A versatile and automatic on-line screening method: Transverse diffusion of laminar flow profiles-based capillary electrophoresis for exploring PTP1B inhibitors in natural products.

Natural products (NPs) play an important role in drug discovery and drug development due to their diverse chemical properties and biological activities. In the present work, an on-line capillary electrophoresis (CE) method was developed and applied to screen protein tyrosine phosphatase 1B (PTP1B) inhibitors in NPs. As a generic technique, transverse diffusion of laminar flow profiles (TDLFP) was utilized to mix all reactants in the capillary for on-line enzymatic reaction.

Effect of IV Thrombolysis With Alteplase in Patients With Vessel Occlusion in the WAKE-UP Trial.

Background And Objectives: Data from randomized trials on the treatment effect of pure thrombolysis in patients with vessel occlusion are lacking. We examined data from a corresponding subsample of patients from the multicenter, randomized, placebo-controlled WAKE-UP trial to determine whether MRI-guided IV thrombolysis with alteplase in unknown-onset ischemic stroke benefits patients presenting with vessel occlusion.

Methods: Patients with an acute ischemic lesion visible on MRI diffusion-weighted imaging but no marked parenchymal hyperintensity on fluid-attenuated inversion recovery images were randomized to treatment with IV alteplase or placebo.

C21ORF2 mutations point towards primary cilia dysfunction in amyotrophic lateral sclerosis.

Progressive loss of motor neurons is the hallmark of the neurodegenerative disease amyotrophic lateral sclerosis (ALS), but the underlying disease mechanisms remain incompletely understood. In this study, we investigate the effects of C21ORF2 mutations, a gene recently linked to ALS, and find that primary cilia are dysfunctional. Human patient-derived mutant C21ORF2 motor neurons have a reduced ciliary frequency and length.

4-Oxo-β-lactams as Covalent Inhibitors of the Mitochondrial Intramembrane Protease PARL.

Rhomboid proteases play a variety of physiological roles, but rhomboid protease inhibitors have been mostly developed for the model rhomboid GlpG. In this work, we screened different electrophilic scaffolds against the human mitochondrial rhomboid PARL and found 4-oxo-β-lactams as submicromolar inhibitors. Multifaceted computations suggest explanations for the activity at the molecular scale and provide models of covalently bound complexes.

Neural tracking of the speech envelope predicts binaural unmasking.

Binaural unmasking is a remarkable phenomenon that it is substantially easier to detect a signal in noise when the interaural parameters of the signal are different from those of the noise - a useful mechanism in so-called cocktail party scenarios. In this study, we investigated the effect of binaural unmasking on neural tracking of the speech envelope. We measured EEG in 8 participants who listened to speech in noise at a fixed signal-to-noise ratio, in two conditions: one where speech and noise had the same interaural phase difference (both speech and noise having an opposite waveform across ears, SπNπ), and one where the interaural phase difference of the speech was different from that of the noise (only the speech having an opposite waveform across ears, SπN).

Nitrogen dioxide sterilization of a set of five ophthalmic active pharmaceutical ingredients: Impact on impurity profile and content.

Literature about sterilization of pharmaceutical substances is limited. The aim of this study was to evaluate the effect of nitrogen dioxide (NO) sterilization, a new emerging technology, on five different ophthalmic active pharmaceutical ingredients, i.e.

The volume-outcome relation for pulmonary endarterectomy in chronic thrombo-embolic pulmonary hypertension.

Background: We conducted a volume-outcome (V-O) meta-analysis of PEA procedures for chronic thromboembolic pulmonary hypertension (CTEPH), to objectively determine the minimum required annual case load that can define a high-volume centre.

Methods: Three electronic databases were systematically queried until May 1st, 2024. Centres were divided in volume tertiles (Ts).

Graft-versus-host disease after anti-CD19 chimeric antigen receptor T-cell therapy following allogeneic hematopoietic cell transplantation: a transplant complications and paediatric diseases working parties joint EBMT study.

In patients diagnosed with B-acute lymphoblastic leukemia (B-ALL) or B-non-Hodgkin's lymphoma (B-NHL) relapsing after allogeneic stem cell transplantation (allo-HCT), it is a standard practice to perform anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. When collected from the patient after allo-HCT, the produced CAR-T cells are likely to be donor T-cell-derived, creating unknown safety risks due to their potential allo-reactivity. We therefore performed an EBMT registry-based study on the incidence of graft-versus-host disease (GvHD) in this setting.

APOE from astrocytes restores Alzheimer's Aβ-pathology and DAM-like responses in APOE deficient microglia.

The major genetic risk factor for Alzheimer's disease (AD), APOE4, accelerates beta-amyloid (Aβ) plaque formation, but whether this is caused by APOE expressed in microglia or astrocytes is debated. We express here the human APOE isoforms in astrocytes in an Apoe-deficient AD mouse model. This is not only sufficient to restore the amyloid plaque pathology but also induces the characteristic transcriptional pathological responses in Apoe-deficient microglia surrounding the plaques.

Reliability, concurrent validity and clinical feasibility of measurement methods determining local tissue water in patients with lower limb lymphedema and healthy controls.

Purpose: To investigate reliability, concurrent validity and clinical feasibility of local tissue water measurements in patients with lower limb lymphedema and healthy controls.

Methods: In this cross-sectional study the Moisture Meter D Compact device (MMDC) measurement and "pitting test" were performed three times by two assessors to test intra- and inter-rater reliability in 47 patients and 30 healthy controls. To investigate the between-session reliability, 29 patients and 21 healthy controls were reassessed two weeks later.

Postoperative ileus-Immune mechanisms and potential therapeutic interventions.

Background: Postoperative ileus (POI) is a condition marked by a temporary suppression of gastrointestinal motility following abdominal surgery. The mechanism of POI encompasses various factors and is characterized by two phases: the early neurogenic phase involving both adrenergic and non-adrenergic neural pathways; the later immune-mediated phase is characterized by a sterile inflammatory response that lasts several days. Activation of muscularis macrophages triggers a sterile inflammatory process that results in dysfunction of the enteric nervous system (ENS) and a reversible inhibition of gastrointestinal motility.

From breast cancer diagnosis to survivorship: Analyzing perioperative biopsychosocial phenotypes and their relationship to pain on long term.

Persistent breast cancer treatment-related pain affects up to 40% of patients, decreasing their quality of life (QoL). While current research typically utilizes correlation and regression analysis to identify biopsychosocial phenotypes contributing to this pain, this study employs cluster analysis to identify qualitatively different phenotypes based on somatosensory and psychosocial characteristics both before and one week post-breast cancer surgery. Further, it investigates how these phenotypes are related to pain intensity one year post-surgery and examines the evolution of phenotype membership from pre- to post-surgery.

Assessment of communication skills in health professions education; Ottawa 2024 consensus statement.

Despite the increasing inclusion of communication skills in accreditation standards and an increase in time dedicated to teaching these skills, communication is often regarded as a separate skill and is therefore, not consistently represented in overall systems of assessment in Health Professions Education (HPE). The ascendence of competency-based medical education, programmatic assessment, artificial intelligence, and widespread use of telehealth, alongside changing patient expectations warrant an update in thinking about the assessment of communication skills in health professions education. This consensus statement draws on existing literature, expert pinion, and emerging challenges to situate the assessment of communication skills in the contemporary health professions education context.