Access to a diverse array of bridged benzo[1,5]oxazocine and benzo[1,4]diazepine structures

The preparation of bridged benzo[1,5]oxazocines and benzo[1,4]diazepines is demonstrated from simple aniline and aldehyde starting materials. A one-pot condensation/6π electrocyclization is followed by an intramolecular trapping of the 2,3-dihydroquinoline intermediate by nitrogen or oxygen nucleophiles to give bridged seven- and eight-membered products. Using 3-hydroxypyridinecarboxaldehydes results in a stable zwitterionic structure that can undergo a diastereoselective reduction under hydrogenative conditions. A similar cyclization/hydrogenation pathway with excellent diastereoselectivity is also demonstrated from 2-pyridyl-substituted 1,2,3,4-tetrahydroquinolines.PostprintPeer reviewe

Elevated ratio of acylated to unacylated ghrelin in children and young adults with Prader–Willi syndrome

Prader–Willi syndrome (PWS) is characterized by a switch from failure to thrive to excessive weight gain and hyperphagia in early childhood. Hyperghrelinemia may be involved in the underlying mechanisms of the switch. The purpose of this study is to evaluate acylated ghrelin (AG) and unacylated ghrelin (UAG) levels in PWS and investigate their associations with hyperphagia. This is a cross-sectional clinical study conducted in three PWS expert centers in the Netherlands and France. Levels of AG and UAG and the AG/UAG ratio were determined in 138 patients with PWS (0.2–29.4 years) and compared with 50 age-matched obese subjects (4.3–16.9 years) and 39 healthy controls (0.8–28.6 years). AEBSF was used to inhibit deacylation of AG. As a group, PWS patients had higher AG but similar UAG levels as healthy controls (AG 129.1 vs 82.4 pg/ml, p = 0.016; UAG 135.3 vs 157.3 pg/ml, resp.), resulting in a significantly higher AG/UAG ratio (1.00 vs 0.61, p = 0.001, resp.). Obese subjects had significantly lower AG and UAG levels than PWS and controls (40.3 and 35.3 pg/ml, resp.), but also a high AG/UAG ratio (1.16). The reason for the higher AG/UAG ratio in PWS and obese was, however, completely different, as PWS had a high AG and obese a very low UAG. PWS patients without weight gain or hyperphagia had a similar AG/UAG ratio as age-matched controls, in contrast to those with weight gain and/or hyperphagia who had an elevated AG/UAG ratio. The switch to excessive weight gain in PWS seems to coincide with an increase in the AG/UAG ratio, even prior to the start of hyperphagia

Access to a diverse array of bridged benzo[1,5]oxazocine and benzo[1,4]diazepine structures

The preparation of bridged benzo[1,5]oxazocines and benzo[1,4]diazepines is demonstrated from simple aniline and aldehyde starting materials. A one-pot condensation/6π electrocyclization is followed by an intramolecular trapping of the 2,3-dihydroquinoline intermediate by nitrogen or oxygen nucleophiles to give bridged seven- and eight-membered products. Using 3-hydroxypyridinecarboxaldehydes results in a stable zwitterionic structure that can undergo a diastereoselective reduction under hydrogenative conditions. A similar cyclization/hydrogenation pathway with excellent diastereoselectivity is also demonstrated from 2-pyridyl-substituted 1,2,3,4-tetrahydroquinolines

Spatial epidemiology of urban health risks in select West African cities

West African cities face critical societal challenges that are linked to environmental and health changes. These challenges are further exacerbated by urbanization dynamics, climate change, socio-economic mutation and lack of capacity for sustainable urban development, governance and basic services delivery. The deficiency of environmental sanitation and ecosystem services have led to high complexity of urban health risks inequalities, resulting in the need for more research on efficient urban health policies. The purpose of this contribution is to present the main findings on the spatial epidemiology of diarrhaea and malaria, and their associated risks factors in the following select West African cities. Spatial variability of exposure to diarrhaea and malaria transmission is linked to several health risks such as lack of access to water and sanitation, solid wastes management, urban flooding

Rethinking slavery heritage tourism

This paper argues that the investigation of slavery heritage within a ‘thana’- or ‘dark’ tourism framework invariably fails to appreciate the subtleties, power relationships and various contestations that are at play in both the presentation and consumption of former Transatlantic Slave Trade (TAST) sites. Instead, the authors argue that a combination of Halbwachs’ collective memory theory and Tunbridge and Ashworth’s concept of dissonant heritage can provide a deeper understanding of tourism linked to such sites. A study of TAST sites in Ghana identified six key groups of stakeholders involved in the interpretation of slavery heritage, each with its own agenda, desire to remember or forget slave memories and desire to compose different narratives. By analysing collective slave memories, the study proposes a framework that demonstrates that tourism to TAST-related sites is complex and nuanced because it relates to the nature of the historic event itself, intrinsic qualities of TAST-related sites in terms of current relevance and the closeness of the event or site to each stakeholder.School of Hotel and Tourism Managemen