Functionalized regioisomers of the natural product phenazines myxin and iodinin as potent inhibitors of Mycobacterium tuberculosis and human acute myeloid leukemia cells.

The natural bioactive products myxin and iodinin are phenazine 5,10-dioxides possessing potent anti-bacterial and anti-cancer activity in vitro. This work describes the synthesis and derivatization of new myxin and iodinin regioisomers, developed from 1,3-dihydroxyphenazine 5,10-dioxide. Compounds were evaluated for activity towards M.

Leveraging Transformers-based models and linked data for deep phenotyping in radiology.

Background And Objective: Despite significant investments in the normalization and the standardization of Electronic Health Records (EHRs), free text is still the rule rather than the exception in clinical notes. The use of free text has implications in data reuse methods used for supporting clinical research since the query mechanisms used in cohort definition and patient matching are mainly based on structured data and clinical terminologies. This study aims to develop a method for the secondary use of clinical text by: (a) using Natural Language Processing (NLP) for tagging clinical notes with biomedical terminology; and (b) designing an ontology that maps and classifies all the identified tags to various terminologies and allows for running phenotyping queries.

Transformative knowledge of polar polycyclic aromatic hydrocarbons via high-resolution mass spectrometry.

Polycyclic aromatic hydrocarbons (PAHs) are toxic contaminants with a widespread presence in diverse environmental contexts. Transformation processes of PAHs via degradation and biotransformation have parallels in humans, animals, plants, fungi, and bacteria. Mapping the transformation products of PAHs is therefore crucial for assessing their toxicological impact and developing effective monitoring strategies.

Post-COVID symptoms after SARS-CoV-2 omicron infection and the effect of booster vaccination: A population-based cohort study.

Background: The impact of vaccination on the type and risk of specific post-COVID symptoms after Omicron infection is not clear. We aimed to investigate the excess risk and patterns of 22 symptoms 3-5 months after Omicron infection, comparing uninfected and infected subjects with and without recent booster vaccination.

Methods: We conducted a population-based prospective study based on four questionnaire-based cohorts linked to national health registries.

Detection of Echinococcus spp. and other taeniid species in lettuces and berries: Two international multicenter studies from the MEmE project.

Cystic and alveolar echinococcosis are severe zoonotic diseases characterized by long asymptomatic periods lasting months or years. Viable Echinococcus spp. eggs released into the environment through the feces of canids can infect humans through accidental ingestion via hand-to-mouth contact or consumption of contaminated food or water.

Marine and atmospheric transport modeling supporting nuclear preparedness in Norway: Recent achievements and remaining challenges.

Numerical transport models are important tools for nuclear emergency decision makers in that they rapidly provide early predictions of dispersion of released radionuclides, which is key information to determine adequate emergency protective measures. They can also help us understand and describe environmental processes and can give a comprehensive assessment of transport and transfer of radionuclides in the environment. Transport of radionuclides in air and ocean is affected by a number of different physico-chemical processes.

Heating up three cold cases in Norway using investigative genetic genealogy.

With the advent of commercial DNA databases, investigative genetic genealogy (IGG) has emerged as a powerful forensic tool, rivalling the impact of STR analyses, introduced four decades ago. IGG has been frequently applied in the US and tested in other countries, but never in Norway. Here, we apply IGG to three cold criminal cases and successfully identify the donor of the DNA in two of these cases.

Status of Sepsis Care in European Hospitals: Results from an International Cross-Sectional Survey.

Rationale: Early detection, standardized therapy, adequate infrastructure and strategies for quality improvement should constitute essential components of every hospital's sepsis plan.

Objectives: To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute hospitals.

Methods: A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals.

Systematic Review: Efficacy of Medical Therapy on Outcomes Important to Pediatric Patients with X-Linked Hypophosphatemia.

Objective: To examine the evidence addressing the management of X-linked hypophosphatemia (XLH) in children to inform treatment recommendations.

Methods: We searched Embase, MEDLINE, Web of Science, and Cochrane Central up to May 2023. Eligible studies included RCTs and observational studies of individuals less than 18yrs with clinically or genetically confirmed XLH.

Recruitment, follow-up and survival in an 11-country cohort study of patients at the end of life and their relatives.

Background: Large, international cohort studies generate high-level evidence, but are resource intense. In end-of-life care such studies are scarce. Hence, planning for future studies in terms of data on screening, recruitment, retention and survival remains a challenge.

Multilayered Nanocarriers as a New Strategy for Delivering Drugs with Protective and Anti-inflammatory Potential: Studies in Hippocampal Organotypic Cultures Subjected to Experimental Ischemia.

Oxidative stress and neuroinflammation play a pivotal role in pathomechanisms of brain ischemia. Our research aimed to formulate a nanotheranostic system for delivering carnosic acid as a neuroprotective agent with anti-oxidative and anti-inflammatory properties to ischemic brain tissue, mimicked by organotypic hippocampal cultures (OHCs) exposed to oxygen-glucose deprivation (OGD). In the first part of this study, the nanocarriers were formulated by encapsulating two types of nanocores (nanoemulsion (AOT) and polymeric (PCL)) containing CA into multilayer shells using the sequential adsorption of charged nanoobjects method.

Quantitative imaging of loop extruders rebuilding interphase genome architecture after mitosis.

How cells establish the interphase genome organization after mitosis is incompletely understood. Using quantitative and super-resolution microscopy, we show that the transition from a Condensin to a Cohesin-based genome organization occurs dynamically over 2 h. While a significant fraction of Condensins remains chromatin-bound until early G1, Cohesin-STAG1 and its boundary factor CTCF are rapidly imported into daughter nuclei in telophase, immediately bind chromosomes as individual complexes, and are sufficient to build the first interphase TAD structures.

Biomarkers.

Background: Alzheimer's Disease (AD) is associated with sleep disturbances. Moreover, individuals with sleep disturbances have been reported to have a higher risk for developing AD. The measurement of sleep behavior therefore opens the opportunity for a potential digital biomarker of AD.

Biomarkers.

Background: Several studies have investigated the link between sleep disturbances and allostatic load (AL), but the results are varied, and less is known about the associations in clinical samples. The goal of this study is to assess the associations between sleep disturbances and AL among memory clinic participants, and to examine differences according to sex, beta-amyloid status and history of burnout status.

Method: The study was based on 146 memory clinic participants diagnosed with either Mild Cognitive Impairment (MCI) or Subjective Cognitive Impairment (SCI) in the Cortisol and Stress in Alzheimer's Disease Study (Co-STAR) (Sweden).

Biomarkers.

Background: Alzheimer disease (AD) plasma biomarkers change in the preclinical stage of AD. However, the robustness of the discrimination performance of these biomarkers, as well as their association with longitudinal primary pathology (amyloid and tau) changes, is less understood. We aimed to determine the ability of baseline and longitudinal plasma amyloid-β (Aβ)42/40, p-tau181, GFAP and NfL to detect primary pathology in CU individuals at risk of AD.

Biomarkers.

Background: Current models of AD posit neurodegeneration and cognitive decline occur downstream in a pathophsyiological cascade initiated by amyloid (Aβ), yet lifespan research suggests the brain regions and cognitive functions impacted most by AD exhibit the steepest, steady decline rates across life. We hypothesised adult lifespan neurodegeneration in AD-vulnerable brain regions would predict memory decline rates detectable in healthy adults as they age, independent of Aβ.

Method: We combined MRI scans across three large longitudinal cohorts of cognitively healthy adults (age 30-96 years) to estimate brain change relative to the change expected given a person's age (2-14 timepoints; 4125 scans of 1027 individuals; cohorts: LCBC, the Berkeley Aging Cohort Study [BACS]; ADNI [stable cognitively healthy]).

Biomarkers.

Background: Neurodevelopmental origins of functional variation through the lifespan are acknowledged, but pathways need to be identified. The objectives of the project Set-to-change is to test whether and how early life environmental factors and genetic makeup regulate brain and cognition and its change, as well as neurocognitive plasticity in response to training through the lifespan.

Method: Preliminary analyses for the first months are presented.

Biomarkers.

Background: Individuals with dual decline in gait and cognition have a greater risk of developing dementia. Understanding when gait speed declines relative to measures affected early in Alzheimer's disease can improve risk assessment.

Method: Using data for 761 participants (1,108 cognitively unimpaired visits) from the Baltimore Longitudinal Study of Aging, we estimated the trajectories of gait speed, memory (California Verbal Learning Test [CVLT] immediate recall score), hippocampal volume, and plasma Aβ/Aβ, glial fibrillary acidic protein (GFAP), and p-tau181.

Biomarkers.

Background: Patterns of regional atrophy and hypometabolism have been observed in dementia with Lewy bodies (DLB). However, determinants of regional vulnerability to structural and functional neurodegeneration remain largely unexplored. First, we investigated the association between regional gene expression and grey matter volumes in probable DLB patients.

Biomarkers.

Background: We examined whether brain amyloid PET, hippocampal volume, or plasma biomarkers are better predictors of conversion to mild cognitive impairment (MCI).

Method: In the Baltimore Longitudinal Study of Aging (BLSA), plasma Aβ, Aβ, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) concentrations were measured using Quanterix Simoa Neurology 4-plex E. Plasma p-tau181 and p-tau231 concentrations were measured using in-house Simoa assays at University of Gothenburg.

Biomarkers.

Background: Mitophagy is a process of intracellular protein homeostasis through which cells eliminate senescent and dysfunctional mitochondria. Altered mitophagy contributes to Alzheimer´s disease (AD) pathology and is associated with worse cognitive functions. We evaluated association of levels of mitophagy proteins (ULK1, BNIP3L, PINK1, and TFEB in serum and ULK1 and PINK 1 in cerebrospinal fluid [CSF]) with spatial egocentric (body-centered) and allocentric (world-centered) navigation performance, which is typically impaired in early stages of AD.

Biomarkers.

Background: Co-pathology between Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB) remains poorly understood but is relevant for trial design. We aimed to compare CSF markers of amyloid, tau, and neurodegeneration (ATN) and α-synuclein between AD, PD, DLB and controls, and investigate the influence of demographical, genetic, and clinical factors on amyloid positivity.

Method: As part of the EPND study, we included 337 individuals with AD, PD, DLB and controls from 6 centers.

Biomarkers.

Background: With no effective therapy targeting the pathology of genetic frontotemporal lobar degeneration (FTLD), there is a need for easily accessible biomarkers enabling the development of therapeutic agents and for clinical diagnostics. Thus, we aimed to investigate the proteomic changes in plasma of progranulin (GRN) mutation carriers using a novel ultrasensitive antibody-based platform.

Methods: We cross-sectionally evaluated carriers of pathogenic GRN mutations (GRN+) and age- and sex-matched cognitively healthy non-carriers (GRN-) from the University of Brescia.

Biomarkers.

Background: Recently, the development of ultra-sensitive immunoassays has allowed for the detection, in blood, of proteins related to the pathophysiology of Alzheimer's disease (AD), with phosphorylated tau (p-tau) being the most promising. However, current methods are often limited by their ability to measure one analyte, lacking the potential for discovery and inclusion of additional biomarkers with supplemental value. In this pilot study, we explored proteomic changes using the novel NUcleic acid Linked Immuno-Sandwich Assay (NULISA™) platform, focusing on patients with mild cognitive impairment (MCI).