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.

Measuring Residents' Competence in Chest Tube Insertion on Thiel-Embalmed Bodies: A Validity Study.

Introduction: Chest tube insertions (CTIs) have a high complication rate, prompting the training of technical skills in simulated settings. However, assessment tools require validity evidence prior to their implementation. This study aimed to collect validity evidence for assessment of technical skills in CTI on Thiel-embalmed human bodies.

Loading Speed and Intensity in Eccentric Calf Training Impact Acute Changes in Achilles Tendon Thickness and Stiffness: A Randomized Crossover Trial.

Purpose: Eccentric calf training for Achilles tendinopathy shows variable success in athletes. Recent insights suggest a role for tendon fluid flow (exudation or redistribution) during exercise, which explains post-exercise reductions in thickness and increases in stiffness of the tendon. This fluid flow is thought to be beneficial as it may promote tendon remodeling, reduce intratendinous pressure, and alleviate pain.

Les Cartes Porcelaine of the Mid 19th Century.

A unique type of advertising trade card was popular in Europe, mostly Belgium, between 1840 and 1865. These cards were produced with a coating of a white lead substance that gave them a lustrous appearance and feel, resembling porcelain. As attractive as these cards were, producing them oftentimes resulted in lead poisoning for the printers, so few were produced after 1865.

Exploring evolution to uncover insights into protein mutational stability.

Determining the impact of mutations on the thermodynamic stability of proteins is essential for a wide range of applications such as rational protein design and genetic variant interpretation.Since protein stability is a major driver of evolution, evolutionary data are often used to guide stability predictions. Many state-of-the-art stability predictors extract evolutionary information from multiple sequence alignments (MSA) of proteins homologous to a query protein, and leverage it to predict the effects of mutations on protein stability.

Intact Neural Responding to Hearing One's Own Name in Children with Autism.

Diminished responding to one's own name is one of the strongest and earliest predictors of autism. However, research on the neural correlates of this response in autism is scarce. Here we investigate neural responses to hearing the own name in school-aged children with and without autism.

Exploring the Tomato Root Protein Network Exploited by Core Type 3 Effectors from the Species Complex.

Proteomics has become a powerful approach for the identification and characterization of type III effectors (T3Es). Members of the species complex (RSSC) deploy T3Es to manipulate host cells and to promote root infection of, among others, a wide range of solanaceous plants such as tomato, potato, and tobacco. Here, we used TurboID-mediated proximity labeling (PL) in tomato hairy root cultures to explore the proxeomes of the core RSSC T3Es RipU, RipD, and RipB.

Biomarkers.

Background: In AD, tauopathy and atrophy start in the mesiotemporal lobe, including the amygdala-hippocampal complex. Until recently, subnuclei and subfields within these structures were indistinguishable in-vivo. FreeSurfer 7.

Biomarkers.

Background: Alzheimer's disease (AD) is a complex disorder with a strong genetic component, yet many genetic risk factors remain unknown. Integrating genome-wide association studies (GWAS) and high-throughput proteomic platforms is a useful strategy to evaluate protein quantitative trait loci (pQTLs) and to detect candidate genes and pathways involved in AD. Due to the novelty of these techniques, the identification of reliable protein measures through a comprehensive quality control is mandatory.

Biomarkers.

Background: As new anti-amyloid immunotherapies emerge for Alzheimer's disease (AD), it is clear that early diagnosis of AD pathology is crucial for treatment success. This can be challenging in atypical presentations of AD and, together with our reliance on CSF or PET scans, can, at times, lead to delayed diagnosis. Here, we further explore the possible role of plasma tau phosphorylated at threonine 217 (P-tau217) for the detection of primary AD or AD co-pathology when frontotemporal dementia spectrum disorders are the main clinical presentation.

Biomarkers.

Background: Alzheimer's disease (AD) blood biomarkers alone can detect amyloid-β (Aβ) pathology in cognitively unimpaired (CU) individuals. We assessed whether combining different plasma biomarkers improves the detection of Aβ-positivity and identifies rapid amyloid deposition in CU individuals.

Method: CU participants from the ALFA+ cohort were included.

Biomarkers.

Background: The performance of blood-based phosphorylated tau (pTau) immunoassays to detect asymptomatic Alzheimer's disease (AD) has important implications for therapeutic trials. pTau217 is often recommended as the preferred epitope due to its high fold changes in AD. The current study investigates the ability of a novel pTau217 assay to predict the dynamic phase of amyloid-β (Aβ) accumulation in comparison to the best-performing pTau181 assay.

Biomarkers.

Background: Neurodegenerative diseases are a heterogeneous group of illnesses. Differences across patients exist in the underlying biological drivers of disease. Furthermore, cross-diagnostic disease mechanisms exist, and different pathologies often co-occur in the brain.

Biomarkers.

Background: The retina, an integral part of the central nervous system, can exhibit protein accumulation (Aβ and pTau) associated with neurodegenerative diseases such as Alzheimer's disease (AD). Biochemical analysis revealed the existence of a distinct primary retinal tauopathy (PReT), differing from AD and primary age-related tauopathy (PART) brain lysates, suggesting it as a potential precursor for AD tauopathy with possible diagnostic value. However, it remains unclear whether retinal pTau pathology can spread from the eye into the brain.

Biomarkers.

Background: Synaptic dysfunction occurs in the early stages of neurodegenerative diseases and leads to the breakdown of connections within neuronal networks. Therefore, biomarkers reflecting this process, such as neurogranin (Ng), might be useful to study disease pathophysiology and aid in diagnostics. Ng is crucial for long-term potentiation and memory consolidation, and plays a central role in synaptic plasticity.

Biomarkers.

Background: Dementia with Lewy bodies (DLB) is a an α-synucleinopathy characterized by dementia and a combination of parkinsonism, visual hallucinations, fluctuating cognition or REM sleep behaviour disorder. Specific biomarkers for DLB are lacking. DLB-related pattern (DLBRP) is a metabolic network imaging biomarker which expression can be quantified on a single patient basis.

Biomarkers.

Background: Different patterns of atrophy exist in the dementia stage of AD. However, little is known about the heterogeneity of atrophy patterns and the mechanisms that drive subsequent propagation of the disease in the preclinical stages.

Method: From the AMYPAD-PNHS cohort, we included a total of 1323 non-demented individuals, including 1094 amyloid-negative, and 229 amyloid-positive participants (Table 1).

A weight of evidence review on the mode of action, adversity, and the human relevance of xylene's observed thyroid effects in rats.

Xylene substances have wide industrial and consumer uses and are currently undergoing dossier and substance evaluation under Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) for further toxicological testing including consideration of an additional neurotoxicological testing cohort to an extended one-generation reproduction toxicity (EOGRT) study. New repeated dose study data on xylenes identify the thyroid as a potential target tissue, and therefore a weight of evidence review is provided to investigate whether or not xylene-mediated changes on the hypothalamus-pituitary-thyroid (HPT) axis are secondary to liver enzymatic induction and are of a magnitude that is relevant for neurological human health concerns. Multiple published studies confirm xylene-mediated increases in liver weight, hepatocellular hypertrophy, and liver enzymatic induction the oral or inhalation routes, including an increase in uridine 5'-diphospho-glucuronosyltransferase (UDP-GT) activity, the key step in thyroid hormone metabolism in rodents.

Use and limitations of clinical data in the identification and classification of low molecular weight chemicals (LMWCs) as respiratory sensitizers: recommendations for improvement.

While progress has been made in recent years, there are still no suitable and accepted , or models that can be used to accurately predict whether a chemical substance has the intrinsic property to cause immune-mediated chemical respiratory allergy, typically manifested as allergic asthma or allergic rhinitis which represents a severe health hazard. Regulatory authorities have relied primarily on clinical evidence (case reports, clinical databases, worker exposure studies) to classify substances as respiratory sensitizers, but this evidence can lack a proven immunological mechanism which is necessary to identify substances which can cause life-long sensitization and clinically relevant allergic symptoms in the respiratory tract in an exposed population (such respiratory allergens may be considered as "true" sensitizers, in analogy to the definition of skin sensitization, and in contrast to respiratory irritants). In light of this, the European Center for Ecotoxicology and Toxicology of Chemicals convened a Task Force to evaluate the types of clinical methods and data sources and the implications of relying on such data for regulatory decision making from a scientific perspective.

Biomarkers.

Background: Fluid biomarkers provide a convenient way to predict AD pathophysiology. However, few studies have focused on determining associations with tau neurofibrillary tangle pathology in the early preclinical AD continuum, relevant to prevention strategies.

Methods: Ninety-nine cognitively unimpaired individuals from the ALFA+ cohort with valid F-RO-948 and F-flutemetamol PET, T1-weighted MRI, cognition, CSF, and plasma biomarkers were included.

Biomarkers.

Background: Tau-PET imaging allows in-vivo detection of neurofibrillary tangles. One tau-PET tracer (i.e.

Optimal Word Reading Rate as Evidenced by Frequency-tagging Electrophysiology.

Fast periodic visual stimulation (FPVS) coupled with EEG has been used for a decade to measure word-selective neural responses in (a)typical adults and developmental readers. Here, we used this FPVS-EEG approach to evaluate suitable and optimal stimulation frequency rates for prelexical and lexical word-selective responses and relate these rates to typical reading speed and interindividual variability in reading performance. EEG was recorded in 41 healthy adults who viewed words inserted periodically (1 Hz) at four different stimulation frequency rates (4 Hz, 6 Hz, 10 Hz, and 20 Hz).

Biomarkers.

Background: A novel method using diffusion-weighted imaging (DWI) allows for assessing microstructural injury in the gray matter by measuring cortical mean diffusivity (cMD). Previous studies have shown that altered cMD is related to amyloid (Aβ) cross-sectionally and can predict longitudinal cognitive decline and clinical progression, suggesting utility in clinical trials. However, the longitudinal associations between these measures are unknown.

Biomarkers.

Background: Alzheimer's Disease (AD) is a complex disorder and much of its etiopathology is still unknown. Here, we applied dimensionality reduction methods to disentangle cyptic patterns in CSF proteomic and lipidomic data.

Method: We studied 1121 CSF samples using targeted lipidomics based on liquid chromatography (LC)-MS/MS (mass spectrometry), generated by Lipometrix (Lueven, Belgium), and proteomic data generated by Somalogic (Boulder, Colorado) using the SOMAscan 7k Assay.

Biomarkers.

Background: Precision neuroscience is emerging as a transformative approach that aims to identify the right treatment for the right patient at the right time. To enable this, it is important to move beyond the categorization of patients based on clinical symptoms towards a biological definition of disease. For Alzheimer's disease, significant progress has been made in this direction, with the development of the "A/T/N" biomarker framework that classifies patients based on underlying pathophysiology.