Comparison of human macrophages derived from peripheral blood and bone marrow.

Macrophage differentiation, phenotype, and function have been assessed extensively in vitro by predominantly deriving human macrophages from peripheral blood. It is accepted that there are differences between macrophages isolated from different human tissues; however, the importance of anatomical source for in vitro differentiation and characterization is less clear. Here, phenotype and function were evaluated between human macrophages derived from bone marrow or peripheral blood.

Evaluation of efficiency and effectiveness of different recruitment strategies for the FINGER-NL multidomain lifestyle intervention trial via the Dutch Brain Research Registry.

Introduction: Recruitment of participants for intervention studies is challenging. We evaluated the effectiveness and efficiency of a participant recruitment campaign through an online registry for the FINGER-NL study, a multi-domain lifestyle intervention trial targeting cognitively healthy individuals aged 60-79 with dementia prevention potential. Additionally, we explored which recruitment strategy successfully reached individuals from underrepresented groups in research.

Developing a 3D bone model of osteosarcoma to investigate cancer mechanisms and evaluate treatments.

Osteosarcoma is the most common primary bone cancer, occurring frequently in children and young adults. Patients are treated with surgery and multi-agent chemotherapy, and despite the introduction of mifamurtide in 2011, there has been little improvement in survival for decades. 3-dimensional models offer the potential to understand the complexity of the osteosarcoma tumor microenvironment and aid in developing new treatment approaches.

Development of the Dutch Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) Diet and its scoring system, alongside the modification of a brief FFQ for assessing dietary adherence.

The Mediterranean-Dietary Approach to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND) diet is a dietary pattern designed to prevent cognitive decline. Dietary adherence is assessed with the MIND diet scoring system, which is currently based on the American diet and serving sizes. It is known that serving sizes and consumed food products differ between countries.

Predictive Blood Biomarkers of Targeted Intervention for Chronic Mental Health Symptoms following Traumatic Brain Injury.

The purpose of this study was to assess the performance of predictive blood biomarkers for responsiveness to targeted treatments for chronic psychological issues years after traumatic brain injury (TBI). Targeted Evaluation Action and Monitoring of TBI was a prospective 6-month interventional trial of participants with chronic TBI sequelae ( = 95). Plasma biomarkers were analyzed pre-intervention: glial fibrillary acidic protein (GFAP), tau, hyperphosphorylated tau Thr231 (p-Tau), von Willebrand factor (vWF), brain lipid-binding protein (BLBP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), vascular endothelial growth factor-a (VEGFa), and claudin-5 (CLDN5).

A multidomain lifestyle intervention to maintain optimal cognitive functioning in Dutch older adults-study design and baseline characteristics of the FINGER-NL randomized controlled trial.

Background: Evidence on the effectiveness of multidomain lifestyle interventions to prevent cognitive decline in older people without dementia is mixed. Embedded in the World-Wide FINGERS initiative, FINGER-NL aims to investigate the effectiveness of a 2-year multidomain lifestyle intervention on cognitive functioning in older Dutch at risk individuals.

Methods: Multi-center, randomized, controlled, multidomain lifestyle intervention trial with a duration of 24 months.

The Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) Diet for the Aging Brain: A Systematic Review.

The Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet seems a promising approach to preserve brain function during aging. Previous systematic reviews have demonstrated benefits of the MIND diet for cognition and dementia, though an update is needed. Additionally, other outcomes relevant to brain aging have not been summarized.

Psychometric properties of the NIH Toolbox Cognition and Emotion Batteries among children and adolescents with congenital heart defects.

The NIH Toolbox offers brief, computerized measures of cognitive and psychosocial functioning. However, its psychometric properties were established among typically developing children and adolescents. The current study provides the first comprehensive assessment of its psychometric properties among young patients with congenital heart defects (CHD).

Effects of inpatient rehabilitation after acute care on motor, neuropsychological and behavioral outcomes in children with severe traumatic brain injury.

Purpose: An observational study of children with severe traumatic brain injury (TBI) (Approaches and Decisions in Acute Pediatric TBI [ADAPT] Trial) demonstrated the benefits of inpatient rehabilitation on functional outcomes for those with more severely impaired consciousness when medically stable. We conducted a secondary analysis to assess whether using an inpatient rehabilitation or skilled nursing facility after acute hospitalization was associated with better motor, neuropsychological, and behavioral outcomes compared to receiving only non-inpatient rehabilitation among children with severe TBI.

Materials And Methods: We included 180 children who used an inpatient rehabilitation or skilled nursing facility and 74 children who only received non-inpatient rehabilitation from the ADAPT trial.

Agonist Antibodies for Cancer Immunotherapy: History, Hopes, and Challenges.

Immunotherapy is among the most promising new treatment modalities to arise over the last two decades; antibody drugs are delivering immunotherapy to millions of patients with many different types of cancer. Initial success with antibody therapeutics came in the form of direct targeting or cytotoxic antibodies, such as rituximab and trastuzumab, which bind directly to tumor cells to elicit their destruction. These were followed by immunomodulatory antibodies that elicit antitumor responses by either stimulating immune cells or relieving tumor-mediated suppression.

Sedation Research in Critically Ill Pediatric Patients: Proposals for Future Study Design From the Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research IV Workshop.

Objectives: Sedation and analgesia for infants and children requiring mechanical ventilation in the PICU is uniquely challenging due to the wide spectrum of ages, developmental stages, and pathophysiological processes encountered. Studies evaluating the safety and efficacy of sedative and analgesic management in pediatric patients have used heterogeneous methodologies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) IV hosted a series of multidisciplinary meetings to establish consensus statements for future clinical study design and implementation as a guide for investigators studying PICU sedation and analgesia.

Multi-modal MRI of hippocampal morphometry and connectivity after pediatric severe TBI.

This investigation explores memory performance using the California Verbal Learning Test in relation to morphometric and connectivity measures of the memory network in severe traumatic brain injury. Twenty-two adolescents with severe traumatic brain injury were recruited for multimodal MRI scanning 1-2 years post-injury at 13 participating sites. Analyses included hippocampal volume derived from anatomical T1-weighted imaging, fornix white matter microstructure from diffusion tensor imaging, and hippocampal resting-state functional magnetic resonance imaging connectivity as well as diffusion-based structural connectivity.

Cerebral Spinal Fluid Volumetrics and Paralimbic Predictors of Executive Dysfunction in Congenital Heart Disease: A Machine Learning Approach Informing Mechanistic Insights.

The relationship between increased cerebral spinal fluid (CSF) ventricular compartments, structural and microstructural dysmaturation, and executive function in patients with congenital heart disease (CHD) is unknown. Here, we leverage a novel machine-learning data-driven technique to delineate interrelationships between CSF ventricular volume, structural and microstructural alterations, clinical risk factors, and sub-domains of executive dysfunction in adolescent CHD patients. We trained random forest regression models to predict measures of executive function (EF) from the NIH Toolbox, the Delis-Kaplan Executive Function System (D-KEFS), and the Behavior Rating Inventory of Executive Function (BRIEF) and across three subdomains of EF - mental flexibility, working memory, and inhibition.

Design and Harmonization Approach for the Multi-Institutional Neurocognitive Discovery Study (MINDS) of Adult Congenital Heart Disease (ACHD) Neuroimaging Ancillary Study: A Technical Note.

Dramatic advances in the management of congenital heart disease (CHD) have improved survival to adulthood from less than 10% in the 1960s to over 90% in the current era, such that adult CHD (ACHD) patients now outnumber their pediatric counterparts. ACHD patients demonstrate domain-specific neurocognitive deficits associated with reduced quality of life that include deficits in educational attainment and social interaction. Our hypothesis is that ACHD patients exhibit vascular brain injury and structural/physiological brain alterations that are predictive of specific neurocognitive deficits modified by behavioral and environmental enrichment proxies of cognitive reserve (e.

The role of three-dimensional in vitro models in modelling the inflammatory microenvironment associated with obesity in breast cancer.

Obesity is an established risk factor for breast cancer in postmenopausal women. However, the underlying biological mechanisms of how obesity contributes to breast cancer remains unclear. The inflammatory adipose microenvironment is central to breast cancer progression and has been shown to favour breast cancer cell growth and to reduce efficacy of anti-cancer treatments.

Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation.

Antibodies can mediate immune recruitment or clearance of immune complexes through the interaction of their Fc domain with cellular Fc receptors. Clustering of antibodies is a key step in generating sufficient avidity for efficacious receptor recognition. However, Fc receptors may be saturated with prevailing, endogenous serum immunoglobulin and this raises the threshold by which cellular receptors can be productively engaged.

Assessment of Brain Magnetic Resonance and Spectroscopy Imaging Findings and Outcomes After Pediatric Cardiac Arrest.

Importance: Morbidity and mortality after pediatric cardiac arrest are chiefly due to hypoxic-ischemic brain injury. Brain features seen on magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) after arrest may identify injury and aid in outcome assessments.

Objective: To analyze the association of brain lesions seen on T2-weighted MRI and diffusion-weighted imaging and N-acetylaspartate (NAA) and lactate concentrations seen on MRS with 1-year outcomes after pediatric cardiac arrest.

Efficacy of a Vibrating Crib Mattress to Reduce Pharmacologic Treatment in Opioid-Exposed Newborns: A Randomized Clinical Trial.

Importance: Pharmacologic agents are often used to treat newborns with prenatal opioid exposure (POE) despite known adverse effects on neurodevelopment. Alternative nonpharmacological interventions are needed.

Objective: To examine efficacy of a vibrating crib mattress for treating newborns with POE.

Obesity Is Associated with Immunometabolic Changes in Adipose Tissue That May Drive Treatment Resistance in Breast Cancer: Immune-Metabolic Reprogramming and Novel Therapeutic Strategies.

White adipose tissue (WAT) represents an endocrinologically and immunologically active tissue whose primary role is energy storage and homeostasis. Breast WAT is involved in the secretion of hormones and proinflammatory molecules that are associated with breast cancer development and progression. The role of adiposity and systemic inflammation in immune responses and resistance to anti-cancer treatment in breast cancer (BC) patients is still not clear.

Tri-Lineage Differentiation Potential of Osteosarcoma Cell Lines and Human Bone Marrow Stromal Cells from Different Anatomical Locations.

The bone cancer osteosarcoma, found mainly in adolescents, routinely forms around the growth plate/metaphysis of long bones. Bone marrow composition changes with age, shifting from a more hematopoietic to an adipocyte-rich tissue. This conversion occurs in the metaphysis during adolescence, implicating a link between bone marrow conversion and osteosarcoma initiation.

Psychometric Properties of the NIH Toolbox Cognition and Emotion Batteries Among Children and Adolescents with Congenital Heart Defects.

Objective: The NIH Toolbox offers brief, computerized measures of cognitive and psychosocial functioning. However, its psychometric properties were established among typically developing children and adolescents. The current study provides the first comprehensive assessment of its psychometric properties among young patients with congenital heart defects (CHD).

Pediatric Intensive Care Unit Patients: Sedation, Monitoring, and Neurodevelopmental Outcomes.

The design and conduct of pediatric sedation studies in critically ill patients have historically been challenging due to the complexity of the pediatric intensive care unit (PICU) environment and the difficulty of establishing equipoise. Clinical trials, for instance, represent 1 important means of advancing our knowledge in this field, but there is a paucity of such studies in the literature. Accounting for ground-level factors in planning for each trial phase (eg, enrollment, intervention, assessment, and follow-up) and the presence of broader system limitations is of key importance.

ATM Regulates Differentiation of Myofibroblastic Cancer-Associated Fibroblasts and Can Be Targeted to Overcome Immunotherapy Resistance.

Unlabelled: Myofibroblastic cancer-associated fibroblast (myoCAF)-rich tumors generally contain few T cells and respond poorly to immune-checkpoint blockade. Although myoCAFs are associated with poor outcome in most solid tumors, the molecular mechanisms regulating myoCAF accumulation remain unclear, limiting the potential for therapeutic intervention. Here, we identify ataxia-telangiectasia mutated (ATM) as a central regulator of the myoCAF phenotype.