An open source autoregulation-based neuromonitoring algorithm shows PRx and optimal CPP association with pediatric traumatic brain injury.

This study aimed to develop an open-source algorithm for the pressure-reactivity index (PRx) to monitor cerebral autoregulation (CA) in pediatric severe traumatic brain injury (sTBI) and compared derived optimal cerebral perfusion pressure (CPPopt) with real-time CPP in relation to long-term outcome. Retrospective study in children (< 18 years) with sTBI admitted to the pediatric intensive care unit (PICU) for intracranial pressure (ICP) monitoring between 2016 and 2023. ICP was analyzed on an insult basis and correlated with outcome.

Boundary-work in genomic medicine: Safeguarding the future of diagnostic next-generation sequencing in the clinic.

Next-generation sequencing (NGS) technologies - which allow to look at large parts or even the whole genome at once - are making their way into diagnostic clinical care. With trends towards 'mainstreaming' genetic services into general medicine, significant ethical challenges, and a disputed clinical utility and cost-benefit ratio, genomic medicine's autonomy and dominance in defining and offering NGS care may come under increased pressure from the outside (e.g.

Current status of peptide receptor radionuclide therapy in grade 1 and 2 gastroenteropancreatic neuroendocrine tumours.

Peptide receptor radionuclide therapy (PRRT) using [Lu-DOTA,Tyr]octreotate (Lu-DOTATATE) represents an established treatment modality for somatostatin receptor-positive, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NET) of grade 1 or 2. The studies have demonstrated that four cycles of PRRT with Lu-DOTATATE prolongs progression-free survival and preserves quality of life, in patients with grade 1 and 2 advanced GEP NET. Notably, first-line PRRT using Lu-DOTATATE in grade 2 and 3 GEP NET patients has also shown efficacy and safety.

Associations of pre- and postnatal per- and polyfluoroalkyl substance exposure with adolescents' eating behaviors.

Background: Per- and polyfluoroalkyl substances (PFAS), persistent environmental chemicals, may act as obesogens by interacting with neuroendocrine pathways regulating energy homeostasis and satiety signals influencing adolescent eating behaviors.

Methods: In 211 HOME Study adolescents (Cincinnati, OH; recruited 2003-2006), we measured PFAS concentrations in serum collected during pregnancy, at delivery, and at ages 3, 8, and 12 years. Caregivers completed the Child Eating Behavior Questionnaire (CEBQ) at age 12, and we calculated food approach and food avoidance scores.

Blood integrin- and cytokine-producing T cells are associated with stage and genetic risk score in age-related macular degeneration.

Age-related macular degeneration (AMD) remains a leading cause of vision loss in the geriatric population. There are age-related changes in peripheral blood leukocyte composition, but their significance for AMD remains unclear. We aimed to determine changes in immune cell populations in the blood of AMD patients.

Leukemia inhibitory factor receptor inhibition by EC359 reduces atherosclerotic stenosis grade in Ldlr mice.

Cytokines are involved in all stages of atherosclerosis, generally contributing to disease progression. Previously, members of the Interleukin (IL)-6 cytokine family, such as IL-6, oncostatin M, and cardiotrophin-1, have been extensively studied in atherosclerosis. However, the role of leukemia inhibitory factor (LIF), member of the IL-6 family, and its receptor (LIFR), remains to be further elucidated.

Applying Latent Variable Models to Estimate Cumulative Exposure Burden to Chemical Mixtures and Identify Latent Exposure Subgroups: A Critical Review and Future Directions.

Environmental mixtures, which reflect joint exposure to multiple environmental agents, are a major focus of environmental health and risk assessment research. Advancements in latent variable modeling and psychometrics can be used to address contemporary questions in environmental mixtures research. In particular, latent variable models can quantify an individual's cumulative exposure burden to mixtures and identify hidden subpopulations with distinct exposure patterns.

A Randomized Controlled Trial Comparing "Early" Versus "Late" Periosteal Patch Attachment to Knee Chondral Defects in Autologous Chondrocyte Implantation.

Objective: Traditional autologous chondrocyte implantation (ACI) involves arthroscopically harvesting a cartilage biopsy (stage 1), followed by arthrotomy 3 to 4 weeks later to apply a periosteal patch and implant culture-expanded chondrocytes underneath (stage 2). This study aimed to determine if patch application during stage 1 rather than stage 2 improved clinical outcome.

Design: A randomized controlled trial was conducted from 1998 to 2001.

Integrated metabolic-transcriptomic network identifies immunometabolic modulations in human macrophages.

Macrophages exhibit diverse phenotypes and respond flexibly to environmental cues through metabolic remodeling. In this study, we present a comprehensive multi-omics dataset integrating intra- and extracellular metabolomes with transcriptomic data to investigate the metabolic impact on human macrophage function. Our analysis establishes a metabolite-gene correlation network that characterizes macrophage activation.

Outcomes of Traumatic Brain Injury Patients Managed in a Non-Intensive Care Unit Setting.

Introduction: The management of traumatic brain injury (TBI) requires significant health-care resources. The modified Brain Injury Guidelines (mBIG) stratifies TBI patients by severity to help guide disposition and management. We sought to analyze the outcomes of TBI patients managed in a non-intensive care unit (ICU) setting after stratifying them using the mBIG criteria.

Lower cell number, lateral defect location and milder grade are associated with improved autologous chondrocyte implantation outcome.

Purpose: To investigate patient demographic, injury and surgery/treatment-associated factors that can influence the patient-reported outcome (Lysholm score), following autologous chondrocyte implantation (ACI) in a large, 'real-world', nonuniform, prospective data examined retrospectively.

Methods: Knee patients treated at the Robert Jones and Agnes Hunt Orthopaedic Hospital, UK, using ACI between 1996 and 2020 were eligible. All longitudinal postoperative Lysholm scores collected between 1 and 23 years after ACI treatment and before any second major procedure (e.

Metadata for Data dIscoverability aNd Study rEplicability in obseRVAtional Studies (MINERVA): Development and Pilot of a Metadata List and Catalogue in Europe.

Purpose: Metadata for data dIscoverability aNd study rEplicability in obseRVAtional studies (MINERVA), a European Medicines Agency-funded project (EUPAS39322), defined a set of metadata to describe real-world data sources (RWDSs) and piloted metadata collection in a prototype catalogue to assist investigators from data source discoverability through study conduct.

Methods: A list of metadata was created from a review of existing metadata catalogues and recommendations, structured interviews, a stakeholder survey, and a technical workshop. The prototype was designed to comply with the FAIR principles (findable, accessible, interoperable, reusable), using MOLGENIS software.

Single-cell profiling identifies a CD8 CD244 Natural Killer cell subset that reflects disease activity in HLA-A29-positive birdshot chorioretinopathy.

Birdshot chorioretinopathy is an inflammatory eye condition strongly associated with MHC-I allele HLA-A29. The striking association with MHC-I suggests involvement of T cells, whereas natural killer (NK) cell involvement remains largely unstudied. Here we show that HLA-A29-positive birdshot chorioretinopathy patients have a skewed NK cell pool containing expanded CD16 positive NK cells which produce more proinflammatory cytokines.

A mathematical model of signalling molecule-mediated processes during regeneration of osteochondral defects after chondrocyte implantation.

Treating bone-cartilage defects is a fundamental clinical problem. The ability of damaged cartilage to self-repair is limited due to its avascularity. Left untreated, these defects can lead to osteoarthritis.

Associations of a toenail metal mixture with attention and memory in the Gulf long-term follow-up (GuLF) study.

Background: Research on metal-associated neurodegeneration has largely focused on single metals. Since metal exposures typically co-occur as combinations of both toxic and essential elements, a mixtures framework is important for identifying risk and protective factors. This study examined associations between toenail levels of an eight-metal mixture and attention and memory in men living in US Gulf states.

Sexual dimorphism in atherosclerotic plaques of aged Ldlr mice.

Background: Atherosclerosis, the main underlying pathology of cardiovascular disease, is a chronic inflammatory disease characterized by lipid accumulation and immune cell responses in the vascular wall, resulting in plaque formation. It is well-known that atherosclerosis prevalence and manifestation vary by sex. However, sexual dimorphism in the immune landscape of atherosclerotic plaques has up to date not been studied at high-resolution.

Urinary concentrations of phthalate metabolites in relation to preeclampsia and other hypertensive disorders of pregnancy in the environmental influences on child health outcomes (ECHO) program.

Background: Phthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking.

Objectives: To evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP.

Methods: Using data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy.

Immunoproteasomal Inhibition With ONX-0914 Attenuates Atherosclerosis and Reduces White Adipose Tissue Mass and Metabolic Syndrome in Mice.

Background: Atherosclerosis is the major underlying pathology of cardiovascular disease and is driven by dyslipidemia and inflammation. Inhibition of the immunoproteasome, a proteasome variant that is predominantly expressed by immune cells and plays an important role in antigen presentation, has been shown to have immunosuppressive effects.

Methods: We assessed the effect of ONX-0914, an inhibitor of the immunoproteasomal catalytic subunits LMP7 (proteasome subunit β5i/large multifunctional peptidase 7) and LMP2 (proteasome subunit β1i/large multifunctional peptidase 2), on atherosclerosis and metabolism in LDLr and APOE*3-Leiden.

Resident Memory T Cells in the Atherosclerotic Lesion Associate With Reduced Macrophage Content and Increased Lesion Stability.

Background: Tissue resident memory T (T) cells are a T-cell subset that resides at the site of prior antigen recognition to protect the body against reoccurring encounters. Besides their protective function, T cells have also been implicated in inflammatory disorders. T cells are characterized by the expression of CD69 and transcription factors Hobit (homolog of Blimp-1 [B lymphocyte-induced maturation protein 1] in T cells) and Blimp-1.