Pathology-oriented multiplexing enables integrative disease mapping.

The expression and location of proteins in tissues represent key determinants of health and disease. Although recent advances in multiplexed imaging have expanded the number of spatially accessible proteins, the integration of biological layers (that is, cell structure, subcellular domains and signalling activity) remains challenging. This is due to limitations in the compositions of antibody panels and image resolution, which together restrict the scope of image analysis.

Altered brain function and structure in youth-onset type 2 diabetes.

Objective: Despite the aggressive clinical trajectory of youth-onset type 2 diabetes (Y-T2D) and consistent evidence of cognitive dysfunction and poor brain health in adults with T2D, the impact of Y-T2D on brain function and structure is understudied.

Design: This study aimed to characterize brain function and structure in a cross-sectional sample of young people with Y-T2D and compare these brain attributes to peers with obesity alone (OB) or healthy weight (HW) without T2D.

Methods: Brain structure and function were measured via magnetic resonance imaging.

Lessons learned for preventing health disparities in future pandemics: the role of social vulnerabilities among children diagnosed with severe COVID-19 early in the pandemic.

Background: Hispanic ethnicity is associated with an increased risk for severe disease in children with COVID-19. Identifying underlying contributors to this disparity can lead to improved health care utilization and prevention strategies.

Methods: This is a retrospective cohort study of children 2-20 years of age with positive SARS-CoV-2 testing from March-October 2020.

Relationships among biological sex, body composition, and bone mineral density in young persons with and without diabetes.

Objectives: Bone mineral density (BMD) is influenced by factors including age, sex, body composition, and diabetes. However, data regarding these relationships in young individuals is limited. The objective of this study was to address this gap in the literature.

Unveiling mechanisms underlying kidney function changes during sex hormone therapy.

BACKGROUNDMen with chronic kidney disease (CKD) experience faster kidney function decline than women. Studies in individuals undergoing sex hormone therapy suggest a role for sex hormones, as estimated glomerular filtration rate (eGFR) increases with feminizing therapy and decreases with masculinizing therapy. However, effects on measured GFR (mGFR), glomerular and tubular function, and involved molecular mechanisms remain unexplored.

Not all controls are made equal: Definition of human kidney reference samples by single cell gene expression profiles.

Unlabelled: Identifying kidney disease mechanisms often requires comparing samples from disease states with healthy reference tissues. However, the effect of variations in sample procurement, storage and donor baseline characteristics of reference samples has thus far not been evaluated. Three distinct kidney reference sample types were evaluated for integrity and injury biomarkers and in their ability to define differentially expressed genes (DEGs) when compared to three different diabetic kidney disease (DKD) states.

Cellular pharmacology of tenofovir alafenamide and emtricitabine in neutrophils and platelets in people with and without HIV.

Background: Previous studies have primarily focused on nucleos(t)ide reverse transcriptase inhibitor pharmacology in peripheral blood mononuclear cells (PBMCs) and erythrocytes via dried blood spots (DBS), but not other major blood cells.

Objectives: Our objectives were to describe and compare the concentrations of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) in DBS, PBMCs, neutrophils, and platelets in people with HIV (PWH) and people without HIV (PWOH).

Methods: DBS, PBMCs, neutrophils, and platelets were isolated from whole blood drawn from PWH and PWOH receiving tenofovir alafenamide and emtricitabine.

Unraveling Diabetic Kidney Disease: The Roles of Mitochondrial Dysfunction and Immunometabolism.

Mitochondria are essential for cellular energy production and are implicated in numerous diseases, including diabetic kidney disease (DKD). Current evidence indicates that mitochondrial dysfunction results in alterations in several metabolic pathways within kidney cells, thereby contributing to the progression of DKD. Furthermore, mitochondrial dysfunction can engender an inflammatory milieu, leading to the activation and recruitment of immune cells to the kidney tissue, potentially perturbing intrarenal metabolism.

Unraveling Sex Differences in Kidney Health and CKD: A Review of the Effect of Sex Hormones.

Sexual dimorphism plays an important role in the pathogenesis and progression of CKD. Men with CKD often exhibit faster kidney function decline, leading to higher rates of kidney failure and mortality compared with women. Studies suggest that sex hormones may influence this apparent dimorphism, although the mechanisms underlying these influences remain poorly understood.

Association of Urinary Epidermal Growth Factor, Fatty Acid-Binding Protein 3, and Vascular Cell Adhesion Molecule 1 Levels with the Progression of Early Diabetic Kidney Disease.

Introduction: Diabetic kidney disease (DKD) is a common cause of chronic kidney disease with around 25-40% of patients with diabetes being affected. The course of DKD is variable, and estimated glomerular filtration rate (eGFR) and albuminuria, the currently used clinical markers, are not able to accurately predict the individual disease trajectory, in particular in early stages of the disease. The aim of this study was to assess the association of urine levels of selected protein biomarkers with the progression of DKD at an early stage of disease.

Attenuated kidney oxidative metabolism in young adults with type 1 diabetes.

BACKGROUNDIn type 1 diabetes (T1D), impaired insulin sensitivity may contribute to the development of diabetic kidney disease (DKD) through alterations in kidney oxidative metabolism.METHODSYoung adults with T1D (n = 30) and healthy controls (HCs) (n = 20) underwent hyperinsulinemic-euglycemic clamp studies, MRI, 11C-acetate PET, kidney biopsies, single-cell RNA-Seq, and spatial metabolomics to assess this relationship.RESULTSParticipants with T1D had significantly higher glomerular basement membrane (GBM) thickness compared with HCs.

Proteomic Analysis Uncovers Multiprotein Signatures Associated with Early Diabetic Kidney Disease in Youth with Type 2 Diabetes Mellitus.

Key Points: Proteomics analyses identified seven proteins predictive of time to development of albuminuria among youth with type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth cohort, 118 proteins predictive of time to development of hyperfiltration, and three proteins predictive of time to rapid eGFR decline. Seven proteins were predictive of all three outcomes (SEM4A, PSB3, dihydroxyphenylalanine decarboxylase, C1RL1, T132A, pyruvate carboxylase, and C1-esterase inhibitor) and have been implicated in immune regulatory mechanisms, metabolic dysregulation, proteostasis, and cellular signaling pathways. Elastic net Cox proportional hazards model identified distinct multiprotein signatures (38–68 proteins) of time to albuminuria, hyperfiltration, and rapid eGFR decline with concordance for models with clinical covariates and selected proteins between 0.

Biomarkers of Neurodegeneration and Alzheimer's Disease Neuropathology in Adolescents and Young Adults with Youth-Onset Type 1 or Type 2 Diabetes: A Proof-of-Concept Study.

Adult-onset diabetes increases one's risk of neurodegenerative disease including Alzheimer's disease (AD); however, the risk associated with youth-onset diabetes (Y-DM) remains underexplored. We quantified plasma biomarkers of neurodegeneration and AD in participants with Y-DM from the SEARCH cohort at adolescence and young adulthood (Type 1, n = 25; Type 2, n = 25; 59% female; adolescence, age = 15 y/o [2.6]; adulthood, age = 27.

Kidney Energetics and Cyst Burden in Autosomal Dominant Polycystic Kidney Disease: A Pilot Study.

Rationale & Objective: In this pilot study, we hypothesized that autosomal dominant polycystic kidney disease (ADPKD) is characterized by impaired kidney oxidative metabolism that associates with kidney size and cyst burden.

Study Design: Cross-sectional study.

Setting & Participants: Twenty adults with ADPKD (age, 31±6 years; 65% women; body mass index [BMI], 26.

The effect of Bruton's tyrosine kinase (BTK) inhibitor in the eosinophilic asthma model of mouse.

Bruton's Tyrosine kinase (BTK) plays a pivotal role as the key mediator in B cell signaling. Recent research has revealed that it is also expressed in cells critical to asthma development, such as T cells, and eosinophils. This study aims to investigate the potential of BTK inhibitor in eosinophilic asthma mouse model.

Glycoprotein Acetyls Associate With Intraglomerular Hemodynamic Dysfunction, Albuminuria, Central Adiposity, and Insulin Resistance in Youth With Type 1 Diabetes.

Objectives: Glycoprotein acetyls (GlycA's) are biomarkers of systemic inflammation and cardiovascular disease, yet little is known about their role in type 1 diabetes (T1D). In this study we examined the associations among GlycA's, central adiposity, insulin resistance, and early kidney injury in youth with T1D.

Methods: Glomerular filtration rate and renal plasma flow by iohexol and p-aminohippurate clearance, urine albumin-to-creatinine ratio (UACR), central adiposity by dual-energy x-ray absorptiometry, and estimated insulin sensitivity were assessed in 50 youth with T1D (16±3.

Insulin Secretion, Sensitivity, and Kidney Function in Young Individuals With Type 2 Diabetes.

Objective: β-Cell dysfunction and insulin resistance magnify the risk of kidney injury in type 2 diabetes. The relationship between these factors and intraglomerular hemodynamics and kidney oxygen availability in youth with type 2 diabetes remains incompletely explored.

Research Design And Methods: Fifty youth with type 2 diabetes (mean age ± SD 16 ± 2 years; diabetes duration 2.

Evaluating the Efficacy of Hyperbaric Oxygen Therapy in Digital Frostbite.

Frostbite is a limb threatening, cold-induced tissue injury most commonly affecting the extremities. Hyperbaric oxygen therapy (HBOT) is a proposed adjunctive treatment for this condition, which acts by increasing cellular oxygen availability in damaged tissues. Currently, there is a lack of data regarding the effectiveness of HBOT.

Intracellular Islatravir-Triphosphate in Dried Blood Spots and Peripheral Blood Mononuclear Cells from Pig-Tailed Macaques.

The purpose of this study was to evaluate the relationship between intracellular islatravir-triphosphate (ISL-TP) in paired peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS). Three pig-tailed macaques (PMs) were dosed with a single intravaginal extended-release ISL-etonogestrel film for a period of 31 days. After extraction and quantification, repeated measures correlation (r) was assessed between log-transformed DBS and PBMC ISL-TP concentrations.

Changing Characteristics of Children With COVID-19 in Colorado Admitted During Different Variant Periods.

Background: Data are lacking on the impact of different severe acute respiratory syndrome coronavirus 2 variants in children and on pediatric vaccine effectiveness. We examined differences among children requiring hospital admission associated with coronavirus disease 2019 (COVID-19) during wild type, Delta and Omicron variant periods and calculated vaccine effectiveness at preventing symptomatic hospitalization during the Delta and Omicron variant periods.

Methods: We conducted a retrospective review of children younger than 21 years of age hospitalized with symptomatic COVID-19.

Investigational medications in 9,638 hospitalized patients with severe COVID-19: lessons from the "fail-and-learn" strategy during the first two waves of the pandemic in 2020.

Background: The early surge of the novel coronavirus disease 2019 (COVID-19) pandemic introduced a significant clinical challenge due to the high case-fatality rate in absence of evidence-based recommendations. The empirical treatment modalities were relegated to historical expertise from the traditional management of acute respiratory distress syndrome (ARDS) in conjunction with off-label pharmaceutical agents endorsed under the "emergency use authorization" (EUA) paradigm by regulatory agencies. This study was designed to evaluate the insights from the "fail-and-learn" strategy in 2020 before the availability of COVID-19 vaccines and access to reliable insights from high-quality randomized controlled trials.

Nursing opinions on collaborating with residents in new and legacy OB/GYN programs.

Collaboration among physicians and nurses is vital and has shown to lead to better patient care and improve outcomes. Our study surveyed two groups of Labor and Delivery nurses in two regionally similar community hospitals in midwestern United States: one group from a new Obstetrics and Gynecology (OB/GYN) residency program (n = 49) and another from an established (legacy) OB/GYN residency program (n = 49). The survey asked nurses from the hospital with new and legacy residency program about preparedness for working with residents, perceptions of nurse-resident-patient relationships, collaboration and opinions about how resident physicians impact patient safety.

Assessing Nursing Sentiments on Nurse-Resident Physician Collaboration and Administrative Support in the Labor and Delivery Setting: Development and Validation of a Novel Instrument.

Objective: To develop a survey instrument that: 1) investigates the dynamics of collaboration in multidisciplinary care units such as labor and delivery (L&D); and (2) uniquely determines the collaborative relationships between nurses and resident physicians.

Background: An effective interprofessional collaboration between healthcare providers is considered a critical component in delivering high-quality care to patients and lies at the root of ensuring positive patient outcomes.

Methods: Two samples of responses (n = 98) were collected from L&D nurses working in 2 hospitals: 1 with novel obstetrics and gynecology (OB/GYN) residency program and 1 with legacy OB/GYN residency program.

Data Mining Framework for Discovering and Clustering Phenotypes of Atypical Diabetes.

Context: Some individuals present with forms of diabetes that are "atypical" (AD), which do not conform to typical features of either type 1 diabetes (T1D) or type 2 diabetes (T2D). These forms of AD display a range of phenotypic characteristics that likely reflect different endotypes based on unique etiologies or pathogenic processes.

Objective: To develop an analytical approach to identify and cluster phenotypes of AD.