Transitional Care for Patients with Congenital Colorectal Diseases: An EUPSA Network Office, ERNICA, and eUROGEN Joint Venture

Background: Transition of care (TOC; from childhood into adulthood) of patients with anorectal malformations (ARM) and Hirschsprung disease (HD) ensures continuation of care for these patients. The aim of this international study was to assess the current status of TOC and adult care (AC) programs for patients with ARM and HD. Methods: A survey was developed by members of EUPSA, ERN eUROGEN, and ERNICA, including patient representatives (ePAGs), comprising of four domains: general information, general questions about transition to adulthood, and disease-specific questions regarding TOC and AC programs. Recruitment of centres was done by the ERNs and EUPSA, using mailing lists and social media accounts. Only descriptive statistics were reported. Results: In total, 82 centres from 21 different countries entered the survey. Approximately half of them were ERN network members. Seventy-two centres (87.8%) had a self-reported area of expertise for both ARM and HD. Specific TOC programs were installed in 44% of the centres and AC programs in 31% of these centres. When comparing centres, wide variation was observed in the content of the programs. Conclusion: Despite the awareness of the importance of TOC and AC programs, these programs were installed in less than 50% of the participating centres. Various transition and AC programs were applied, with considerable heterogeneity in implementation, content and responsible caregivers involved. Sharing best practice examples and taking into account local and National Health Care Programs might lead to a better continuation of care in the future. Level of Evidence: III

A review of the systematic biology of fossil and living bony-tongue fishes, Osteoglossomorpha (Actinopterygii: Teleostei)

The bony-tongue fishes, Osteoglossomorpha, have been the focus of a great deal of morphological, systematic, and evolutionary study, due in part to their basal position among extant teleostean fishes. This group includes the mooneyes (Hiodontidae), knifefishes (Notopteridae), the abu (Gymnarchidae), elephantfishes (Mormyridae), arawanas and pirarucu (Osteoglossidae), and the African butterfly fish (Pantodontidae). This morphologically heterogeneous group also has a long and diverse fossil record, including taxa from all continents and both freshwater and marine deposits. The phylogenetic relationships among most extant osteoglossomorph families are widely agreed upon. However, there is still much to discover about the systematic biology of these fishes, particularly with regard to the phylogenetic affinities of several fossil taxa, within Mormyridae, and the position of Pantodon. In this paper we review the state of knowledge for osteoglossomorph fishes. We first provide an overview of the diversity of Osteoglossomorpha, and then discuss studies of the phylogeny of Osteoglossomorpha from both morphological and molecular perspectives, as well as biogeographic analyses of the group. Finally, we offer our perspectives on future needs for research on the systematic biology of Osteoglossomorpha

Common coding variant in SERPINA1 increases the risk for large artery stroke

Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation in LAS by analyzing variants on the HumanExome BeadChip in a total of 3,127 cases and 9,778 controls from Europe, Australia, and South Asia. We report on a nonsynonymous single-nucleotide variant in serpin family A member 1 (SERPINA1) encoding alpha-1 antitrypsin [AAT; p.V213A; P = 5.99E-9, odds ratio (OR) = 1.22] and confirm histone deacetylase 9 (HDAC9) as a major risk gene for LAS with an association in the 3'-UTR (rs2023938; P = 7.76E-7, OR = 1.28). Using quantitative microscale thermophoresis, we show that M1 (A213) exhibits an almost twofold lower dissociation constant with its primary target human neutrophil elastase (NE) in lipoprotein-containing plasma, but not in lipid-free plasma. Hydrogen/deuterium exchange combined with mass spectrometry further revealed a significant difference in the global flexibility of the two variants. The observed stronger interaction with lipoproteins in plasma and reduced global flexibility of the Val-213 variant most likely improve its local availability and reduce the extent of proteolytic inactivation by other proteases in atherosclerotic plaques. Our results indicate that the interplay between AAT, NE, and lipoprotein particles is modulated by the gate region around position 213 in AAT, far away from the unaltered reactive center loop (357-360). Collectively, our findings point to a functionally relevant balance between lipoproteins, proteases, and AAT in atherosclerosis

Continuous measurement of oxygen tensions in the air-breathing organ of Pacific tarpon (Megalops cyprinoides) in relation to aquatic hypoxia and exercise

The original publication can be found at www.springerlink.comThe Pacific tarpon is an elopomorph teleost fish with an air-breathing organ (ABO) derived from a physostomous gas bladder. Oxygen partial pressure (PO(2)) in the ABO was measured on juveniles (238 g) with fiber-optic sensors during exposure to selected aquatic PO(2) and swimming speeds. At slow speed (0.65 BL s(-1)), progressive aquatic hypoxia triggered the first breath at a mean PO(2) of 8.3 kPa. Below this, opercular movements declined sharply and visibly ceased in most fish below 6 kPa. At aquatic PO(2) of 6.1 kPa and swimming slowly, mean air-breathing frequency was 0.73 min(-1), ABO PO(2) was 10.9 kPa, breath volume was 23.8 ml kg(-1), rate of oxygen uptake from the ABO was 1.19 ml kg(-1) min(-1), and oxygen uptake per breath was 2.32 ml kg(-1). At the fastest experimental speed (2.4 BL s(-1)) at 6.1 kPa, ABO oxygen uptake increased to about 1.90 ml kg(-1) min(-1), through a variable combination of breathing frequency and oxygen uptake per breath. In normoxic water, tarpon rarely breathed air and apparently closed down ABO perfusion, indicated by a drop in ABO oxygen uptake rate to about 1% of that in hypoxic water. This occurred at a wide range of ABO PO(2) (1.7-26.4 kPa), suggesting that oxygen level in the ABO was not regulated by intrinsic receptors.Roger S. Seymour, Anthony P. Farrell, Keith Christian, Timothy D. Clark, Michael B. Bennett, Rufus M. G. Wells and John Baldwi

Common coding variant in <em>SERPINA1 </em>increases the risk for large artery stroke.

Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation in LAS by analyzing variants on the HumanExome BeadChip in a total of 3,127 cases and 9,778 controls from Europe, Australia, and South Asia. We report on a nonsynonymous single-nucleotide variant in serpin family A member 1 (SERPINA1) encoding alpha-1 antitrypsin [AAT; p.V213A; P = 5.99E-9, odds ratio (OR) = 1.22] and confirm histone deacetylase 9 (HDAC9) as a major risk gene for LAS with an association in the 3&#39;-UTR (rs2023938; P = 7.76E-7, OR = 1.28). Using quantitative microscale thermophoresis, we show that M1 (A213) exhibits an almost twofold lower dissociation constant with its primary target human neutrophil elastase (NE) in lipoprotein-containing plasma, but not in lipid-free plasma. Hydrogen/deuterium exchange combined with mass spectrometry further revealed a significant difference in the global flexibility of the two variants. The observed stronger interaction with lipoproteins in plasma and reduced global flexibility of the Val-213 variant most likely improve its local availability and reduce the extent of proteolytic inactivation by other proteases in atherosclerotic plaques. Our results indicate that the interplay between AAT, NE, and lipoprotein particles is modulated by the gate region around position 213 in AAT, far away from the unaltered reactive center loop (357-360). Collectively, our findings point to a functionally relevant balance between lipoproteins, proteases, and AAT in atherosclerosis