Most genetic variants for colorectal cancer (CRC) identified in genome-wide association studies (GWAS) are located in intergenic regions, implying pathogenic dysregulations of gene expression. However, comprehensive assessments of target genes in CRC remain to be explored. We conducted a multi-omics analysis using transcriptome and/or DNA methylation data from the Genotype-Tissue Expression, The Cancer Genome Atlas and the Colonomics projects. We identified 116 putative target genes for 45 GWAS-identified variants. Using summary-data-based Mendelian randomization approach (SMR), we demonstrated that the CRC susceptibility for 29 out of the 45 CRC variants may be mediated by cis-effects on gene regulation. At a cutoff of the Bonferroni-corrected PSMR  less then  0.05, we determined 66 putative susceptibility genes, including 39 genes that have not been previously reported. We further performed in vitro assays for two selected genes, DIP2B and SFMBT1, and provide functional evidence that they play a vital role in colorectal carcinogenesis via disrupting cell behavior, including migration, invasion and epithelial-mesenchymal transition. Our study reveals a large number of putative novel susceptibility genes and provides additional insight into the underlying mechanisms for CRC genetic risk loci.
  Current recovery guidelines following sport-related concussion (SRC) include 24-48 hours of rest followed by gradual return-to-activity with heart rate (HR) maintained below symptom threshold. Additionally, the monitoring of physical activity (PA) post-SRC using ActiGraph accelerometers can provide further objective insight on amounts of activity associated with recovery trajectories. Cut-point algorithms for these devices allow minute-by-minute PA to be classified into intensity domains; however, studies have shown different algorithms employed on the same healthy participant dataset can produce varying classifications.
 
  To identify the most physiologically appropriate cut-point algorithm (Evenson or Romanzini) to analyze ActiGraph data in concussed youth with comparisons to HR response on the Buffalo Concussion Treadmill Test (BCTT).
 
  Prospective cohort study.
 
  Sport-concussion clinic within a university setting.
 
  Eleven high-school students (5 male, 6 female; median [range] age =16 years [15-17], heivenson algorithm better characterizes the HR response during a standardized exercise test in concussed individuals and therefore should be used to analyze ActiGraph PA data in a concussed paediatric population.
  Shoulder range of motion (ROM) and strength are key injury evaluation components for overhead athletes. Most normative values are derived from male baseball players with limited information specific to female softball players.
 
  To determine between-limb differences in shoulder ROM and strength in healthy collegiate softball players.
 
  Descriptive laboratory study.
 
  University research laboratory and collegiate athletic training room Participants Twenty-three healthy collegiate softball players (age=19.9 ± 1.2y; height=170.5 ± 4.3cm; mass=78.4 ± 11.3kg).
 
  Outcome measures included shoulder ROM (internal [IR] and external rotation [ER]), isometric strength (IR, ER, flexion, abduction [135 degrees], and horizontal abduction), and a measure of dynamic strength (Upper Quarter Y Balance Test [UQYBT]).
 
  Paired sample t-tests were used to determine between limb differences for each outcome measure.
 
  Participants had significantly more ER ROM (12° more) and significantly less IR ROM (12° less) on the dominant arm, relative to the non-dominant arm. There were no significant differences between limbs for any of the isometric strength measures or for the UQYBT reach directions.
 
  While female collegiate softball players demonstrated typical changes in ER and IR ROM in the dominant arm, they demonstrated relatively symmetrical performance across strength measures, which contrasts with previous studies using male baseball players.
 While female collegiate softball players demonstrated typical changes in ER and IR ROM in the dominant arm, they demonstrated relatively symmetrical performance across strength measures, which contrasts with previous studies using male baseball players.Long non-coding RNAs (lncRNAs) are crucial players in tumor progression. Herein, this work was designated to decipher the clinical significance, function and molecular mechanism of an lncRNA, differentiation antagonizing non-coding RNA (DANCR) in colorectal cancer (CRC). Quantitative real-time PCR (qRT-PCR) was adopted to examine DANCR, miR-185-5p and HMGA2 mRNA expressions in CRC tissues and cells. Both gain-of-function and loss-of-function cell models for DANCR were established, and then MTT, wound healing and Transwell, flow cytometry assays were carried out to detect the proliferation, migration, invasion, cell cycle and apoptosis of CRC cells. Dual luciferase reporter gene assay and RIP assay were utilized to validate the targeting relationships between DANCR and miR-185-5p. Western blot was employed for detecting high mobility group A2 (HMGA2) expressions in CRC cells. In this study, we demonstrated that the expression of DANCR was elevated in CRC tissues and cell lines, and its high expression was significantly associated with increased TNM stage and positive lymph node metastasis. DANCR overexpression promoted CRC cell proliferation, migration, invasion and cell cycle progression, but inhibited apoptosis; while knocking down DANCR caused the opposite effects. DANCR was further identified as a molecular sponge for miR-185-5p, and DANCR could indirectly increase the expression of HMGA2 via repressing miR-185-5p. In conclusion, DANCR/miR-185-5p/HMGA2 axis participated in the progression of CRC.The biological half-life (t1/2) of methylmercury (MeHg) shows considerable individual variability (t1/2 120 days), highlighting the importance of mechanisms controlling MeHg metabolism and elimination.  https://www.selleckchem.com/products/cerdulatinib-prt062070-prt2070.html  Building on a prior physiologically based pharmacokinetic (PBPK) model, we elucidate parameters that have the greatest influence on variability of MeHg t1/2 in the human body. Employing a dataset of parameters for mean organ volumes and blood flow rates appropriate for man and woman (25-35 years) and child (4 - 6 years), we demonstrate model fitness by simulating data from our prior controlled study of MeHg elimination in people. Model predictions give MeHg t1/2 of 46.9, 38.9, and 31.5 days and steady-state blood MeHg of 2.6, 2.6, and 2.3 µg/l in man, woman, and child, respectively, subsequent to a weekly dose of 0.7 µg/kg body weight. The major routes of elimination are biotransformation to inorganic Hg in the gut lumen (73% in adults, 61% in child) and loss of MeHg via excretion within growing hair (13% in adults, 24% in child).