Methotrexate for Juvenile Idiopathic Arthritis.

PubMed · 2025-05-01 · 2 citations

Pregnant Woman With Abnormal Ultrasound

Annals of Emergency Medicine · 2023-04-19

In patients with concussion symptoms, do SSRIs aid in recovery?

Evidence-Based Practice · 2023-05-08

University of Missouri Family and Community Medicine Residency Program, Columbia, MO The corresponding author is Joshua Smothers; [email protected] The author team declares no conflict of interest.

Vitamin D Supplementation Improves Health-Related Quality of Life and Physical Performance in Children with Sickle Cell Disease and in Healthy Children

Journal of Pediatric Health Care · 2020-06-05 · 29 citations

The Role of Endogenous Opioids in Cerebral Glucose Uptake Following Acute Exercise

Medicine & Science in Sports & Exercise · 2019-06-01

Exercise has been linked to several opioid mediated phenomena including exercise mediated analgesia, euphoria “runner’s high” and addiction. The role of the endogenous opioid system in these events have all been verified using the opioid receptor blocker naltrexone. Despite this, a full understanding on how the endogenous opioid system influences brain activity under acute exercise conditions is lacking PURPOSE: To investigate the role of the endogenous opioid system on brain glucose uptake following an acute bout of exercise with and without administration of naltrexone. METHODS: To assess cerebral glucose uptake mice were fasted overnight and scanned using positron emission tomography (PET) in one of four assigned conditions: control (CON), exercise (EX), naltrexone injection (NTX) or exercise + naltrexone injection (EX+NTX). Mice were delivered a dose of 18F-fluorodeoxyglucose (FDG) 1 hour prior to scanning. Mice that underwent exercise performed 50 minutes of forced swimming (FS) following a week of familiarization, which consisted of 5-25 minutes of FS. NTX was given via intraperitoneal injection (4 mg/kg) 15 minutes prior to exercise or FDG administration. Data was imaged using VivoQuant software and analyzed using PMOD software by a technician blinded to the experimental conditions. Data was calculated as average standardized uptake values (SUV) for 19 regions of interest (ROI) and made relative to the SUV of the whole brain. RESULTS: Exercise increased the SUV of glucose in the cerebellum (EX=1.27 ± 0.14; P<0.05) relative to mice under CON (0.98 ± 0.07) or NTX (0.85 ± 0.03) conditions. The exercise mediated increase in activity in the cerebellum was abolished (P<0.05) with the addition of NTX (0.88 ± 0.10). The combination of EX+NTX increased the SUV of glucose in the hypothalamus region relative to all groups (P<0.05). CONCLUSIONS: The cerebellum is largely responsible for the regulation of voluntary muscular activity. Exercise appears to have a potent effect on brain activity specific to this region and may be at least partially mediated by endogenous opioids. Further, the endogenous opioid system may play a role in the attenuation of the hypothalamic-pituitary adrenal system during exercise.

Abstract 3385: Comparison of genomic biomarkers identified by the whole exome, RNASeq and whole genome sequencing pipelines developed for the PDMR

Cancer Research · 2019-07-01

Abstract Background: The National Cancer Institute (NCI) has developed a Patient-Derived Models Repository (PDMR; www.pdmr.cancer.gov) of patient-derived xenografts (PDXs) with clinical annotation and comprehensive genomic characterization using whole exome sequencing (WES) and RNASeq. An in-house data analysis pipeline has been developed and validated to call germline and somatic variants and to perform transcriptional profiling in these models. There is a need to incorporate additional biomarkers into standard data analysis pipeline, including loss of heterozygosity (LOH), microsatellite instability (MSI), structure variants (SVs)/fusions and copy number variation (CNV) for identifying appropriate PDX models for preclinical drug studies. Validation of the methods used for the assessment of these and other genomic biomarkers is a crucial aspect in the development of the PDMR data analysis pipeline. Methods: WGS, WES and RNASeq were conducted on 58 PDX samples and genomic biomarkers were derived from different assays. For LOH calling, a set of ~800,000 heterozygous SNPs was first constructed from a population level genomic database (gnomAD) and a specific list of ~3000 highly heterozygous SNPs from a previous study. LOH regions were detected using Runs of Homozygosity (BCFtools/RoH) based on the genotypes of ~800,000 SNPs. Finally, percent of genomic LOH was calculated as the percent of eligible LOH regions in the whole genome. For MSI calling. mSINGS was used to assign a microsatellite instability score based on the fraction of unstable microsatellite loci. Gene fusions were detected using Tophat-fusion and Fusion-catcher from RNASeq data and Manta from WGS. CNVs were derived from WGS and WES using CNVkit. Results: Genomic biomarkers derived from WES and RNASeq were highly concordant with the ones derived from WGS. Specifically, we found 1) the percent of genomic LOH was highly correlated between WGS and WES across 52 samples with R2=0.99, where LOH% ranged from &amp;lt;1% to ~50% and specimens within the same models had consistent data; 2) a strong concordance rate (91%) of MSI score was observed between WGS and WES across 49 samples; 3) clinically and diagnostically relevant structural variants/fusions (e.g. FGFR3-TACC3 and EWSR1-FLI1) detected from RNASeq data can be detected and validated from WGS data; and 4) CNV genomic profiles were highly correlated between WGS and WES and amplifications/deletions in clinically relevant genes were consistently detected by the two assays. Conclusions: We observed excellent consistency between WGS, WES and RNASeq data in the assessment of percent of LOH, MSI score, SVs/fusions and CNVs. Our data analysis pipeline can accurately call genomic biomarkers from WES and RNASeq data, which facilitates the molecular characterization and prioritization of PDMR models for preclinical drug treatment. Citation Format: Li Chen, Rajesh Patidar, Biswajit Das, Chris Karlovich, Tomas Vilimas, Corinne Camalier, Vivekananda Datta, Shahanawaz Jiwani, William Walsh, Palmer Fliss, Sean McDermott, Justine N. McCutcheon, Amanda Peach, Michelle Ahalt-Gottholm, Carrie Bonomi, Kelly Dougherty, John Carter, Sergio Y. Alcoser, Tiffanie Chase, Raymond Divelbiss1, Marion Gibson, Kelly Hedger, Candace Mallow, Chelsea McGlynn, Malorie Morris, Marianne Radzyminski, Howard Stotler, Jesse Stottlemyer, Debbie Trail, Yvonne Evrard, Melinda G. Hollingshead, Mickey Williams, James H. Doroshow. Comparison of genomic biomarkers identified by the whole exome, RNASeq and whole genome sequencing pipelines developed for the PDMR [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3385.

Differential developmental refinement of the intrinsic electrophysiological properties of CA1 pyramidal neurons from the rat dorsal and ventral hippocampus

Hippocampus · 2019-09-06 · 13 citations

Abstract The dorsal and ventral regions of the rat longitudinal hippocampal axis are functionally distinct. That is, each region is associated with different behavioral tasks and disease susceptibilities due to underlying anatomical, and physiological differences. These differences are especially pronounced in area CA1, where significant differences in morphology, synaptic physiology, intrinsic excitability, and gene expression have been reported between CA1 pyramidal neurons from the dorsal (DHC) and ventral hippocampus (VHC). However, despite a significant amount of recent attention, a cogent picture of the intrinsic electrophysiological profile of DHC and VHC neurons has remained elusive, due, in part, to experiments performed on rats at different developmental time points. Moreover, the resulting intrinsic electrophysiological profiles are sufficiently different as to warrant a thorough investigation of the spatial and temporal changes in the intrinsic excitability of CA1 pyramidal neurons across developmental time. Accordingly, in this study, I have characterized the intrinsic electrophysiological properties of CA1 pyramidal neurons from acute hippocampal slices prepared from the DHC and VHC throughout an approximately 3‐week developmental period (P14–P37). DHC and VHC neurons exhibited distinct intra‐region changes (DHC or VHC) and inter‐region differences (DHC versus VHC) in their intrinsic electrophysiological properties, which yielded two developmental timelines: (a) a common developmental timeline describing changes observed in both DHC and VHC neurons, and (b) a differential developmental timeline highlighting unique features observed in DHC neurons. Specifically, DHC neurons exhibited significant inter‐region differences in RMP, input resistance, threshold, and spike frequency adaptation relative to VHC neurons, as well as an intra‐region change in the rebound slope (a proxy for I h ). These observations both integrate and reconcile previous work performed with rats at different developmental stages and suggest a distinct developmental trajectory for DHC neurons that might shed light on the normal physiological functions and disease susceptibility of the DHC.

Seven Year Old Patient With Acute Flaccid Myelitis Regains Function After Locomotor Training: Case Study

Archives of Physical Medicine and Rehabilitation · 2019-11-22

Changes in Analgesia, Hyperphagia and Depression are Mediated by Endogenous Opioids Following Forced Swimming Exercise

Medicine & Science in Sports & Exercise · 2019-06-01

Exercise is specifically linked to at least three phenomena that are likely to involve opioid release; the ‘athlete’s high’, increased pain tolerance, and addiction to exercise. Exercise studies that have examined the effects of the opiate receptor blocker naltrexone, found that its administration prior to exercise alter these before mentioned phenomena. PURPOSE: The purpose of this study was twofold: 1) to establish an exercise modality that is sufficient to stimulate the release of endogenous opioids and 2) to examine the role endogenous opioids play in post-exercise pain tolerance and depression. METHODS: Following a week of familiarization, mice underwent a 50-minute (min) bout of forced swimming (FS). Mice were injected with either saline (S; 0.9%) or the opioid blocker naltrexone (NTX; 4g/kg) 15 mins prior to exercise. Following exercise mice were challenged with a tail suspension test (TST), pain tolerance test or monitored for post exercise food consumption for 2 hours. RESULTS: NXT injection decreased total FS time (46 ± 1.2 mins. vs. 35 ± 1.6 mins; p<0.05). Forced swimming increased food consumption by 88% ± 11 (p<0.05) two hours following exercise but was abolished by NXT (p<0.05), verifying an increase in opioid mediated hyperphagia. An increase in hot water tail immersion time following exercise (S = 2.72 s ± 0.13 vs. FS = 4.28 ± 0.19; p<0.05) demonstrated an improvement in pain tolerance. Pain tolerance decreased by 20% ± 0.05 with the addition of NXT (P<0.05). Finally, a TST demonstrated that following a bout of exercise, mice spent 49 ± 3.1% less time immobile (p<0.05), signifying lower depression levels. This effect was reversed with the opioid blockade (p<0.05). CONCLUSIONS: Fifty minutes of forced swimming is an effective stimulus for the release of endogenous opioids and modulates behavioral changes specific to the release endogenous opioids in mice.

Muscle Strength, Power, and Torque Deficits in Children With Type SS Sickle Cell Disease

Journal of Pediatric Hematology/Oncology · 2018-04-04 · 21 citations

In African-American children aged 5 to 17 years with and without type SS sickle cell disease (SCD-SS), dominant hand maximal handgrip strength, peak power, and plantar flexion isometric maximal voluntary contraction (MVC) torque were compared with adjustments for body size and composition. Children with SCD-SS (n=21; age, 11±1 y) compared with healthy control children (n=23; 10±1 y) did not differ by age, sex, or maturation stage, but had significantly lower Z scores for height, weight, body mass index, arm circumference, upper arm muscle area, and lean mass-for-height. Children with SCD-SS had significantly lower unadjusted handgrip strength (16±2 vs. 23±2 kg, P<0.01), peak power (1054±107 vs. 1488±169 W, P<0.04) and MVC torques at 2 angles (10 degrees: 27±3 vs. 42±5 Nm; 20 degrees: 21±3 vs. 34±4 Nm; all P<0.05). Performance decrements persisted when handgrip strength was adjusted for lean body mass and fat mass explaining 66% of the variance; peak power adjusted for age, lean body mass, fat mass, and height explaining 91% of the variance; and the highest MVC torque (10-degree angle) adjusted for left leg length, lean mass-for-height, and fat mass-for-height Z scores explaining 65% of the variance. This suggests additional factors contribute to the attenuated anaerobic performance.