Longitudinal Study on Metabolic Health in Adults SGA During 5 Years After GH With or Without 2 Years of GnRHa Treatment

BACKGROUND: In children born small for gestational age (SGA) with persistent short stature, 2 years of gonadotropin-releasing hormone analogue (GnRHa), in addition to long-term growth hormone (GH) treatment, can improve adult height. We assessed safety on metabolic and bone health of GnRHa/GH treatment during 5 years after cessation of GH. METHODS: A total of 363 young adults born SGA, previously treated with combined GnRHa/GH or GH-only, were followed for 5 years after attainment of adult height at GH cessation and 2 and 5 years thereafter. Data at 5 years after GH cessation, at age 21 years, were also compared with 145 age-matched adults born appropriate for gestational age (AGA). Frequently sampled intravenous glucose tolerance (FSIGT) tests were used to assess insulin sensitivity, acute insulin response, and β-cell function. Body composition and bone mineral density (BMD) was determined by dual-energy x-ray absorptiometry (DXA) scans. FINDINGS: In the GnRHa/GH and GH-only groups, fat mass increased during the 5 years after GH cessation, but the changes in FSIGT results, body composition, blood pressure, serum lipid levels, and BMD were similar in both groups. At age 21 years, the GnRHa/GH group had similar fat mass, FSIGT results, blood pressure, serum lipid levels and BMD-total body as the GH-only group and the AGA control group, a higher BMD-lumbar spine and lower lean body mass than the AGA control group. INTERPRETATION: This study during 5 years after GH cessation shows that addition of 2 years of GnRHa treatment to long-term GH treatment of children short in stature born SGA has no unfavorable effects on metabolic and bone health in early adulthood. CLINICAL TRIAL REGISTRATION: ISRCTN96883876, ISRCTN65230311 and ISRCTN18062389

10,20-Metanorhodopsins: (7E,9E,13E)-10,20-methanorhodopsin and (7E,9Z,13Z)-10,20-methanorhodopsin: 11-cis-locked rhodopsin analog pigments with unusual thermal and photo-stability

Bio-organic Synthesi

3D fusion of intravascular ultrasound and coronary computed tomography for in-vivo wall shear stress analysis: A feasibility study

Wall shear stress, the force per area acting on the lumen wall due to the blood flow, is an important biomechanical parameter in the localization and progression of atherosclerosis. To calculate shear stress and relate it to atherosclerosis, a 3D description of the lumen and vessel wall is required. We present a framework to obtain the 3D reconstruction of human coronary arteries by the fusion of intravascular ultrasound (IVUS) and coronary computed tomography angiography (CT). We imaged 23 patients with IVUS and CT. The images from both modalities were registered for 35 arteries, using bifurcations as landmarks. The IVUS images together with IVUS derived lumen and wall contours were positioned on the 3D centerline, which was derived from CT. The resulting 3D lumen and wall contours were transformed to a surface for calculation of shear stress and plaque thickness. We applied variations in selection of landmarks and investigated whether these variations influenced the relation between shear stress and plaque thickness. Fusion was successfully achieved in 31 of the 35 arteries. The average length of the fused segments was 36.4 ± 15.7 mm. The length in IVUS and CT of the fused parts correlated excellently (R2= 0.98). Both for a mildly diseased and a very diseased coronary artery, shear stress was calculated and related to plaque thickness. Variations in the selection of the landmarks for these two arteries did not affect the relationship between shear stress and plaque thickness. This new framework can therefore successfully be applied for shear stress analysis in human coronary arteries

Blood pressure in the first 6 hours following endovascular treatment for ischemic stroke is associated with outcome

Background and Purpose: Optimal blood pressure (BP) management in the acute phase of ischemic stroke remains an unresolved issue. It is uncertain whether guidelines for BP management during and after intravenous alteplase can be extrapolated to endovascular treatment (EVT) for stroke due to large artery occlusion in the anterior circulation. We evaluated the associations between systolic BP (SBP) in the first 6 hours following EVT and functional outcome as well as symptomatic intracranial hemorrhage. Methods: Patients of 8 MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry centers, with available data on SBP in the 6 hours following EVT, were analyzed. We evaluated maximum, minimum, and mean SBP. Study outcomes were functional outcome (modified Rankin Scale) at 90 days and symptomatic intracranial hemorrhage. We used multivariable ordinal and binary regression analysis to adjust for important prognostic factors and studied possible effect modification by successful reperfusion. Results: Post-EVT SBP data were available for 1161/1796 patients. Higher maximum SBP (per 10 mm Hg increments) was associated with worse functional outcome (adjusted common odds ratio, 0.93 [95% CI, 0.88-0.98]) and a higher rate of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.17 [95% CI, 1.02-1.36]). The association between minimum SBP and functional outcome was nonlinear with an inflection point at 124 mm Hg. Minimum SBP lower and higher than the inflection point were associated with worse functional outcomes (adjusted common odds ratio, 0.85 per 10 mm Hg decrements [95% CI, 0.76-0.95] and adjusted common odds ratio, 0.81 per 10 mm Hg increments [95% CI, 0.71-0.92]). No association between mean SBP and functional outcome was observed. Successful reperfusion did not modify the relation of SBP with any of the outcomes. Conclusions: Maximum SBP in the first 6 hours following EVT is positively associated with worse functional outcome and an increased risk of symptomatic intracranial hemorrhage. Both lower and higher minimum SBP are associated with worse outcomes. A randomized trial to evaluate whether modifying post-intervention SBP results in better outcomes after EVT for ischemic stroke seems justified.Neuro Imaging Researc

Levels of explanation in biological psychology

Until recently, the notions of function and multiple realization were supposed to save the autonomy of psychological explanations. Furthermore, the concept of supervenience presumably allows both dependence of mind on brain and non-reducibility of mind to brain, reconciling materialism with an independent explanatory role for mental and functional concepts and explanations. Eliminativism is often seen as the main or only alternative to such autonomy. It gladly accepts abandoning or thoroughly reconstructing the psychological level, and considers reduction if successful as equivalent with elimination. In comparison with the philosophy of mind, the philosophy of biology has developed more subtle and complex ideas about functions, laws, and reductive explanation than the stark dichotomy of autonomy or elimination. It has been argued that biology is a patchwork of local laws, each with different explanatory interests and more or less limited scope. This points to a pluralistic, domain-specific and multi-level view of explanations in biology. Explanatory pluralism has been proposed as an alternative to eliminativism on the one hand and methodological dualism on the other hand. It holds that theories at different levels of description, like psychology and neuroscience, can co-evolve, and mutually influence each other, without the higher-level theory being replaced by, or reduced to, the lower-level one. Such ideas seem to tally with the pluralistic character of biological explanation. In biological psychology, explanatory pluralism would lead us to expect many local and non-reductive interactions between biological, neurophysiological, psychological and evolutionary explanations of mind and behavior. This idea is illustrated by an example from behavioral genetics, where genetics, physiology and psychology constitute distinct but interrelated levels of explanation. Accounting for such a complex patchwork of related explanations seems to require a more sophisticated and precise way of looking at levels than the existing ideas on (reductive and non-reductive) explanation in the philosophy of mind

Clinically relevant potential drug-drug interactions in intensive care patients: a large retrospective observational multicenter study

Purpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. Materials & methods: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. Results: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when con -sidering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. Conclusions: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients. ? 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study

Purpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. Materials & methods: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. Results: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. Conclusions: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness