Contraversive neglect? A modulation of visuospatial neglect in association with contraversive pushing

Objective: Contraversive pushing (CP) is a neurologic disorder characterized by a lateral postural imbalance. Pusher patients actively push toward their contralesional side due to a misperception of the body's orientation in relation to gravity. Although not every patient with CP suffers from spatial neglect (SN), both phenomena are highly correlated in right-hemispheric patients. The present study investigates whether peripersonal visuospatial functioning differs in neglect patients with versus without CP (NP+ vs. NP+ patients). Method: Eighteen right-hemispheric stroke patients with SN were included, of which 17 in a double-blind case-control study and 1 single case with posterior pushing to supplement the discourse. A computer-based visuospatial navigation task, in which lateralized deviation can freely emerge, was used to quantify visuospatial behavior. In addition, visuospatial orienting was monitored using line bisection. Results: Significant intergroup differences were found. The NP+ patients demonstrated a smaller ipsilesional navigational deviation and more cross-over (contralesional instead of ipsilesional deviation) in long line bisection. As such, they demonstrated a contraversive (contralesionally directed) shift in comparison with the NP+ patients. Conclusions: These findings highlight the similarity between 2 systems of space representation. They are consistent with a coherence between the neural processing system that mainly provides for postural control, and the one responsible for nonpredominantly postural, visuospatial behavior

A Characterization of right coideals of quotient type and its application to classification of Poisson boundaries

Let $G$ be a co-amenable compact quantum group. We show that a right coideal of $G$ is of quotient type if and only if it is the range of a conditional expectation preserving the Haar state and is globally invariant under the left action of the dual discrete quantum group. We apply this result to theory of Poisson boundaries introduced by Izumi for discrete quantum groups and generalize a work of Izumi-Neshveyev-Tuset on $SU_q(N)$ for co-amenable compact quantum groups with the commutative fusion rules. More precisely, we prove that the Poisson integral is an isomorphism between the Poisson boundary and the right coideal of quotient type by maximal quantum subgroup of Kac type. In particular, the Poisson boundary and the quantum flag manifold are isomorphic for any q-deformed classical compact Lie group.Comment: 28 pages, Remark 4.9 adde

The Potential of Stem Cell Therapy to Repair White Matter Injury in Preterm Infants: Lessons Learned From Experimental Models

Diffuse white matter injury (dWMI) is a major cause of morbidity in the extremely preterm born infant leading to life-long neurological impairments, including deficits in cognitive, motor, sensory, psychological, and behavioral functioning. At present, no treatment options are clinically available to combat dWMI and therefore exploration of novel strategies is urgently needed. In recent years, the pathophysiology underlying dWMI has slowly started to be unraveled, pointing towards the disturbed maturation of oligodendrocytes (OLs) as a key mechanism. Immature OL precursor cells in the developing brain are believed to be highly sensitive to perinatal inflammation and cerebral oxygen fluctuations, leading to impaired OL differentiation and eventually myelination failure. OL lineage development under normal and pathological circumstances and the process of (re)myelination have been studied extensively over the years, often in the context of other adult and pediatric white matter pathologies such as stroke and multiple sclerosis (MS). Various studies have proposed stem cell-based therapeutic strategies to boost white matter regeneration as a potential strategy against a wide range of neurological diseases. In this review we will discuss experimental studies focusing on mesenchymal stem cell (MSC) therapy to reduce white matter injury (WMI) in multiple adult and neonatal neurological diseases. What lessons have been learned from these previous studies and how can we translate this knowledge to application of MSCs for the injured white matter in the preterm infant? A perspective on the current state of stem cell therapy will be given and we will discuss different important considerations of MSCs including cellular sources, timing of treatment and administration routes. Furthermore, we reflect on optimization strategies that could potentially reinforce stem cell therapy, including preconditioning and genetic engineering of stem cells or using cell-free stem cell products, to optimize cell-based strategy for vulnerable preterm infants in the near future

Dose-linearity of the pharmacokinetics of an intravenous [C-14]midazolam microdose in children

Aims Drug disposition in children may vary from adults due to age-related variation in drug metabolism. Microdose studies present an innovation to study pharmacokinetics (PK) in paediatrics; however, they should be used only when the PK is dose linear. We aimed to assess dose linearity of a [C-14]midazolam microdose, by comparing the PK of an intravenous (IV) microtracer (a microdose given simultaneously with a therapeutic midazolam dose), with the PK of a single isolated microdose. Methods Preterm to 2-year-old infants admitted to the intensive care unit received [C-14]midazolam IV as a microtracer or microdose, followed by dense blood sampling up to 36 hours. Plasma concentrations of [C-14]midazolam and [C-14]1-hydroxy-midazolam were determined by accelerator mass spectrometry. Noncompartmental PK analysis was performed and a population PK model was developed. Results Of 15 infants (median gestational age 39.4 [range 23.9-41.4] weeks, postnatal age 11.4 [0.6-49.1] weeks), 6 received a microtracer and 9 a microdose of [C-14]midazolam (111 Bq kg(-1); 37.6 ng kg(-1)). In a 2-compartment PK model, bodyweight was the most significant covariate for volume of distribution. There was no statistically significant difference in any PK parameter between the microdose and microtracer, nor in the area under curve ratio [C-14]1-OH-midazolam/[C-14]midazolam, showing the PK of midazolam to be linear within the range of the therapeutic and microdoses. Conclusion Our data support the dose linearity of the PK of an IV [C-14]midazolam microdose in children. Hence, a [C-14]midazolam microdosing approach may be used as an alternative to a therapeutic dose of midazolam to study developmental changes in hepatic CYP3A activity in young children

Dose-linearity of the pharmacokinetics of an intravenous [C-14]midazolam microdose in children

Aims Drug disposition in children may vary from adults due to age-related variation in drug metabolism. Microdose studies present an innovation to study pharmacokinetics (PK) in paediatrics; however, they should be used only when the PK is dose linear. We aimed to assess dose linearity of a [C-14]midazolam microdose, by comparing the PK of an intravenous (IV) microtracer (a microdose given simultaneously with a therapeutic midazolam dose), with the PK of a single isolated microdose. Methods Preterm to 2-year-old infants admitted to the intensive care unit received [C-14]midazolam IV as a microtracer or microdose, followed by dense blood sampling up to 36 hours. Plasma concentrations of [C-14]midazolam and [C-14]1-hydroxy-midazolam were determined by accelerator mass spectrometry. Noncompartmental PK analysis was performed and a population PK model was developed. Results Of 15 infants (median gestational age 39.4 [range 23.9-41.4] weeks, postnatal age 11.4 [0.6-49.1] weeks), 6 received a microtracer and 9 a microdose of [C-14]midazolam (111 Bq kg(-1); 37.6 ng kg(-1)). In a 2-compartment PK model, bodyweight was the most significant covariate for volume of distribution. There was no statistically significant difference in any PK parameter between the microdose and microtracer, nor in the area under curve ratio [C-14]1-OH-midazolam/[C-14]midazolam, showing the PK of midazolam to be linear within the range of the therapeutic and microdoses. Conclusion Our data support the dose linearity of the PK of an IV [C-14]midazolam microdose in children. Hence, a [C-14]midazolam microdosing approach may be used as an alternative to a therapeutic dose of midazolam to study developmental changes in hepatic CYP3A activity in young children

COPD care delivery pathways in five European Union countries : mapping and health care professionals' perceptions

Background: COPD is among the leading causes of chronic morbidity and mortality in the European Union with an estimated annual economic burden of €25.1 billion. Various care pathways for COPD exist across Europe leading to different responses to similar problems. Determining these differences and the similarities may improve health and the functioning of health services. Objective: The aim of this study was to compare COPD patients’ care pathway in five European Union countries including England, Ireland, the Netherlands, Greece, and Germany and to explore health care professionals’ (HCPs) perceptions about the current pathways. Methods: HCPs were interviewed in two stages using a qualitative, semistructured email interview and a face-to-face semistructured interview. Results: Lack of communication among different health care providers managing COPD and comorbidities was a common feature of the studied care pathways. General practitioners/family doctors are responsible for liaising between different teams/services, except in Greece where this is done through pulmonologists. Ireland and the UK are the only countries with services for patients at home to shorten unnecessary hospital stay. HCPs emphasized lack of communication, limited resources, and poor patient engagement as issues in the current pathways. Furthermore, no specified role exists for pharmacists and informal carers. Conclusion: Service and professional integration between care settings using a unified system targeting COPD and comorbidities is a priority. Better communication between health care providers, establishing a clear role for informal carers, and enhancing patients’ engagement could optimize current care pathways resulting in a better integrated system

Successful Use of [14C]Paracetamol Microdosing to Elucidate Developmental Changes in Drug Metabolism

Background: We previously showed the practical and ethical feasibility of using [14C]-microdosing for pharmacokinetic studies in children. We now aimed to show that this approach can be used to elucidate developmental changes in drug metabolism, more specifically, glucuronidation and sulfation, using [14C]paracetamol (AAP). Methods: Infants admitted to the intensive care unit received a single oral [14C]AAP microdose while receiving intravenous therapeutic AAP every 6 h. [14C]AAP pharmacokinetic parameters were estimated. [14C]AAP and metabolit

Pediatric Microdose Study of [14C]Paracetamol to Study Drug Metabolism Using Accelerated Mass Spectrometry: Proof of Concept

Results: Ten infants (aged 0.1–83.1 months) were included; one was excluded as he vomited shortly after administration. In nine patients, [14C]AAP and metabolites in blood samples were detectable at expected concentrations: median (range) maximum concentration (Cmax) [14C]AAP 1.68 (0.75–4.76) ng/L, [14C]AAP-Glu 0.88 (0.34–1.55) ng/L, and [14C]AAP-4Sul 0.81 (0.29–2.10) ng/L. Dose-normalized oral [14C]AAP Cmax approached median intravenous average concentrations (Cav): 8.41 mg/L (3.75–23.78 mg/L) and 8.87 mg/L (3.45–12.9 mg/L), respectively.Conclusions: We demonstrate the feasibility of using a [14C]labeled microdose to study AAP pharmacokinetics, including metabolite disposition, in young children.Background: Pediatric drug development is hampered by practical, ethical, and scientific challenges. Microdosing is a promising new method to obtain pharmacokinetic data in children with minimal burden and minimal risk. The use of a labeled oral microdose offers the added benefit to study intestinal and hepatic drug disposition in children already receiving an intravenous therapeutic drug dose for clinical reasons.Methods: In an open-label microdose pharmacokinetic pilot study, infants (0–6 years of age) received a single oral [14C]AAP microdose (3.3 ng/kg, 60 Bq/kg) in addition to intravenous therapeutic doses of AAP (15 mg/kg intravenous every 6 h). Blood samples were taken from an indwelling catheter. AAP blood concentrations were measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and [14C]AAP and metabolites ([14C]AAP-Glu and [14C]AAP-4Sul) were measured by accelerator mass spectrometry.Objective: The objective of this study was to present pilot data of an oral [14C]paracetamol [acetaminophen (AAP)] microdosing study as proof of concept to study developmental pharmacokinetics in children