RESUMEN

Most drugs used to treat viral disease target a virus-coded product. They inhibit a single virus or virus family, and the pathogen can readily evolve resistance. Host-targeted antivirals can overcome these limitations. The broad-spectrum activity achieved by host targeting can be especially useful in combating emerging viruses and for treatment of diseases caused by multiple viral pathogens, such as opportunistic agents in immunosuppressed patients. We have developed a family of compounds that modulate sirtuin 2, an NAD+-dependent deacylase, and now report the properties of a member of that family, FLS-359. Biochemical and x-ray structural studies show that the drug binds to sirtuin 2 and allosterically inhibits its deacetylase activity. FLS-359 inhibits the growth of RNA and DNA viruses, including members of the coronavirus, orthomyxovirus, flavivirus, hepadnavirus, and herpesvirus families. FLS-359 acts at multiple levels to antagonize cytomegalovirus replication in fibroblasts, causing modest reductions in viral RNAs and DNA, together with a much greater reduction in infectious progeny, and it exhibits antiviral activity in humanized mouse models of infection. Our results highlight the potential of sirtuin 2 inhibitors as broad-spectrum antivirals and set the stage for further understanding of how host epigenetic mechanisms impact the growth and spread of viral pathogens.

Asunto(s)

RESUMEN

BACKGROUND: Hyperglycaemia in pregnancy contributes to adverse outcomes for women and their children. The postpartum period is an opportune time to support women to reduce cardiometabolic and diabetes risk in subsequent pregnancies. AIMS: To identify strengths and gaps in current care for Aboriginal women after a pregnancy complicated by hyperglycaemia. METHODS: A retrospective review of the 12 month postpartum care provided by primary health centres in remote Australia in 2013-2014 identified 195 women who experienced hyperglycaemia in pregnancy (gestational diabetes (GDM) (n = 147), type 2 diabetes (T2D) (n = 39), and unclear diabetes status (n = 9)). RESULTS: Only 80 women (54%) with GDM had postpartum glycaemic checks. Of these, 32 women were diagnosed with prediabetes (n = 24) or diabetes (n = 8). Compared to women with GDM, women with T2D were more likely to have their weight measured (75% vs. 52%, p <0.01), and smoking status documented as "discussed" (65% vs. 34%, p < 0.01). Most women (97%) accessed the health centre at least once in the 12 month postpartum period but, during these visits, only 52% of women had service provision, either structured or opportunistic, related to diabetes. CONCLUSION: High rates of dysglycaemia among women screened for T2D after GDM in the 12 month postpartum period highlight the need for increased screening and early intervention to prevent the development of T2D and its complications. Whilst a clear strength was high postpartum attendance, many women did not attend health services for diabetes screening or management.

Asunto(s)

RESUMEN

Investment in the capabilities of the world's 1·2 billion adolescents is vital to the UN's Sustainable Development Agenda. We examined investments in countries of low income, lower-middle income, and upper-middle income covering the majority of these adolescents globally to derive estimates of investment returns given existing knowledge. The costs and effects of the interventions were estimated by adapting existing models and by extending methods to create new modelling tools. Benefits were valued in terms of increased gross domestic product and averted social costs. The initial analysis showed high returns for the modelled interventions, with substantial variation between countries and with returns generally higher in low-income countries than in countries of lower-middle and upper-middle income. For interventions targeting physical, mental, and sexual health (including a human papilloma virus programme), an investment of US$4·6 per capita each year from 2015 to 2030 had an unweighted mean benefit to cost ratio (BCR) of more than 10·0, whereas, for interventions targeting road traffic injuries, a BCR of 5·9 (95% CI 5·8-6·0) was achieved on investment of $0·6 per capita each year. Interventions to reduce child marriage ($3·8 per capita each year) had a mean BCR of 5·7 (95% CI 5·3-6·1), with the effect high in low-income countries. Investment to increase the extent and quality of secondary schooling is vital but will be more expensive than other interventions-investment of $22·6 per capita each year from 2015 to 2030 generated a mean BCR of 11·8 (95% CI 11·6-12·0). Investments in health and education will not only transform the lives of adolescents in resource-poor settings, but will also generate high economic and social returns. These returns were robust to substantial variation in assumptions. Although the knowledge base on the impacts of interventions is limited in many areas, and a major research effort is needed to build a more complete investment framework, these analyses suggest that comprehensive investments in adolescent health and wellbeing should be given high priority in national and international policy.

Asunto(s)

RESUMEN

Literary scholars are generally suspicious of the concept of universals: there are presently no candidates for literary universals that a high proportion of literary scholars would accept as valid. This paper reports results from a content analysis of patterns of characterization in folktales from 48 culture areas, aimed at identifying patterns of characterization that apply across regions of the world and levels of cultural complexity. The search for these patterns was guided by evolutionary theory and the findings are consistent with previous research on patterns of altruism, sex differences in mate preferences, sex differences in reproductive strategy, and differing emphases on male and female physical attractiveness. World literature, especially originally oral literature, represents a vast and neglected repository of information that researchers can use to more precisely map the contours of human nature.