Cross-disease modeling of peripheral blood identifies biomarkers of type 2 diabetes predictive of Alzheimer's disease.

Type 2 diabetes (T2D) is a significant risk factor for Alzheimer's disease (AD). Despite multiple studies reporting this connection, the mechanism by which T2D exacerbates AD is poorly understood. It is challenging to design studies that address co-occurring and comorbid diseases, limiting the number of existing evidence bases.

Cross-Species Modeling Identifies Gene Signatures in Type 2 Diabetes Mouse Models Predictive of Inflammatory and Estrogen Signaling Pathways Associated with Alzheimer's Disease Outcomes in Humans.

Alzheimer's disease (AD), the predominant form of dementia, is influenced by several risk factors, including type 2 diabetes (T2D), a metabolic disorder characterized by the dysregulation of blood sugar levels. Despite mouse and human studies reporting this connection between T2D and AD, the mechanism by which T2D contributes to AD pathobiology is not well understood. A challenge in understanding mechanistic links between these conditions is that evidence between mouse and human experimental models must be synthesized, but translating between these systems is difficult due to evolutionary distance, physiological differences, and human heterogeneity.

The Translational Science Benefits Model, a new training tool for demonstrating implementation science impact: A pilot study.

Introduction: Demonstrating the impact of implementation science presents a new frontier for the field, and operationalizing downstream impact is challenging. The Translational Science Benefits Model (TSBM) offers a new approach for assessing and demonstrating research impact. Here we describe integration of the TSBM into a mentored training network.

Alcohol consumption confers lasting impacts on prefrontal cortical neuron intrinsic excitability and spontaneous neurotransmitter signaling in the aging brain in mice.

Both alcohol use disorder (AUD) and cognitive decline include disruption in the balance of excitation and inhibition in the cortex, but the potential role of alcohol use on excitation and inhibition on the aging brain is unclear. We examined the effect of moderate voluntary binge alcohol consumption on the aged, pre-disease neuronal environment by measuring intrinsic excitability and spontaneous neurotransmission on prefrontal cortical pyramidal (excitatory, glutamatergic) and non-pyramidal (inhibitory, GABAergic) neurons following a prolonged period of abstinence from alcohol in mice. Results highlight that binge alcohol consumption has lasting impacts on the electrophysiological properties of prefrontal cortical neurons.

A Qualitative Exploration of Peer Supporters' Experiences of Undertaking a Co-Produced Mental Health and Emotional Well-Being Training Programme.

Introduction: Peer supporters play a crucial role in mental health and support services, but their own mental health and emotional well-being are often neglected by themselves, and, frequently, their organisations. Here, we report findings from a qualitative interview study of peer supporters who completed a co-produced emotional well-being training programme.

Method: Ten semi-structured interviews with peer supporters working in the North East of England were conducted to explore their experiences of the training programme.

The American Cancer Society National Lung Cancer Roundtable strategic plan: Lung cancer in women.

Lung cancer in women is a modern epidemic and represents a global health crisis. Cigarette smoking remains the most important risk factor for lung cancer in all patients and, among women globally, rates of smoking continue to increase. Although some data exist supporting sex-based differences across the continuum of lung cancer, there is currently a dearth of research exploring the differences in risk, biology, and treatment outcomes in women.

Microglial Drivers of Alzheimer's Disease Pathology: An Evolution of Diverse Participating States.

Microglia, the resident immune-competent cells of the brain, become dysfunctional in Alzheimer's disease (AD), and their aberrant immune responses contribute to the accumulation of pathological proteins and neuronal injury. Genetic studies implicate microglia in the development of AD, prompting interest in developing immunomodulatory therapies to prevent or ameliorate disease. However, microglia take on diverse functional states in disease, playing both protective and detrimental roles in AD, which largely overlap and may shift over the disease course, complicating the identification of effective therapeutic targets.

Cost-effectiveness of train-the-trainer versus expert consultation training models for implementing interpersonal psychotherapy in college mental health settings: evidence from a national cluster randomized trial.

Background: This study is a cost-effectiveness study of two implementation strategies designed to train therapists in college and university counseling centers to deliver interpersonal psychotherapy. Costs of implementing a train-the-trainer (TTT) strategy versus an expert consultation strategy were estimated, and their relative effects upon therapist outcomes were calculated and compared.

Methods: Twenty four counseling centers were recruited across the United States.

A common variant in the iron regulatory gene (Hfe) alters the metabolic and transcriptional landscape in brain regions vulnerable to neurodegeneration.

The role of iron dyshomeostasis in neurodegenerative disease has implicated the involvement of genes that regulate brain iron. The homeostatic iron regulatory gene (HFE) has been at the forefront of these studies given the role of the H63D variant (H67D in mice) in increasing brain iron load. Despite iron's role in oxidative stress production, H67D mice have shown robust protection against neurotoxins and improved recovery from intracerebral hemorrhage.

Decreased Alpha Klotho Expression in Placentas Exposed to Severe Maternal Vascular Malperfusion.

Background: Placental maternal vascular malperfusion (MVM) is characterized by accelerated villous maturation and has been associated with a decrease in the antiaging protein, alpha-klotho (AK). Our aim was to characterize AK protein and gene expression in the placenta and fetal organs.

Methods: We utilized 2 cohorts.

Differential responses of primary neuron-secreted MCP-1 and IL-9 to type 2 diabetes and Alzheimer's disease-associated metabolites.

Type 2 diabetes (T2D) is implicated as a risk factor for Alzheimer's disease (AD), the most common form of dementia. In this work, we investigated neuroinflammatory responses of primary neurons to potentially circulating, blood-brain barrier (BBB) permeable metabolites associated with AD, T2D, or both. We identified nine metabolites associated with protective or detrimental properties of AD and T2D in literature (lauric acid, asparagine, fructose, arachidonic acid, aminoadipic acid, sorbitol, retinol, tryptophan, niacinamide) and stimulated primary mouse neuron cultures with each metabolite before quantifying cytokine secretion via Luminex.

Everolimus alleviates CD4 T cell inflammation by regulating autophagy and cellular redox homeostasis.

Aging is associated with the onset and progression of multiple diseases, which limit health span. Chronic low-grade inflammation in the absence of overt infection is considered the simmering source that triggers age-associated diseases. Failure of many cellular processes during aging is mechanistically linked to inflammation; however, the overall decline in the cellular homeostasis mechanism of autophagy has emerged as one of the top and significant inducers of inflammation during aging, frequently known as inflammaging.

MODERATE ALCOHOL CONSUMPTION INDUCES LASTING IMPACTS ON PREFRONTAL CORTICAL SIGNALING IN MICE.

Both alcohol use disorder (AUD) and Alzheimer's Disease and Related Dementias (ADRD) appear to include disruption in the balance of excitation and inhibition in the cortex, but their potential interactions are unclear. We examined the effect of moderate voluntary binge alcohol consumption on the aged, pre-disease neuronal environment by measuring intrinsic excitability and spontaneous neurotransmission on prefrontal cortical pyramidal (excitatory, glutamatergic) and non-pyramidal (inhibitory, GABAergic) neurons following a prolonged period of abstinence from alcohol in mice. Results highlight that binge alcohol consumption has lasting impacts on the electrophysiological properties of prefrontal cortical neurons.

Cytokine expression patterns predict suppression of vulnerable neural circuits in a mouse model of Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disorder characterized by progressive amyloid plaque accumulation, tau tangle formation, neuroimmune dysregulation, synapse an neuron loss, and changes in neural circuit activation that lead to cognitive decline and dementia. Early molecular and cellular disease-instigating events occur 20 or more years prior to presentation of symptoms, making them difficult to study, and for many years amyloid-β, the aggregating peptide seeding amyloid plaques, was thought to be the toxic factor responsible for cognitive deficit. However, strategies targeting amyloid-β aggregation and deposition have largely failed to produce safe and effective therapies, and amyloid plaque levels poorly correlate with cognitive outcomes.

Molecular characterization of the interaction between human IgG and the M-related proteins from Streptococcus pyogenes.

Group A Streptococcal M-related proteins (Mrps) are dimeric α-helical-coiled-coil cell membrane-bound surface proteins. During infection, Mrp recruit the fragment crystallizable region of human immunoglobulin G via their A-repeat regions to the bacterial surface, conferring upon the bacteria enhanced phagocytosis resistance and augmented growth in human blood. However, Mrps show a high degree of sequence diversity, and it is currently not known whether this diversity affects the Mrp-IgG interaction.

Differential responses of primary neuron-secreted MCP-1 and IL-9 to type 2 diabetes and Alzheimer's disease-associated metabolites.

Type 2 diabetes (T2D) is implicated as a risk factor for Alzheimer's disease (AD), the most common form of dementia. In this work, we investigated neuroinflammatory responses of primary neurons to potentially circulating, blood-brain barrier (BBB) permeable metabolites associated with AD, T2D, or both. We identified nine metabolites associated with protective or detrimental properties of AD and T2D in literature (lauric acid, asparagine, fructose, arachidonic acid, aminoadipic acid, sorbitol, retinol, tryptophan, niacinamide) and stimulated primary mouse neuron cultures with each metabolite before quantifying cytokine secretion via Luminex.

Dynamic neuroinflammatory profiles predict Alzheimer's disease pathology in microglia-containing cerebral organoids.

Neuroinflammation and the underlying dysregulated immune responses of microglia actively contribute to the progression and, likely, the initiation of Alzheimer's disease (AD). Fine-tuned therapeutic modulation of immune dysfunction to ameliorate disease cannot be achieved without the characterization of diverse microglial states that initiate unique, and sometimes contradictory, immune responses that evolve over time in chronic inflammatory environments. Because of the functional differences between human and murine microglia, untangling distinct, disease-relevant reactive states and their corresponding effects on pathology or neuronal health may not be possible without the use of human cells.

Association of organizational culture and climate with variation in the clinical outcomes of collaborative care for maternal depression in community health centers.

Background: Organizational factors may help explain variation in the effectiveness of evidence-based clinical innovations through implementation and sustainment. This study tested the relationship between organizational culture and climate and variation in clinical outcomes of the Collaborative Care Model (CoCM) for treatment of maternal depression implemented in community health centers.

Method: Organizational cultures and climates of 10 community health centers providing CoCM for depression among low-income women pregnant or parenting were assessed using the organizational social context (OSC) measure.

Application of the Expert Recommendations for Implementing Change (ERIC) compilation of strategies to health intervention implementation in low- and middle-income countries: a systematic review.

Background: The Expert Recommendations for Implementing Change (ERIC) project developed a compilation of implementation strategies that are intended to standardize reporting and evaluation. Little is known about the application of ERIC in low- and middle-income countries (LMICs). We systematically reviewed the literature on the use and specification of ERIC strategies for health intervention implementation in LMICs to identify gaps and inform future research.

STAT3 modulates CD4 T mitochondrial dynamics and function in aging.

Aging promotes numerous intracellular changes in T cells that impact their effector function. Our data show that aging promotes an increase in the localization of STAT3 to the mitochondria (mitoSTAT3), which promotes changes in mitochondrial dynamics and function and T-cell cytokine production. Mechanistically, mitoSTAT3 increased the activity of aging T-cell mitochondria by increasing complex II.