Acyloxylation of Cyclic Enones: Synthesis of Densely Oxygenated Guaianolides

The α′-acyloxylation of cyclic enones with linear carboxylic acids is described. The reaction is promoted by KMnO4 in the presence of a carboxylic acid and its corresponding carboxylic anhydride. The optimization of the reaction has been carried out using the statistical methodology known as design of experiments. The optimized reaction conditions have been evaluated in terms of substrate scope and compatibility with different functional groups. The methodology has been applied to the synthesis of densely oxygenated guaianes and guaianolides

Daily rhythms of the sleep-wake cycle

The amount and timing of sleep and sleep architecture (sleep stages) are determined by several factors, important among which are the environment, circadian rhythms and time awake. Separating the roles played by these factors requires specific protocols, including the constant routine and altered sleep-wake schedules. Results from such protocols have led to the discovery of the factors that determine the amounts and distribution of slow wave and rapid eye movement sleep as well as to the development of models to determine the amount and timing of sleep. One successful model postulates two processes. The first is process S, which is due to sleep pressure (and increases with time awake) and is attributed to a 'sleep homeostat'. Process S reverses during slow wave sleep (when it is called process S'). The second is process C, which shows a daily rhythm that is parallel to the rhythm of core temperature. Processes S and C combine approximately additively to determine the times of sleep onset and waking. The model has proved useful in describing normal sleep in adults. Current work aims to identify the detailed nature of processes S and C. The model can also be applied to circumstances when the sleep-wake cycle is different from the norm in some way. These circumstances include: those who are poor sleepers or short sleepers; the role an individual's chronotype (a measure of how the timing of the individual's preferred sleep-wake cycle compares with the average for a population); and changes in the sleep-wake cycle with age, particularly in adolescence and aging, since individuals tend to prefer to go to sleep later during adolescence and earlier in old age. In all circumstances, the evidence that sleep times and architecture are altered and the possible causes of these changes (including altered S, S' and C processes) are examined

Association between sleep duration and blood pressure in adolescents

In adults, sleep has an important role in the development of cardiovascular diseases. However, in young adolescents, the effect is unclear. The purpose of this cross-sectional study was to evaluate the association between sleep duration and blood pressure (BP) in subjects of 13 years of age. We evaluated 1771 adolescents as part of a population-based cohort (Epidemiological Health Investigation of Teenagers). Sleep duration was estimated based on the difference between self-reported usual bedtimes and wake-up times, and adolescents were classified into three categories: 8.5 h (reference class), >8.5 h and 8.5 and <9.5 h: OR=1.56, 95% CI 1.07–2.27; 9.5 h: OR=1.83, 95% CI 1.23–2.70). Among males, no significant association was found between sleep duration and BP. Sleep duration was positively associated with BP in both sexes, although after adjustment for potential confounders, this association was significant only for female adolescents

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

A Transtheoretical, Case Management Approach to the Treatment of Pediatric Obesity

Objective: The percentage of obese children in the United States has increased dramatically over the past three decades, particularly among ethnic/ racial minorities. This study sought to examine the impact of a clinical case-management intervention based upon the Transtheoretical Model (TTM) to reduce obesity and increase physical activity in children. Methods: Nineteen obese African-American children ages 8-12 were recruited from two pediatric clinics and were randomized to either a 12-week intervention group or a control group. Dependent variables included body mass index (BMI) percentile, physical activity, and stage of change for the child and parent. Results: In comparison to the control group, the intervention group demonstrated significant decreases in BMI and improvements in daily vigorous physical activity. The children in the intervention group demonstrated movement toward action/maintenance stages of change. Conclusions: A 12-week TTM-based case management intervention can have a favorable impact on obesity and physical activity in African-American child

Duração do sono em adolescentes de diferentes níveis socioeconômicos Sleep duration in adolescents of different socioeconomic status

OBJETIVO: Investigar a duração de sono na adolescência em diferentes níveis socioeconômicos. MÉTODO: Foram investigados 863 adolescentes de 10 a 19 anos em duas escolas de São Paulo, SP, Brasil. As coletas foram realizadas por meio de questionários para identificação de informações sobre os hábitos de sono e nível socioeconômico. RESULTADOS: A duração média de sono nos dias da semana foi de 8,83(1,87) horas e a prevalência de adolescentes com duração de sono de oito ou menos horas diárias foi de 39,0% nos dias com aula. Adolescentes da classe baixa apresentaram menor duração do sono (p = 0,043). Na análise ajustada, a idade, o nível socioeconômico e o hábito de tirar a sesta foram os principais fatores associados a poucas horas de sono. Os participantes de 18 a 19 anos apresentaram maior prevalência de poucas horas de sono em comparação aos de 10 a 11 anos (PR = 4,78; CI95%: 1,98-11,53), assim como os adolescentes da classe alta em comparação com a classe baixa (PR = 1,48; CI95%: 1,20-1,83). CONCLUSÃO: Os resultados mostraram associações entre o nível socioeconômico e os hábitos de sono de adolescentes.<br>OBJECTIVE: To investigate the sleep duration in adolescents of different socioeconomic status. METHOD: We investigated 863 adolescents from 10 to 19 years in two schools in São Paulo, SP, Brazil. Sleep habits data and socioeconomic status were obtained by questionnaires. RESULTS: Mean sleep duration on days of the week was 8.83(1.87) hours and the prevalence of adolescents with eight or fewer hours/day was 39.0% on school days (p = 0.043). On adjusted analysis, age, socioeconomic status and taking a nap habit were the main factors associated with few hours of sleep. Older students (aged 18 to 19 years) showed higher prevalence of few hours of sleep when compared to younger students (10 to 11 years) (RP = 4.78; IC95%: 1.98-11.53), as well as for upper class adolescents when compared to those with lower socioeconomic status. CONCLUSION: Results showed the association between socioeconomic status and adolescents' sleep/wake habits