Selective amylin antagonist suppresses rise in plasma lactate after intravenous glucose in the rat Evidence for a metabolic role of endogenous amylin

AbstractData presented here provide the first demonstration that circulating amylin regulates metabolism in vivo, and support an endocrine hormonal role that is distinct from its autocrine action at pancreatic islets. When rats were pre-treated with the potent amylin antagonist AC187 (n = 18), and then administered a 2 mmol glucose load, the rise in plasma lactate was less than in rats administered glucose only (n = 27; P < 0.02). When rats were treated so that plasma glucose and insulin profiles were similar (n = 8), the increase in plasma lactate in the presence of AC187 was only 50.3% as high as the increase when AC187 was absent (P < 0.001). These experimental results fit with the view that some of the lactate appearing in plasma after a glucose load comes from insulin-sensitive tissues. The experiments also support the view that an important fraction of the increase in lactate depends on processes inhibited by a selective amylin antagonist, most likely amylin action in muscle

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Enhancing the Tissue Donor Pool through Donation after Death in the Field

Introduction: Tissue transplantation is an important adjunct to modern medical care and is used daily to save or improve patient lives. Tissue allografts include bone, tendon, corneas, heart valves and others. Increasing utilization may lead to tissue shortages, and tissue procurement organizations continue to explore ways to expand the cadaveric donor pool. Currently more than half of all deaths occur outside the acute care setting. Hypothesis: Many who suffer prehospital deaths might be eligible for non-organ tissue donation. Methods: A retrospective review of electronic prehospital medical records was conducted from May 1, 2008 through December 31, 2009. All prehospital deaths were included irrespective of cause. Once identified, additional medical history was obtained from prehospital, inpatient, and emergency department records. Age, medical history, and time of death were compared to exclusion criteria for four tissue procurement organizations (MTF, LifeNet, LifeCell, EyeBank). After analysis, percentages of eligible donors were calculated. Results: Over 50,000 prehospital records were reviewed; 432 subjects died in the field and were eligible for analysis. Ages ranged from four to 103 years of age; the average was 68.3 (SD = 20.1) years. After exclusion for age, medical conditions, and time of death, 185 unique patients (42.8%) were eligible for donation to at least one of the four tissue procurement organizations (range 11.6%-34.3%). Conclusions: After prehospital death, many individuals may be eligible for tissue donation. These findings suggest that future prospective studies exploring tissue donation after prehospital death are indicated. These studies should aim to clarify eligibility criteria, create protocols and infrastructure, and explore the ethical implications of expanding tissue donation to include this population

Problems in young children

Emotional and behaviour problems in preschool children have been found to be common and persistent through early childhood (Richman et al., 1982).They may occur because of difficulties with the interaction of the child’s developmental skills, his temperament and the parenting the child receives. The parenting the child receives will depend on the parenting skills of the parent, which in turn would depend on the parents’ background, knowledge and the style of parenting they received as a child, the parents’ own temperament, emotional health and ‘space’ for parenting.This would depend on the support the parent had for the task of parenting and what other pressures impinge on the parent, e.g. financial and housing pressures

Missense SLC25A38 variations play an important role in autosomal recessive inherited sideroblastic anemia

BACKGROUND: Congenital sideroblastic anemias are rare disorders with several genetic causes; they are characterized by erythroblast mitochondrial iron overload, differ greatly in severity and some occur within a syndrome. The most common cause of non-syndromic, microcytic sideroblastic anemia is a defect in the X-linked 5-aminolevulinate synthase 2 gene but this is not always present. Recently, variations in the gene for the mitochondrial carrier SLC25A38 were reported to cause a non-syndromic, severe type of autosomal-recessive sideroblastic anemia. Further evaluation of the importance of this gene was required to estimate the proportion of patients affected and to gain further insight into the range and types of variations involved. DESIGN AND METHODS: In three European diagnostic laboratories sequence analysis of SLC25A38 was performed on DNA from patients affected by congenital sideroblastic anemia of a non-syndromic nature not caused by variations in the 5-aminolevulinate synthase 2 gene. RESULTS: Eleven patients whose ancestral origins spread across several continents were homozygous or compound heterozygous for ten different SLC25A38 variations causing premature termination of translation (p.Arg117X, p.Tyr109LeufsX43), predicted splicing alteration (c.625G>C; p.Asp209His) or missense substitution (p.Gln56Lys, p.Arg134Cys, p.Ile147Asn, p.Arg187Gln, p.Pro190Arg, p.Gly228Val, p.Arg278Gly). Only three of these variations have been described previously (p.Arg117X, p.Tyr109LeufsX43 and p.Asp209His). All new variants reported here are missense and affect conserved amino acids. Structure modeling suggests that these variants may influence different aspects of transport as described for mutations in other mitochondrial carrier disorders. CONCLUSIONS: Mutations in the SLC25A38 gene cause severe, non-syndromic, microcytic/hypochromic sideroblastic anemia in many populations. Missense mutations are shown to be of importance as are mutations that affect protein production. Further investigation of these mutations should shed light on structure-function relationships in this protein

Home Owners' Loan Corporation Neighborhood Grades Composite Shapefile, Manhattan, 1937

This polygon shapefile represents neighborhood boundaries and Home Owners' Loan Corporation (HOLC) "grades" and notes for major metropolitan areas in Manhattan in 1937. The layer is a polygon rendering of a print map that has been scanned, vectorized, and transcribed by the University of Richmond Digital Scholarship Lab. Using data and evaluations organized by local real estate professionals, lenders, developers, and real estate appraisers in Manhattan, the HOLC assigned "grades" to residential neighborhoods that reflected their "mortgage security" that would then be visualized on color-coded maps. Neighborhoods receiving the highest grade of "A"--colored green on the maps--were deemed minimal risks for banks and other mortgage lenders when they were determining who should received loans and which areas in the city were safe investments. Those receiving the lowest grade of "D," colored red, were considered "hazardous." The creation and circulation of these maps has been widely proven to contribute to the intergenerational oppression of Black Americans and people of color in Manhattan. Refer to the documentation for geoprocessing lineage and more information and visit https://dsl.richmond.edu/panorama/redlining/#loc=5/39.1/-94.58&text=intro/

Home Owners' Loan Corporation Neighborhood Grades Composite Shapefile, United States, 1935

This polygon shapefile represents neighborhood boundaries and Home Owners' Loan Corporation (HOLC) "grades" and notes for major metropolitan areas in the United States in 1935. The layer is a polygon rendering of many print maps that have been scanned, vectorized, and transcribed by the University of Richmond Digital Scholarship Lab. Using data and evaluations organized by local real estate professionals, lenders, developers, and real estate appraisers in each city in the 1930s, the HOLC assigned "grades" to residential neighborhoods that reflected their "mortgage security" that would then be visualized on color-coded maps. Neighborhoods receiving the highest grade of "A"--colored green on the maps--were deemed minimal risks for banks and other mortgage lenders when they were determining who should received loans and which areas in the city were safe investments. Those receiving the lowest grade of "D," colored red, were considered "hazardous." The creation and circulation of these maps has been widely proven to contribute to the intergenerational oppression of Black Americans and people of color in the United States. Refer to the documentation for geoprocessing lineage and more information and visit https://dsl.richmond.edu/panorama/redlining/#loc=5/39.1/-94.58&text=intro/