Monounsaturated fatty acids from plant or animal sources and risk of type 2 diabetes in three large prospective cohorts of men and women.

Aims/hypothesis: Existing evidence on the relationship between intake of monounsaturated fatty acids (MUFAs) and type 2 diabetes is conflicting. Few studies have examined whether MUFAs from plant or animal sources (MUFA-Ps and MUFA-As, respectively) exhibit differential associations with type 2 diabetes. We examined associations of intakes of total MUFAs, MUFA-Ps and MUFA-As with type 2 diabetes risk.

Measurement Properties of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia.

Introduction: The Friedreich Ataxia Rating Scale-Activities of Daily Living (FARS-ADL) is a valid, highly utilized measure for assessing ADL impacts in patients with Friedreich ataxia. We provide evidence of the psychometric validity of the FARS-ADL in two cohorts of patients with spinocerebellar ataxia (SCA).

Methods: Using data from a cohort of real-world subjects with SCA (recruited at Massachusetts General Hospital [MGH]; n = 33) and a phase 3 trial of troriluzole in adults with SCA (NCT03701399 [Study 206]; n = 217), comprising a subset of patients with the SCA3 genotype (n = 89), the psychometric measurement properties and minimal change thresholds of the FARS-ADL were examined.

Evaluation of Drug-Drug Interactions in Pharmacoepidemiologic Research.

Drug-drug interactions (DDIs) represent a significant concern for clinical care and public health, but the health consequences of many DDIs remain largely underexplored. This knowledge gap underscores the critical need for pharmacoepidemiologic research to evaluate real-world health outcomes of DDIs. In this review, we summarize the definitions commonly used in pharmacoepidemiologic DDI studies, discuss common sources of bias, and illustrate through examples how these biases can be mitigated.

Bilingual Perspectives of Functional Dyspepsia Management in People from Underserved Areas.

Introduction: Disorders of gut-brain interaction (DGBIs), like functional dyspepsia (FD), are prevalent and challenging conditions. In other gastrointestinal (GI) disorders, individuals from underserved areas (UAs) have difficulty accessing care. Little is known about UA FD patient perspectives of their care, especially in those with limited English proficiency (LEP).

The Last Decade in Cardiac Amyloidosis: Advances in Understanding Pathophysiology, Diagnosis and Quantification, Prognosis, Treatment Strategies, and Monitoring Response.

Cardiac amyloidosis represents a unique disease process characterized by amyloid fibril deposition within the myocardial extracellular space. Advances in multimodality cardiac imaging enable accurate diagnosis and facilitate prompt initiation of disease-modifying therapies. Furthermore, rapid advances in multimodality imaging have enriched understanding of the underlying pathogenesis, enhanced prognostication, and resulted in the development of imaging-based markers that reflect the amyloid burden, which is of increasing importance when assessing the response to treatment.

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.

The Impact of Blood Pressure Below Personalized Lower Cerebral Autoregulation Limit on Outcomes After Cardiac Surgery: A Retrospective Study.

Objective: The clinical importance of individualized blood pressure management in optimizing cerebral perfusion during cardiac surgery has been well established. However, consensus on blood pressure goals is lacking. The authors studied the associations between cerebral autoregulation metrics, hemodynamic parameters, and postoperative outcomes, and hypothesized that increased time of mean arterial pressure (MAP) below the lower limit of autoregulation (LLA) is associated with major morbidity and mortality (MMOM) incidence.

Carotid artery atherosclerosis: mechanisms of instability and clinical implications.

Cardiovascular disease remains a prominent cause of disability and premature death worldwide. Within this spectrum, carotid artery atherosclerosis is a complex and multifaceted condition, and a prominent precursor of acute ischaemic stroke and other cardiovascular events. The intricate interplay among inflammation, oxidative stress, endothelial dysfunction, lipid metabolism, and immune responses participates in the development of lesions, leading to luminal stenosis and potential plaque instability.

Epistaxis Versus Nonepistaxis Bleeding in Anticoagulated Patients With Atrial Fibrillation: Results From the ENGAGE AF-TIMI 48 Trial.

Background: Epistaxis is common with antithrombotic therapy and is often troublesome to patients, yet its frequency, severity, and outcomes are poorly characterized.

Methods And Results: Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) randomized 21 105 patients with atrial fibrillation and CHADS2 risk score ≥2 to higher-dose edoxaban regimen (60 mg daily, dose-reduced to 30 mg), lower-dose edoxaban regimen (30 mg, dose reduced to 15 mg, daily), or warfarin. Bleeds were adjudicated using International Society on Thrombosis and Haemostasis criteria.

Developing an EEG-based model to predict awakening after cardiac arrest using partial processing with the BIS Engine.

Introduction: Accurate prognostication in comatose survivors of cardiac arrest is a challenging and high-stakes endeavor. We sought to determine whether internal EEG subparameters extracted by the Bispectral Index (BIS) monitor, a device commonly used to estimate depth-of-anesthesia intraoperatively, could be repurposed to predict recovery of consciousness after cardiac arrest.

Methods: In this retrospective cohort study, we trained a 3-layer neural network to predict recovery of consciousness to the point of command following versus not based on 48 hours of continuous EEG recordings in 315 comatose patients admitted to a single US academic medical center after cardiac arrest (Derivation cohort: N=181; Validation cohort: N=134).

A specific and adaptable approach to track CD206 macrophages by molecular MRI and fluorescence imaging.

The mannose receptor (CD206, expressed by the gene ) is a surface marker overexpressed by anti-inflammatory and pro-tumoral macrophages. As such, CD206 macrophages play key roles in the immune response to different pathophysiological conditions and represent a promising diagnostic and therapeutic target. However, methods to specifically target these cells remain challenging.

Coffee drinking timing and mortality in US adults.

Background And Aims: To identify the patterns of coffee drinking timing in the US population and evaluate their associations with all-cause and cause-specific mortality.

Methods: This study included 40 725 adults from the National Health and Nutrition Examination Survey 1999-2018 who had complete information on dietary data and 1463 adults from the Women's and Men's Lifestyle Validation Study who had complete data on 7-day dietary record. Clustering analysis was used to identify patterns of coffee drinking timing.

Sugar-sweetened or artificially sweetened beverage consumption, physical activity and risk of type 2 diabetes in US adults.

Aims/hypothesis: A positive association between sugar-sweetened beverages (SSBs) and diabetes risk has been shown, with inconsistent evidence between artificially sweetened beverages (ASBs) and diabetes. Moreover, it is uncertain if physical activity can mitigate the negative effects of these beverages on diabetes development. Therefore, we aimed to evaluate the independent and joint associations between SSB or ASB consumption and physical activity on the risk of type 2 diabetes.

Aspirin and Hemocompatibility After LVAD Implantation in Patients With Atherosclerotic Vascular Disease: A Secondary Analysis From the ARIES-HM3 Randomized Clinical Trial.

Importance: The Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure (ARIES-HM3) study demonstrated that aspirin may be safely eliminated from the antithrombotic regimen after HeartMate 3 (HM3 [Abbott Cardiovascular]) left ventricular assist device (LVAD) implantation. This prespecified analysis explored whether conditions requiring aspirin (prior percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], stroke, or peripheral vascular disease [PVD]) would influence outcomes differentially with aspirin avoidance.

Objective: To analyze aspirin avoidance on hemocompatibility-related adverse events (HRAEs) at 1 year after implant in patients with a history of CABG, PCI, stroke, or PVD.

Alpha-Synuclein Effects on Mitochondrial Quality Control in Parkinson's Disease.

The maintenance of healthy mitochondria is essential for neuronal survival and relies upon mitochondrial quality control pathways involved in mitochondrial biogenesis, mitochondrial dynamics, and mitochondrial autophagy (mitophagy). Mitochondrial dysfunction is critically implicated in Parkinson's disease (PD), a brain disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Consequently, impaired mitochondrial quality control may play a key role in PD pathology.

Same-Slide Spatial Multi-Omics Integration Reveals Tumor Virus-Linked Spatial Reorganization of the Tumor Microenvironment.

The advent of spatial transcriptomics and spatial proteomics have enabled profound insights into tissue organization to provide systems-level understanding of diseases. Both technologies currently remain largely independent, and emerging same slide spatial multi-omics approaches are generally limited in plex, spatial resolution, and analytical approaches. We introduce IN-situ DEtailed Phenotyping To High-resolution transcriptomics (IN-DEPTH), a streamlined and resource-effective approach compatible with various spatial platforms.

Association between somatic microsatellite instability, hypermutation status, and specific T cell subsets in colorectal cancer tumors.

Background: Microsatellite instability-high (MSI-high) tumors comprise ~15% of sporadic colorectal cancers (CRC) and are associated with elevated T cell infiltration. However, the universality of this response across T cell subtypes with distinct functions is unknown.

Methods: Including 1,236 CRC tumors from three observational studies, we conducted T cell profiling using a customized 9-plex (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, and DAPI) multispectral immunofluorescence assay.

Co-occurring Psychopathology in Children With and Without Autism Spectrum Disorder (ASD): Differences by Sex in the ECHO Cohorts.

Purpose: Our goals were to: 1) examine the occurrence of behavioral and emotional symptoms in children on the autism spectrum in a large national sample, stratifying by sex, and 2) evaluate whether children with increased autism-related social communication deficits also experience more behavioral and emotional problems.

Methods:  Participants (n = 7,998) were from 37 cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program. Cross-sectional information on demographic factors, parent-report of an ASD diagnosis by clinician, Social Responsiveness Scale (SRS) scores, and Child Behavior Checklist (CBCL) scores were obtained for children aged 2.

Assessing the Risk for Falls in Older Adults After Initiating Gabapentin Versus Duloxetine.

Background: The evidence informing the harms of gabapentin use are at risk of bias from comparing users with nonusers.

Objective: To describe the risk for fall-related outcomes in older adults starting treatment with gabapentin versus duloxetine.

Design: New user, active comparator study using a target trial emulation framework.

Defective removal of invariant chain peptides from MHC class II suppresses tumor antigen presentation and promotes tumor growth.

Tumor-draining lymph node dendritic cells (DCs) are poor stimulators of tumor antigen-specific CD4 T cells; however, the mechanism behind this defect is unclear. We now show that, in tumor-draining lymph node DCs, a large proportion of major histocompatibility complex class II (MHC-II) molecules retains the class II-associated invariant chain peptide (CLIP) fragment of the invariant chain bound to the MHC-II peptide binding groove due to reduced expression of the peptide editor H2-M and enhanced activity of the CLIP-generating proteinase cathepsin S. The net effect of this is that MHC-II molecules are unable to efficiently bind antigenic peptides.