Locus coeruleus signal intensity and emotion regulation in agitation in Alzheimer's disease.

Hyperphosphorylated tau accumulation is seen in the noradrenergic locus coeruleus from the earliest stages of Alzheimer's disease onwards and has been associated with symptoms of agitation. It is hypothesized that compensatory locus coeruleus-noradrenaline system overactivity and impaired emotion regulation could underlie agitation propensity, but to our knowledge this has not previously been investigated. A better understanding of the neurobiological underpinnings of agitation would help the development of targeted prevention and treatment strategies.

Informal care for people with dementia in Europe.

Introduction: Informal care estimates for use in health-economic models are lacking. We aimed to estimate the association between informal care time and dementia symptoms across Europe.

Methods: A secondary analysis was performed on 13,529 observations in 5,369 persons from 9 European pooled cohort or trial studies in community-dwelling persons with dementia.

Endometriosis and risk of depression among oral contraceptive users: a pooled analysis of cohort studies from 13 countries.

Study Question: Does endometriosis affect the mental health of women using oral contraceptives?

Summary Answer: Among oral contraceptive users, women with endometriosis have a higher risk of depression compared to those without endometriosis, although the absolute risk increase is small.

What Is Known Already: Previous studies have suggested a potential link between endometriosis and mental health issues, but the impact of endometriosis on depression among oral contraceptive users remains unclear.

Study Design, Size, Duration: A secondary pooled cohort study utilizing data from two longitudinal patient-centric studies (INAS-VIPOS and PRO-E2) was conducted across 11 European countries, Colombia and Australia.

C5 complement inhibition versus FcRn modulation in generalised myasthenia gravis.

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions, leading to fluctuating muscle weakness. While many patients respond well to standard immunosuppression, a substantial subgroup faces ongoing disease activity. Emerging treatments such as complement factor C5 inhibition (C5IT) and neonatal Fc receptor (FcRn) antagonism hold promise for these patients.

Sexual dysfunctions associated with antipsychotic drug intake: a retrospective analysis of the FDA adverse events reporting system (FAERS).

Sexual dysfunctions (SD) are common and debilitating side effects of antipsychotics. The current study analyzes the occurrence of antipsychotic-related SD using data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). FAERS was queried for sexual dysfunction adverse events (encoded by 35 different MedDRA preferred terms) secondary to amisulpride, aripiprazole, chlorprothixene, clozapine, haloperidol, loxapine, olanzapine, pipamperone, quetiapine, risperidone, and ziprasidone from 2000 to 2023.

Large Variations in Phenylalanine Concentrations Associate Adverse Cardiac Remodelling in Adult Patients With Phenylketonuria-A Long-Term CMR Study.

Background: Despite a phenylalanine (Phe) restrictive diet, most adult patients with 'classical' phenylketonuria (PKU) maintain life-long Phe concentrations above the normal range and receive tyrosine (Tyr) and protein-enriched diets to maintain acceptable concentrations and ensure normal development. While these interventions are highly successful in preventing adverse neuropsychiatric complications, their long- term consequences are incompletely explored. We observed early cardiomyopathic characteristics and associated hemodynamic changes in adult PKU patients and present here the results of a longitudinal evaluation of cardiac phenotype.

Effect of Immunoadsorption on clinical presentation and immune alterations in COVID-19-induced and/or aggravated ME/CFS.

Autoreactive antibodies (AAB) are currently being investigated as causative or aggravating factors during post-COVID. In this study we analyze the effect of immunoadsorption therapy on symptom improvement and the relationship with immunological parameters in post-COVID patients exhibiting symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) induced or aggravated by an SARS-CoV-2 infection. This observational study includes 12 post-COVID patients exhibiting a predominance of ME/CFS symptoms alongside increased concentrations of autonomic nervous system receptors (ANSR) autoantibodies and neurological impairments.

Predictive Potential of ECMO Blood Flow for Hemolysis and Outcome of Patients with Severe ARDS.

Treatment with veno-venous extracorporeal membrane oxygenation (VV ECMO) has become a frequently considered rescue therapy in patients with severe acute respiratory distress syndrome (ARDS). Hemolysis is a common complication in patients treated with ECMO. Currently, it is unclear whether increased ECMO blood flow (Q̇) contributes to mortality and might be associated with increased hemolysis.

Strategies in Diagnosis and Therapy of External Outflow Graft Obstruction in Patients with a Fully Magnetically Levitated Left Ventricular Assist Device: A Meta-Analysis and Systematic Review.

The HeartMate 3 (HM3, Abbott) left ventricular assist device (LVAD) is the only commercially available option considered suitable for long-term circulatory support. External compression of the outflow graft causing obstruction (eOGO) is a serious adverse event affecting patients on long-term support. The obstruction occurs due to the accumulation of gelatinous substance between the bend relief and outflow graft.

Correction: Peisen et al. Can Delta Radiomics Improve the Prediction of Best Overall Response, Progression-Free Survival, and Overall Survival of Melanoma Patients Treated with Immune Checkpoint Inhibitors? 2024, , 2669.

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Association of Serum Polyunsaturated Fatty Acids (PUFAs) and Children's Dietary Inflammatory Index (C-DII) with Recurrent Respiratory Infections in Children: A Cross-Sectional Study.

To assess the associations between serum and dietary polyunsaturated fatty acids (PUFAs), as well as the inflammatory potential of diet measured by the Children's Dietary Inflammatory Index (C-DII), and recurrent respiratory infections (RRIs) in children. We enrolled 44 children aged 3-16 years with RRIs and 44 healthy controls. Dietary intake was assessed using a 7-day food record from which PUFA intake and C-DII were calculated.

Standardization to Characterize the Complexity of Vessel Network Using the Aortic Ring Model.

Regeneration after ischemia requires to be promoted by (re)perfusion of the affected tissue, and, to date, there is no therapy that covers all needs. In treatment with mesenchymal stem cells (MSC), the secretome acts via paracrine mechanisms and has a positive influence on vascular regeneration via proangiogenic factors. A lack of standardization and the high complexity of vascular structures make it difficult to compare angiogenic readouts from different studies.

Mind the G(ap): bridging prevention needs and approaches for GHB/GBL users and their social environment.

Background: Gamma-hydroxybutyrate (GHB) and its precursors gamma-butyrolactone (GBL) and 1,4-butanediol (BD) have become a significant concern due to the increase in their recreational use and the high risks associated with it (e.g., overdose, addiction, life-threatening withdrawal syndromes).

The proline-rich antimicrobial peptide Api137 disrupts large ribosomal subunit assembly and induces misfolding.

The proline-rich antimicrobial designer peptide Api137 inhibits protein expression in bacteria by binding simultaneously to the ribosomal polypeptide exit tunnel and the release factor (RF), depleting the cellular RF pool and leading to ribosomal arrest at stop codons. This study investigates the additional effect of Api137 on the assembly of ribosomes using an Escherichia coli reporter strain expressing one ribosomal protein per 30S and 50S subunit tagged with mCherry and EGFP, respectively. Separation of cellular extracts derived from cells exposed to Api137 in a sucrose gradient reveals elevated levels of partially assembled and not fully matured precursors of the 50S subunit (pre-50S).

Medical history predicts phenome-wide disease onset and enables the rapid response to emerging health threats.

The COVID-19 pandemic exposed a global deficiency of systematic, data-driven guidance to identify high-risk individuals. Here, we illustrate the utility of routinely recorded medical history to predict the risk for 1741 diseases across clinical specialties and support the rapid response to emerging health threats such as COVID-19. We developed a neural network to learn from health records of 502,489 UK Biobank participants.

The α-synuclein seed amplification assay: Interpreting a test of Parkinson's pathology.

The α-synuclein seed amplification assay (αSyn-SAA) sensitively detects Lewy pathology, the amyloid state of α-synuclein, in the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD). The αSyn-SAA harnesses the physics of seeding, whereby a superconcentrated solution of recombinant α-synuclein lowers the thermodynamic threshold (nucleation barrier) for aggregated α-synuclein to act as a nucleation catalyst ("seed") to trigger the precipitation (nucleation) of monomeric α-synuclein into pathology. This laboratory setup increases the signal for identifying a catalyst if one is present in the tissue examined.

Easy to use particle-mediated transport of various dissolved active agents into the hair follicles - A novel platform technology.

The use of nanoparticulate systems for the transport of active ingredients into hair follicles has been researched for almost two decades, resulting in countless publications with a wide variety of particle types, release mechanisms and active ingredients. The production of a stable dispersion is often time-consuming and costly. In this publication, we demonstrate for the first time that simply adding diverse submicron particles to a drug solution significantly increases follicular penetration depth by over 160% to 190%, allowing the targeting of subinfundibular structures.

Real-world effectiveness and safety of bulevirtide monotherapy for up to 96 weeks in patients with HDV-related cirrhosis.

Background And Aims: Bulevirtide (BLV) 2 mg/day is EMA approved for treatment of compensated chronic hepatitis due to Delta virus (HDV) infection, however real-life data in large cohorts of patients with cirrhosis are lacking.

Methods: Consecutive HDV-infected patients with cirrhosis starting BLV 2 mg/day since September 2019 were included in a European retrospective multicenter real-life study (SAVE-D). Patient characteristics before and during BLV treatment were collected.

A lever hypothesis for Synaptotagmin-1 action in neurotransmitter release.

Neurotransmitter release is triggered in microseconds by Ca-binding to the Synaptotagmin-1 C-domains and by SNARE complexes that form four-helix bundles between synaptic vesicles and plasma membranes, but the coupling mechanism between Ca-sensing and membrane fusion is unknown. Release requires extension of SNARE helices into juxtamembrane linkers that precede transmembrane regions (linker zippering) and binding of the Synaptotagmin-1 CB domain to SNARE complexes through a "primary interface" comprising two regions (I and II). The Synaptotagmin-1 Ca-binding loops were believed to accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers, or helping bridge the membranes, but SNARE complex binding through the primary interface orients the Ca-binding loops away from the fusion site, hindering these putative activities.

Predicting the risk of intensive care unit admission in patients with COVID-19 presenting in the emergency room: Development and evaluation of the CROSS score.

Background: Existing risk evaluation tools underperform in predicting intensive care unit (ICU) admission for patients with the Coronavirus Disease 2019 (COVID-19). This study aimed to develop and evaluate an accurate and calculator-free clinical tool for predicting ICU admission at emergency room (ER) presentation.

Methods: Data from patients with COVID-19 in a nationwide German cohort (March 2020-January 2023) were analyzed.

Ultrasound pupillometry for the detection of a relative afferent pupillary defect (RAPD): Systematic evaluation in patients with optic neuritis and comparison with infrared video pupillometry.

Purpose: A relative afferent pupillary defect (RAPD) is a characteristic clinical sign of optic neuritis (ON). Here, we systematically evaluated ultrasound pupillometry (UP) for the detection of an RAPD in patients with ON, including a comparison with infrared video pupillometry (IVP), the gold standard for objective pupillometry.

Materials And Methods: We enrolled 40 patients with acute (n = 9) or past (n = 31) ON (ON+), 31 patients with multiple sclerosis (MS) without prior ON, and 50 healthy controls (HC) in a cross-sectional observational study.

Guardian Knowledge in Primary Congenital Glaucoma: A Cross-Sectional Study.

Prcis: Guardian education level and frequency of surgical interventions are key determinants of knowledge in primary congenital glaucoma, highlighting the need for targeted educational strategies.

Background: Management of congenital glaucoma poses unique challenges, particularly concerning the patient guardians' understanding of the condition, which is crucial for treatment adherence and follow-up compliance. This study aimed to assess guardians' knowledge levels and identify the influencing factors.

The ability of pentose pathways to form all essential metabolites provides clues to the origins of metabolism.

The structure of the early metabolic network is unknown. Here, we report that when considered together, pentose utilization pathways form all life-essential precursors. We speculate that the chemistry preserved in pentose metabolism could therefore have been a central structural element in early metabolism.

Variations and Opportunities in Postnatal Management of Hemolytic Disease of the Fetus and Newborn.

Importance: Preventive efforts in pregnancy-related alloimmunization have considerably decreased the prevalence of hemolytic disease of the fetus and newborn (HDFN). International studies are therefore essential to obtain a deeper understanding of the postnatal management and outcomes of HDFN. Taken together with numerous treatment options, large practice variations among centers may exist.