Clinical Meaningfulness in Alzheimer's Disease Clinical Trials. A Report from the EU-US CTAD Task Force.

Recent positive results of three phase III anti-amyloid monoclonal antibody trials are transforming the landscape of disease-modifying therapeutics for Alzheimer's disease, following several decades of failures. Indeed, all three trials have met their primary endpoints. However, the absolute size of the benefit measured in these trials has generated a debate on whether the change scores observed on clinical outcome assessments represent a clinically meaningful benefit to patients.

Molecular Pathways and Animal Models of Atrioventricular Septal Defect.

The development of a fully functional four-chambered heart is critically dependent on the correct formation of the structures that separate the atrial and ventricular chambers. Perturbation of this process typically results in defects that allow mixing of oxygenated and deoxygenated blood. Atrioventricular septal defects (AVSD) form a class of congenital heart malformations that are characterized by the presence of a primary atrial septal defect (pASD), a common atrioventricular valve (cAVV), and frequently also a ventricular septal defect (VSD).

Inflow Tract Development.

The development of the inflow tract is undoubtedly one of the most complex remodeling events in the formation of the four-chambered heart. It involves the creation of two separate atrial chambers, the formation of an atrial/atrioventricular (AV) septal complex, the incorporation of the caval veins and coronary sinus into the right atrium, and the remodeling events that result in pulmonary venous return draining into the left atrium. In these processes, the atrioventricular mesenchymal complex, consisting of the major atrioventricular (AV) cushions, the mesenchymal cap on the primary atrial septum (pAS), and the dorsal mesenchymal protrusion (DMP), plays a crucial role.

The significance of BAP1 and MTAP/CDKN2A expression in well-differentiated papillary mesothelial tumour: a series of 21 cases and a review of the literature.

The nomenclature and diagnostic criteria of well-differentiated papillary mesothelial tumour (WDPMT) have been changed in the 2021 World Health Organization (WHO) classification of thoracic tumours, and a new entity, mesothelioma in situ (MIS), introduced. Histologically these two entities may be similar. However, MIS is regarded as a precursor to invasive mesothelioma and requires demonstration of loss of BAP1 and/or MTAP/CDKN2A for diagnosis, whereas performance of these ancillary tests is desirable but not essential for a diagnosis of WDPMT, in which the significance of BAP1 and/or MTAP/CDKN2A loss is not well understood or well defined.

Sugars and Polyols of Natural Origin as Carriers for Solubility and Dissolution Enhancement.

Crystalline carriers such as dextrose, sucrose, galactose, mannitol, sorbitol, and isomalt have been reported to increase the solubility, and dissolution rates of poorly soluble drugs when employed as carriers in solid dispersions (SDs). However, synthetic polymers dominate the preparation of drugs: excipient SDs have been created in recent years, but these polymer-based SDs exhibit the major drawback of recrystallisation upon storage. Also, the use of high-molecular-weight polymers with increased chain lengths brings forth problems such as increased viscosity and unnecessary bulkiness in the resulting dosage form.

Epicardial deletion of Sox9 leads to myxomatous valve degeneration and identifies Cd109 as a novel gene associated with valve development.

Epicardial-derived cells (EPDCs) are involved in the regulation of myocardial growth and coronary vascularization and are critically important for proper development of the atrioventricular (AV) valves. SOX9 is a transcription factor expressed in a variety of epithelial and mesenchymal cells in the developing heart, including EPDCs. To determine the role of SOX9 in epicardial development, an epicardial-specific Sox9 knockout mouse model was generated.

Modeling of thin-film interference filters on structured substrates: microfacet-based BSDF versus ray tracing.

We compare two model approaches for the ray optical description of PV modules with coloring based on an interference layer system on the inside of the cover glass. The light scattering is described by a microfacet-based bidirectional scattering distribution function (BSDF) model on the one hand and ray tracing on the other hand. We show that the microfacet-based BSDF model is largely sufficient for the structures used in the context of the MorphoColor application.

Effects of a pre- and probiotic mixture and an autogenous vaccine on growth performance in newly weaned piglets experimentally challenged with an enterotoxigenic strain.

Beneficial effects of pro- and prebiotics in weanling piglets are of great interest in livestock production. Similarly, the use of specific vaccines is of interest as alternative to antibiotics to reduce postweaning performance losses. The aim of this study was the assessment of the effect of a dual-strain probiotic ( and ) and a prebiotic (fructo-oligosaccharides) as well as the additional vaccination with an autogenous inactivated vaccine on the performance of newly weaned piglets after experimental infection with an enterotoxigenic Forty piglets at the age of 28 d were randomly allotted to one of five groups: nonchallenged control (NC); challenged positive control (PC); challenged and vaccinated (CV); challenged and diet supplemented with pre- and probiotic mix (CM) and challenged, diet supplemented with pro- and prebiotic mix and vaccinated (CMV).

Dietary fiber and its role in performance, welfare, and health of pigs.

Dietary fiber (DF) is receiving increasing attention, and its importance in pig nutrition is now acknowledged. Although DF for pigs was frowned upon for a long time because of reductions in energy intake and digestibility of other nutrients, it has become clear that feeding DF to pigs can affect their well-being and health. This review aims to summarize the state of knowledge of studies on DF in pigs, with an emphasis on the underlying mode of action, by considering research using DF in sows as well as suckling and weaned piglets, and fattening pigs.

Impact of dietary supplementation of l-Arginine, l-Glutamine, and the combination of both on nursing performance of multiparous sows.

Dietary supplementation with arginine (Arg) or glutamine (Gln) has been considered as an option to improve nursing performance in reproductive sows. This study investigated whether a low-level supplementation of Arg or Gln or a blend of both could modify milk nutrients and improve piglets' growth beyond weaning. Seventy-two multiparous sows were assigned to four groups: one group fed a control diet, three treatment groups fed the control diet supplemented with either 0.

Clostridioides difficile-mesocolonic oedema in neonatal suckling piglets develops regardless of the fibre composition in sow's diets.

Maternal dietary factors have been reported to influence Clostridioides difficile colonisation in the offspring. Twenty suckling piglets from sows fed diets supplemented with high-fermentable sugar beet pulp (SBP) or low-fermentable lignocellulose (LNC) fibres during gestation and lactation were dissected in the first week after birth. Postmortem analysis included clinical mesocolon and faecal scoring, concentration of C.

Disease progression model using the integrated Alzheimer's Disease Rating Scale.

Introduction: An Alzheimer's disease (AD) dementia disease progression model was developed based on the integrated Alzheimer's Disease Rating Scale (iADRS).

Methods: Data from 3483 placebo participants in six AD trials were used to develop the disease progression model with NONMEM (version 7.4.

Sox9 Expression in the Second Heart Field; A Morphological Assessment of the Importance to Cardiac Development with Emphasis on Atrioventricular Septation.

Failure to form the septal structures that separate the left and right cardiac chambers results in defects that allow shunting of blood from one side of the heart to the other, leading to the mixing of oxygenated and de-oxygenated blood. The atrioventricular (AV) mesenchymal complex, consisting of the AV cushions, the Dorsal Mesenchymal Protrusion (DMP), and the mesenchymal cap, plays a crucial role in AV septation. Cells found in these structures derive from different cell lineages.

Digital spacer data driven COPD inhaler adherence education: The OUTERSPACE proof-of-concept study.

Pressurized metered dose inhalers are recommended to be used in combination with spacers, yet inhaler technique and adherence are poor. A novel digital "smart" spacer can record spacer use and technique errors and could facilitate personalized education. In this proof-of-concept study, we assessed the usability of the digital spacer and explored its effects on inhaler technique, adherence, long-term systemic drug exposure and clinical outcomes in COPD.

Influence of the Gut Microbiome on Feed Intake of Farm Animals.

With the advancement of microbiome research, the requirement to consider the intestinal microbiome as the "last organ" of an animal emerged. Through the production of metabolites and/or the stimulation of the host's hormone and neurotransmitter synthesis, the gut microbiota can potentially affect the host's eating behavior both long and short-term. Based on current evidence, the major mediators appear to be short-chain fatty acids (SCFA), peptide hormones such as peptide YY (PYY) and glucagon-like peptide-1 (GLP-1), as well as the amino acid tryptophan with the associated neurotransmitter serotonin, dopamine and γ-Aminobutyrate (GABA).

Outcomes of hospitalised patients with hyperkalaemia at a South African tertiary healthcare centre.

Background: Hyperkalaemia is a common electrolyte disorder in hospitalised patients. There is a lack of data from Africa on the prevalence, causes and outcomes of patients with hyperkalaemia. We aimed to identify the frequency of hyperkalaemia in hospitalised adults, and to identify any risk factors for in-hospital death.

Demonstration of Clinical Meaningfulness of the Integrated Alzheimer's Disease Rating Scale (iADRS): Association Between Change in iADRS Scores and Patient and Caregiver Health Outcomes.

Background: The integrated Alzheimer's Disease Rating Scale (iADRS) is a validated cognitive/functional composite that effectively captures cognitive and functional decline over a broad spectrum of disease. The clinical meaningfulness of change on iADRS can be supported by establishing an association with changes on important health outcome measures.

Objective: To evaluate the relationship between change on the iADRS and changes in health outcomes in individuals with mild cognitive impairment (MCI) due to Alzheimer's disease (AD), or mild or moderate AD dementia using placebo data from four AD clinical trials and data from one AD observational study.

Integrated Alzheimer's Disease Rating Scale: Clinically meaningful change estimates.

Introduction: The Integrated Alzheimer's Disease Rating Scale (iADRS) has been used to detect differences in disease progression in early Alzheimer's disease (AD). The objectives of this study were to enhance understanding of iADRS point changes within the context of clinical trials, and to establish a minimal clinically important difference (MCID) on the iADRS.

Methods: Data from AMARANTH and EXPEDITION3 were analyzed using various approaches, including anchor-based, distribution-based, regression analyses, and cumulative distribution function (CDF) plots.

Modeling the optical properties of Morpho-inspired thin-film interference filters on structured surfaces.

We present a method for modeling the optical properties of interference layer systems on structured surfaces as used in the MorphoColor technology for coloring integrated photovoltaic modules. By combining a microfacet-based bidirectional scattering distribution function model with a transfer matrix formalism, we can simulate the spectrally resolved reflection and transmission properties of the system in good agreement with measurement data. To consider the MorphoColor technology in an overall optical system and compare the application on the front side of the module glass with the application in the composite, the model is additionally combined with a formalism called Optical Properties of Textured Optical Sheets.

Extending the viability of human precision-cut intestinal slice model for drug metabolism studies.

Human Precision-cut intestinal slices (hPCIS) are used to study intestinal physiology, pathophysiology, drug efficacy, toxicology, kinetics, and metabolism. However, the use of this ex vivo model is restricted to approximately a 24 h timeframe because of declining viability of the hPCIS during traditional culture. We hypothesized that we could extend the hPCIS viability by using organoid medium.

Fiber Composition in Sows' Diets Modifies Clostridioides difficile Colonization in Their Offspring.

Dietary fiber has a potential to modulate the gut microbiota in sows. We hypothesized that a maternal diet rich in either high- or low-fermentable fiber during gestation and lactation influences Clostridioides difficile gut colonization in suckling piglets. Twenty sows were fed gestation and lactation diets enriched with either high-fermentable sugar beet pulp (SBP) or low-fermentable lignocellulose (LNC) fibers.