Exploring fluorinated heptose phosphate analogues as inhibitors of HldA and HldE, key enzymes in the biosynthesis of lipopolysaccharide.

The growing threat of bacterial resistance to antibiotics has led to the rise of anti-virulence strategies as a promising approach. These strategies aim to disarm bacterial pathogens and improve their clearance by the host immune system. Lipopolysaccharide, a key virulence factor in Gram-negative bacteria, has been identified as a potential target for anti-virulence agents.

Monitoring postures and motions of hospitalized patients using sensor technology: a scoping review.

Background: Sensor technology could provide solutions to monitor postures and motions and to help hospital patients reach their rehabilitation goals with minimal supervision. Synthesized information on device applications and methodology is lacking.

Objectives: The purpose of this scoping review was to provide an overview of device applications and methodological approaches to monitor postures and motions in hospitalized patients using sensor technology.

[The Medical Informatics Initiative at a glance-establishing a health research data infrastructure in Germany].

The Medical Informatics Initiative (MII) funded by the Federal Ministry of Education and Research (BMBF) 2016-2027 is successfully laying the foundations for data-based medicine in Germany. As part of this funding, 51 new professorships, 21 junior research groups, and various new degree programs have been established to strengthen teaching, training, and continuing education in the field of medical informatics and to improve expertise in medical data sciences. A joint decentralized federated research data infrastructure encompassing the entire university medical center and its partners was created in the form of data integration centers (DIC) at all locations and the German Portal for Medical Research Data (FDPG) as a central access point.

Deconvolving Passive and Active Targeting of Liposomes Bearing LDL Receptor Binding Peptides Using the Zebrafish Embryo Model.

Improving target versus off-target ratio in nanomedicine remains a major challenge for increasing drug bioavailability and reducing toxicity. Active targeting using ligands on nanoparticle surfaces is a key approach but has limited clinical success. A potential issue is the integration of targeting ligands also changes the physicochemical properties of nanoparticles (passive targeting).

Stroke patients' motivation for home-based upper extremity rehabilitation with eHealth tools.

Purpose: eHealth-based exercise therapies were developed to increase stroke patients' adherence to home-based motor rehabilitation. However, these eHealth tools face a rapid decrease in use after a couple of weeks. This study investigates stroke patients' motivation for home-based upper extremity rehabilitation with eHealth tools and their relation with Basic Psychological Needs.

Validation of the Activ8 Activity Monitor for Monitoring Postures, Motions, Transfers, and Steps of Hospitalized Patients.

Sedentary behaviors and low physical activity among hospitalized patients have detrimental effects on health and recovery. Wearable activity monitors are a promising tool to promote mobilization and physical activity. However, existing devices have limitations in terms of their outcomes and validity.

Mild Stroke, Serious Problems: Limitations in Balance and Gait Capacity and the Impact on Fall Rate, and Physical Activity.

Background: After mild stroke persistent balance limitations may occur, creating a risk factor for fear of falling, falls, and reduced activity levels. To investigate whether individuals in the chronic phase after mild stroke show balance and gait limitations, elevated fall risk, reduced balance confidence, and physical activity levels compared to healthy controls.

Methods: An observational case-control study was performed.

Daily patterns of fatigue after subarachnoid haemorrhage: an ecological momentary assessment study.

Objective: To examine the daily course of, and factors associated with, momentary fatigue after subarachnoid haemorrhage, and to explore subgroups of patients with distinct diurnal patterns of fatigue.

Design: Observational study using ecological momentary assessment.

Subjects: A total of 41 participants with subarachnoid haemorrhage.

Unraveling the interplay between daily life fatigue and physical activity after subarachnoid hemorrhage: an ecological momentary assessment and accelerometry study.

Background: Fatigue is one of the most commonly reported symptoms after subarachnoid hemorrhage (SAH) and is indirectly associated with physical activity (PA). Associations between fatigue and PA are primarily examined based on conventional measures (i.e.

A Sensor-Based Feedback Device Stimulating Daily Life Upper Extremity Activity in Stroke Patients: A Feasibility Study.

Unlabelled: This study aims to evaluate the feasibility and explore the efficacy of the Arm Activity Tracker (AAT). The AAT is a device based on wrist-worn accelerometers that provides visual and tactile feedback to stimulate daily life upper extremity (UE) activity in stroke patients.

Methods: A randomised, crossover within-subject study was conducted in sub-acute stroke patients admitted to a rehabilitation centre.

Assessment of 24-hour physical behaviour in adults via wearables: a systematic review of validation studies under laboratory conditions.

Background: Wearable technology is used by consumers and researchers worldwide for continuous activity monitoring in daily life. Results of high-quality laboratory-based validation studies enable us to make a guided decision on which study to rely on and which device to use. However, reviews in adults that focus on the quality of existing laboratory studies are missing.

Improved Physical and Mental Health After a Combined Lifestyle Intervention with Cognitive Behavioural Therapy for Obesity.

Background: Obesity is a multifactorial, chronic, progressive disease associated with decreased health-related quality of life, comorbidities, and increased mortality risk. Lifestyle interventions, focusing on dietetics, physical exercise, and behavioral therapy, are a cornerstone of therapy. Despite this very multidisciplinary treatment approach, the definition of treatment success is often based only on a weight loss of ≥ 5%.

Requirements for home-based upper extremity rehabilitation using wearable motion sensors for stroke patients: a user-centred approach.

Purpose: Telerehabilitation systems have the potential to enable therapists to monitor and assist stroke patients in achieving high-intensity upper extremity exercise in the home environment. We adopted an iterative user-centred approach, including multiple data sources and meetings with end-users and stakeholders to define the user requirements for home-based upper extremity rehabilitation using wearable motion sensors for subacute stroke patients.

Methods: We performed a requirement analysis consisting of the following steps: 1) context & groundwork; 2) eliciting requirements; 3) modelling & analysis; 4) agreeing requirements.

Polysarcosine-based lipid formulations for intracranial delivery of mRNA.

Messenger RNA (mRNA) is revolutionizing the future of therapeutics in a variety of diseases, including neurological disorders. Lipid formulations have shown to be an effective platform technology for mRNA delivery and are the basis for the approved mRNA vaccines. In many of these lipid formulations, polyethylene glycol (PEG)-functionalized lipid provides steric stabilization and thus plays a key role in improving the stability both ex vivo and in vivo.

Phase-Separated Liposomes Hijack Endogenous Lipoprotein Transport and Metabolism Pathways to Target Subsets of Endothelial Cells In Vivo.

Plasma lipid transport and metabolism are essential to ensure correct cellular function throughout the body. Dynamically regulated in time and space, the well-characterized mechanisms underpinning plasma lipid transport and metabolism offers an enticing, but as yet underexplored, rationale to design synthetic lipid nanoparticles with inherent cell/tissue selectivity. Herein, a systemically administered liposome formulation, composed of just two lipids, that is capable of hijacking a triglyceride lipase-mediated lipid transport pathway resulting in liposome recognition and uptake within specific endothelial cell subsets is described.

Development of a Combined Lipid-Based Nanoparticle Formulation for Enhanced siRNA Delivery to Vascular Endothelial Cells.

Low transfection efficiency in endothelial cells (EC) is still a bottleneck for the majority of siRNA-based vascular delivery approaches. In this work, we developed a lipid-based nanoparticle (LNP) formulation based on a combination of a permanently charged cationic lipid-DOTAP and a conditionally ionized cationic lipid-MC3 (DOTAP/MC3) for the enhanced delivery of siRNA into EC. Compared with a single DOTAP or MC3-based benchmark LNP, we demonstrated that the DOTAP/MC3 LNP formulation shows the best transfection efficiency both in primary EC in vitro and in endothelium in zebrafish.

Quality Evaluation of Free-living Validation Studies for the Assessment of 24-Hour Physical Behavior in Adults via Wearables: Systematic Review.

Background: Wearable technology is a leading fitness trend in the growing commercial industry and an established method for collecting 24-hour physical behavior data in research studies. High-quality free-living validation studies are required to enable both researchers and consumers to make guided decisions on which study to rely on and which device to use. However, reviews focusing on the quality of free-living validation studies in adults are lacking.

Assessment of 24-hour physical behaviour in children and adolescents via wearables: a systematic review of free-living validation studies.

Objectives: Studies that assess all three dimensions of the integrative 24-hour physical behaviour (PB) construct, namely, intensity, posture/activity type and biological state, are on the rise. However, reviews on validation studies that cover intensity, posture/activity type and biological state assessed via wearables are missing.

Design: Systematic review.

Investigating 3R In Vivo Approaches for Bio-Distribution and Efficacy Evaluation of Nucleic Acid Nanocarriers: Studies on Peptide-Mimicking Ionizable Lipid.

Formulations based on ionizable amino-lipids have been put into focus as nucleic acid delivery systems. Recently, the in vitro efficacy of the lipid formulation OH4:DOPE has been explored. However, in vitro performance of nanomedicines cannot correctly predict in vivo efficacy, thereby considerably limiting pre-clinical translation.

Stabilin 1 and 2 are important regulators for cellular uptake of apolipoprotein B-containing lipoproteins in zebrafish.

Background And Aims: Scavenger receptors form a superfamily of membrane-bound receptors that bind and internalize different types of ligands, including pro-atherogenic oxidized low-density lipoproteins (oxLDLs). In vitro studies have indicated a role for the liver sinusoidal endothelial cell receptors stabilin 1 (stab1) and 2 (stab2) in oxLDL clearance. In this study, we evaluated the potential role of stab1 and stab2 in lipoprotein uptake in zebrafish, an upcoming model for studying cholesterol metabolism and atherosclerosis.

Anionic Lipid Nanoparticles Preferentially Deliver mRNA to the Hepatic Reticuloendothelial System.

Lipid nanoparticles (LNPs) are the leading nonviral technologies for the delivery of exogenous RNA to target cells in vivo. As systemic delivery platforms, these technologies are exemplified by Onpattro, an approved LNP-based RNA interference therapy, administered intravenously and targeted to parenchymal liver cells. The discovery of systemically administered LNP technologies capable of preferential RNA delivery beyond hepatocytes has, however, proven more challenging.