338 research outputs found

    Birth characteristics and early-life social characteristics predict unequal educational outcomes across the lifecourse and across generations: Data from a Swedish cohort born 1915-1929 and their grandchildren born 1973-1980

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    We investigated the effects of adverse birth characteristics and social disadvantage upon educational outcomes over the lifecourse and across generations. Our subjects were 12,674 Swedish infants born 1915-1929 and 9,706 of their grandchildren born 1973-1980. Within both cohorts, better school achievement (schoolmarks in elementary school) was predicted by: heavier birthweight, lower birth order, older mother, married mother and higher family social class. These effects persisted after mutual-adjustment, and birth characteristics and family composition did not play a major role in explaining social class effects. There were no independent effects of pre-term or twin status, but weak evidence of a disadvantage to post-term infants. The predictors of education continuation (secondary school attendance and entrance to tertiary education) were very similar, with family composition and social class effects persisting even after adjusting for school achievement. In cross-generational analyses, better educational outcomes in the grandchildren were predicted by heavier birthweight, lower birth order and higher social class in the grandparents. These associations became non-significant and/or were substantially attenuated after adjusting for grandchild socio-economic position in childhood, suggesting that this was the major mechanism for this effect. We conclude that multiple early-life characteristics predict educational outcomes across the lifecourse and across generations. This includes birth characteristics and family composition effects which typically receive far less attention than socio-economic influences. Most effects were remarkably stable across the half-century separating our cohorts, suggesting their potential relevance for understanding educational inequalities in populations around the world

    The combined influence of parental education and preterm birth on school performance.

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    BACKGROUND: Social background and birth characteristics are generally found to be independently associated with school achievements but the underlying mechanisms are not fully understood. This study aimed to explore how parental education and shorter gestational age jointly influence school performance in a cohort of Swedish children. METHODS: 10,835 children born between 1973 and 1981 were studied, the third generation of the register-based Uppsala Multigenerational Birth Cohort. Ordinal logistic regression models were fitted to estimate OR of achieving middle and high grades in Swedish language at age 16 years, relative to low grade, by parental education and own gestational age, adjusting for potential confounders. RESULTS: In children from families with lower parental education, the adjusted OR of receiving a higher grade was 0.54 (95% CI 0.41 to 0.71) for preterm (<37 completed weeks) compared with full-term births. This estimate did not change when adjusted for several potential confounders (0.59; CI 0.44 to 0.79). When different cut-points were selected to define preterm birth, the estimated OR for those with low parental education decreased linearly from 0.83 (CI 0.72 to 0.96) using less than 39 weeks as the cut-point, to 0.52 (CI 0.30 to 0.90) using less than 35 weeks. There was no evidence of significant effects of shorter gestational age for children with parents from other educational groups. CONCLUSIONS: The disadvantage of shorter gestational age on the chance of achieving higher grades in Swedish language was confined to children from families in which none of the parents had higher education. This suggests that the detrimental influence of shorter gestational age on school performance in language may be avoidable

    Supercooling Agent Icilin Blocks a Warmth-Sensing Ion Channel TRPV3

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    Transient receptor potential vanilloid subtype 3 (TRPV3) is a thermosensitive ion channel expressed in a variety of neural cells and in keratinocytes. It is activated by warmth (33–39°C), and its responsiveness is dramatically increased at nociceptive temperatures greater than 40°C. Monoterpenoids and 2-APB are chemical activators of TRPV3 channels. We found that Icilin, a known cooling substance and putative ligand of TRPM8, reversibly inhibits TRPV3 activity at nanomolar concentrations in expression systems like Xenopus laeves oocytes, HEK-293 cells, and in cultured human keratinocytes. Our data show that icilin's antagonistic effects for the warm-sensitive TRPV3 ion channel occurs at very low concentrations. Therefore, the cooling effect evoked by icilin may at least in part be due to TRPV3 inhibition in addition to TRPM8 potentiation. Blockade of TRPV3 activity by icilin at such low concentrations might have important implications for overall cooling sensations detected by keratinocytes and free nerve endings in skin. We hypothesize that blockage of TRPV3 might be a signal for cool-sensing systems (like TRPM8) to beat up the basal activity resulting in increased cold perception when warmth sensors (like TRPV3) are shut off

    The Effect of Pungent and Tingling Compounds from Piper nigrum L. on Background K+ Currents

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    Black peppercorns (Piper nigrum L.) elicit a pungent and tingling oral impression. Their pungency is partially explained by the agonist activity of some of their active principles, especially piperine, on TRP channels. However, we recently showed that piperine, as well as other pungent compounds, also possess a marked effect on two-pore domain (KCNK, K2P) K+ channels. Members of this family play a key role in maintaining the resting membrane potential of excitable cells. Interestingly, tingling compounds have been shown to induce neuronal excitation by inhibiting KCNK channels. We addressed the question of whether it was plausible that KCNK channels could constitute a physiologically relevant target for the sensory active compounds present in black peppercorns. Because previous studies have demonstrated that mouse trigeminal neurons respond to several pungent compounds, to which humans are also sensitive, we used a primary culture of mouse trigeminal neurons to investigate whether the effect of piperine on these cell types could also be mediated by KCNK channels. We observed that even in the presence of classical TRP-antagonists, piperine was still able to activate a fraction of trigeminal neurons. Furthermore, our results showed that piperine is capable of inducing neuronal depolarization by a mechanism that does not require extracellular Na+ or Ca2+. This depolarization was mediated by the inhibition of a background K+ conductance, most likely corresponding to the KCNK channels of the TASK subfamily. We then performed a screening with 12 other pungent and/or tingling chemosensates isolated from black peppercorns. These compounds were evaluated on Xenopus laevis oocytes expressing the human orthologues of KCNK3, KNCK9 and KCNK18, which we previously showed to be inhibited by piperine. Remarkably, almost all of the isolated chemosensates inhibited the basal activity of hKCNK3, with 1-(octadeca-2E,4E,13/12Z-trienoyl)pyrrolidine acting as one of the most potent natural blockers for hKCNK3 found to date. Our results suggest that KCNK channels, especially KCNK3, are likely to play a complementary role to TRP channels in the complex orosensory impression elicited by black peppercorns, while they also help to expand the pharmacological knowledge of KCNK channels

    Odorant Receptor 51E2 Agonist beta-ionone Regulates RPE Cell Migration and Proliferation

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    The odorant receptor 51E2 (OR51E2), which is well-characterized in prostate cancer cells and epidermal pigment cells, was identified for the first time as the most highly expressed OR in human fetal and adult retinal pigment epithelial (RPE) cells. Immunofluorescence staining and Western blot analysis revealed OR51E2 localization throughout the cytosol and in the plasma membrane. Additionally, immunohistochemical staining of diverse layers of the eye showed that the expression of OR51E2 is restricted to the pigment cells of the RPE and choroid. The results of Ca2+-imaging experiments demonstrate that activation of OR51E2 triggers a Ca2+ dependent signal pathway in RPE cells. Downstream signaling of OR51E2 involves the activation of adenylyl cyclase, ERK1/2 and AKT. The activity of these protein kinases likely accounts for the demonstrated increase in the migration and proliferation of RPE cells upon stimulation with the OR51E2 ligand beta-ionone. These findings suggest that OR51E2 is involved in the regulation of RPE cell growth. Thus, OR51E2 represents a potential target for the treatment of proliferative disorders

    Odorant-Dependent Generation of Nitric Oxide in Mammalian Olfactory Sensory Neurons

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    The gaseous signalling molecule nitric oxide (NO) is involved in various physiological processes including regulation of blood pressure, immunocytotoxicity and neurotransmission. In the mammalian olfactory bulb (OB), NO plays a role in the formation of olfactory memory evoked by pheromones as well as conventional odorants. While NO generated by the neuronal isoform of NO synthase (nNOS) regulates neurogenesis in the olfactory epithelium, NO has not been implicated in olfactory signal transduction. We now show the expression and function of the endothelial isoform of NO synthase (eNOS) in mature olfactory sensory neurons (OSNs) of adult mice. Using NO-sensitive micro electrodes, we show that stimulation liberates NO from isolated wild-type OSNs, but not from OSNs of eNOS deficient mice. Integrated electrophysiological recordings (electro-olfactograms or EOGs) from the olfactory epithelium of these mice show that NO plays a significant role in modulating adaptation. Evidence for the presence of eNOS in mature mammalian OSNs and its involvement in odorant adaptation implicates NO as an important new element involved in olfactory signal transduction. As a diffusible messenger, NO could also have additional functions related to cross adaptation, regeneration, and maintenance of MOE homeostasis

    A population-based study of effect of multiple birth on infant mortality in Nigeria

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    <p>Abstract</p> <p>Background</p> <p>Multi-foetal pregnancies and multiple births including twins and higher order multiples births such as triplets and quadruplets are high-risk pregnancy and birth. These high-risk groups contribute to the higher rate of childhood mortality especially during early period of life.</p> <p>Methods</p> <p>We examined the relationship between multiple births and infant mortality using univariable and multivariable survival regression procedure with Weibull hazard function, controlling for child's sex, birth order, prenatal care, delivery assistance; mother's age at child birth, nutritional status, education level; household living conditions and several other risk factors.</p> <p>Results</p> <p>Children born multiple births were more than twice as likely to die during infancy as infants born singleton (hazard ratio = 2.19; 95% confidence interval: 1.50, 3.19) holding other factors constant. Maternal education and household asset index were associated with lower risk of infant mortality.</p> <p>Conclusion</p> <p>Multiple births are strongly negatively associated with infant survival in Nigeria independent of other risk factors. Mother's education played a protective role against infant death. This evidence suggests that improving maternal education may be key to improving child survival in Nigeria. A well-educated mother has a better chance of satisfying important factors that can improve infant survival: the quality of infant feeding, general care, household sanitation, and adequate use of preventive and curative health services.</p
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