Transcriptome sequencing reveals two subtypes of cortisol-secreting adrenocortical tumours in dogs and identifies CYP26B1 as a potential new therapeutic target

Cushing's syndrome (CS) is a serious endocrine disorder that is relatively common in dogs, but rare in humans. In ~15%–20% of cases, CS is caused by a cortisol-secreting adrenocortical tumour (csACT). To identify differentially expressed genes that can improve prognostic predictions after surgery and represent novel treatment targets, we performed RNA sequencing on csACTs (n = 48) and normal adrenal cortices (NACs; n = 10) of dogs. A gene was declared differentially expressed when the adjusted p-value was 2 or < −2. Between NACs and csACTs, 98 genes were differentially expressed. Based on the principal component analysis (PCA) the csACTs were separated in two groups, of which Group 1 had significantly better survival after adrenalectomy (p =.002) than Group 2. Between csACT Group G1 and Group 2, 77 genes were differentially expressed. One of these, cytochrome P450 26B1 (CYP26B1), was significantly associated with survival in both our canine csACTs and in a publicly available data set of 33 human cortisol-secreting adrenocortical carcinomas. In the validation cohort, CYP26B1 was also expressed significantly higher (p =.012) in canine csACTs compared with NACs. In future studies it would be interesting to determine whether CYP26B1 inhibitors could inhibit csACT growth in both dogs and humans

Locational memory of macrovessel vascular cells is transcriptionally imprinted

Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems

Clinical practice: neonatal resuscitation. A Dutch consensus

The updated Dutch guidelines on Neonatal Resuscitation assimilate the latest evidence in neonatal resuscitation. Important changes with regard to the 2004 guidelines and controversial issues concerning neonatal resuscitation are reviewed, and recommendations for daily practice are provided and argued in the context of the ILCOR 2005 consensus

Increase in treatment of retinopathy of prematurity in the Netherlands from 2010 to 2017

Purpose: Compare patients treated for Retinopathy of Prematurity (ROP) in two consecutive periods. Methods: Retrospective inventory of anonymized neonatal and ophthalmological data of all patients treated for ROP from 2010 to 2017 in the Netherlands, subdivided in period (P)1: 1-1-2010 to 31-3-2013 and P2: 1-4-2013 to 31-12-2016. Treatment characteristics, adherence to early treatment for ROP (ETROP) criteria, outco

Umbilical artery perforation: A potentially life-threatening complication of umbilical artery catheterisation

Umbilical artery catheterisation is frequently performed in preterm or critically ill newborn infants for invasive monitoring of blood pressure and blood sampling for laboratory tests. It is associated with well-known complications like catheter-related infections, thromboembolic events and aneurysmal formation of the aorta. In this report, we present another major complication of umbilical artery catheterisation: Umbilical artery perforation. This complication occurred in a prematurely born infant and resulted in severe haemorrhagic shock, subsequent renal failure and severe periventricular leukomalacia. Ultimately, the patient deceased 3 weeks after birth. Review of the literature identified only a few case reports and retrospective postmortem studies describing this complication. Neonatologists and paediatricians performing umbilical artery catheterisation should be aware of this rare, but potentially life-threatening complication

Umbilical artery perforation: a potentially life-threatening complication of umbilical artery catheterisation

Umbilical artery catheterisation is frequently performed in preterm or critically ill newborn infants for invasive monitoring of blood pressure and blood sampling for laboratory tests. It is associated with well-known complications like catheter-related infections, thromboembolic events and aneurysmal formation of the aorta. In this report, we present another major complication of umbilical artery catheterisation: umbilical artery perforation. This complication occurred in a prematurely born infant and resulted in severe haemorrhagic shock, subsequent renal failure and severe periventricular leukomalacia. Ultimately, the patient deceased 3 weeks after birth. Review of the literature identified only a few case reports and retrospective postmortem studies describing this complication. Neonatologists and paediatricians performing umbilical artery catheterisation should be aware of this rare, but potentially life-threatening complicatio

The prognostic value of NIRS in preterm infants with (suspected) late-onset sepsis in relation to long term outcome: A pilot study

Late-onset sepsis is frequently seen in preterm infants and is associated with poor neurodevelopmental outcome. White matter damage is proposed as substrate of poor outcome, with contributing factors as regional hypoxia and effects of cytokines on oligodendrocytes. We investigated the relation between cerebral oxygenation during (suspected) late-onset sepsis and neurodevelopmental outcome. Prospective cohort study, including preterm infants (gestational age <32 weeks and/or birthweight <1500 grams) with (suspected) late-onset sepsis underwent NIRS registration during the first 72 hours of suspected late-onset sepsis. At two years corrected age neurodevelopment was scored using the Bayley Scales of Infant Development-II. Thirty-two infants were included. Twenty-seven infants were identified with proven late-onset sepsis and five infants had clinical sepsis without positive blood culture. In this study, late-onset sepsis was predominantly caused by coagulase negative staphylococci (CoNS) (72%). All NIRS values were within normal limits. No association was found between NIRS and impaired neurodevelopmental outcome (n = 4) at corrected age two years: composite cognitive score 105 (80–115), composite motor score 103 (82–118) (median and range). In this pilot study, late-onset sepsis (predominantly caused by CoNS with a relatively mild clinical course), was not associated with aberrant NIRS values, nor with impaired neurodevelopmental outcome. Further research might establish our findings and elucidate effects of other micro-organisms on cerebral perfusion

La Babel étudiante

Conçue au lendemain de la Première Guerre mondiale pour répondre aux besoins de logements étudiants à Paris, et pour satisfaire aux critères de construction hygiénistes du tournant du siècle, la Cité internationale universitaire de Paris accueille entre-deux-guerres jusqu'à 2 400 étudiants par an, d'une trentaine de nationalités. Investie dès l'origine par les pouvoirs publics français d'une double mission, elle a vocation à attirer en France les flux d'étudiants en mobilité que se disputent alors les capitales européennes, et à faire germer, en amont de la récente Société des Nations, les graines du pacifisme genevois et de la coopération au sein de l'élite d'une jeunesse mondiale en formation. Mais l'ensemble de ses acteurs français et étrangers (universitaires et étudiants, parlementaires et diplomates, mécènes et philanthropes, architectes) n'y projette pas les mêmes ambitions ni les mêmes desseins. À travers l'étude croisée des discours et pratiques de ces acteurs multiples, rapportés à leurs itinéraires et à leurs positions sociales, et par la restitution de moments-clés de consensus affichés ou de dissonances, le présent ouvrage, issu d'un colloque international, dresse le bilan des travaux existants et, à partir de nouvelles sources, entend ouvrir des perspectives de recherche. Consacré aux premières décennies d'existence d'une institution aujourd'hui presque centenaire, il invite à considérer cet objet complexe comme un espace social transnational, marqué par les tensions qui courent de sa fondation au début des années 1950, entre logiques impériales et nationales, et logiques internationalistes

Evaluation of a real-time PCR assay for detection and quantification of bacterial DNA directly in blood of preterm neonates with suspected late-onset sepsis

Background: Rapid and accurate diagnosis of neonatal sepsis is highly warranted because of high associated morbidity and mortality. The aim of this study was to evaluate the performance of a novel multiplex PCR assay for diagnosis of late-onset sepsis and to investigate the value of bacterial DNA load (BDL) determination as a measure of infection severity. Methods: This cross-sectional study was conducted in a neonatal intensive care unit. Preterm and/or very low birth weight infants suspected for late-onset sepsis were included. Upon suspicion of sepsis, a whole blood sample was drawn for multiplex PCR to detect the eight most common bacteria causing neonatal sepsis, as well as for blood culture. BDL was determined in episodes with a positive multiplex PCR. Results: In total, 91 episodes of suspected sepsis were investigated, and PCR was positive in 53 (58%) and blood culture in 60 (66%) episodes, yielding no significant difference in detection rate (p = 0.17). Multiplex PCR showed a sensitivity of 77%, specificity of 81%, positive predictive value of 87%, and negative predictive value of 68% compared with blood culture. Episodes with discordant results of PCR and blood culture included mainly detection of coagulase-negative staphylococci (CoNS). C-reactive protein (CRP) level and immature to total neutrophil (I/T) ratio were lower in these episodes, indicating less severe disease or even contamination. Median BDL was high (4.1 log10 cfu Eq/ml) with a wide range, and was it higher in episodes with a positive blood culture than in those with a negative blood culture (4.5 versus 2.5 log10 cfu Eq/ml; p < 0.0001). For CoNS infection episodes BDL and CRP were positively associated (p = 0.004), and for Staphylococcus aureus infection episodes there was a positive association between BDL and I/T ratio (p = 0.049). Conclusions: Multiplex PCR provides a powerful assay to enhance rapid identification of the causative pathogen in late-onset sepsis. BDL measurement may be a useful indicator of severity of infection

Characterization of Endothelial and Smooth Muscle Cells From Different Canine Vessels

Vasculature performs a critical function in tissue homeostasis, supply of oxygen and nutrients, and the removal of metabolic waste products. Vascular problems are implicated in a large variety of pathologies and accurate in vitro models resembling native vasculature are of great importance. Unfortunately, existing in vitro models do not sufficiently reflect their in vivo counterpart. The complexity of vasculature requires the examination of multiple cell types including endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), as well as vessel location in the body from which they originate. The use of canine blood vessels provides a way to study vasculature with similar vessel size and physiology compared to human vasculature. We report an isolation procedure that provides the possibility to isolate both the endothelial and smooth muscle cells from the same vessels simultaneously, enabling new opportunities in investigating vasculature behavior. Canine primary ECs and VSMCs were isolated from the vena cava, vena porta and aorta. All tissue sources were derived from three donors for accurate comparison and to reduce inter-animal variation. The isolation and purification of the two distinct cell types was confirmed by morphology, gene- and protein-expression and function. As both cell types can be derived from the same vessel, this approach allows accurate modeling of vascular diseases and can also be used more widely, for example, in vascular bioreactors and tissue engineering designs. Additionally, we identified several new genes that were highly expressed in canine ECs, which may become candidate genes for novel EC markers. In addition, we observed transcriptional and functional differences between arterial- and venous-derived endothelium. Further exploration of the transcriptome and physiology of arteriovenous differentiation of primary cells may have important implications for a better understanding of the fundamental behavior of the vasculature and pathogenesis of vascular disease