Improving the Capacity of Non-Physician Primary Care Providers to Address Child and Youth Mental Health Through Mental Health Literacy Approaches.

Introduction And Objectives: Canadians rely on their primary care providers to address their mental health needs, but there are longstanding system gaps that must be addressed to enhance their ability to deliver mental health care. The present study addressed the gap in pediatric mental health care through the development, delivery, and evaluation of a mental health literacy training among non-physician primary care providers.

Methods: We delivered the training among 97 participants, with all completed the pre-test survey, and 74 completed the post-test survey on knowledge, attitudes toward mental health, and help-seeking intentions.

Using a Bacterial Protein to Selectively Target Bacterial Biofilms: Treatment of S. epidermidis Biofilms with Targeted Photothermal Gold Nanoparticles.

Biofilm-related infections are associated with high mortality and morbidity, combined with increased treatment costs. Traditional antibiotics are becoming less effective due to the emergence of drug-resistant bacterial strains. The need to treat biofilms on medical implants is particularly acute, and one persistent challenge is selectively directing nanoparticles to the biofilm site.

Loss-of-function mutations in Dnmt3a and Tet2 lead to accelerated atherosclerosis and concordant macrophage phenotypes.

Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the presence of a cancer-associated somatic mutation in white blood cells in the absence of overt hematological malignancy. It arises most commonly from loss-of-function mutations in the epigenetic regulators DNMT3A and TET2. CHIP predisposes to both hematological malignancies and atherosclerotic cardiovascular disease in humans.

Spatial Patterning Analysis of Cellular Ensembles (SPACE) discovers complex spatial organization at the cell and tissue levels.

Spatial patterns of cells and other biological elements drive both physiologic and pathologic processes within tissues. While many imaging and transcriptomic methods document tissue organization, discerning these patterns is challenging, especially when they involve multiple elements in complex arrangements. To address this challenge, we present Spatial Patterning Analysis of Cellular Ensembles (SPACE), an R package for analysis of high-plex spatial data.

Single-Cell Imaging Maps Inflammatory Cell Subsets to Pulmonary Arterial Hypertension Vasculopathy.

Unraveling immune-driven vascular pathology in pulmonary arterial hypertension (PAH) requires a comprehensive understanding of the immune cell landscape. Although patients with hereditary (H)PAH and bone morphogenetic protein receptor type 2 (BMPR2) mutations have more severe pulmonary vascular pathology, it is not known whether this is related to specific immune cell subsets. This study aims to elucidate immune-driven vascular pathology by identifying immune cell subtypes linked to severity of pulmonary arterial lesions in PAH.

Robust phenotyping of highly multiplexed tissue imaging data using pixel-level clustering.

While technologies for multiplexed imaging have provided an unprecedented understanding of tissue composition in health and disease, interpreting this data remains a significant computational challenge. To understand the spatial organization of tissue and how it relates to disease processes, imaging studies typically focus on cell-level phenotypes. However, images can capture biologically important objects that are outside of cells, such as the extracellular matrix.

Spatial proteomics reveals human microglial states shaped by anatomy and neuropathology.

Microglia are implicated in aging, neurodegeneration, and Alzheimer's disease (AD). Traditional, low-plex, imaging methods fall short of capturing cellular states and interactions in the human brain. We utilized Multiplexed Ion Beam Imaging (MIBI) and data-driven analysis to spatially map proteomic cellular states and niches in healthy human brain, identifying a spectrum of microglial profiles, called the microglial state continuum (MSC).

Single-cell spatial proteomic imaging for human neuropathology.

Neurodegenerative disorders are characterized by phenotypic changes and hallmark proteopathies. Quantifying these in archival human brain tissues remains indispensable for validating animal models and understanding disease mechanisms. We present a framework for nanometer-scale, spatial proteomics with multiplex ion beam imaging (MIBI) for capturing neuropathological features.

Combined protein and nucleic acid imaging reveals virus-dependent B cell and macrophage immunosuppression of tissue microenvironments.

Understanding the mechanisms of HIV tissue persistence necessitates the ability to visualize tissue microenvironments where infected cells reside; however, technological barriers limit our ability to dissect the cellular components of these HIV reservoirs. Here, we developed protein and nucleic acid in situ imaging (PANINI) to simultaneously quantify DNA, RNA, and protein levels within these tissue compartments. By coupling PANINI with multiplexed ion beam imaging (MIBI), we measured over 30 parameters simultaneously across archival lymphoid tissues from healthy or simian immunodeficiency virus (SIV)-infected nonhuman primates.

Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma.

Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor to invasive breast cancer (IBC). To understand the changes in the tumor microenvironment (TME) accompanying transition to IBC, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) and a 37-plex antibody staining panel to interrogate 79 clinically annotated surgical resections using machine learning tools for cell segmentation, pixel-based clustering, and object morphometrics. Comparison of normal breast with patient-matched DCIS and IBC revealed coordinated transitions between four TME states that were delineated based on the location and function of myoepithelium, fibroblasts, and immune cells.

The immunoregulatory landscape of human tuberculosis granulomas.

Tuberculosis (TB) in humans is characterized by formation of immune-rich granulomas in infected tissues, the architecture and composition of which are thought to affect disease outcome. However, our understanding of the spatial relationships that control human granulomas is limited. Here, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) to image 37 proteins in tissues from patients with active TB.

Rhesus Macaque CODEX Multiplexed Immunohistochemistry Panel for Studying Immune Responses During Ebola Infection.

Non-human primate (NHP) animal models are an integral part of the drug research and development process. For some biothreat pathogens, animal model challenge studies may offer the only possibility to evaluate medical countermeasure efficacy. A thorough understanding of host immune responses in such NHP models is therefore vital.

Multiplexed imaging reveals an IFN-γ-driven inflammatory state in nivolumab-associated gastritis.

Immune checkpoint blockade using PD-1 inhibition is an effective approach for treating a wide variety of cancer subtypes. While lower gastrointestinal (GI) side effects are more common, upper gastrointestinal adverse events are rarely reported. Here, we present a case of nivolumab-associated autoimmune gastritis.

Multiplexed Ion Beam Imaging: Insights into Pathobiology.

Next-generation tools for multiplexed imaging have driven a new wave of innovation in understanding how single-cell function and tissue structure are interrelated. In previous work, we developed multiplexed ion beam imaging by time of flight, a highly multiplexed platform that uses secondary ion mass spectrometry to image dozens of antibodies tagged with metal reporters. As instrument throughput has increased, the breadth and depth of imaging data have increased as well.

The Economic Impact of Providing Evidence-Based Pediatric Mental Health Literacy Training to Primary Care Physicians.

Objective: This paper presents a review of the current state of child and adolescent mental health literacy and provides current evidence of the economic impact of a pediatric mental health literacy (MHL) training program.

Methods: Employing a case-series-comparison design, physician referrals to urgent and specialized mental health services were linked with patient-specific information comparing referrals from MHL participants and non-participating physicians. The economic impact analysis was based on changes in the admitted referral frequency and lengths of stay for the MHL group, compared to themselves pretraining, and over the same time period compared to non-participating physicians.

Single-cell metabolic profiling of human cytotoxic T cells.

Cellular metabolism regulates immune cell activation, differentiation and effector functions, but current metabolic approaches lack single-cell resolution and simultaneous characterization of cellular phenotype. In this study, we developed an approach to characterize the metabolic regulome of single cells together with their phenotypic identity. The method, termed single-cell metabolic regulome profiling (scMEP), quantifies proteins that regulate metabolic pathway activity using high-dimensional antibody-based technologies.

Radiation therapy for augmenting the efficacy of immunotherapy in advanced non-small cell lung cancer: a case-controlled study.

http://bit.ly/3btOFSL.

MIBI-TOF: A multiplexed imaging platform relates cellular phenotypes and tissue structure.

Understanding tissue structure and function requires tools that quantify the expression of multiple proteins while preserving spatial information. Here, we describe MIBI-TOF (multiplexed ion beam imaging by time of flight), an instrument that uses bright ion sources and orthogonal time-of-flight mass spectrometry to image metal-tagged antibodies at subcellular resolution in clinical tissue sections. We demonstrate quantitative, full periodic table coverage across a five-log dynamic range, imaging 36 labeled antibodies simultaneously with histochemical stains and endogenous elements.

Survival outcomes in patients with non-small-cell lung cancer treated with erlotinib.

Erlotinib is used to treat non-small-cell lung cancer (NSCLC). Erlotinib was subsidized on the Pharmaceutical Benefits Schedule in Australia for the treatment of advanced stage (IIIB or IV) NSCLC (August 2008). In the pivotal trial supporting initial subsidy, erlotinib increased overall survival (OS) by 2 months compared with placebo (adjusted hazard ratio, 0.

Pembrolizumab-Induced Encephalopathy: A Review of Neurological Toxicities with Immune Checkpoint Inhibitors.

The use of immune checkpoint inhibitor (ICI) therapy in the treatment of solid organ malignancies is becoming increasingly common. This has prompted the recognition of a new class of immune-related adverse effects (irAEs) stemming from the upregulation of T-cell activity causing autoimmunity. Neurological irAEs are a rare complication of ICIs that can lead to long-term morbidity.

Mental health literacy in primary care: Canadian Research and Education for the Advancement of Child Health (CanREACH).

The effectiveness of a continuing education programme in paediatric psychopharmacology designed for primary healthcare providers was objectively measured based on the assumption that training would lead to measurable changes in referral patterns and established clinical measures of referred patients. Using established, valid and reliable measures of clinical urgency embedded in to a regional healthcare system since 2002, the referrals to child and adolescent psychiatric services of physicians who participated in the training (n=99) were compared pretraining and post-training, and to non-participating/untrained referring physicians (n=7753) making referrals over the same time period. Referrals were analysed for evidence of change based on frequencies and measures of clinical urgency.

A Rare Case of Omentum Invasive Prostate Cancer: Staging With PSMA PET/CT Imaging and Response to Systemic Therapy.

The omentum is a rare metastatic site for prostatic adenocarcinoma. We present a case of metastatic castrate-resistant prostate cancer, with progressive omentum invasive prostate cancer identified on prostate-specific membrane antigen (PSMA) PET/CT scan. Omental biopsy revealed metastatic prostate adenocarcinoma, and cabazitaxel chemotherapy was instituted with a prostate-specific antigen biochemical response.