IMPACT OF REPEAT HLA MISMATCHES ON KIDNEY GRAFT SURVIVAL: A CONTEMPORARY COLLABORATIVE TRANSPLANT STUDY (CTS) ANALYSIS.

Repeat HLA mismatches (RMM) have been historically associated with an increased risk of graft loss after repeat kidney transplantation, in particular HLA-DR RMM in sensitized recipients. As routine use of sensitive assays can at present prevent the transplantation of RMM in hosts with donor-specific antibodies, we hypothesized that RMM would no longer be associated with graft loss. We performed a registry analysis of the Collaborative Transplant Study database including 6711 patients who received a second kidney transplant (2 KT) between 2010 and 2021, with at least one HLA-A, -B or -DR mismatch.

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.

Luteinizing hormone profiles during ovarian stimulation in assisted reproductive treatment.

Introduction: Few data is available on the natural course of luteinizing hormone (LH) during ovarian stimulation, but it has been suggested that 'oversuppressed' LH could decrease fertility outcomes. Our aim with this study is to evaluate the changes in LH depending on the used stimulation protocol to better define LH oversuppressioin.

Methods: Patients undergoing oocyte retrieval in a tertiary fertility center between 01-01-2015 and 30-09-2020 after stimulation with a short-agonist (SA) or antagonist (A) protocol were included.

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.

Diagnostic work-up of bile duct strictures: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

1: ESGE recommends the combination of endoscopic ultrasound-guided tissue acquisition (EUS-TA) and endoscopic retrograde cholangiopancreatography (ERCP)-based tissue acquisition as the preferred diagnostic approach for tissue acquisition in patients with jaundice and distal extrahepatic biliary stricture in the absence of a pancreatic mass. 2: ESGE suggests that brushing cytology should be completed along with fluoroscopy-guided biopsies, wherever technically feasible, in patients with perihilar biliary strictures. 3: ESGE suggests EUS-TA for perihilar strictures when ERCP-based modalities yield insufficient results, provided that curative resection is not feasible and/or when cross-sectional imaging has shown accessible extraluminal disease.

Rome Foundation and international neurogastroenterology and motility societies' consensus on idiopathic gastroparesis.

To establish a consensus on the definition and management of idiopathic gastroparesis, international experts (selected by neurogastroenterology and motility societies and initiated by the Rome Foundation) devised 144 statements using the Delphi method, with at least 80% agreement required. This consensus defined idiopathic gastroparesis as the presence of symptoms associated with delayed gastric emptying in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms.

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).

Tracking the journey: Gastrointestinal transit and intraluminal pH dynamics in aging populations using wireless motility capsule.

Introduction: Gastrointestinal (GI) changes may alter drug absorption, potentially impacting both efficacy and safety of oral pharmacotherapy. However, the GI physiology is rarely studied in the aging population. This study aimed to explore GI transit time and pH in geriatric inpatients and older adults, and compare these findings with those from young volunteers.

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.

Translocation of black carbon particles to human intestinal tissue.

Background: Evidence is accumulating that elevated levels of particulate air pollution, including black carbon, have been linked to gastrointestinal disorders and a lower intestinal bacterial richness and diversity. One of the hypothesized underlying mechanisms is the absorption of air pollution-related particles from the gastrointestinal tract.

Methods: We visualized and quantified black carbon particles via white light generation under femtosecond-pulsed laser illumination in ileum and colon biopsies of five human patients.

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).

International practice patterns and perspectives on endovascular therapy for the treatment of cerebral venous thrombosis.

Background: Cerebral venous thrombosis (CVT) accounts for 0.5-1% of all strokes. The role of endovascular therapy (EVT) in the management of CVT remains controversial and variations in practice patterns are not well known.

Similar Weaning Success Rate with High-Intensity and Sham Inspiratory Muscle Training: A Randomized Controlled Trial (IMweanT).

Rationale: Inspiratory muscle training (IMT) improves respiratory muscle function in patients with weaning difficulties. IMT protocols involve performing daily sets of breaths against external loads. However, the impact of IMT on weaning outcomes while incorporating sham control interventions remains unclear.

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.

Intra- and Postoperative Complications in 4565 vNOTES Hysterectomies: International Registry Cohort Study.

Objective: To present the rates of intra- and postoperative complications and conversions in a large cohort of unselected vNOTES hysterectomies, performed by surgeons with different levels of expertise.

Design: International register-based cohort study.

Setting: Hysterectomies in the iNOTESs registry, 2015 to January 2024, performed by 201 surgeons from multiple countries.

Assessing upper limb functional use in daily life using accelerometry: A systematic review.

Background: Upper limb dysfunctions are common and disabling in daily life. Accelerometer data are commonly used to describe upper limb use. However, different data analyzing methods are used to describe or classify upper limb use.

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.