A Phase 1, Open-Label, Randomized, Two-Part Study in Healthy Adult Volunteers to Evaluate the Bioavailability of the Maribavir Powder for Oral Suspension, as Well as Food Effect and Impact of Rabeprazole.

The relative bioavailability and impact of food and the proton pump inhibitor rabeprazole on the pharmacokinetics of a maribavir powder-for-oral-suspension formulation was investigated in a Phase 1 open-label study in healthy adult volunteers. A single 200-mg maribavir dose was administered as the commercial tablet (Treatment A), powder formulation (Treatment B), or powder formulation with a high-fat/high-calorie meal (Treatment C) in Part 1, and as the powder formulation alone (Treatment D) or following administration of rabeprazole 20 mg once daily for 5 days (Treatment E) in Part 2. Maribavir maximum plasma concentration following Treatment B was 18% lower versus Treatment A, whereas the area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration or infinity were similar.

The good, the bad, and the unknown nature of decreased GD3 synthase expression.

This paper explores the physiological consequences of decreased expression of GD3 synthase (GD3S), a biosynthetic enzyme that catalyzes the synthesis of b-series gangliosides. GD3S is a key factor in tumorigenesis, with overexpression enhancing tumor growth, proliferation, and metastasis in various cancers. Hence, inhibiting GD3S activity has potential therapeutic effects due to its role in malignancy-associated pathways across different cancer types.

Dragonflies (Odonata) as bioindicators of radioactivity.

Bioindicators are living organisms that are successfully used for monitoring changes in the environmental health due to natural and/or anthropogenic influences. Dragonflies (Odonata) are considered to be good indicators of water quality; however, research on dragonflies as potential indicators of radioactivity is scarce. The aim of this study was to evaluate dragonflies as potential biological indicators of ionising radiation in nature by measuring Cs activity concentrations in the dragonfly and river water samples.

The Correlation between Cardiac Magnetic Resonance Findings and Post-COVID-19: The Impact of Myocardial Injury on Quality of Life.

Background: In the post-COVID-19 era, there is growing concern regarding its impact on cardiovascular health and the following effects on the overall quality of life of affected individuals. This research seeks to investigate cardiac magnetic resonance (CMR) findings following COVID-19 and their impact on the quality of life of affected individuals.

Methods: An observational, cross-sectional study was conducted in consecutive patients with persistent cardiovascular symptoms after COVID-19 who were referred to CMR due to suspected myocardial injury.

Effect of Food, Crushing of Tablets, and Antacid Coadministration on Maribavir Pharmacokinetics in Healthy Adult Participants: Results From 2 Phase 1, Open-Label, Randomized, Crossover Studies.

The effect of food composition, tablet crushing, and antacid coadministration on maribavir pharmacokinetics was assessed in 2 Phase 1 studies in healthy adults. In the first, a single maribavir 400-mg dose was administered under fasting conditions, with a low-fat/low-calorie or a high-fat/high-calorie meal. In the second, a single maribavir 100-mg dose was administered under fasting conditions, as a crushed tablet, or as a whole tablet alone or with an antacid.

Science-based evidence on pathways and effects of human exposure to micro- and nanoplastics.

Human exposure to plastic particles has raised great concern among all relevant stakeholders involved in the protection of human health due to the contamination of the food chain, surface waters, and even drinking water as well as due to their persistence and bioaccumulation. Now more than ever, it is critical that we understand the biological fate of plastics and their interaction with different biological systems. Because of the ubiquity of plastic materials in the environment and their toxic potential, it is imperative to gain reliable, regulatory-relevant, science-based data on the effects of plastic micro- and nanoparticles (PMNPs) on human health in order to implement reliable risk assessment and management strategies in the circular economy of plastics.

Physiologically Based Pharmacokinetic Modeling for Maribavir to Inform Dosing in Drug-Drug Interaction Scenarios with CYP3A4 Inducers and Inhibitors.

Maribavir, an orally available antiviral agent, has been approved in multiple countries for the treatment of patients with refractory post-transplant cytomegalovirus (CMV) infection and/or disease. Maribavir is primarily metabolized by CYP3A4; coadministration with CYP3A4 inducers and inhibitors may significantly alter maribavir exposure, thereby affecting its efficacy and safety. The effect of CYP3A4 inducers and inhibitors on maribavir exposure was evaluated based on a drug-drug interaction (DDI) study and physiologically-based pharmacokinetic (PBPK) modeling.

Mental Imagery in Dreams of Congenitally Blind People.

It is unclear to what extent the absence of vision affects the sensory sensitivity for oneiric construction. Similarly, the presence of visual imagery in the mentation of dreams of congenitally blind people has been largely disputed. We investigate the presence and nature of oneiric visuo-spatial impressions by analysing 180 dreams of seven congenitally blind people identified from the online database DreamBank.

SLUG and SNAIL as Potential Immunohistochemical Biomarkers for Renal Cancer Staging and Survival.

Renal cell carcinoma (RCC) is the deadliest urological neoplasm. Up to date, no validated biomarkers are included in clinical guidelines for the screening and follow up of patients suffering from RCC. Slug (Snail2) and Snail (Snail1) belong to the Snail superfamily of zinc finger transcriptional factors that take part in the epithelial-mesenchymal transition, a process important during embryogenesis but also involved in tumor progression.

Sex differences in alpha-synucleinopathies: a systematic review.

Background: Past research indicates a higher prevalence, incidence, and severe clinical manifestations of alpha-synucleinopathies in men, leading to a suggestion of neuroprotective properties of female sex hormones (especially estrogen). The potential pathomechanisms of any such effect on alpha-synucleinopathies, however, are far from understood. With that aim, we undertook to systematically review, and to critically assess, contemporary evidence on sex and gender differences in alpha-synucleinopathies using a bench-to-bedside approach.

Visuo-spatial imagery in dreams of congenitally and early blind: a systematic review.

Background: The presence of visual imagery in dreams of congenitally blind people has long been a matter of substantial controversy. We set to systematically review body of published work on the presence and nature of oneiric visuo-spatial impressions in congenitally and early blind subjects across different areas of research, from experimental psychology, functional neuroimaging, sensory substitution, and sleep research.

Methods: Relevant studies were identified using the following databases: EMBASE, MEDLINE and PsychINFO.

Pharmacokinetics and Safety Evaluation of Maribavir in Healthy Japanese and Matched White Participants: A Phase 1, Open-Label Study.

This phase I study compared pharmacokinetics and safety of maribavir in Japanese and White participants, and evaluated dose proportionality in Japanese participants. Under fasting conditions, 12 healthy adult participants of Japanese descent and 12 matched White participants received a single 400-mg dose of maribavir. Japanese participants received 2 further doses of maribavir: 200 mg and 800 mg, or 800 mg and 200 mg, separated by a ≥72-hour washout period.

Mortality of Malignant Melanoma in Central Serbia, in the Period 1999-2015.

Introduction: Malignant melanoma is one of the rarest forms of skin cancer but it is the most deadly.

Objective: The objective of this paper was to analyze the epidemiological characteristics and trends of mortality from malignant melanoma in the population of Central Serbia in the period 1999-2015.

Methods: The study was designed as a retrospective descriptive epidemiological study.

An In Vitro Dosimetry Tool for the Numerical Transport Modeling of Engineered Nanomaterials Powered by the Enalos RiskGONE Cloud Platform.

A freely available "in vitro dosimetry" web application is presented enabling users to predict the concentration of nanomaterials reaching the cell surface, and therefore available for attachment and internalization, from initial dispersion concentrations. The web application is based on the distorted grid (DG) model for the dispersion of engineered nanoparticles (NPs) in culture medium used for in vitro cellular experiments, in accordance with previously published protocols for cellular dosimetry determination. A series of in vitro experiments for six different NPs, with Ag and Au cores, are performed to demonstrate the convenience of the web application for calculation of exposure concentrations of NPs.

Toxicity of nanomixtures to human macrophages: Joint action of silver and polystyrene nanoparticles.

Increasing use of nano-enabled products provides many benefits in various industrial processes and medical applications, but it also raises concern about release of nanoparticles (NPs) into the environment and subsequent human exposure. While potential toxicity of individual NPs types has been well described in scientific literature, exposure and health-related effects of nanomixtures has been poorly described. This study aimed to evaluate the combined effect of silver (AgNP) and polystyrene NPs (PSNP) on the human macrophages.

Maribavir Pharmacokinetics and Safety in Participants With Moderate Hepatic Impairment: A Phase 1, Open-Label, Single-Dose, Parallel Group Study.

Maribavir, an orally bioavailable antiviral, has shown superior activity against posttransplant cytomegalovirus infection compared with conventional antivirals. It is primarily metabolized in the liver. This open-label, single-center study evaluated the effect of hepatic impairment on the pharmacokinetics of maribavir in nontransplant participants.

Start Me Up: How Can Surrounding Gangliosides Affect Sodium-Potassium ATPase Activity and Steer towards Pathological Ion Imbalance in Neurons?

Gangliosides, amphiphilic glycosphingolipids, tend to associate laterally with other membrane constituents and undergo extensive interactions with membrane proteins in or configurations. Studies of human diseases resulting from mutations in the ganglioside biosynthesis pathway and research on transgenic mice with the same mutations implicate gangliosides in the pathogenesis of epilepsy. Gangliosides are reported to affect the activity of the Na/K-ATPase, the ubiquitously expressed plasma membrane pump responsible for the stabilization of the resting membrane potential by hyperpolarization, firing up the action potential and ion homeostasis.

NLRP1 Inflammasome Activation in the Hippocampal Formation in Alzheimer's Disease: Correlation with Neuropathological Changes and Unbiasedly Estimated Neuronal Loss.

Neuroinflammation is one of the core pathological features of Alzheimer's disease (AD) as both amyloid β (Aβ) and tau monomers and oligomers can trigger the long-term pro-inflammatory phenotype of microglial cells with consequent overactivation of the inflammasomes. To investigate the NLRP1 inflammasome activation in AD, we analyzed the expression of NLRP1, ASC, cleaved gasdermin (cGSDMD), and active caspase-6 (CASP-6) proteins in each hippocampal subdivision (hilar part of CA3, CA2/3, CA1, subiculum) of postmortem tissue of 9 cognitively healthy controls (HC) and 11 AD patients whose disease duration varied from 3 to 7 years after the clinical diagnosis. The total number of neurons, along with the total number of neurofibrillary tangles (NFTs), were estimated in Nissl- and adjacent modified Bielschowsky-stained sections, respectively, using the optical disector method.

Gangliosidome of a Human Hippocampus in Temporal Lobe Epilepsy Resolved by High-Resolution Tandem Mass Spectrometry.

In this study, we developed a high-resolution tandem mass spectrometry (HR MS) approach to assess presumed changes in gangliosidome of a human hippocampus affected by temporal lobe epilepsy (TLE) in comparison with a normal hippocampus. Gangliosides, membrane glycolipids, are particularly diverse and abundant in the human brain, and participate in ion transport and modulation of neuronal excitability. Changes in structural ganglioside pattern potentially linked to TLE molecular pathogenesis have not been explored in detail.

Imaging mass spectrometry differentiates the effects of doxorubicin formulations on non-targeted tissues.

Administration of cytotoxic agents like doxorubicin (DOX) is restrained by the effects on different non-targeted/non-cancerous tissues, which instigates the development of nano-enabled drug delivery systems, among others. In this study, imaging mass spectrometry (IMS) was selected to examine the effects of DOX nanoformulations on non-targeted tissues. Chemical alterations induced by liposomal (LPS) and poly (lactic--glycolic acid) (PLG) nanoformulations were assessed against the ones induced by the conventional (CNV) formulation.

Cytotoxicity of nanomixture: Combined action of silver and plastic nanoparticles on immortalized human lymphocytes.

Background: Silver nanoparticles (AgNP) are one of the most commercialized types of nanomaterials, with a wide range of applications owing to their antimicrobial activity. They are particularly important in hospitals and other healthcare settings, where they are used to maintain sterility of surfaces, textiles, catheters, medical implants, and more. However, AgNP can not only harm bacteria, but also damage mammalian cells and tissue.

Relevance of sleep and associated structural changes in GBA1 mouse to human rapid eye movement behavior disorder.

Rapid eye movement (REM) sleep behaviour disorder (RBD) is a REM parasomnia that often predicts the later occurrence of alpha-synucleinopathies. Variants in the gene encoding for the lysosomal enzyme glucocerebrosidase, GBA, strongly increase the risk of RBD. In a GBA1-mouse model recently shown to mimic prodromal stages of α-synucleinopathy, we now demonstrate striking REM and NREM electroencephalographic sleep abnormalities accompanied by distinct structural changes in the more widespread sleep neurocircuitry.