BACKGROUND-Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy.

Of all plant constituents, coffee has one of the highest concentrations of chlorogenic acids. When roasting coffee, some of these are transformed into chlorogenic acid lactones (CGL). We have studied the formation of CGL during the roasting of coffee beans in Coffea arabica cv. Bourbon; C. arabicacv. Longberry; and C. canephora cv. Robusta. Individual CGL levels were determined by comparison of HPLC peaks with those of synthetic CGL standards. Seven CGL were identified: 3-caffeoylquinic-1,5-lactone (3-CQL), 4- caffeoylquinic-1,5-lactone (4-CQL), 3-coumaroylquinic-1,5-lactone (3-pCoQL), 4-coumaroylquinic-1,5-lactone (4-pCoQL), 3-feruloylquinic-1,5-lactone (3-FQL), 4-feruloylquinic-1,5-lactone (4-FQL), and 3,4-dicaffeoylquinic-1,5-lactone (3,4-diCQL). 3-CQL was the most abundant lactone in C. arabica and C. canephora, reaching peak values of 230 +/- 9 and 254 +/- 4 mg/100 g (dry weight), respectively, at light medium roast ( approximately 14% weight loss). 4-CQL was the second most abundant lactone (116 +/- 3 and 139 +/- 2 mg/100 g, respectively. The maximum amount of CGL represents approximately 30% of the available precursors. The relative levels of 3-CQL and 4-CQL in roasted coffee were reverse to those of their precursors in green coffee. This suggests that roasting causes isomerization of chlorogenic acids prior to the formation of lactones and that the levels of lactones in roasted coffee do not reflect the levels of precursors in green coffee.

Background Submicroscopic deletions in 14q12 spanning FOXG1 or intragenic mutations have been reported in patients with a developmental disorder described as a congenital variant of Rett syndrome. We aimed to further characterize and delineate the phenotype of FOXG1-mutation positive patients. Method We mapped the breakpoints of a 2;14 translocation by fluorescence in situ hybridization and analyzed three chromosome rearrangements in 14q12 by cytogenetic analysis and/or array CGH. We sequenced the FOXG1 gene in 210 patients, including 129 patients with unexplained developmental disorders and 81 MECP2-mutation negative individuals. Results We report one known mutation, seen in 2 patients, and 9 novel mutations of FOXG1 including 2 deletions, 2 chromosome rearrangements disrupting or displacing putative cis-regulatory elements from FOXG1, and 7 sequence changes. Analysis of our 11 patients, and further 15 patients reported in the literature, demonstrates a complex constellation of features including mild postnatal growth deficiency, severe postnatal microcephaly, severe mental retardation with absent language development, deficient social reciprocity resembling autism, combined stereotypies and frank dyskinesias, epilepsy, poor sleep patterns, irritability in infancy, unexplained episodes of crying, recurrent aspiration, and gastroesophageal reflux. Brain imaging studies reveal simplified gyral pattern and reduced white matter volume in the frontal lobes, corpus callosum hypogenesis, and variable mild frontal pachgyria. Conclusions We significantly expanded the number of FOXG1 mutations and identified two affecting possible cis-regulatory elements. While the phenotype of the patients overlaps both classic and congenital Rett syndrome, extensive clinical evaluation demonstrates a distinctive and clinically recognizable phenotype which we suggest to designate as the FOXG1 syndrome.

Additional theoretical work is needed to better understand successful aging, including the way it can encompass disability and death and dying. The extent of rapid social and technological change influencing views on successful aging also deserves more consideration.