Oestrogen and progesterone fluctuate cyclically in women throughout their adult lives. Although these hormones cross the blood-retinal barrier and bind to intraocular receptors, their effects remain unclear. We present the first review to date on associations between posterior pole structures-specifically the macula, choroid, and optic disc-and both the menstrual cycle and post-menopausal period, utilising multimodal imaging techniques in healthy adult non-pregnant women.
View Article and Find Full Text PDFThe P2X4 receptor is implicated in various pathological conditions, including neuropathic pain and cancer. This study reports the development of 1,4-naphthodiazepinedione-based P2X4 receptor antagonists aimed at both therapeutic applications and potential use as PET tracers for imaging P2X4 receptor expression in cancer. Structure-activity relationship studies aided by docking studies and molecular dynamics simulations led to a series of compounds with potent P2X4 receptor antagonism, promising inhibition of interleukin-1β release in THP-1 cells and suitability for radiolabeling with fluorine-18.
View Article and Find Full Text PDF: Sinonasal malignancies are rare and highly diverse cancers that pose significant diagnostic challenges due to their variable histological features and complex anatomical locations. Accurate diagnosis is critical for guiding treatment, yet conventional methods often require multiple biopsies. This study aimed to evaluate the potential of confocal laser endomicroscopy (CLE) for real-time imaging of sinonasal tumors to characterize specific features of different entities and improve diagnostic precision.
View Article and Find Full Text PDFBackground: PSEN1, PSEN2, and APP mutations cause Alzheimer's disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earlier AAO; however, certain PSEN1 mutations cause a later AAO, similar to those observed in PSEN2 and APP.
Methods: We examined whether common disease endotypes exist across these mutations with a later AAO (~ 55 years) using hiPSC-derived neurons from familial Alzheimer's disease (FAD) patients harboring mutations in PSEN1, PSEN2, and APP and mechanistically characterized by integrating RNA-seq and ATAC-seq.
Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance in the circulation, robust CTC expansion protocols are urgently needed to effectively study disease progression and therapy responses. Here we present the establishment of long-term CTC-derived organoids from female individuals with metastatic breast cancer.
View Article and Find Full Text PDFBacteria frequently employ carbohydrate-binding proteins, so-called lectins, to colonize and persist in a host. Thus, bacterial lectins are attractive targets for the development of new antiinfectives. To find new potential targets for antiinfectives against pathogenic bacteria, we searched for homologs of Pseudomonas aeruginosa lectins and identified homologs of LecA in Enterobacter species.
View Article and Find Full Text PDFis a critical priority pathogen and causes life-threatening acute and biofilm-associated chronic infections. The choice of suitable treatment for complicated infections requires lengthy culturing for species identification from swabs or an invasive biopsy. To date, no fast, pathogen-specific diagnostic tools for infections are available.
View Article and Find Full Text PDFBackground: The insulin-like growth factor 1 receptor (IGF-1R) and the thyrotropin receptor (TSH-R) are expressed on orbital cells and thyrocytes. These receptors are targeted in autoimmune-induced thyroid eye disease (TED). Effective therapeutic treatment of TED inhibits activation of the IGF-1R/TSH-R complex.
View Article and Find Full Text PDFObjectives: To determine incidence and risk factors for hypertension in childhood nephrotic syndrome.
Study Design: Using data from the Insight into Nephrotic Syndrome (INSIGHT) study, a prospective observational childhood nephrotic syndrome cohort from Toronto, Canada, we evaluated hypertension incidence and time-to-hypertension overall and stratified by 1) steroid-resistance or steroid-sensitivity, and 2) frequently-relapsing, steroid dependent, or infrequently-relapsing. Hypertension was defined as stage 1-2 hypertensive blood pressure on two consecutive visits or anti-hypertensive medication initiation.
Background: Lumbar microdiscectomy remains the most commonly performed surgical procedure for symptomatic lumbar disk herniation (LDH). Despite advances in surgical techniques, recurrent LDH (rLDH) ranges from 5% to 24%, representing the most common cause of surgical failure and revision surgery. Optimal treatment of reherniation remains controversial.
View Article and Find Full Text PDFOwing to their rapid cooling rate and hence loss-limited propagation distance, cosmic-ray electrons and positrons (CRe) at very high energies probe local cosmic-ray accelerators and provide constraints on exotic production mechanisms such as annihilation of dark matter particles. We present a high-statistics measurement of the spectrum of CRe candidate events from 0.3 to 40 TeV with the High Energy Stereoscopic System, covering 2 orders of magnitude in energy and reaching a proton rejection power of better than 10^{4}.
View Article and Find Full Text PDFThere is growing interest in lifestyle interventions as stand-alone and add-on therapies in mental health care due to their potential benefits for both physical and mental health outcomes. We evaluated lifestyle interventions focusing on physical activity, diet, and sleep in adults with severe mental illness (SMI) and the evidence for their effectiveness. To this end, we conducted a meta-review and searched major electronic databases for articles published prior to 09/2022 and updated our search in 03/2024.
View Article and Find Full Text PDFOestradiol and progesterone levels are higher in menstruating women than men of the same age, and their receptors are present in their neurosensory retina and retinal pigment epithelium. However, the impact of this hormonal environment on retinal physiology in women remains unclear. Using self-reported menstrual cycle phases as a surrogate for fluctuating hormonal levels, we investigated associations with retinovascular indices on colour fundus photograph and retinal thickness in optical coherence tomography across regularly menstruating women in the UK Biobank.
View Article and Find Full Text PDFLocal detection of hydrogen concentration in metals is of central importance for many areas of hydrogen technology, such as hydrogen storage, detection, catalysis, and hydrogen embrittlement. A novel approach to measure the hydrogen concentration in a model system consisting of cubic palladium nanoparticles (Pd NPs), with a lateral resolution down to 4 nm is demonstrated. By measuring the shift of the Pd bulk plasmon peak with scanning transmission electron microscopy (STEM) combined with energy electron loss spectroscopy (EELS) during in situ hydrogen gas loading and unloading, local detection of the hydrogen concentration is achieved in TEM.
View Article and Find Full Text PDFRiverine suspended matter (river-SPM) contains large amounts of natural particles consisting of cellulose and lignin, posing a challenge for microplastic (MPs) analysis. Additionally, organic matter composition under seasonal and discharge-related dynamics varies for each river. Therefore, this study attempted to identify a universally applicable clean-up procedure to remove matrix particles with high organic matter content, mainly plant debris, from the river-SPM samples.
View Article and Find Full Text PDFSynthetic data, generated through artificial intelligence technologies such as generative adversarial networks and latent diffusion models, maintain aggregate patterns and relationships present in the real data the technologies were trained on without exposing individual identities, thereby mitigating re-identification risks. This approach has been gaining traction in biomedical research because of its ability to preserve privacy and enable dataset sharing between organisations. Although the use of synthetic data has become widespread in other domains, such as finance and high-energy physics, use in medical research raises novel issues.
View Article and Find Full Text PDFBackground: Dietary supplements (DS) are often used by patients to enhance their health and well-being. General practitioners (GPs) are commonly the first point of contact for patients who enquire about DS. The aim of this study was to explore GPs' views on DS.
View Article and Find Full Text PDFThe first search for soft unclustered energy patterns (SUEPs) is performed using an integrated luminosity of 138 fb^{-1} of proton-proton collision data at sqrt[s]=13 TeV, collected in 2016-2018 by the CMS detector at the LHC. Such SUEPs are predicted by hidden valley models with a new, confining force with a large 't Hooft coupling. In events with boosted topologies, selected by high-threshold hadronic triggers, the multiplicity and sphericity of clustered tracks are used to reject the background from standard model quantum chromodynamics.
View Article and Find Full Text PDFPlasma biomarkers represent promising tools for the screening and diagnosis of patients with neurodegenerative conditions. However, it is crucial to account for the effects of aging on biomarker profiles, especially in the oldest segments of the population. Additionally, biomarkers in this sample can offer in vivo insights into the physiological mechanisms underlying brain aging while concomitantly supporting cognitive preservation.
View Article and Find Full Text PDFPerit Dial Int
November 2024
Background: Peritoneal dialysis (PD) is commonly performed using either intermittent or tidal exchanges, whereas other exchange techniques such as continuous flow PD are little used. Previous research indicated that stirring the intra-peritoneal dialysate markedly increases small solute clearances. Here, we tested the hypothesis that stirring of the dialysate increases small solute clearances by using a novel exchange technique where the dialysate is pulsed back and forth during the treatment without addition of fresh fluid.
View Article and Find Full Text PDFTo promote intracellular survival and infection, Legionella spp. translocate hundreds of effector proteins into eukaryotic host cells using a type IV b protein secretion system (T4bSS). T4bSS are well known to translocate soluble as well as transmembrane domain-containing effector proteins (TMD-effectors) but the mechanisms of secretion are still poorly understood.
View Article and Find Full Text PDFIt is estimated that over 16 million people are living with opioid use disorder (OUD) worldwide, with 2.1 million people in the United States. Opioid addiction is theorized to be associated with strong dopaminergic response to opioid receptor stimulations that contributes to reward-seeking behaviors and individuals' experiences with opioids.
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