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How public health policy can be informed by neuroscience

Behavioural Public Policy 2019年第1期3卷 37-46页

作者： Andrew B. Wolf Felsen, Gidon Department of Physiology and Biophysics University of Colorado School of Medicine United States Medical Scientist Training Program University of Colorado School of Medicine United States Center for Bioethics and Humanities University of Colorado Anschutz Medical Campus United States

Many public policies are designed to counteract commonly made decisions that result in poor health. These policies have primarily been informed by the behavioural economics of decision making. Underappreciated in this conversation has been the perspective from neuroscience, despite its recent success - and the likelihood of future progress - in advancing our understanding of the neural basis for health-related decisions. Using tobacco control as an example, we provide a concise overview of how public health policies can and should be informed by neuroscience. We propose that such input can improve policies by increasing their effectiveness, improving screening efficiency and informing relevant ethical considerations. Finally, we recognise limitations and highlight roles that key stakeholders can play in incorporating neuroscientific evidence for the benefit of public policy. Copyright © Cambridge University Press 2018 .

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Informed consent in the psychiatric application of deep brain stimulation technology

Informed consent in the psychiatric application of deep brai...

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IEEE International Symposium on Ethics in Science, Technology and Engineering

作者： Andrew Koivuniemi Medical Scientist Training Program Indiana University School of Medicine Indianapolis IN

Deep brain stimulation offers a promising new therapeutic option for individuals with treatment resistant psychiatric illness. Prior to surgery, patients and their surgeons discuss the procedure in a practice known as informed consent. During this discussion, patients are educated about how the surgery will be performed, the possible risks of an adverse event, and the likelihood of a therapeutic benefit. However, while these elements of discussion are appropriate and sufficient for traditional surgeries of the body, they are likely inadequate for surgeries of the mind because they fail to establish a definition of “mind” for the patient and treatment team. This paper seeks to demonstrate some of the issues that might arise when the term “mind” is not adequately defined prior to deep brain stimulation and proposes a framework definition of “mind” to help facilitate addressing this topic during informed consent.

关键词： Satellite broadcasting Neurosurgery Brain stimulation Hemorrhaging Educational institutions

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Multivariate curve resolution on two-photon fluorescence images of human skin

Multivariate curve resolution on two-photon fluorescence ima...

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European Congress on Computational Methods in Applied Sciences and Engineering, ECCOMAS 2004

作者： Tkaczyk, Eric R. Laiho, Lily H. So, Peter T. Medical Scientist Training Program 2965 Taubman Medical Library University of Michigan 1150 W. Medical Center Drive Ann Arbor MI 48109-0619 United States Cambridge MA 02139 United States

Two-photon fluorescence microscopy has been demonstrated as a high-resolution 3-D tissue imaging technique. If the dream of a noninvasive optical biopsy is to be realized upon this technology, biochemically relevant information must be extracted from the data thus obtained. The current study investigated the ability of different Gram-Schmidt modifications to Orthogonal Projection Multivariate Curve Resolution (MCR) to find the emission spectra and distributions of fluorophores in volume images. A two-photon microscope, incorporating a high-power femtosecond Ti: Sapphire laser and a high sensitivity multianode photomultiplier spectrally resolved detector, was used to obtain spectroscopic data for each point in a volume of the sample. The MCR algorithm was developed and tested by first examining fluorescent beads. MCR analysis on images obtained from ex vivo human skin provided recognizable structural resolution with no a priori information, suggesting that the resolved spectra correspond to different endogenous fluorophores.

关键词： Harmonic generation

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Kayexalate (Sodium Polystyrene Sulfonate) as a Hallmark and Cause of Gastrointestinal Tract Injury: Two Case Reports and a Review of the Literature

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Academic Forensic Pathology 2014年第2期4卷 235-239页

作者： Palte, Michael J. Barasch, Samuel P. Mandal, Rakesh Brooks, Erin G. University of Wisconsin School of Medicine and Public Health - Medical Scientist Training Program Madison WI United States University of Wisconsin Hospital and Clinics - Pathology and Laboratory Medicine Madison WI United States

Kayexalate (sodium polystyrene sulfonate) is a cation exchange resin that is commonly used for the treatment for hyperkalemia. With the increasing prevalence of type II diabetes mellitus in developed nations, there has been a concordant rise in renal disease and hyperkalemic patients receiving Kayexalate therapy. Gastrointestinal necrosis is a rare but major complication associated with Kayexalate use that has not been previously well characterized in the forensic literature. Kayexalate crystals have a distinctive “mosaic” appearance on hematoxylin and eosin stained sections and a characteristic coloration with periodic acid-Schiff (PAS) and acid-fast stains. As they are relatively easily identified in histologic sections, and may represent a primary or contributory cause of death, it is suggested that forensic pathologists become familiar with these features. We present two cases in which Kayexalate crystals were detected at autopsy. In one case, the crystals were located within the intestinal lumen and mucosa in areas of mucosal ulceration, while in the other, crystals were located on the intestinal serosal surface without apparent mucosal ulceration. We discuss how to interpret the significance of Kayexalate crystals, review prior literature on Kayexalate therapy-related gastrointestinal necrosis, and explain how to notify the Food and Drug Administration of an adverse Kayexalate reaction detected at autopsy. © 2014 Academic Forensic Pathology International.

关键词： Forensic pathology Gastrointestinal necrosis Hyperkalemia Kayexalate Sodium polystyrene sulfonate Therapeutic complication

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Ethics in population-based genetic research

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Accountability in Research 2004年第1期11卷 1-26页

作者： DeCamp, Matthew Sugarman, Jeremy Duke University Medical Scientist Training Program School of Medicine Department of Philosophy Durham NC United States Phoebe R. Berman Bioethics Institute Johns Hopkins University Baltimore MD United States

Population-based genetic research, including genetic epidemiology, shows tremendous potential to elucidate the role of genes as causal factors in complex and common human diseases. Like all research with human subjects, full realization of these benefits requires careful attention to its ethical conduct, establishing an appropriate balance between individual protections and the advancement of scientific and medical knowledge. This article reviews the growing literature on genetics research and ethics to describe some of the fundamental ethical issues in population-based genetics research, including research design, recruitment and informed consent, and dealing with research results. Its focus is on areas where consensus is forming and where future work is needed. © Taylor & Francis Inc.

关键词： Ethics Genetics research Informed consent Population genetics Research standards Research subjects

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Intrinsic Stochastic Fluorescence Spectra and Photophysical Parameters of Nucleic Acids under Visible Light Illumination

Intrinsic Stochastic Fluorescence Spectra and Photophysical ...

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Optics and the Brain, BRAIN 2023 - Part of Optica Biophotonics Congress: Optics in the Life Sciences 2023

作者： Gong, Ruyi Almassalha, Luay Backman, Vadim Department of Biomedical Engineering Northwestern University EvanstonIL60208 United States Medical Scientist Training Program Feinberg School of Medicine Northwestern University EvanstonIL60611 United States

The spectra and photophysical parameters of DNA molecules under visible light illumination of different wavelengths are measured for the first time, which may lead to a new label-free super-resolution imaging techniqu... 详细信息

ISBN: (纸本)9781957171210

关键词： Emission Illumination Imaging techniques Optical microscopy Spectroscopy Visible light

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Distance Metrics for Gamma Distributions

arXiv

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arXiv 2018年

作者： McCrimmon, Colin M. Medical Scientist Training Program University of California IrvineCA United States

Here I present the analytic form of two common distance metrics, the symmetrised Kullback-Leibler Divergence and the Kolmogorov-Smirnov statistic, as well as an extension of the Kolmogorov-Smirnov statistic for comparing theoretical gamma distributions. In doing so, I also present the analytic solution to the intersection of two gamma distributions. Lastly, I provide examples that demonstrate the similarity between these distance metrics and their usefulness in describing the separability of gamma distributions. Copyright © 2018, The Authors. All rights reserved.

关键词： Computational complexity

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Short-term high fat diet impairs memory, exacerbates the neuroimmune response, and evokes synaptic degradation via a complement-dependent mechanism in a mouse model of Alzheimer's disease

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BRAIN BEHAVIOR AND IMMUNITY 2024年 121卷 56-69页

作者： Mackey-Alfonso, Sabrina E. Butler, Michael J. Taylor, Ashton M. Williams-Medina, Alberto R. Muscat, Stephanie M. Fu, Hongjun Barrientos, Ruth M. Ohio State Univ Med Scientist Training Program Columbus OH USA Ohio State Univ Neurosci Grad Program Columbus OH USA Ohio State Univ Inst Behav Med Res 460 Medical Ctr Dr Columbus 43210 OH USA Ohio State Univ Dept Psychiat & Behav Hlth 460 Medical Ctr Dr Columbus 43210 OH USA Ohio State Univ Dept Neurosci Columbus OH USA Ohio State Univ Chron Brain Injury Program Columbus OH USA

Alzheimer's Disease (AD) is a neurodegenerative disease characterized by profound memory impairments, synaptic loss, neuroinflammation, and hallmark pathological markers. High-fat diet (HFD) consumption increases the risk of developing AD even after controlling for metabolic syndrome, pointing to a role of the diet itself in increasing risk. In AD, the complement system, an arm of the immune system which normally tags redundant or damaged synapses for pruning, becomes pathologically overactivated leading to tagging of healthy synapses. While the unhealthy diet to AD link is strong, the underlying mechanisms are not well understood in part due to confounding variables associated with long-term HFD which can independently influence the brain. Therefore, we experimented with a short-term diet regimen to isolate the diet's impact on brain function without causing obesity. This project investigated the effect of short-term HFD on 1) memory, 2) neuroinflammation including complement, 3) AD pathology markers, 4) synaptic markers, and 5) in vitro microglial synaptic phagocytosis in the 3xTg-AD mouse model. Following the consumption of either standard chow or HFD, 3xTg-AD and non-Tg mice were tested for memory impairments. In a separate cohort of mice, levels of hippocampal inflammatory markers, complement proteins, AD pathology markers, and synaptic markers were measured. For the last set of experiments, BV2 microglial phagocytosis of synapses was evaluated. Synaptoneurosomes isolated from the hippocampus of 3xTg-AD mice fed chow or HFD were incubated with equal numbers of BV2 microglia. The number of BV2 microglia that phagocytosed synaptoneurosomes was tracked over time with a live-cell imaging assay. Finally, we incubated BV2 microglia with a complement receptor inhibitor (NIF) and repeated the assay. Behavioral analysis showed 3xTg-AD mice had significantly impaired long-term contextual and cued fear memory compared to non-Tg mice that was further impaired by HFD. HFD s

关键词： Alzheimer's disease High-fat diet Neuroinflammation Memory deficit Complement cascade Neutrophil inhibitory factor

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Evidence of Synergistic Effect of Idasanutlin and Navitoclax Using T-Cell Acute Lymphoblastic Leukemia Patient-Derived Xenografts

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BLOOD 2020年 136卷 41-41页

作者： Johansson, Kimberly B. Gauthier, Megan Gao, Feng Link, Daniel C. Medical Scientist Training Program Washington University in St. Louis St Louis MO Division of Oncology Department of Medicine Washington University School of Medicine Saint Louis MO Washington University School of Medicine Saint Louis MO

T-cell acute lymphoblastic leukemia (T-ALL) is diagnosed in approximately 2,500 individuals in the United States each year. The five-year event-free survival rate for this aggressive hematologic malignancy declines with age, ranging from 70-75% for pediatric patients to 21.7% for patients aged 60-79. Thus, there is an unmet clinical need for better therapies for T-ALL. Mutations that result in Notch activation are present in the majority of T-ALL and are thought to induce transformation, in part, through activation of c-Myc. Increased expression of c-Myc induces apoptosis through a p19(ARF)-Mdm2-p53 tumor suppressor pathway. Thus, it is not surprising that over 70% of T-ALL cases have inactivating mutations in CDKN2A (p19Arf). Of note, greater than 95% of primary T-ALL cases and 75% of relapsed cases maintain wild type p53. Based on these observations, we hypothesize that treatment with MDM2 inhibitors, by bypassing the loss of ARF, will increase p53 expression and lead to T-ALL cell apoptosis. We further hypothesize that inhibition of pro-survival BH3 domain proteins, in particular BCLXL, will synergize with MDM2 inhibition to kill T-ALL cells. Of note, a prior study showed that most T-ALL (~62%) respond to treatment with ABT-263 (navitoclax), an inhibitor of BCL2, BCLXL, and BCLW, although most responses were transient. To test this hypothesis, we assessed the response of four different T-ALL xenografts to treatment with idasanutlin (a second generation MDM2 inhibitor) alone, ABT-263 (navitoclax) alone, or their combination. In each case, human T-ALL cells were injected into immunodeficient NSG (***- Prkdc scid Il2rg tm1Wjl ) mice. Leukemic burden was measured in the blood by flow cytometry for human CD45+ cells. Once engraftment of T-ALL was observed, mice were randomized to one of four treatments: 1) ABT-263 100 mg/kg by oral gavage daily for 14 days; 2) idasanutlin 40 mg/kg by oral gavage daily on a 5-days-on 2-days-off schedule for 14 days; 3) combined idas

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In children with attention-deficit/hyperactivity disorder, less task-related up-modulation of motor cortex during response inhibition

Annals of the Child Neurology Society

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Annals of the Child Neurology Society 2025年

作者： Donald L. Gilbert Deana Crocetti Paul S. Horn Steve W. Wu David A. Huddleston Jacqueline M. Ehrman Karlee Y. Migneault Stewart H. Mostofsky Division of Neurology Cincinnati Children's Hospital Medical Center Cincinnati Ohio USA Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Ohio USA Center for Neurodevelopmental and Imaging Research Kennedy Krieger Institute Baltimore Maryland USA Departments of Neurology and Psychiatry Johns Hopkins University School of Medicine Baltimore Maryland USA Medical Scientist Training Program University of Cincinnati College of Medicine Cincinnati Ohio USA

Objective The aim of this study was to identify a quantitative, brain-based measure reflecting impaired response inhibition in children with attention-deficit/hyperactivity disorder (ADHD). Methods In this cross-sectional study, we used transcranial magnetic stimulation (TMS) to evoke potentials in hand muscle during both a simple reaction time and a response inhibition task in 8-to-12-year-old children, 41 with ADHD (42% girls, 76% white, mean age 10.3 years) and 38 typically developing controls (53% girls, 74% white, mean age 9.8 years). We used mixed-model linear regressions of evoked potential amplitudes to compare motor cortex excitability at (1) task-onset (“START”: 550 ms prior to action); (2) preparing-to-go (“GO”: 150 ms prior to action); and (3) selecting-to-stop (“STOP”: 150 ms after stop cue). We hypothesized that task-related up-modulation of motor cortex excitability (motor evoked potential amplitudes) would depend both on task (STOP > GO > START) and on diagnosis (controls > patients). Results Motor cortex up-modulation was significantly greater for STOP trials than during GO or START. Children with ADHD had both worse response inhibition performance (longer stop-signal reaction times) and significantly less task effect on motor cortex up-modulation. The largest diagnostic difference in motor cortex activation occurred during STOP trials. Reduced up-modulation during stopping was also associated with higher parent-rated symptom severity. Interpretation Our findings suggest that motor cortex up-modulation of excitability, assessed indirectly by TMS motor evoked potentials, reflects the cognitive load during response inhibition tasks and may be a quantitative, brain-based indicator of impaired response inhibition in children with ADHD.

关键词： attention-deficit/hyperactivity disorder children motor cortex response inhibition transcranial magnetic stimulation task-related up-modulation (TRUM)

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