77 research outputs found

    Early Onset Hypertension Is Associated With Hypertensive End-Organ Damage Already by MidLife

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    Early onset hypertension confers increased risk for cardiovascular mortality in the community. Whether early onset hypertension also promotes the development of target end-organ damage (TOD), even by midlife, has remained unknown. We studied 2680 middle-aged CARDIA (coronary artery risk development in young adults) Study participants (mean age 50±4 years, 57% women) who underwent up to 8 serial blood pressure measurements between 1985 and 2011 (age range at baseline 18-30 years) in addition to assessments of echocardiographic left ventricular hypertrophy, coronary calcification, albuminuria, and diastolic dysfunction in 2010 to 2011. Age of hypertension onset was defined as the age at first of 2 consecutively attended examinations with blood pressure ≥140/90 mm Hg or use of antihypertensive medication. Participants were divided in groups by hypertension onset age (<35 years, 35-44 years, ≥45 years, or no hypertension). While adjusting for TOD risk factors, including systolic blood pressure, we used logistic regression to calculate odds ratios for cases (participants with TOD) versus controls (participants without TOD) to examine the relation of hypertension onset age and hypertensive TOD. Compared with normotensive individuals, hypertension onset at age <35 years was related to odds ratios of 2.29 (95% CI, 1.36-3.86), 2.94 (95% CI, 1.57-5.49), 1.12 (95% CI, 0.55-2.29), and 2.06 (95% CI, 1.04-4.05) for left ventricular hypertrophy, coronary calcification, albuminuria, and diastolic dysfunction, respectively. In contrast, hypertension onset at age ≥45 years was not related to increased odds of TOD. Our findings emphasize the importance of assessing age of hypertension onset in hypertensive patients to identify high-risk individuals for preventing hypertensive complications

    Annexin A2 antibodies but not inhibitors of the annexin A2 heterotetramer impair productive HIV-1 infection of macrophages in vitro

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    During sexual transmission of human immunodeficiency virus (HIV), macrophages are initial targets for HIV infection. Secretory leukocyte protease inhibitor (SLPI) has been shown to protect against HIV infection of macrophages through interactions with annexin A2 (A2), which is found on the macrophage cell surface as a heterotetramer (A2t) consisting of A2 and S100A10. Therefore, we investigated potential protein-protein interactions between A2 and HIV-1 gp120 through a series of co-immunoprecipitation assays and a single molecule pulldown (SiMPull) technique. Additionally, inhibitors of A2t (A2ti) that target the interaction between A2 and S100A10 were tested for their ability to impair productive HIV-1 infection of macrophages. Our data suggest that interactions between HIV-1 gp120 and A2 exist, though this interaction may be indirect. Furthermore, an anti-A2 antibody impaired HIV-1 particle production in macrophages in vitro, whereas A2ti did not indicating that annexin A2 may promote HIV-1 infection of macrophages in its monomeric rather than tetrameric form

    CDK-Mediated Regulation of Cell Functions via c-Jun Phosphorylation and AP-1 Activation

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    Cyclin-dependent kinases (CDKs) and their targets have been primarily associated with regulation of cell-cycle progression. Here we identify c-Jun, a transcription factor involved in the regulation of a broad spectrum of cellular functions, as a newly recognized CDK substrate. Using immune cells from mouse and human, and several complementary in vitro and in vivo approaches including dominant negative protein expression, pharmacologic inhibitors, kinase assays and CDK4 deficient cells, we demonstrate the ability of CDK4 to phosphorylate c-Jun. Additionally, the activity of AP-1, a ubiquitous transcription factor containing phosphorylated c-Jun as a subunit, was inhibited by abrogating CDK4. Surprisingly, the regulation of c-Jun phosphorylation by CDK4 occurred in non-dividing cells, indicating that this pathway is utilized for cell functions that are independent of proliferation. Our studies identify a new substrate for CDK4 and suggest a mechanism by which CDKs can regulate multiple cellular activation functions, not all of which are directly associated with cell cycle progression. These findings point to additional roles of CDKs in cell signaling and reveal potential implications for therapeutic manipulations of this kinase pathway

    Estimating fine-root production by tree species and understorey functional groups in two contrasting peatland forests

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    Background and aims Estimation of root-mediated carbon fluxes in forested peatlands is needed for understanding ecosystem functioning and supporting greenhouse gas inventories. Here, we aim to determine the optimal methodology for utilizing ingrowth cores in estimating annual fine-root production (FRP) and its vertical distribution in trees, shrubs and herbs. Methods We used 3-year data obtained with modified ingrowth core method and tested two calculation methods: 'ingrowth-dividing' and `ingrowth-subtracting'. Results The ingrowth-dividing method combined with a 2-year incubation of ingrowth cores can be used for the 'best estimate' of FRP. The FRP in the nutrient-rich fen forest (561 g m(-2)) was more than twice that in the nutrient-poor bog forest (244 g m(-2)). Most FRP occurred in the top 20-cm layer (76-82 %). Tree FRP accounted for 71 % of total FRP in the bog and 94 % in the fen forests, respectively, following the aboveground vegetation patterns; however, in fen forest the proportions of spruce and birch in FRP were higher than their proportions in stand basal area. Conclusions Our methodology may be used to study peatland FRP patterns more widely and will reduce the volume of labour-intensive work, but will benefit from verification with other methods, as is the case in all in situ FRP studies.Peer reviewe

    Self-medication for infants with colic in Lagos, Nigeria

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    <p>Abstract</p> <p>Background</p> <p>Infantile colic is a self-limiting condition that is distributed worldwide. It is often misdiagnosed as an organic disease for which an infant is admitted to the hospital. Many studies have described the aetiopathogenesis, pharmacologic and non-pharmacologic management of colic but none has evaluated self-medication for infants with colic. The aim of this study was therefore to determine the knowledge of Nigerian mothers about colic, their home-based management, extent of self-medication for the infants with colic and the types of medicines involved.</p> <p>Methods</p> <p>It is a prospective study conducted at the vaccination clinics of 20 primary health care centres, each from different Local Government Areas in Lagos, Nigeria. Eight hundred mothers that brought their infants for vaccination between April and September, 2006 were interviewed with open-and close-ended questionnaire.</p> <p>Results</p> <p>Six hundred and eighty three (85.4%) mothers claimed they had a good knowledge of colic. Incessant and excessive cry was the main clinical feature of colic identified by 430(62.9%) mothers. Three hundred and seventy eight (67.7%) infants were treated by self-medication, 157 (28.1%) sought medical intervention and 17 (3.1%) were treated at a traditional birth attendant home. Herbal medicines constituted 51.8% of the self-medicated medicines, of which 48 (26.2%) were "Ororo Ogiri". Nospamin<sup>® </sup>(49.5%) and Gripe water<sup>® </sup>(43.0%) were the two frequently prescribed and self-medicated medicines for infants with colic.</p> <p>Conclusion</p> <p>Nigerian mothers are deficient in their knowledge of colic. Self-medication was the most frequently used home-based intervention. Health education would appear necessary to improve parental management of this self-limiting condition.</p

    Evolution of sex-specific pace-of-life syndromes: genetic architecture and physiological mechanisms

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    Sex differences in life history, physiology, and behavior are nearly ubiquitous across taxa, owing to sex-specific selection that arises from different reproductive strategies of the sexes. The pace-of-life syndrome (POLS) hypothesis predicts that most variation in such traits among individuals, populations, and species falls along a slow-fast pace-of-life continuum. As a result of their different reproductive roles and environment, the sexes also commonly differ in pace-of-life, with important consequences for the evolution of POLS. Here, we outline mechanisms for how males and females can evolve differences in POLS traits and in how such traits can covary differently despite constraints resulting from a shared genome. We review the current knowledge of the genetic basis of POLS traits and suggest candidate genes and pathways for future studies. Pleiotropic effects may govern many of the genetic correlations, but little is still known about the mechanisms involved in trade-offs between current and future reproduction and their integration with behavioral variation. We highlight the importance of metabolic and hormonal pathways in mediating sex differences in POLS traits; however, there is still a shortage of studies that test for sex specificity in molecular effects and their evolutionary causes. Considering whether and how sexual dimorphism evolves in POLS traits provides a more holistic framework to understand how behavioral variation is integrated with life histories and physiology, and we call for studies that focus on examining the sex-specific genetic architecture of this integration

    Micronutrient fortification of food and its impact on woman and child health: A systematic review

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    Background: Vitamins and minerals are essential for growth and metabolism. The World Health Organization estimates that more than 2 billion people are deficient in key vitamins and minerals. Groups most vulnerable to these micronutrient deficiencies are pregnant and lactating women and young children, given their increased demands. Food fortification is one of the strategies that has been used safely and effectively to prevent vitamin and mineral deficiencies.Methods: A comprehensive search was done to identify all available evidence for the impact of fortification interventions. Studies were included if food was fortified with a single, dual or multiple micronutrients and impact of fortification was analyzed on the health outcomes and relevant biochemical indicators of women and children. We performed a meta-analysis of outcomes using Review Manager Software version 5.1.Results: Our systematic review identified 201 studies that we reviewed for outcomes of relevance. Fortification for children showed significant impacts on increasing serum micronutrient concentrations. Hematologic markers also improved, including hemoglobin concentrations, which showed a significant rise when food was fortified with vitamin A, iron and multiple micronutrients. Fortification with zinc had no significant adverse impact on hemoglobin levels. Multiple micronutrient fortification showed non-significant impacts on height for age, weight for age and weight for height Z-scores, although they showed positive trends. The results for fortification in women showed that calcium and vitamin D fortification had significant impacts in the post-menopausal age group. Iron fortification led to a significant increase in serum ferritin and hemoglobin levels in women of reproductive age and pregnant women. Folate fortification significantly reduced the incidence of congenital abnormalities like neural tube defects without increasing the incidence of twinning. The number of studies pooled for zinc and multiple micronutrients for women were few, though the evidence suggested benefit. There was a dearth of evidence for the impact of fortification strategies on morbidity and mortality outcomes in women and children.Conclusion: Fortification is potentially an effective strategy but evidence from the developing world is scarce. Programs need to assess the direct impact of fortification on morbidity and mortality

    Public Preferences for Forest Ecosystem Management in Japan with Emphasis on Species Diversity

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    We carried out online choice experiments (CE) to investigate what value Japanese individuals assign to rare versus familiar species in forest ecosystem, and to determine how preference heterogeneity arises. CE attributes comprised a forestry charge as the price attribute and rare versus familiar species of animals or plants as the good to be valued. Species numbers in a 5 km-mesh forest area were evaluated without the use of species names to focus purely on responses to numerical changes. Positional effects were also tested to validate results regarding alternatives and attributes other than the price attribute. A random parameter logit model was adopted to capture preferences for species diversity. After confirming that no positional effects existed, we found that (1) rare animals were valued more highly than rare plants, (2) familiar plants were assigned a positive value, but familiar animals were not assigned significant value at the mean parameter estimate, and (3) preference heterogeneities existed for all species. The sources of preference heterogeneity were analyzed with a latent class model having principal components of environmental attitudes. The influence of such attitudes was shown to be significant and suggested that attention should be paid to belief systems rather than solely demographics
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