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Biomarker Assessment of Nicotine Exposure Among Adolescent E-Cigarette Users: 2018-2019
No full textBackground: Despite the increasing prevalence of vaping e-cigarettes among adolescents, there remains a lack of population-level assessments regarding the objective measurement of nicotine exposure.
Methods: This study analyzed a nationally representative sample of adolescents aged 13 to 17 years from Wave 5 of the Population Assessment of Tobacco and Health Study conducted between 2018 and 2019. Urinary nicotine metabolites, including cotinine and trans-3\u27-hydroxycotinine (3-HC), were assessed among exclusive nonnicotine e-cigarette users (n = 56), exclusive nicotine e-cigarette users (n = 200), and nonusers (n = 1059). We further examined nicotine exposure by past 30-day vaping frequency (ie, occasional [1-5 days], intermittent [6-19 days], and frequent [20+ days]) and flavor types among nicotine e-cigarette users. Multivariable linear regressions tested pairwise group effects, and biomarkers were normalized by the log transformation.
Results: Compared with nonusers, both nonnicotine and nicotine e-cigarette users exhibited higher levels of cotinine and 3-HC. Nicotine e-cigarette users had mean cotinine concentrations (61.3; 95% confidence interval, 23.8-158.0, ng/mg creatinine) approximately 146 times higher (P \u3c .0001) than nonusers (0.4; 0.3-0.5), whereas nonnicotine users (4.9; 1.0-23.2) exhibited cotinine concentrations ∼12 times higher (P = .02). Among nicotine e-cigarette users, the levels of cotinine and 3-HC increased by vaping frequency, with cotinine increasing from 10.1 (2.5-40.1) among occasional users to 73.6 (31.8-170.6) among intermittent users and 949.1 (482.5-1866.9) among frequent users. Nicotine exposure was not significantly different by flavor type.
Conclusions: E-cigarette use poses health-related risks resulting from nicotine exposure among adolescents. Comprehensive regulations of e-cigarette products and marketing, vaping prevention, cessation, and public policies are needed to prevent youth from developing nicotine addiction
Caregiver Perceptions of Child Health Behaviors and Weight During Treatment for Acute Lymphoblastic Leukemia
No full textBackground: Changes in health behaviors and weight are common during the early phases of pediatric acute lymphoblastic leukemia treatment, and may negatively impact treatment tolerability.. Given that ALL is most prevalent in children, caregivers play an essential role in shaping health behaviors during treatment. This study presents a qualitative analysis of semi-structured interviews with caregivers of youth in the early phases of ALL treatment.
Procedure: Caregivers (N = 17, 95% female) of a child (M age = 6.76 years) diagnosed with ALL and on treatment for less than 1 year (M = 8.7 months since diagnosis) completed a semi-structured interview about perceptions of their child\u27s nutrition, physical activity, sedentary time, and weight during ALL treatment. Thematic analysis followed Braun and Clark\u27s six-step framework (2006). Two coders established reliability (alpha = .88) and used a multi-pass coding system to extract themes.
Results: Caregivers\u27 concerns around their child\u27s weight during ALL treatment primarily centered around avoiding malnutrition. Weight gain during treatment was less of a concern and often viewed as protective. Caregivers reported encouraging their child to eat palatable, calorie-dense foods to mitigate risk for weight loss. Caregivers also expressed concern that children were less active and more sedentary due to treatment-related pain. Caregivers discussed health behaviors during treatment as being child-directed, rather than parent- or provider-directed.
Conclusion: Future interventions may consider strategies to engage in joint parent-child decisions and caregiver education around risks of excessive weight gain during treatment. Interventions should include anticipatory guidance and aim to support parents in developing skills to support their child\u27s health behaviors during treatment
Lipid-Based Nanoparticle Combination Immunotherapy With Sitravatinib for the Systemic Treatment of High-Risk Neuroblastoma
No full textWe seek to develop a systemic, innate immunomodulatory nanoparticle therapy that combines synergistically with sitravatinib for the treatment of high-risk neuroblastoma, where metastasis is the largest hurdle for current treatment modalities. Here, we utilize a unique lipid-based nanoparticle (LNP) system comprised of co-encapsulated agonists of the Stimulator of Interferon Genes (STING) and Toll-like Receptor 4 (TLR4) pathways (immuno-NPs) that can be safely administered in the systemic blood circulation for delivery to the tumor microenvironment (TME) and uptake by perivascular innate antigen-presenting cells (APCs). STING/TLR4 agonists together promote the synergistic production of Type I interferon β (IFNβ), a key activator of anti-tumor immunity from the TME itself. Here, we also focus on sitravatinib, an investigational drug shown to inhibit receptor tyrosine kinases such as discoidin domain receptor 2 (DDR2), which can inhibit the sustained remodeling of collagen around primary tumors. The inhibition of such is vital to treatment as sustained collagen remodeling can facilitate the metastasis of cancer cells via epithelial-mesenchymal transition (EMT). We hypothesize that the downstream effects of sitravatinib treatment will augment tumor clearance and increase the therapeutic efficacy of immuno-NPs with respect to recruiting APCs. Our early pilot studies in humanized mice bearing orthotopic SH-5YSY tumors show that immuno-NPs are effective at tumor clearance. We found that mice inoculated subcutaneously with syngeneic 9464D-GD2 tumors showed decreased tumor growth when treated with our novel combination therapy in comparison to monotherapy controls. In both humanized and syngeneic tumor models, our ongoing mechanistic studies involve quantification of EMT in primary tumors, systemic nanoparticle deposition at metastatic sites, and the mechanistic impact of combination therapy on IFNβ-promoted elimination of metastasis. Here, we have proposed and tested an immunotherapy with great promise for treating neuroblastoma. However, the impact of nanoparticle-based immunotherapy reaches far beyond neuroblastoma: it has the potential to be a platform for the development of immunotherapies specific to other highly metastatic cancer types
Quantum Computing in the Realm of Neurosurgery
No full textQuantum computing leverages the principles of quantum mechanics to provide unprecedented computational power by processing data in a fundamentally different way from classical binary computers. Quantum computers use qubits which superimpose 0 and 1. Because qubits can exist in multiple states at the same time, quantum computers can perform quantum parallelism wherein data are processed simultaneously rather than sequentially. The quantum parallelism is what enables the computer to have exponentially larger processing capabilities and consider all potential outcomes simultaneously to derive solutions. Our study aims to explore aspects of neurosurgery through which quantum computing could improve patient outcomes and enhance quality of care. Quantum computing has the potential for future applications in neuroprosthetics, neurostimulation, surgical precision, diagnosis, and patient privacy and security. It promises improved patient outcomes, enhanced surgical precision, and personalized healthcare delivery. With its inherent sensitivity and precision, quantum computing could advance the understanding of disease processes and development, providing neurosurgeons with deeper insight into patient pathologies. Challenges such as biocompatibility, cost, and ethical considerations remain significant barriers to integrating the technology into neurosurgical practice. Addressing these challenges will be crucial for realizing the transformative potential of quantum computing in advancing neurosurgical care and improving clinical outcomes
Oral PCSK9 Inhibitors
No full textPurpose of review: In this review, we will discuss the data from early clinical studies of MK-0616 and summarize clinical trials of other oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.
Recent findings: The success of PCSK9 inhibition with monoclonal antibody injections has fueled the development of additional therapies targeting PCSK9, including oral formulations, the most advanced of which is MK-0616. MK-0616 is a novel, orally administered macrocyclic peptide that binds to PCSK9 and inhibits binding of PCSK9 to the LDL receptor, thereby decreasing plasma levels of LDL-C. Clinical trial data on the safety and efficacy of MK-0616 are promising and report LDL-C-lowering efficacy comparable to that provided by injectable PCSK9 inhibitors. Ongoing and future studies of oral PCSK9 inhibitors in development will evaluate the safety, efficacy, and effectiveness of these agents and their potential role in preventing cardiovascular disease events
Cognitive Decline in Cushing\u27s Syndrome: A Systematic Review
No full textThe neurocognitive and psychiatric effects of Cushing\u27s syndrome (CS) are well recognized and negatively impact quality of life. The aim of this systematic review is to compare neurocognitive disease, psychiatric symptoms, and structural brain changes in patients with Cushing\u27s disease (CD)/CS and those with non-functioning pituitary adenoma (NFPA), both before and after surgical treatment, and in comparison to healthy controls. Possible predictors of persistent neurocognitive symptoms and reduced quality of life in patients with CS are highlighted. We reviewed the English literature published in Medline/Pubmed until 2021 to identify eligible studies. This systematic review was registered on Prospero and reported following the PRISMA statement guidelines. The initial literature search yielded 1772 articles, of which 1096 articles remained after removing duplicates. After excluding case reports, animal studies, narrative reviews, comparative reviews, and articles not in English, 86 papers underwent full-text review. Studies eligible for inclusion met the following criteria: (1) described patients with CD/CS, (2) reports of psychiatric symptoms, (3) written in English or with available English translation, and (4) published in a peer-reviewed journal. The full-text review process identified 40 eligible studies. The 40 studies included a total of 2603 participants with CD or CS, with 45.2% of the total participants having CD. The majority of studies were case–control studies and used validated questionnaires such as the Beck\u27s Depression Index, Trail Making Test, Hospital Anxiety and Depression Scale, and Cushing Quality of Life for screening. Compared to NFPA controls, patients with CD who had greater baseline serum cortisol levels had worse cognitive function, even after surgical remission. This suggests a possible association between greater baseline cortisol levels in patients with CS and persistent cognitive impairment. A longer duration of uncontrolled CS was associated with worse cognitive function; however, there was no association found between the length of remission and memory. Overall brain volume was increased in patients in remission from CD compared to active disease. However, temporal and frontal lobe volumes did not recover to normal volumes. Patients with CS experience neurocognitive dysfunction, psychiatric disorders, and diminished quality of life, and symptoms may persist after curative surgery. We found several factors consistently associated with persistent cognitive and neuropsychiatric symptoms in patients with CS including higher pre-operatively baseline cortisol production, longer duration of disease, frontal and temporal lobe atrophy, and the presence of cognitive and neuropsychiatric symptoms at baseline. Larger prospective studies are required to validate these findings
Medical Student Perception of Force Application: An Accuracy Assessment and Pilot Training Program
Get PDFBackground:
It is unclear how accurately students can reproduce specific forces that are often required for physical examination maneuvers. This study aimed to determine the baseline accuracy of force application for preclinical medical students, evaluate the effectiveness of a quantitative visual feedback intervention, and investigate whether certain demographics influence accuracy.
Materials and Methods:
First- and second-year medical students were enrolled and demographic data were collected. Students blindly applied their estimation of 15 lbs (6.8 kg), 3 lbs (1.4 kg), 10 lbs (4.5 kg), 1.5 lbs (0.7 kg), and 6 lbs (2.7 kg) of force on a scale. Visual feedback training was then performed wherein students applied a series of additional forces unblinded five times, and then blindly administered the same five initial forces 12 minutes and one week later. Accuracy was compared at each time point and a regression analysis was evaluated for predictors of accuracy.
Results:
Thirty-three students participated. The mean baseline accuracy was 38.3%, 41.1% immediately following intervention, and 35.6% one week later (P = 0.66). Accuracy was significantly higher at higher intended forces compared to lower forces (P \u3c 0.05). The number of prior occupations was a positive independent predictor (P = 0.04), and the number of sports played was noted to be a negative predictor (P = 0.01), of baseline accuracy.
Conclusions:
Medical students’ ability to accurately reproduce clinically relevant forces is poor. There is a clear need to implement a robust training program in medical education, and students may need multiple training sessions to refine this skill
