Application of Quantitative Systems Pharmacology Approaches to Support Pediatric Labeling in Rare Diseases.

Quantitative Systems Pharmacology (QSP) models offer a promising approach to extrapolate drug efficacy across different patient populations, particularly in rare diseases. Unlike conventional empirical models, QSP models can provide a mechanistic understanding of disease progression and therapeutic response by incorporating current disease knowledge into the descriptions of biomarkers and clinical endpoints. This allows for a holistic representation of the disease and drug response.

VIVALDI ASCOT and Ethnography Study: protocol for a mixed-methods longitudinal study to evaluate the impact of COVID-19 and other respiratory infection outbreaks on care home residents' quality of life and psychosocial well-being.

Introduction: Older adults in care homes experienced some of the highest rates of mortality from SARS-CoV-2 globally and were subjected to strict and lengthy non-pharmaceutical interventions, which severely impacted their daily lives. The VIVALDI ASCOT and Ethnography Study aims to assess the impact of respiratory outbreaks on care home residents' quality of life, psychological well-being, loneliness, functional ability and use of space. This study is linked to the VIVALDI-CT, a randomised controlled trial of staff's asymptomatic testing and sickness payment support in care homes (ISRCTN13296529).

Shaping care home COVID-19 testing policy: a protocol for a pragmatic cluster randomised controlled trial of asymptomatic testing compared with standard care in care home staff (VIVALDI-CT).

Introduction: Care home residents have experienced significant morbidity, mortality and disruption following outbreaks of SARS-CoV-2. Regular SARS-CoV-2 testing of care home staff was introduced to reduce transmission of infection, but it is unclear whether this remains beneficial. This trial aims to investigate whether use of regular asymptomatic staff testing, alongside funding to reimburse sick pay for those who test positive and meet costs of employing agency staff, is a feasible and effective strategy to reduce COVID-19 impact in care homes.

A qualitative process evaluation using the behaviour change wheel approach: Did a whole genome sequence report form (SRF) used to reduce nosocomial SARS-CoV-2 within UK hospitals operate as anticipated?

Purpose: The aim of this study was to conduct a process evaluation of a whole-genome sequence report form (SRF) used to reduce nosocomial SARS-CoV-2 through changing infection prevention and control (IPC) behaviours within the COVID-19 pandemic.

Methods: We used a three-staged design. Firstly, we described and theorized the purported content of the SRF using the behaviour change wheel (BCW).

Burial of microplastics in freshwater sediments facilitated by iron-organo flocs.

Microplastics are ubiquitous in standing freshwater bodies, consequently lakes and reservoirs may be important sinks for these contaminants. However, the mechanisms governing the deposition of microplastics and their interactions with the sediments are understudied. We demonstrate how aggregation-based transport facilitates the sinking and infiltration of buoyant microplastics into freshwater reservoir sediments by employing experiments with intact sediment cores.

Interaction of cyanobacteria with calcium facilitates the sedimentation of microplastics in a eutrophic reservoir.

Low-density microplastics are frequently found in sediments of many lakes and reservoirs. The processes leading to sedimentation of initially buoyant polymers are poorly understood for inland waters. This study investigated the impact of biofilm formation and aggregation on the density of buoyant polyethylene microplastics.

A Quantitative Systems Pharmacology Model of Gaucher Disease Type 1 Provides Mechanistic Insight Into the Response to Substrate Reduction Therapy With Eliglustat.

Gaucher's disease type 1 (GD1) leads to significant morbidity and mortality through clinical manifestations, such as splenomegaly, hematological complications, and bone disease. Two types of therapies are currently approved for GD1: enzyme replacement therapy (ERT), and substrate reduction therapy (SRT). In this study, we have developed a quantitative systems pharmacology (QSP) model, which recapitulates the effects of eliglustat, the only first-line SRT approved for GD1, on treatment-naïve or patients with ERT-stabilized adult GD1.

Biofouling, metal sorption and aggregation are related to sinking of microplastics in a stratified reservoir.

Microplastic particles entering aquatic systems are rapidly colonized by microbial biofilms. The presence of microbial biomass may cause sinking of particles and as a consequence prevent their transport to the oceans. We studied microbial colonization of different polymer particles exposed in the epi-, meta- and hypolimnion of a freshwater reservoir during late summer for 47 days.

Emergence of localized patterns in globally coupled networks of relaxation oscillators with heterogeneous connectivity.

Oscillations in far-from-equilibrium systems (e.g., chemical, biochemical, biological) are generated by the nonlinear interplay of positive and negative feedback effects operating at different time scales.

Human Anti-Lipopolysaccharid (LPS) antibodies against Legionella with high species specificity.

Legionella are Gram-negative bacteria that are ubiquitously present in natural and man-made water reservoirs. When humans inhale aerosolized water contaminated with Legionella, alveolar macrophages can be infected, which may lead to a life-threatening pneumonia called Legionnaires' disease. Due to the universal distribution of Legionella in water and their potential threat to human health, the Legionella concentration in water for human use must be strictly monitored, which is difficult since the standard detection still relies on lengthy cultivation and analysis of bacterial morphology.

A morphological analysis of the transition between the embryonic primitive intestine and yolk sac in bovine embryos and fetuses.

The yolk sac (YS) is the main source of embryonic nutrition during the period when the placenta has not yet formed. It is also responsible for hematopoiesis because the blood cells develop from it as part of the primitive embryonic circulation. The objective of this study was to characterize the transitional area between the YS and primitive gut using the techniques of light microscopy, transmission electron microscopy, and immunohistochemistry to detect populations of pluripotent cells by labeling with Oct4 antibody.

Somatic cell nuclear transfer is associated with altered expression of angiogenic factor systems in bovine placentomes at term.

Low efficiency of somatic cell cloning by nuclear transfer has been associated with alterations of placental vascular architecture. Placental growth and function depend on the growth of blood vessels; VEGF-A and bFGF are the most important factors controlling neovascularization and vascular permeability in the placenta. We hypothesize that the VEGF-A and bFGF systems are disrupted in placentomes from cloned animals, contributing to the placental abnormalities that are common in these clones.

Morpho-physical recording of bovine conceptus (Bos indicus) and placenta from days 20 to 70 of pregnancy.

The study is based on 141 pregnant Bos indicus cows, from days 20 to 70 post-insemination. First, special attention was given to the macroscopically observable phenomena of attachment of the conceptus to the uterus, i.e.

Immunohistochemical localization of oestrogen receptors alpha and beta, progesterone receptor and aromatase in the equine placenta.

The functions of placental oestrogens during equine pregnancy are still unclear. Yet, they may act predominantly as local regulators of growth and differentiation in the microplacentomes. Thus, expression patterns of oestrogen receptors (ERs) alpha and beta were investigated in the microcotyledonary placenta from pregnant mares at 110, 121, 179, 199 and 309 days of gestation by immunohistochemistry.

Influence of the magnesium aspartate hydrochloride administration to the maternal circuit on the aspartate concentration of the fetal circuit under in vitro perfusion of human placenta.

Objectives: Magnesium aspartate hydrochloride (Magnesiocard, Mg-Asp-HCl) is proposed as a substitute of magnesium sulfate for the treatment of preeclampsia and premature labor. After an i.v.

Evaluation of differences between breeds for substance P, vasoactive intestinal polypeptide, and neurofilament 200 in the abomasal wall of cattle.

Objective: To compare the content of substance P, vasoactive intestinal polypeptide, and neurofilament 200 in biopsy specimens taken from the abomasal wall of healthy cows of 2 breeds.

Sample Population: Biopsy specimens taken from different sites of the abomasal wall from 20 German Holstein cows and 20 German Fleckvieh cows.

Procedures: Biopsy specimens were examined immunohistochemically, and the content of substance P, vasoactive intestinal polypeptide, and neurofilament 200 was determined by measuring the immunoreactive areas.

Gross and microscopic anatomy of the pineal gland in Nasua nasua--coati (Linnaeus, 1766).

Nasua nasua, coati, is a mammal of the Carnivora order and Procyonidae family. It lives in bands composed of females and young males. The pineal gland or epiphysis of brain is endocrine, producing the melatonin.

Psittacine beak and feather disease infected cells show a pattern of apoptosis in psittacine skin.

Skin biopsies from 23 birds with psittacine beak and feather disease (PBFD) were examined by light and electron microscopy. Affected cells, preferentially found in the cell layers of the feather follicles, could be clearly identified by the presence of intracytoplasmic virus inclusion bodies. Ultrastructurally, the degenerative process in these cells was morphologically suggestive of apoptosis.

Integrin activation in bovine placentomes and in caruncular epithelial cells isolated from pregnant cows.

In the bovine synepitheliochorial placenta, restricted trophoblast invasion requires complex interactions of integrin receptors with proteins of the extracellular matrix (ECM) and integrin receptors of neighboring cells. Activated integrins assemble to focal adhesions and are linked to the actin cytoskeleton via signaling molecules including alpha-actinin (ACTN), focal adhesion kinase (PTK2 or FAK), phosphotyrosine, and talin (TLN1). Aims of this study were to assess integrin activation and focal adhesion assembly within epithelial cells of bovine placentomes and low-passage (not transformed) placentomal caruncular epithelial cells cultured on dishes coated with ECM proteins.

Histological changes of the feline cervix, endometrium and placenta after mid-gestational termination of pregnancy with aglepristone.

This study was conducted to investigate endometrial and placental structural changes that occurred in response to mid-gestational termination of pregnancy in queens using aglepristone, a progesterone receptor antagonist. Thirteen European Shorthair pregnant queens were either treated with aglepristone (10 mg/kg body weight; subcutaneously) twice on days 25 and 26 after first mating (am; group I; n = 9), or remained untreated and served as control (group II; n = 4). Queens of group I were ovariohysterectomized between days 30 and 41 am, either at the onset (n = 3) or during (n = 1) abortion and 12 h (n = 1), 24 h (n = 3) or 10 days after abortion (n = 1).

Light and scanning electron microscopic study on the blood vascular system of the donkey placenta.

The donkey placenta is diffuse and epitheliochorial with numerous microplacentomes consisting of a fetal microcotyledonary and a maternal microcaruncular part. The microplacentomal vasculature during the last third of pregnancy has been investigated by light microscopy in comparison to scanning electron microscopy of the materno-fetal contact surface and corrosion casts of blood vessels after plastic instillation from either the microcotyledonary or the microcaruncular side, and, for the first time in a perissodactyle, from both sides. Morphological data were semiquantitatively evaluated.

Bovine caruncular epithelial cell line (BCEC-1) isolated from the placenta forms a functional epithelial barrier in a polarised cell culture model.

In the bovine synepitheliochorial placenta key sites of fetal-maternal interaction are placentomes consisting of maternal caruncles interdigitating with fetal cotyledons. The aim of this study was to establish an epithelial cell line from caruncles of pregnant cows and to develop a model to study restricted trophoblast invasion, pathogenesis of pregnancy associated diseases and pathways of infection and transport. Primary epithelial cells were isolated, successfully subcultured for 32 passages and cryopreserved at various stages.

Development of an in vitro model for bovine placentation: a comparison of the in vivo and in vitro expression of integrins and components of extracellular matrix in bovine placental cells.

Background/aims: Interaction of trophoblastic integrins with the extracellular matrix plays a role in embryo implantation and trophoblast invasion. The phenomenon of restricted trophoblast invasion, observed in the bovine epitheliochorial placenta offers intriguing conditions to study invasive processes. The migration of bovine trophoblast giant cells is accompanied by the expression of specific integrins and corresponding extracellular matrix ligands.

Validation of primary epitheloid cell cultures isolated from bovine placental caruncles and cotyledons.

In order to study feto-maternal interactions in the bovine synepitheliochorial placenta primary cell cultures of both placentomal components throughout pregnancy, namely caruncular epithelial cells and trophoblast cells were developed. The aim of this study was to validate and improve a method to culture caruncular epithelial cells and fetal trophoblast from manually separated placentomes. Prior to seeding the presence of fetal cells in caruncular samples and vice-versa could be demonstrated by the detection of the Y-chromosome via fluorescence in situ hybridization (FISH) provided the fetus was male.

Age-dependent changes in the pigeon bursa of Fabricius vasculature: a comparative study using light microscopy and scanning electron microscopy of vessel casts.

The present study was carried out to analyse the vascularization of the pigeon bursa cloacalis of Fabricius and to determine whether it undergoes age-dependent changes during its functionally most important growth period after hatching of the pigeon. Morphological assessment of vascular corrosion casts, studied qualitatively and quantitatively, was applied for the first time to investigate the vascularization of the pigeon pigeon bursa of Fabricius. This also allowed us to analyse the microvasculature and morphological aspects of the vessel interrelationships as occurring in the natural state.