Drug Development.

Background: Alzheimer's disease neuropathology involves the deposition in brain of aggregates enriched with microtubule-binding-region (MTBR) of tau adopting an abnormal conformation between residues 306-378 in the core of aggregates. Anti-tau drugs targeting around this domain have the potential to interfere with the cell-to-cell propagation of pathological tau. Bepranemab is a humanized monoclonal Ig4 antibody binding to tau residues 235-250.

Drug Development.

Background: Accumulation of misfolded a-synuclein protein in intracellular inclusion bodies of dopaminergic neurons underlies the pathogenesis of synucleinopathies, which include Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). Therefore, clearance of misfolded α-synuclein from dopaminergic neurons could in principle offer a an approach for modifying synucleinopathies, which currently remain untreatable.

Method: In this study, we employ the Affinity-directed PROtein Missile (AdPROM) system consisting of the substrate receptor of the CUL2-E3 ligase complex VHL and a nanobody selectively recognising the human α-synuclein protein RESULT: We demonstrate targeted degradation of endogenous α-synuclein from human cell lines with exquisite selectivity.

Drug Development.

Background: To improve clinical translatability of non-clinical in-vivo Alzheimer's disease (AD) models, a humanized APP knock-in mouse model (APP) was recently created (Xia, D. et al., 2022).

Drug Development.

An overview is given of surrogate marker evaluation, starting from the original definition of Prentice and his criteria, the estimation framework of Freedman, the meta-analytic framework, and the evaluation of surrogate endpoints from a causal inference point of view. Attention will be given, in particular, to evaluating tau-PET as a reasonably likely surrogate in Alzheimer's Disease. A meta-analytic surrogate marker evaluation approach will be followed, for a continuous surrogate and a continuous true endpoint.

Drug Development.

Background: In the brain as in other organs, complement contributes to immune defence and housekeeping to maintain homeostasis. Sources of complement may include local production by brain cells and influx from the periphery, the latter severely restricted by the blood brain barrier (BBB) in healthy brain. Dysregulation of complement leads to excessive inflammation, direct damage to self-cells and propagation of injury.

Drug Development.

Background: Pathological tau accumulation is the primary constituent of neurofibrillary tangles and other tau aggregates seen in various neurodegenerative diseases collectively known as tauopathies. Recently, immunotherapeutic strategies focused on tau have shown promise in reducing tauopathy in both cellular and animal models.

Method: We previously used humanized yeast models to purify recombinant hyper-phosphorylated human Tau for mouse immunizations and the isolation of a high-affinity anti-Tau monoclonal antibody (mAb) with enhanced diagnostic and prognostic capacities.

Drug Development.

Background: Clinical assessments utilized in trials to measure progression in sporadic Alzheimer's disease (SAD) such as the MMSE, ADAS-Cog, CDR-SB and ADCS-ADL are well established. Distinct assessments are utilized for Down Syndrome-related Alzheimer's disease (DSAD). Although these assessments are less well established, they probe comparable domains of cognition and function.

Drug Development.

Gamma-secretases play a pivotal role in the generation of Aβ peptides. Mutations in these enzymes that cause early-onset, autosomal dominant AD shift Aβ production towards generation of longer peptides. We have recently shown that the mutation-induced shifts in the ratio of short-to-long Aβ peptides not only inform about mutation pathogenicity but also allow experimental prediction of the age at dementia onset.

Analysis of the NMR Parameters Shielding and Spin-Spin Coupling Constants of Glycine Conformers.

In this study, we worked at the CCSD/aug-cc-pVTZ level to obtain the conformers of glycine in its neutral and zwitterionic forms in the gas and water phases. We then computed the NMR properties (spin-spin coupling constants and nuclear magnetic shieldings) at the SOPPA/aug-cc-pVTZ-J level. We attempt to elucidate the apparent discrepancy arising from two previous works by Valverde et al.

Bombay blood and the 'Swab-Lite' method of blood conservation.

Bombay blood (hh blood) is a rare blood group (4 per million), with no expression of the H antigen present in blood group O. Bombay blood patients can only receive Bombay blood, with autodonation used for elective surgery. We present a Bombay patient (haemoglobin 12.

Dementia Care Practice.

Aims: The Alzheimer Association (AA) has proposed new diagnostic criteria for Alzheimer's disease (AD) based on biomarkers coinciding with β-amyloidosis onset. However, there are concerns regarding the implications of these criteria.

Methods: We reviewed several perspectives, including disease definition, public health, philosophy, therapeutic, and diagnostic.

Removal of lithium from aqueous solutions by precipitation with sodium and choline alkanoate soaps.

In order to comply with the expected tightening of discharge limits for lithium to surface waters, the lithium-ion battery industry will need access to methods to reduce the concentration of lithium in wastewater down to ppm levels. In this Communication, we discuss the possibility of using sodium and choline soaps as precipitating agents for lithium, comparing the two soap classes and probing the influence of the carbon chain length. It was found that lithium concentrations down to 10 ppm can be reached with sodium stearate, and down to 1 ppm with choline stearate, using a slight excess of the precipitating agent.

The Hyperdense Right Hemidiaphragm Sign: A Novel Radiological Indicator of Diffuse Fatty Liver Infiltration on Non-Enhanced CT.

Objectives The primary objective of this study is to describe and evaluate the diagnostic performance of the hyperdense right hemidiaphragm sign (HRHS) as a novel radiological indicator for diffuse fatty infiltration of the liver on non-enhanced CT (NECT) scans. This includes assessing its sensitivity, specificity, positive predictive value, and negative predictive value, and comparing these metrics with other established NECT signs. Methods This cross-sectional multicenter retrospective study included all patients over 12 years of age who underwent both abdominal MRI and NECT scans of the abdomen within a period not exceeding six months at two tertiary hospitals (The Royal Hospital and Armed Forces Hospital, Muscat, Sultanate of Oman) between January 2010 and December 2022.

Breakthrough Psoriasis in Patients Receiving Biologicals.

Background: Biological therapies, including TNF-alpha, IL12/23, IL17 and IL23 antagonists, adequately control a very high number of patients with moderate-to-severe psoriasis with an excellent long-term safety profile. However, on occasion, patients on biological therapy with stabilized disease or complete remission report episodes of sudden breakthrough psoriasis.

Aim: To study prospectively in a monocentric tertiary setting, the clinical characteristics of patients presenting a sudden breakthrough psoriasis although completely stabilized (PASI 90-100) under biological therapy.

The digit triplet test for school-age hearing screening: comparing languages, school grades and scoring methods in a large sample.

Objective: To investigate the reliability of a bilingual school-age hearing screening in four school grades based on the Digit Triplet Test (DTT) in two languages and to investigate three calculation methods for referral values in their ability to detect hearing losses and avoid false-positive results.

Design And Study Sample: 3255 children, aged between 10 and 17 years old, were tested during a systematic hearing screening program in a bilingual, French-German area in Belgium. French speaking children were tested with a French DTT, German children were tested with a German DTT.

The effect of environmental factors on transepithelial potential in a model Amazonian teleost, the tambaqui (Colossoma macropomum): Implications for sodium balance in harsh environments.

The tambaqui (Colossoma macropomum, G. Cuvier 1818) thrives both in the ion-poor waters of the Amazon and in commercial aquaculture. In both, environmental conditions can be harsh due to low ion levels, occasional high salt challenges (in aquaculture), low pH, extreme PO levels (hypoxia and hyperoxia), high PCO levels (hypercapnia), high ammonia levels (in aquaculture), and high and low temperatures.

Access to HIV prevention, testing and care among people with a migration background in Euregio Meuse-Rhine: a needs and assets assessment.

This study addresses disparities among people with a migration background (PMB) and those in less-urban regions, across the HIV prevention and care continuum (HIVPCC). We conducted a needs assessment and assets assessment to identify gaps between existing initiatives and persisting barriers. The research was conducted in the Euregio Meuse-Rhine (EMR), encompassing bordering regions in Belgium, Germany, and the Netherlands, and involved in-depth interviews with fifteen first-generation PMB, including nine with HIV.

Galloyl Dialkyl Lipids Drive Encapsulation of Peptides into Lipid Nanoparticles by Hydrogen Bonding.

The intracellular delivery of peptides and proteins is crucial for various biomedical applications. Lipid nanoparticles (LNPs) have emerged as a promising strategy for delivering peptides to phagocytic cells. However, the diverse physicochemical properties of peptides necessitate tailored formulations.

Effectiveness of the AF-EduCare and AF-EduApp approach to improve atrial fibrillation knowledge and risk factor awareness in patients with atrial fibrillation: a randomized controlled trial.

Aims: Developing an integrated care pathway for atrial fibrillation (AF) patients is of pivotal importance, given the different treatment strategies. Moreover, knowledge about the condition is an important factor in engaging patients in their care. Patient education formed the core of the integrated AF-EduCare/AF-EduApp approach.

Astaxanthin-loaded PLGA nanoparticles inhibit survival of MKN-45 gastric cancer cell line by modulating JAK2/STAT3/mTOR/PI3K pathway.

Background/aims: Gastric cancer (GC) is a significant global health issue with high incidence rates and poor prognoses, ranking among the top prevalent cancers worldwide. Due to undesirable side effects and drug resistance, there is a pressing need for the development of novel therapeutic strategies. Understanding the interconnectedness of the JAK2/STAT3/mTOR/PI3K pathway in tumorigenesis and the role of Astaxanthin (ASX), a red ketocarotenoid member of xanthophylls and potent antioxidant and anti-tumor activity, can be effective for cancer treatments.

Time Tetris: a longitudinal study on compressed schedules and workplace well-being at IKEA.

Background: Compressed schedules, where workers perform longer daily hours to enjoy additional days off, are increasingly promoted as a workplace well-being intervention. Nevertheless, their implications for work-related well-being outcomes, such as recovery from work and burnout risk, are understudied. This gap leaves employers with little evidence on whether and how the arrangement contributes to workplace well-being.

The microbiota-derived bile acid taurodeoxycholic acid improves hepatic cholesterol levels in mice with cancer cachexia.

Alterations in bile acid profile and pathways contribute to hepatic inflammation in cancer cachexia, a syndrome worsening the prognosis of cancer patients. As the gut microbiota impinges on host metabolism through bile acids, the current study aimed to explore the functional contribution of gut microbial dysbiosis to bile acid dysmetabolism and associated disorders in cancer cachexia. Using three mouse models of cancer cachexia (the C26, MC38 and HCT116 models), we evidenced a reduction in the hepatic levels of several secondary bile acids, mainly taurodeoxycholic (TDCA).