Aspartoacylase-LacZ Knockin Mice: An Engineered Model of Canavan Disease

Canavan Disease (CD) is a recessive leukodystrophy caused by loss of function mutations in the gene encoding aspartoacylase (ASPA), an oligodendrocyte-enriched enzyme that hydrolyses N-acetylaspartate (NAA) to acetate and aspartate. The neurological phenotypes of different rodent models of CD vary considerably. Here we report on a novel targeted aspa mouse mutant expressing the bacterial β-Galactosidase (lacZ) gene under the control of the aspa regulatory elements. X-Gal staining in known ASPA expression domains confirms the integrity of the modified locus in heterozygous aspa lacZ-knockin (aspalacZ/+) mice. In addition, abundant ASPA expression was detected in Schwann cells. Homozygous (aspalacZ/lacZ) mutants are ASPA-deficient, show CD-like histopathology and moderate neurological impairment with behavioural deficits that are more pronounced in aspalacZ/lacZ males than females. Non-invasive ultrahigh field proton magnetic resonance spectroscopy revealed increased levels of NAA, myo-inositol and taurine in the aspalacZ/lacZ brain. Spongy degeneration was prominent in hippocampus, thalamus, brain stem, and cerebellum, whereas white matter of optic nerve and corpus callosum was spared. Intracellular vacuolisation in astrocytes coincides with axonal swellings in cerebellum and brain stem of aspalacZ/lacZ mutants indicating that astroglia may act as an osmolyte buffer in the aspa-deficient CNS. In summary, the aspalacZ mouse is an accurate model of CD and an important tool to identify novel aspects of its complex pathology

The Knight of Malta

BACKGROUND: For most women, participation in decision-making during maternity care has a positive impact on their childbirth experiences. Shared decision-making (SDM) is widely advocated as a way to support people in their healthcare choices. The aim of this study was to identify quality criteria and professional competencies for applying shared decision-making in maternity care. We focused on decision-making in everyday maternity care practice for healthy women. METHODS: An international three-round web-based Delphi study was conducted. The Delphi panel included international experts in SDM and in maternity care: mostly midwives, and additionally obstetricians, educators, researchers, policy makers and representatives of care users. Round 1 contained open-ended questions to explore relevant ingredients for SDM in maternity care and to identify the competencies needed for this. In rounds 2 and 3, experts rated statements on quality criteria and competencies on a 1 to 7 Likert-scale. A priori, positive consensus was defined as 70% or more of the experts scoring >/=6 (70% panel agreement). RESULTS: Consensus was reached on 45 quality criteria statements and 4 competency statements. SDM in maternity care is a dynamic process that starts in antenatal care and ends after birth. Experts agreed that the regular visits during pregnancy offer opportunities to build a relationship, anticipate situations and revisit complex decisions. Professionals need to prepare women antenatally for unexpected, urgent decisions in birth and revisit these decisions postnatally. Open and respectful communication between women and care professionals is essential; information needs to be accurate, evidence-based and understandable to women. Experts were divided about the contribution of professional advice in shared decision-making and about the partner's role. CONCLUSIONS: SDM in maternity care is a dynamic process that takes into consideration women's individual needs and the context of the pregnancy or birth. The identified ingredients for good quality SDM will help practitioners to apply SDM in practice and educators to prepare (future) professionals for SDM, contributing to women's positive birth experience and satisfaction with care

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Foul wind, spirits and witchcraft: illness conceptions and health-seeking behaviour for malaria in the Gambia.

BACKGROUND: As the disease burden in the Gambia has reduced considerably over the last decade, heterogeneity in malaria transmission has become more marked, with infected but asymptomatic individuals maintaining the reservoir. The identification, timely diagnosis and treatment of malaria-infected individuals are crucial to further reduce or eliminate the human parasite reservoir. This ethnographic study focused on the relationship between local beliefs of the cause of malaria and treatment itineraries of suspected cases. METHODS: An ethnographic qualitative study was conducted in twelve rural communities in the Upper River Region and the Central River Region in the Gambia. The data collection methods included in-depth interviews, participant observation, informal conversations, and focus group discussions. RESULTS: While at first glance, the majority of people seek biomedical treatment for 'malaria', there are several constraints to seeking treatment at health centres. Certain folk illnesses, such as Jontinooje and Kajeje, translated and interpreted as 'malaria' by healthcare professionals, are often not considered to be malaria by local populations but rather as self-limiting febrile illnesses--consequently not leading to seeking care in the biomedical sector. Furthermore, respondents reported delaying treatment at a health centre while seeking financial resources, and consequently relying on herbal treatments. In addition, when malaria cases present symptoms, such as convulsions, hallucinations and/or loss of consciousness, the illness is often interpreted as having a supernatural aetiology, leading to diagnosis and treatment by traditional healers. CONCLUSION: Although malaria diagnostics and treatment-seeking in the biomedical sector has been reported to be relatively high in the Gambia compared to other sub-Saharan African countries, local symptom interpretation and illness conceptions can delay or stop people from seeking timely biomedical treatment, which may contribute to maintaining a parasite reservoir of undiagnosed and untreated malaria patients

Carotenoids as a Source of Antioxidants in the Diet

Capítulo del libro Caroteids in Nature, que corresponde al volumen 79 de la serie Subcellular BiochemistryCarotenoids, widely distributed fat-soluble pigments, are responsible for the attractive colorations of several fruits and vegetables commonly present in our daily diet. They are particularly abundant in yellow-orange fruits (carrots, tomatoes, pumpkins, peppers, among others) and, although masked by chlorophylls, in dark green leafy vegetables. Several health benefits have been attributed to carotenoids or to foods rich in these pigments, by means of different mechanisms-of-action, including the role as provitamin A of almost 50 different carotenoids and the antioxidant activity that protects cells and tissues from damage of free radicals and singlet oxygen, providing enhancement of the immune function, protection from sunburn reactions and delaying the onset of certain types of cancer. Common food sources and the efficiency of the absorption of carotenoids, analytical approaches used for measurement of their antioxidant effect and an overview of some epidemiological studies that have been performed to assess the beneficial impact of carotenoids in human health are outlined in this chapter.Peer reviewe