Retinoic Acid-Dependent Signaling Pathways and Lineage Events in the Developing Mouse Spinal Cord

Studies in avian models have demonstrated an involvement of retinoid signaling in early neural tube patterning. The roles of this signaling pathway at later stages of spinal cord development are only partly characterized. Here we use Raldh2-null mouse mutants rescued from early embryonic lethality to study the consequences of lack of endogenous retinoic acid (RA) in the differentiating spinal cord. Mid-gestation RA deficiency produces prominent structural and molecular deficiencies in dorsal regions of the spinal cord. While targets of Wnt signaling in the dorsal neuronal lineage are unaltered, reductions in Fibroblast Growth Factor (FGF) and Notch signaling are clearly observed. We further provide evidence that endogenous RA is capable of driving stem cell differentiation. Raldh2 deficiency results in a decreased number of spinal cord derived neurospheres, which exhibit a reduced differentiation potential. Raldh2-null neurospheres have a decreased number of cells expressing the neuronal marker β-III-tubulin, while the nestin-positive cell population is increased. Hence, in vivo retinoid deficiency impaired neural stem cell growth. We propose that RA has separable functions in the developing spinal cord to (i) maintain high levels of FGF and Notch signaling and (ii) drive stem cell differentiation, thus restricting both the numbers and the pluripotent character of neural stem cells

Real-Time Associations Between Engaging in Leisure and Daily Health and Well-Being

BackgroundEngagement in leisure has a wide range of beneficial health effects. Yet, this evidence is derived from between-person methods that do not examine the momentary within-person processes theorized to explain leisure's benefits.PurposeThis study examined momentary relationships between leisure and health and well-being in daily life.MethodsA community sample (n = 115) completed ecological momentary assessments six times a day for three consecutive days. At each measurement, participants indicated if they were engaging in leisure and reported on their mood, interest/boredom, and stress levels. Next, participants collected a saliva sample for cortisol analyses. Heart rate was assessed throughout the study.ResultsMultilevel models revealed that participants had more positive and less negative mood, more interest, less stress, and lower heart rate when engaging in leisure than when not.ConclusionsResults suggest multiple mechanisms explaining leisure's effectiveness, which can inform leisure-based interventions to improve health and well-being

Three individuals, three stories, three burials from medieval Trondheim, Norway

This article presents the life stories of three individuals who lived in Trondheim, Norway, dur- ing the 13th century. Based on skeletal examinations, facial reconstructions, genetic analy- ses, and stable oxygen isotope analyses, the birthplace, mobility, ancestry, pathology, and physical appearance of these people are presented. The stories are discussed within the relevant historical context. These three people would have been ordinary citizens, without any privileges out of the ordinary, which makes them quite rare in the academic literature. Through the study of individuals one gets a unique look into the Norwegian medieval society

Advanced heart failure: feasibility study of long-term continuous axial flow pump support.

AIMS: A lack of donor hearts has stimulated interest in using blood pumps to treat severe heart failure. We tested the hypothesis that a new continuous flow circulatory assist device could be employed safely to relieve symptoms of heart failure and evaluated the potential to prolong life. METHODS AND RESULTS: An intracardiac axial flow pump was implanted in 17 heart failure patients [idiopathic dilated (12), ischaemic (4), or amyloid cardiomyopathy (1)]. All were deemed ineligible for transplantation. Implantation of the device was by left thoracotomy (15) or median sternotomy (2). Power delivery was by a skull-mounted titanium pedestal. All patients survived surgery. None needed right ventricular support. There were three hospital deaths, two early from subdural haematoma and aortic thrombosis, one late after switching to transplantation. A total of 14 patients left hospital with a cumulative support-time of 15.9 years (median: 293 days, interquartile range: 286 days, 1-44 months). Actuarial 1-, 2-, and 3-year survivals were 56, 47, and 24%, respectively. There was no pump failure. Quality of life scores improved. Two superficial pedestal infections were successfully treated. Four patients had cerebral thrombo-embolism: two early events attributed to inadequate anticoagulation and two late with near-complete resolution. An improved anticoagulant regime addressed this problem. Late death occurred in five patients from battery disconnection, subdural haematoma, bowel ischaemia, respiratory failure, and after cardiac transplantation. CONCLUSION: Continuous flow blood pumps provided symptomatic relief of severe heart failure with high quality of life. Event-free survival reached 4 years. Analysis of adverse events led to improved management strategies. There is potential for widespread use of blood pumps in the community. A controlled trial is required