Lithium is the most effective mood stabilizer for the treatment of bipolar disorder, but it is toxic at only twice the therapeutic dosage and has many undesirable side effects. It is likely that a small molecule could be found with lithium-like efficacy but without toxicity through target-based drug discovery; however, lithium’s therapeutic target remains equivocal. Inositol monophosphatase is a possible target but no bioavailable inhibitors exist. Here we report that the antioxidant ebselen inhibits inositol monophosphatase and induces lithium-like effects on mouse behaviour, which are reversed with inositol, consistent with a mechanism involving inhibition of inositol recycling. Ebselen is part of the National Institutes of Health Clinical Collection, a chemical library of bioavailable drugs considered clinically safe but without proven use. Therefore, ebselen represents a lithium mimetic with the potential both to validate inositol monophosphatase inhibition as a treatment for bipolar disorder and to serve as a treatment itself.

Objective To describe the events leading to the epidemic of congenital rubella syndrome in Greece in 1993 after a major rubella epidemic. Design Retrospective survey and systematic review. Setting Greece (population 10 million), 1950-95. Subjects Children, adolescents, and women of childbearing age. Results Around 1975 in Greece the measles, mumps, and rubella vaccine started being given to boys and girls aged 1 year without policies to attain high vaccination coverage and to protect adolescents and young women. During the 1980s, vaccination coverage for rubella remained consistently below 50%, and the proportion of pregnant women susceptible to rubella gradually increased. In 1993 the incidence of rubella in young adults was higher than in any previous epidemic year. The epidemic of congenital rubella that followed, with 25 serologically confirmed cases (24.6 per 100 000 live births), was probably the largest such epidemic in Greece after 1950. ConclusionsWith low vaccination coverage, the immunisation of boys and girls aged 1 year against rubella carries the theoretical risk of increasing the occurrence of congenital rubella. This phenomenon, which has not been previously reported, occurred in Greece.

Glucocerebrosidase gene (GBA) mutations are the most common genetic contributor to Parkinson's disease (PD) and are associated with decreased glucocerebrosidase (GCase) enzymatic activity in PD. PD patients without GBA mutations also exhibit lower levels of GCase activity in the central nervous system suggesting a potential contribution of the enzyme activity in disease pathogenesis, possibly by alteration of lysosomal function. α-synuclein (ASYN), a protein with a central role in PD pathogenesis, has been shown to be secreted partly in association with exosomes. It is possible that a dysfunction of the endocytic pathway through GCase may result in altered exosome release of ASYN. The aim of this study was to examine whether manipulating GCase activity in vivo and in vitro could affect ASYN accumulation and secretion. GCase overexpression in vitro resulted in a significant decrease of exosome secretion. Chronic inhibition of GCase activity in vivo, by administration of the covalent inhibitor conduritol-B epoxide in A53T-synuclein alpha gene Tg mice significantly elevated intracellular oligomeric ASYN species. Importantly, GCase inhibition, induced a profound increase in the number of brain exosomes released, as well as exosome-associated ASYN oligomers. Finally, virus-mediated expression of mutant GBA in the mouse striatum increased ASYN secretion in the same region. Together, these results provide for the first time evidence that a decrease of GCase or overexpression of mutant GCase in a chronic in vivo setting can affect ASYN secretion. Such effects may mediate enhanced propagation of ASYN, driving pathology in GBA-associated PD.

Objective:To estimate breast-feeding prevalence in Greece in 2007 and 2017, compare breast-feeding indicators and maternity hospital practices between these years, and investigate breast-feeding determinants.Design:Two national cross-sectional studies (2007 and 2017) using systematic cluster sampling of babies with the same sampling design, data collection and analysis methodology.Setting:Telephone interview with babies’ mothers or fathers.Participants:Representative sample of infants who participated in the national neonatal screening programme (n 549 in 2017, n 586 in 2007).Results:We found that breast-feeding indicators were higher in 2017 compared with 10 years before. In 2017, 94 % of mothers initiated breast-feeding. Breast-feeding rates were 80, 56 and 45 % by the end of the 1st, 4th and 6th completed month of age, respectively. At the same ages, 40, 25 and <1 % of babies, respectively, were exclusively breast-feeding. We also found early introduction of solid foods (after the 4th month of age). Maternity hospital practices favouring breast-feeding were more prevalent in 2017, but still suboptimal (63 % experienced rooming-in; 51 % experienced skin-to-skin contact in the first hour after birth; 19 % received free sample of infant formula on discharge).Conclusions:We observed an increasing trend in all breast-feeding indicators in the past decade in Greece, but breast-feeding rates – particularly rates of exclusive breast-feeding – remain low. Systematic public health initiatives targeted to health professionals and mothers are needed in order to change the prevailing baby feeding ‘culture’ and successfully implement the WHO recommendations for exclusive breast-feeding during the first 6 months of life.