Cocoa flavanols adjuvant to an oral nutritional supplement acutely enhances nutritive flow in skeletal muscle without altering leg glucose uptake kinetics in older adults

This is the final version. Available on open access from MDPI via the DOI in this record. Data Availability Statement: The data presented in this study are available on request from the corresponding authors.Ageing is associated with postprandial muscle vascular and metabolic dysfunction, suggesting vascular modifying interventions may be of benefit. Reflecting this, we investigated the impact of acute cocoa flavanol (450–500 mg) intake (versus placebo control) on vascular (via ultrasound) and glucose/insulin metabolic responses (via arterialised/venous blood samples and ELISA) to an oral nutritional supplement (ONS) in twelve healthy older adults (50% male, 72 ± 4 years), in a crossover design study. The cocoa condition displayed significant increases in m. vastus lateralis microvascular blood volume (MBV) in response to feeding at 180 and 240-min after ONS consumption (baseline: 1.00 vs. 180 min: 1.09 ± 0.03, p = 0.05; 240 min: 1.13 ± 0.04, p = 0.002), with MBV at these timepoints significantly higher than in the control condition (p 0.05). Similarly, glucose uptake and insulin increased in response to ONS (p 0.05). Thus, acute cocoa flavanol supplementation can potentiate oral feeding-induced increases in MBV in older adults, but this improvement does not relay to muscle glucose uptake.Abbott NutritionMedical Research Council (MRC)National Institute for Health Research (NIHR

A Novel Role for PECAM-1 (CD31) in Regulating Haematopoietic Progenitor Cell Compartmentalization between the Peripheral Blood and Bone Marrow

Although the expression of PECAM-1 (CD31) on vascular and haematopoietic cells within the bone marrow microenvironment has been recognized for some time, its physiological role within this niche remains unexplored. In this study we show that PECAM-1 influences steady state hematopoietic stem cell (HSC) progenitor numbers in the peripheral blood but not the bone marrow compartment. PECAM-1−/− mice have higher levels of HSC progenitors in the blood compared to their littermate controls. We show that PECAM-1 is required on both progenitors and bone marrow vascular cells in order for efficient transition between the blood and bone marrow to occur. We have identified key roles for PECAM-1 in both the regulation of HSC migration to the chemokine CXCL12, as well as maintaining levels of the matrix degrading enzyme MMP-9 in the bone marrow vascular niche. Using intravital microscopy and adoptive transfer of either wild type (WT) or PECAM-1−/− bone marrow precursors, we demonstrate that the increase in HSC progenitors in the blood is due in part to a reduced ability to migrate from blood to the bone marrow vascular niche. These findings suggest a novel role for PECAM-1 as a regulator of resting homeostatic progenitor cell numbers in the bloo

Communicating Information on Eruptions and Their Impacts from the Earliest Times Until the Late Twentieth Century

Volcanoes hold a fascination for human beings and, before they were recorded by literate observers, eruptions were portrayed in art, were recalled in legends and became incorporated into religious practices: being viewed as agents of punishment, bounty or intimidation depending upon their state of activity and the culture involved. In the Middle East the earliest depiction of an eruption is a wall painting dating from the Neolithic at Çatal Hüyük and the earliest record dates from the third millennium BCE. Knowledge of volcanoes increased over time. In some parts of the world knowledge of eruptions was passed down by oral transmission, but as far as written records were concerned, in the first century CE only 9 volcanoes in the Mediterranean region were recognised, together with Mount Cameroon in West Africa. In the next 1000 years the list grew by 17, some 14 of these volcanoes being in Japan. The first recorded eruptions in Indonesia occurred in 1000 and 1006, and volcanoes in newly settled Iceland increased the number to just 48 in 1380 CE. After this the list continued to increase, with important regions such as New Zealand and Hawaii only being added in the past 200 years. Only from 1900 did the rate of growth decline significantly (Simkin et al. 1981: 23; Simkin, 1993 Siebert et al. 2011; Simkin, 1993), but it is sobering to recall that in the twentieth century major eruptions have occurred from volcanoes that were considered inactive or extinct examples including: Mount Lamington - Papua New Guinea, 1951; Mount Arenal - Costa Rica, 1968 and Nyos - Cameroon, 1986. Although there are instances where the human impact of historical eruptions have been compiled - with examples including the 1883 eruption of Krakatau (Simkin and Fiske (1983) and 1943 -1952 eruption of Parícutin (Luhr and Simkin, 1993) - these are exceptions and there remains a significant gap in knowledge about both the short and long-term effects on societies of major eruptions which occurred before the 1980s. Following a broad review the chapter provides a discussion of the ways in which information has been collected, compiled and disseminated from the earliest times until the 1980s in two case study areas: the Azores Islands (Portugal) and southern Italy. In Italy information on eruptions stretches back to prehistoric times and has become progressively better known over more than 2,000 years of written history, yet even here there remain significant gaps in the record even for events that took place between 1900 and 1990. In contrast, located in the middle of the Atlantic, the Azores have been isolated for much of their history and illustrate the difficulties involved in using indigenous sources to compile, not only assessments of impact, but also at a more basic level a complete list of historical events with accurate dates

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