferring genetic material and proteins to host cells. In consequence, exosomes may serve as surrogate biomarkers for the prognosis and/or diagnosis of a disease. Isolation of exosomes was carried out from healthy controls and from three groups of PNH patients, i.e. i) with no eculizumab treatment; ii) under treatment with eculizumab that have not suffered thrombosis; and iii) under treatment with eculizumab but that have suffered thrombosis. The miRNAome and proteome was analyzed using plasma focus miRNAs PCR panel and LC-MS analysis respectively. We found differential expression of miRNAs miR-148b-3p, miR-423-3p, miR29b-3p, miR15b-5p, let-7e-5p, miR126-3p, miR-125b-5p and miR-376c-3p as well as hemoglobin, haptoglobin, protein S and C4-binding protein in healthy controls vs PNH patients. Our results warrant further research and provide new information on the content of exosomes that could play a role in the hypercoagulable state in this disease. [ABSTRACT FROM AUTHOR]