Pharmacological and Parenteral Nutrition-Based Interventions in Microvillus Inclusion Disease

Microvillus inclusion disease (MVID) is a rare inherited and invariably fatal enteropathy, characterized by severe intractable secretory diarrhea and nutrient malabsorption. No cure exists, and patients typically die during infancy because of treatment-related complications. The need for alternative treatment strategies is evident. Several pharmacological interventions with variable successes have been tried and reported for individual patients as part of their clinical care. Unfortunately, these interventions and their outcomes have remained hidden in case reports and have not been reviewed. Further, recent advances regarding MVID pathogenesis have shed new light on the outcomes of these pharmacological interventions and offer suggestions for future clinical research and trials. Hence, an inventory of reported pharmacological interventions in MVID, their rationales and outcomes, and a discussion of these in the light of current knowledge is opportune. Together with a discussion on MVID-specific pharmacokinetic, -dynamic, and -genetic concerns that pose unique challenges regarding pharmacological strategies, we envision that this paper will aid researchers and clinicians in their efforts to develop pharmacological interventions to combat this devastating disease

Fathers today: design of a randomized controlled trial examining the role of oxytocin and vasopressin in behavioral and neural responses to infant signals

BACKGROUND: Previous research has mostly focused on the hormonal, behavioral and neural correlates of maternal caregiving. We present a randomized, double-blind, placebo-controlled within-subject design to examine the effects of intranasal administration of oxytocin and vasopressin on parenting behavior and the neural and behavioral responses to infant cry sounds and infant threat. In addition, we will test whether effects of oxytocin and vasopressin administration are moderated by fathers' early childhood experiences. METHODS: Fifty-five first-time fathers of a child between two and seven months old will participate in three experimental sessions with intervening periods of one to two weeks. Participants self-administer oxytocin, vasopressin or a placebo. Infant-father interactions and protective parenting responses are observed during play. Functional Magnetic Resonance Imaging (fMRI) is used to examine the neural processing of infant cry sounds and infant threat. A handgrip dynamometer is used to measure use of handgrip force when listening to infant cry sounds. Participants report on their childhood experiences of parental love-withdrawal and abuse and neglect. DISCUSSION: The results of this study will provide important insights into the hormonal, behavioral and neural correlates of fathers' parenting behavior during the early phase of fatherhood. TRIAL REGISTRATION: Dutch Trial Register: NTR (ID: NL8124); Date registered: October 30, 2019

Oxytocin Receptor Gene Associated with the Efficiency of Social Auditory Processing

Oxytocin has been shown to facilitate social aspects of sensory processing, thereby enhancing social communicative behaviors and empathy. Here we report that compared to the AA/AG genotypes, the presumably more efficient GG genotype of an oxytocin receptor gene polymorphism (OXTR rs53576) that has previously been associated with increased sensitivity of social processing is related to less self-reported difficulty in hearing and understanding people when there is background noise. The present result extends associations between oxytocin and social processing to the auditory and vocal domain. We discuss the relevance of our findings for autistic spectrum disorders (ASD), as ASD seems related to specific impairments in the orienting to, and selection of speech sounds from background noise, and some social processing impairments in patients with ASD have been found responsive to oxytocin treatment

Interface formation in K doped poly(dialkoxy-p-phenylene vinylene) light-emitting diodes

Manufacturing of Al/K/OC1C10 poly(p-phenylene vinylene)/indium–tin–oxide light emitting diode structures by physical vapor deposition of K onto the emissive polymer layer has been characterized by electroluminescence and ion spectroscopy. Varying the deposited K areal density from 3.9×1012 to 1.2×1014 atoms cm−2 the external efficiency rises from 0.01 to 1.2 Cd A−1. Spectra obtained by ion scattering analysis demonstrate the overall absence of K at the polymer outermost surface layer, and diffusion up to a depth of 200 Å. Depth profiles have been derived, and were modeled using an irreversible first order “trapping” reaction. Trapping may stem from confinement of the electron at a conjugated segment, that was donated through charge transfer typical for alkali/π-conjugated systems. This study demonstrates that evaporation of low work function metals onto organic systems should not be depicted as simple layered stacking structures. The enhanced electroluminescence with submonolayer K deposition is attributed to the shift of the recombination zone away from the Al cathode, which is demonstrated to prevail over the known exciton quenching mechanism due to the formation of gap states

Influence of a partially oxidized calcium cathode on the performance of polymeric light emitting diodes

We investigated the influence of the presence of oxygen during the deposition of the calcium cathode on the structure and on the performance of polymeric light emitting diodes (pLEDs). The oxygen background pressure during deposition of the calcium cathode of polymeric LEDs was varied. Subsequently, the oxygen depth distribution was measured and correlated with the performance of the pLEDs. The devices have been fabricated in a recently built ultraclean setup. The polymer layers of the pLEDs have been spincoated in a dry nitrogen atmosphere and transported directly into an ultrahigh vacuum chamber where the metal electrodes have been deposited by evaporation. We used indium–tin–oxide as anode, OC1C10 PPV as electroluminescent polymer, calcium as cathode, and aluminum as protecting layer. We achieved reproducibility of about 15% in current and brightness for devices fabricated in an oxygen atmosphere of less than or equal to 10 -9 mbar. For further investigations the calcium deposition was carried out in an oxygen atmosphere from 10 -8 to 10 -5 mbar. We determined the amount of oxygen in the different layers of the current–voltage-light characterized pLEDs with elastic recoil detection analysis and correlated it with the characteristics of the devices. The external efficiency of the pLEDs decreases continuously with increasing oxygen pressure, the current shows a pronounced minimum. The brightness mostly decreases with increasing oxygen with an indication of a slight minimum. PLEDs with completely oxidized calcium are not operational. The first contact of the pLEDs with the dry glove box environment leads to an immediate reduction of current and brightness which is caused by the cooling of the devices by several degrees. Determining reproducible characteristics of pLEDs in the vacuum requires the measurement of their temperature

Reaction-diffusion model for the preparation of polymer gratings by patterned ultraviolet illumination

A model is developed to describe the migration mechanism of monomers during the lithographic preparation of polymer gratings by ultraviolet polymerization. The model is based on the Flory–Huggins theory: a thermodynamic theory that deals with monomer/polymer solutions. During the photoinduced polymerization process, monomer migration is assumed to be driven by a gradient in the chemical potential rather than the concentration. If the chemical potential is used as the driving force, monomer migration is not only driven by a difference in concentration, or volume fraction, but also by other entropic effects such as monomer size and the degree of crosslinking of the polymer network, which is related to the ability of a polymer to swell. Interaction of the monomers with each other or the polymer is an additional energetic term in the chemical potential. The theoretical background of the model is explained and results of simulations are compared with those of nuclear microprobe measurements. A nuclear microprobe is used to determine the spatial monomer distribution in the polymer gratings. It is shown that two-way diffusion is expected if the monomers are both difunctional and have the same size. In some cases, if one monomer is considerably smaller than the other, it can eventually have a higher concentration in the illuminated regions, even when it has a lower reactivity. The model is used to simulate the grating formation process. This results in a calculated distribution of the monomer volume fractions as a function of position in polymer gratings. An excellent agreement with the nuclear microprobe measurements is obtained. ©2004 American Institute of Physics

Complex Housing, but Not Maternal Deprivation Affects Motivation to Liberate a Trapped Cage-Mate in an Operant Rat Task.

Early life environment influences the development of various aspects of social behavior, particularly during sensitive developmental periods. We studied how challenges in the early postnatal period or (early) adolescence affect pro-social behavior. To this end, we designed a lever-operated liberation task, to be able to measure motivation to liberate a trapped conspecific (by progressively increasing required lever pressing for door-opening). Liberation of the trapped rat resulted either in social contact or in liberation into a separate compartment. Additionally, a condition was tested in which both rats could freely move in two separate compartments and lever pressing resulted in social contact. When partners were not trapped, rats were more motivated to press the lever for opening the door than in either of the trapped configurations. Contrary to our expectations, the trapped configuration resulted in a reduced motivation to act. Early postnatal stress (24 h maternal deprivation on postnatal day 3) did not affect behavior in the liberation task. However, rearing rats from early adolescence onwards in complex housing conditions (Marlau cages) reduced the motivation to door opening, both in the trapped and freely moving conditions, while the motivation for a sucrose reward was not affected