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Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain
No full textBackground: Neuroinflammation can modulate brain development; however, the influence of an acute peripheral immune challenge on neuroinflammatory responses in the early postnatal brain is not well characterized. To address this gap in knowledge, we evaluated the peripheral and central nervous system (CNS) immune responses to a mixed immune challenge in early postnatal rats of varying strains and sex. Methods: On postnatal day 10 (P10), male and female Lewis and Brown Norway rats were injected intramuscularly with either a mix of bacterial and viral components in adjuvant, adjuvant-only, or saline. Immune responses were evaluated at 2 and 5 days post-challenge. Cytokine and chemokine levels were evaluated in serum and in multiple brain regions using a Luminex multiplex assay. Multi-factor ANOVAs were used to compare analyte levels across treatment groups within strain, sex, and day of sample collection. Numbers and activation status of astrocytes and microglia were also analyzed in the cortex and hippocampus by quantifying immunoreactivity for GFAP, IBA-1, and CD68 in fixed brain slices. Immunohistochemical data were analyzed using a mixed-model regression analysis. Results: Acute peripheral immune challenge differentially altered cytokine and chemokine levels in the serum versus the brain. Within the brain, the cytokine and chemokine response varied between strains, sexes, and days post-challenge. Main findings included differences in T helper (Th) type cytokine responses in various brain regions, particularly the cortex, with respect to IL-4, IL-10, and IL-17 levels. Additionally, peripheral immune challenge altered GFAP and IBA-1 immunoreactivity in the brain in a strain- and sex-dependent manner. Conclusions: These findings indicate that genetic background and sex influence the CNS response to an acute peripheral immune challenge during early postnatal development. Additionally, these data reinforce that the developmental time point during which the challenge occurs has a distinct effect on the activation of CNS-resident cells
Somatic loss of PIK3R1 may sensitize breast cancer to inhibitors of the MAPK pathway
No full textPurpose: The PI3K pathway, which includes the PI3K catalytic subunits p110α (PIK3CA) and the PI3K regulatory subunit p85α (PIK3R1), is the most frequently altered pathway in cancer. We encountered a breast cancer patient whose tumor contained a somatic alteration in PIK3R1. Some commercial sequencing platforms suggest that somatic mutations in PIK3R1 may sensitize cancers to drugs that inhibit the mammalian target of rapamycin (mTOR). However, a review of the preclinical and clinical literature did not find evidence substantiating that hypothesis. The purpose of this study was to knock out PIK3R1 in order to determine the optimal therapeutic approach for breast cancers lacking p85α. Methods: We created an isogenic cellular system by knocking out both alleles of the PIK3R1 gene in the non-tumorigenic human breast cell line MCF-10A. Knockout cells were compared with wild-type cells by measuring growth, cellular signaling, and response to drugs. Results: We observed hyperphosphorylation of MEK in these knockouts, which sensitized PIK3R1-null cells to a MEK inhibitor, trametinib. However, they were not sensitized to the mTOR inhibitor, everolimus. Conclusions: Our findings suggest that breast cancers with loss of p85α may not respond to mTOR inhibition, but may be sensitive to MEK inhibition
Recommendations towards standards for quantitative MRI (qMRI) and outstanding needs
No full textLevel of Evidence: 5. Technical Efficacy: Stage 5. J. Magn. Reson. Imaging 2019
Perspectives on cannabis as a substitute for opioid analgesics
No full textWith the opioid epidemic reaching new heights in the USA, it has become critical to find suitable alternatives to opioids. Cannabis, an antinociceptive, is a strong contender to help patients reduce their opioid usage. A growing literature has been examining the complex effects cannabis has on pain relief and on opioid usage; whether it is a substitute for opioids or increases their use. This review explores the studies that compare cannabis-opioid interactions and presents some challenges of cannabis research and usage. The practical clinical pharmacology of cannabis as an analgesic, including the route of administration, safety and pharmacokinetics, are discussed to address the concerns, as well as possible solutions, of cannabis as a pain reliever
Dynamic balance during running using running-specific prostheses
No full textRunning is beneficial for physical, social, and emotional health, and participating in physical activity, including running, is becoming more popular for people with an amputation. However, this population has a greater risk of falling relative to people without an amputation, which may be a barrier to running. Understanding how dynamic balance is maintained during running is important for removing this barrier. To investigate dynamic balance, we quantified whole-body angular momentum in eight people with a unilateral transtibial amputation (TTA) using running-specific prostheses (RSPs) compared to eight people without TTA during running at 2.5, 3.0, and 3.5 m/s. People with TTA had greater ranges of whole-body angular momentum compared to people without TTA in the frontal and sagittal planes (p \u3c 0.01). These greater ranges resulted from smaller peak medial, lateral, and braking ground reaction forces from the amputated leg compared to the intact leg and people without TTA. Reduced RSP mass relative to the biological leg also influenced whole-body angular momentum as evidenced by smaller ranges of amputated leg angular momentum compared to the intact leg in the frontal and sagittal planes. Smaller amputated leg angular momentum corresponded with smaller contralateral arm angular momentum in the sagittal plane (p \u3c 0.01). People with TTA maintain balance during running with altered muscle coordination and prosthesis characteristics. Restoring mediolateral force generation through prosthetic design advances may help in regulating the frontal plane component of whole-body angular momentum for people with TTA, with potential to improve their ability to maintain balance during running
Influence of stress, coping and social factors on pain and disability in musculoskeletal practice
No full textContent-Based Music Recommendation using Deep Learning
Get PDFMusic streaming services use recommendation systems to improve the customer experience by generating favorable playlists and by fostering the discovery of new music. State of the art recommendation systems use both collaborative filtering and content-based recommendation methods. Collaborative filtering suffers from the cold start problem; it can only make recommendations for music for which it has enough user data, so content-based methods are preferred. Most current content-based recommendation systems use convolutional neural networks on the spectrograms of track audio. The architectures are commonly borrowed directly from the field of computer vision. It is shown in this study that musically-motivated convolutional neural network architectures outperform architectures that are highly-optimized for image-related tasks. A content-based recommendation model is built using musically-motivated deep learning architectures. The model is shown to be able to map an artist onto an artist embedding space where its nearest neighbors by cosine similarity are related artists and make good recommendations. It is also shown that metadata, such as lyrics, artist origin, and year, significantly improve these mappings when combined with raw audio data
Motor vehicle crash reconstruction: Does it relate to the heterogeneity of whiplash recovery?
No full textWhiplash injury is a common consequence of motor vehicle crashes (MVC), yet it is also one of the most poorly understood. While more than 50% of those injured should expect to rapidly recover, others are not as fortunate with approximately 25% of those exposed to and injured in an MVC transitioning from acute to chronic pain and disability. The purpose of this prospective study was to determine if the severity and direction of collisions involving participants enrolled in a longitudinal study of recovery from whiplash are able to differentiate between different recovery groups based on the neck disability index (NDI) percentage scores at 3-months, and if these crash specific parameters are associated with known risk factors for recovery. Here, we examined objective collision data, repair invoices, and characteristics of the crash for 37 acutely injured participants consented and enrolled at their emergency department visit and further assessed at three time points; \u3c 1 week, 2-weeks, and 3-months post MVC. Collision data were used to reconstruct and estimate the severity of the crash and determine if they aligned with the heterogeneity of whiplash injury recovery. Wilcoxon rank sum tests were used to determine if % scores on the Neck Disability Index (NDI) at 3-months post MVC were associated with the following variables: sex, head turned at time of impact, seatbelt use, whether or not airbags deployed, if the vehicle was struck while stopped or while turning, or the principle direction of force (PDOF). Spearman’s correlation coefficients were used to determine if NDI at 3-months post MVC was associated with age, Body Mass Index, pain-related disability at baseline, signs of post-traumatic distress, intrusion/hyperarousal, negative affect, pain intensity, estimated speed change from the impact, and damage estimates (in US$). There was a significant positive associatio
Computing for the social good in education
No full textAccording to the United Nations, twenty-two global issues face society [31]. Many of these-Health, Food, Water, Poverty, and Migration-relate to Climate Change, while others are social issues related to Democracy, International Law and Justice, Gender Equality, and Human Rights. Each of these issues deserves the attention of the computing community, and in turn, demands the attention of computing educators. As a community, we dare not continue with business as usual. Specifically, we must do our part to fill the pipeline of future computing professionals with practitioners who deeply understand that they can use their unique skills to tackle the major social issues of our time
Deep Learning Convolutional Neural Networks for the Automatic Quantification of Muscle Fat Infiltration Following Whiplash Injury
No full textMuscle fat infiltration (MFI) of the deep cervical spine extensors has been observed in cervical spine conditions using time-consuming and rater-dependent manual techniques. Deep learning convolutional neural network (CNN) models have demonstrated state-of-the-art performance in segmentation tasks. Here, we train and test a CNN for muscle segmentation and automatic MFI calculation using high-resolution fat-water images from 39 participants (26 female, average = 31.7 ± 9.3 years) 3 months post whiplash injury. First, we demonstrate high test reliability and accuracy of the CNN compared to manual segmentation. Then we explore the relationships between CNN muscle volume, CNN MFI, and clinical measures of pain and neck-related disability. Across all participants, we demonstrate that CNN muscle volume was negatively correlated to pain (R = −0.415, p = 0.006) and disability (R = −0.286, p = 0.045), while CNN MFI tended to be positively correlated to disability (R = 0.214, p = 0.105). Additionally, CNN MFI was higher in participants with persisting pain and disability (p = 0.049). Overall, CNN’s may improve the efficiency and objectivity of muscle measures allowing for the quantitative monitoring of muscle properties in disorders of and beyond the cervical spine