The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Dynamics of Ecosystem Services during Forest Transitions in Costa Rica

International audienceThe forest transition framework describes the temporal changes of forest areas with economic development. A first phase of forest contraction is followed by a second phase of expansion once a turning point is reached. This framework does not differentiate forest types or ecosystem services, and describes forests regardless of their contribution to human well-being. For several decades, deforestation in many tropical regions has degraded ecosystem services, such as watershed regulation, while increasing provisioning services from agriculture, for example, food. Forest transitions and expansion have been observed in some countries, but their consequences for ecosystem services are often unclear. We analyzed the implications of forest cover change on ecosystem services in Costa Rica, where a forest transition has been suggested. A review of literature and secondary data on forest and ecosystem services in Costa Rica indicated that forest transition might have led to an ecosystem services transition. We modeled and mapped the changes of selected ecosystem services in the upper part of the Reventazón watershed and analyzed how supply changed over time in order to identify possible transitions in ecosystem services. The modeled changes of ecosystem services is similar to the second phase of a forest transition but no turning point was identified, probably because of the limited temporal scope of the analysis. Trends of provisioning and regulating services and their tradeoffs were opposite in different spatial subunits of our study area, which highlights the importance of scale in the analysis of ecosystem services and forest transitions. The ecosystem services transition framework proposed in this study is useful for analyzing the temporal changes of ecosystem services and linking socio-economic drivers to ecosystem services demand at different scales