Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults, characterized by resistance to conventional therapies and poor survival. Ferroptosis, a form of regulated cell death driven by lipid peroxidation, has recently emerged as a promising therapeutic target for GBM treatment. However, there are currently no non-invasive imaging techniques to monitor the engagement of pro-ferroptotic compounds with their respective targets, or to monitor the efficacy of ferroptosis-based therapies.
View Article and Find Full Text PDF(Mtb) is the causative agent of tuberculosis, the world's deadliest infectious disease. Mtb uses a variety of mechanisms to evade the human host's defenses and survive intracellularly. Mtb's oxidative stress response enables Mtb to survive within activated macrophages, an environment with reactive oxygen species and low pH.
View Article and Find Full Text PDFThe MEK inhibitor selumetinib induces objective responses and provides clinical benefit in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). To evaluate whether similar outcomes were possible in adult patients, in whom PN growth is generally slower than in pediatric patients, we conducted an open-label phase 2 study of selumetinib in adults with NF1 PNs. The study was designed to evaluate objective response rate (primary objective), tumor volumetric responses, patient-reported outcomes and pharmacodynamic effects in PN biopsies.
View Article and Find Full Text PDFThe robust design and conduct of pragmatic cluster randomised trials may be in tension with the ethical requirement to obtain written informed consent from prospective research participants. In our experience, researchers tend to focus on whether a waiver of consent is appropriate for their studies. However, pragmatic cluster randomised trials raise other important questions that have direct implications for determining when an alteration or waiver of consent is permissible.
View Article and Find Full Text PDFBackground: The relationships among treatment exposures, body composition, and estimated glomerular filtration rate (eGFR) in adult survivors of Wilms tumor have not been well studied.
Methods: We evaluated body composition with dual-energy x-ray absorptiometry (DXA) and eGFR with the updated Chronic Kidney Disease Epidemiology Collaboration equations (creatinine only-eGFR, cystatin C only-eGFR, creatinine and cystatin C-eGFR) without race in 134 adults previously treated for unilateral, non-syndromic Wilms tumor at St. Jude Children's Research Hospital between 1964 and 2004 with chemotherapy and with (hemiabdomen [HA] or whole abdomen [WA]) or without radiation therapy (RT).
Objective: We assessed levels of mRNA encoding two glucocorticoid receptor (GR) isoforms (GRα and GRβ) in saliva and examined their relationship with hair cortisol levels and dental caries experience.
Design: Adolescents and young adults were assessed for dental caries experience, and hair cortisol was measured by ELISA. RNA was extracted from whole saliva using TRIzol, followed by quantitative real-time PCR analysis of GRα, GRβ, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH).
Can J Kidney Health Dis
December 2024
Purpose: Using data from Ontario, Canada, this report shows how provincial government-assigned health card numbers can be used for individual-level randomization in large pragmatic trials. We describe how health card numbers are assigned and analyze the distribution of health card digits in a trial setting. We then provide an example of how they can be used for randomization and discuss the methodological and practical considerations of the approach.
View Article and Find Full Text PDFVitamin D is most known for its role in the development and maintenance of the skeletal system. However, recent studies have found that vitamin D modulates the immune system, and at sufficient levels supports optimal immune function. Previous research has examined how vitamin D levels change seasonally and during immune stress challenges in both humans and cattle, but not sheep.
View Article and Find Full Text PDFGenomic profiling often fails to predict therapeutic outcomes in cancer. This failure is, in part, due to a myriad of genetic alterations and the plasticity of cancer signaling networks. Functional profiling, which ascertains signaling dynamics, is an alternative method to anticipate drug responses.
View Article and Find Full Text PDFPurpose: We aim to assess the performance of methods for adjusting estimates of treatment effectiveness for patient nonadherence in the context of health technology assessment using simulation methods.
Methods: We simulated trial datasets with nonadherence, prognostic characteristics, and a time-to-event outcome. The simulated scenarios were based on a trial investigating immunosuppressive treatments for improving graft survival in patients who had had a kidney transplant.
Background: Adult survivors of unilateral, nonmetastatic, non-syndromic Wilms tumor (WT) treated with whole abdomen radiation therapy (WART) are at risk for impaired kidney function. The impact of bias and accuracy on estimated glomerular filtration rate (eGFR) among adult survivors of WT has not been well documented.
Procedure: We clinically evaluated male and female WT survivors with creatinine and cystatin C, calculated eGFR using the Chronic Kidney Disease-Epidemiology equations with and without cystatin C, and measured Tc diethylenetriamine pentaacetic acid (DTPA) plasma clearance.
Sustainable diets can achieve considerable reductions in greenhouse gas emissions and improvements in human health, but changing dietary behavior remains a challenge. We assessed the impacts of two behavioral insights strategies on bridging the intention-action gap related to sustainable and healthy food choices amongst hospital cafeteria patrons. In a pilot survey of hospital staff (N = 1,165), 56% identified limited awareness and availability of sustainable food as barriers to purchasing, although 46% were extremely willing to try sustainable dishes.
View Article and Find Full Text PDFHealth Technol Assess
October 2024
Background: Opioids kill more people than any other drug. Naloxone is an opioid antagonist which can be distributed in take-home 'kits' for peer administration (take-home naloxone).
Aim: To determine the feasibility of carrying out a definitive randomised controlled trial of take-home naloxone in emergency settings.
Background: The burden and functional significance of autonomic dysfunction among survivors of childhood cancer is unknown.
Objectives: We evaluated the prevalence, risk factors, and functional relevance of autonomic dysfunction in survivors.
Methods: We conducted a cross-sectional prospective evaluation of 1,041 adult survivors of childhood cancer treated with anthracyclines (31.
Voxelotor is a small molecule that reduces the polymerization of sickle hemoglobin by increasing its affinity for oxygen. In patients with sickle cell anemia, it has been postulated that increasing hemoglobin-oxygen affinity could limit oxygen offloading from hemoglobin, causing an increase in cerebral metabolic stress. To investigate this hypothetical concern, we used multimodal brain imaging to define the effects of voxelotor on cerebral blood flow and oxygen extraction.
View Article and Find Full Text PDFIntroduction: Foot morphology in the general population has been shown to change with age, and active older adults have reported a need for wide-fitting footwear.
Methods: This study recruited 374 women active in racket sports and team sports in the UK who had their feet scanned while 50% weight bearing. Participants were grouped into 10-year age bands ranging from 18-29 years to 70-79 years.
Queerphobia is defined as society's negative attitude towards LGBTQIA + people, translating into structures that marginalise LGBTQIA + people and contribute to health inequities that cause real harm and can be understood as structural violence. The purpose of this article is to explore what historically marginalised youth in a youth participatory action research (YPAR) project characterise as the big picture issues affecting the lives of LGBTQIA + youth. We used participatory arts-based methods to conduct community and identity building, define research questions and photo prompts, conduct data collection, engage in group thematic analysis, and make recommendations at the state policy level.
View Article and Find Full Text PDFChildren with ETV6::RUNX1 or high-hyperdiploid B-acute lymphoblastic leukemia (B-ALL) have favorable outcomes. The St. Jude (SJ) classification considers these patients low-risk, regardless of their National Cancer Institute (NCI) risk, except when there is slow minimal residual disease (MRD) response or central nervous system/testicular involvement.
View Article and Find Full Text PDFBackground: The presence of dental caries impacts on children's daily lives, particularly among those living in deprived areas. There are successful interventions across the United Kingdom for young children based on toothbrushing with fluoride toothpaste. However, evidence is lacking for oral health improvement programmes in secondary-school pupils to reduce dental caries and its sequelae.
View Article and Find Full Text PDFFront Reprod Health
August 2024
This Perspectives article reflects on findings from our systematic review about adolescent dysmenorrhoea Q, drawing on sociology of diagnosis theory. We consider tensions and uncertainties between presentation with symptoms of dysmenorrhoea and processes of symptom categorisation and diagnosis in adolescents, tracing these through research and clinical guidance, considering possible implications for clinical practice. We argue that challenges in distinguishing between primary and secondary dysmenorrhoea in research translate into challenges in differentiation in clinical practice.
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