To investigate the effect of hyaluronic acid (HA) in patients diagnosed with mild or moderate carpal tunnel syndrome (CTS).
 
  A prospective randomized, double-blinded control study with 6 months of follow-up.
 
  Rehabilitation outpatient clinic of one single medical center.
 
  Thirty-five participants with mild or moderate CTS.
 
  Participants were enrolled and randomly assigned to HA or control groups. The HA group received one ultrasound-guided perineural injection of 2.5 ml HA while the control group received 2.5 ml normal saline injection through in-plane, long-axis approach to separate the median nerve from the flexor retinaculum via nerve hydrodissection. Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) scores were the primary outcome, while secondary outcomes included the numeric rating scale (NRS), electrophysiological domains, and the cross-sectional area of the median nerve. The assessment was conducted prior to injection and during the second week and 1-, 3-, and 6-months post-injection.
 
  Thirty-two patients (17 wrists in HA group and 15 wrists in control group) completed the study. Compared with the control group, the HA group did not show significantly superior outcomes, except in BCTQ and NRS at the second week post-injection (all p < 0.0125).
 
  A single ultrasound guided perineural HA injection may have short-term therapeutic efficacy for mild or moderate CTS; however, the 2-weeks superior efficacy was not beneficial for chronic neuropathy. Further studies with larger sample sizes are required to verify its therapeutic efficacy.
 A single ultrasound guided perineural HA injection may have short-term therapeutic efficacy for mild or moderate CTS; however, the 2-weeks superior efficacy was not beneficial for chronic neuropathy. Further studies with larger sample sizes are required to verify its therapeutic efficacy.Understanding how genes interact is a central challenge in biology. Experimental evolution provides a useful, but underutilized, tool for identifying genetic interactions, particularly those that involve non-loss-of-function mutations or mutations in essential genes. We previously identified a strong positive genetic interaction between specific mutations in KEL1 (P344T) and HSL7 (A695fs) that arose in an experimentally-evolved Saccharomyces cerevisiae population. Because this genetic interaction is not phenocopied by gene deletion, it was previously unknown. Using "evolutionary replay" experiments we identified additional mutations that have positive genetic interactions with the kel1-P344T mutation. We replayed the evolution of this population 672 times from six timepoints.  https://www.selleckchem.com/products/vx-661.html  We identified 30 populations where the kel1-P344T mutation reached high frequency. We performed whole-genome sequencing on these populations to identify genes in which mutations arose specifically in the kel1-P344T background. We reconstructed mutations in the ancestral and kel1-P344T backgrounds to validate positive genetic interactions. We identify several genetic interactors with KEL1, we validate these interactions by reconstruction experiments, and we show these interactions are not recapitulated by loss-of-function mutations. Our results demonstrate the power of experimental evolution to identify genetic interactions that are positive, allele specific, and not readily detected by other methods, shedding light on an under-explored region of the yeast genetic interaction network.Enhancers are often studied as noncoding regulatory elements that modulate the precise spatiotemporal expression of genes in a highly tissue-specific manner. This paradigm has been challenged by recent evidence of individual enhancers acting in multiple tissues or developmental contexts. However, the frequency of these enhancers with high degrees of 'pleiotropy' out of all putative enhancers is not well understood. Consequently, it is unclear how the variation of enhancer pleiotropy corresponds to the variation in expression breadth of target genes. Here we use multi-tissue chromatin maps from diverse human tissues to investigate the enhancer-gene interaction architecture while accounting for (1) the distribution of enhancer pleiotropy, (2) the variations of regulatory links from enhancers to target genes, and (3) the expression breadth of target genes. We show that most enhancers are tissue-specific and that highly pleiotropy enhancers account for less then 1% of all putative regulatory sequences in the human genome. Notably, several genomic features are indicative of increasing enhancer pleiotropy, including longer sequence length, greater number of links to genes, increasing abundance and diversity of encoded transcription factor motifs, and stronger evolutionary conservation. Intriguingly, the number of enhancers per gene remains remarkably consistent for all genes (∼14). However, enhancer pleiotropy does not directly translate to the expression breadth of target genes. We further present a series of Gaussian Mixture Models to represent this organization architecture. Consequently, we demonstrate that a modest trend of more pleiotropic enhancers targeting more broadly expressed genes can generate the observed diversity of expression breadths in the human genome.
  In response to the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic in spring 2020, we developed a caregiver-report measure to understand the extent to which children and families were exposed to events related to COVID-19 and their perceptions of its impact. This article reports on the factor structure and psychometric properties of this measure.
 
  The COVID-19 Exposure and Family Impact Scales (CEFIS) were developed by a multidisciplinary, multi-institutional team using a rapid iterative process. Data from 1805 caregivers recruited from 28 programs at 15 institutions across the United States were collected from May-September 2020. We examined the underlying structure of the CEFIS using exploratory factor analyses and its internal consistency (Cronbach's alpha).
 
  Participants reported a range of COVID-19-related events (M = 8.71 events of 25). On the bidirectional 4-point impact scale, mean scores were mostly above the midpoint, indicating a slightly negative impact. Cronbach's alpha was excellent for Exposure (α = .