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Adult body height appears to be significantly associated with marital outcomes taller men across contexts have been found to be more likely to be married, and more likely to be married at younger ages. We are interested in exploring both outcomes individually and simultaneously, while using an unique, individual-level dataset of Dutch men and their brothers born between 1841 and 1900. To do so, we exploit survival models and cure models. While survival models yield a single estimate for the hazard (or age at) marriage, cure models yield two one for the likelihood of marriage, and one for the hazard of first marriage. Cure models thus account for selection into marriage, while survival models do not. We find that, in the survival analyses, being in the shortest 20 % of heights is associated with later ages of marriage, relative to being average height. However, when we account for selection into marriage with cure models, we find that height is no longer associated with age at marriage. https://www.selleckchem.com/products/tak-981.html Instead, we see that height is associated with the likelihood of being married, with being in the bottom 20 % of heights associated with a 56.1 % decreased likelihood of being married, relative to being average height. We therefore conclude that height may be a gatekeeper for access to marriage, but it appears that other factors - likely related to the ability to set up an independent household - are more important in determining the timing of marriage for our research population.Increasing evidence suggests that adipokines, leptin and adiponectin, produced and secreted by adipocytes, are involved in regulating systemic inflammation and may be important targets for interventions to reduce the chronic systemic inflammation linked to some conditions common in aging (e.g., atherosclerosis). Lower leptin levels and higher adiponectin levels in peripheral circulation have been associated with less systemic inflammation. While some studies have shown that marine-derived omega-3 fatty acids (eicosapentaenoic acid [EPA] and/or docosahexaenoic acid [DHA]) have effects on leptin and adiponectin in the context of inflammation, the extent of their effects remain unclear. The purpose of this systematic review was to summarize findings from randomized, controlled trials that measured effects of EPA+DHA supplementation on circulating levels of leptin and adiponectin to determine the state of the science. PubMed, CINAHL, Web of Science, Scopus, and Cochrane Trials were searched up to June 2018 for studies meeting inclusion criteria. Thirty-one studies included in this review were conducted in 16 countries. Eighteen studies reported lower leptin and/or higher adiponectin levels with EPA+DHA supplementation versus placebo at study end point (9 reported statistically significant differences), but doses, supplementation duration, and population characteristics varied across studies. In 9 studies reporting significantly lower leptin and/or higher adiponectin levels the EPA+DHA dose was 0.52 to 4.2 g/day for 4 to 24 weeks. Additional studies are warranted which assess dose parameters and patient populations similar to studies reporting significant effects of EPA+DHA on leptin or adiponectin in order to evaluate the extent of reproducibility before recommending EPA+DHA as a therapy to target these adipokines.Docosahexaenoic acid (DHA) is one of the most important fatty acids that plays a critical role in maintaining proper brain function and cognitive development. Deficiency of DHA leads to several neurodegenerative disorders and, therefore, dietary supplementations of these fatty acids are essential to maintain cognitive health. However, the complete picture of how DHA is incorporated into the brain is yet to be explored. In general, the de novo synthesis of DHA is poor, and targeting the brain with specific phospholipid carriers provides novel insights into the process of reduction of disease progression. Recent studies have suggested that compared to triacylglycerol form of DHA, esterified form of DHA (i.e., lysophosphatidylcholine [lysoPC]) is better incorporated into the brain. Free DHA is transported across the outer membrane leaflet of the blood-brain barrier via APOE4 receptors, whereas DHA-lysoPC is transported across the inner membrane leaflet of the blood-brain barrier via a specific protein called Mfsd2a. Dietary supplementation of this lysoPC specific form of DHA is a novel therapy and is used to decrease the risk of various neurodegenerative disorders. Currently, structured glycerides of DHA - novel nutraceutical agents - are being widely used for the prevention and treatment of various neurological diseases. However, it is important to fully understand their metabolic regulation and mechanism of transportation to the brain. This article comprehensively reviews various studies that have evaluated the bioavailability of DHA, mechanisms of DHA transport, and role of DHA in preventing neurodegenerative disorders, which provides better insight into the pathophysiology of these disorders and use of structured DHA in improving neurological health.In this work, a series of structurally novel benzoxaborole derivatives were designed, synthesized and biologically evaluated as PDE4 inhibitors for battling atopic dermatitis (AD). Among them, the majority exhibited superior PDE4B inhibitory activities to that of the lead compound Crisaborole, an approved PDE4 inhibitor. In particular, 72, the most potent PDE4B inhibitor throughout this series, displayed 136-fold improved enzymatic activity (IC50 = 0.42 nM) as compared to Crisaborole (IC50 = 57.20 nM), along with favorable isoform specificity. In the phorbol ester (PMA)-induced mouse ear oedema model, 72 exerted remarkably greater efficacy than Crisaborole at the same dosage (P less then 0.05). Moreover, the ointment of 72 exerted dramatically enhanced therapeutic potency than the ointment of Crisaborole (P less then 0.05) in the calcipotriol-induced mouse AD model. In addition to the potent in vitro and in vivo activity, 72 displayed favorable safety in the repeated oral dose toxicity study and did not exhibit phototoxicity. With the above attractive biological performance, 72 is worthy of further functional investigation as a novel anti-AD therapeutic agent.
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