Sweet flavorants enhance palatability and intake of alcohol in adolescent humans. We asked whether sweet flavorants have similar effects in adolescent rats. The inherent flavor of ethanol in adolescent rats is thought to consist of an aversive odor, bitter/sweet taste, and burning sensation. In Experiment 1, we compared ingestive responses of adolescent rats to 10% ethanol solutions with or without added flavorants using brief-access lick tests. We used 4 flavorants, which contained mixtures of saccharin and sucrose or saccharin, sucrose, and maltodextrin. The rats approached (and initiated licking from) the flavored ethanol solutions more quickly than they did unflavored ethanol, indicating that the flavorants attenuated the aversive odor of ethanol. The rats also licked at higher rates for the flavored than unflavored ethanol solutions, indicating that the flavorants increased the naso-oral acceptability of ethanol. In Experiment 2, we offered rats chow, water, and a flavored or unflavored ethanol solution every other day for 8 days. The rats consistently consumed substantially more of the flavored ethanol solutions than unflavored ethanol across the 8 days. When we switched the rats from the flavored to unflavored ethanol for 3 days, daily intake of ethanol plummeted. We conclude that sweet and sweet/maltodextrin flavorants promote high daily intake of ethanol in adolescent rats (i.e., 6-10 g/kg) and that they do so in large part by improving the naso-oral sensory attributes of ethanol.Age-related skeletal muscle degradation known as 'sarcopenia' exerts considerable strain on public health systems globally.  https://www.selleckchem.com/  While the pathogenesis of such atrophy is undoubtedly multifactorial, disruption at the neuromuscular junction (NMJ) has recently gained traction as a key explanatory factor. The NMJ, an essential communicatory link between nerve and muscle, undergoes profound changes with advancing age. Ascertaining whether such changes potentiate the onset of sarcopenia would be paramount in facilitating a timely implementation of targeted therapeutic strategies. Hence, there is a growing level of importance to further substantiate the effects of age on NMJs, in parallel with developing measures to attenuate such changes. As such, this review aimed to establish the current standpoint on age-related NMJ deterioration and consequences for skeletal muscle, while illuminating a role for biomarkers and exercise in ameliorating these alterations. Recent insights into the importance of key biomarkers for NMJ stability are provided, while the stimulative benefits of exercise in preserving NMJ function are demonstrated. Further elucidation of the diagnostic and prognostic relevance of biomarkers, coupled with the therapeutic benefits of regular exercise may be crucial in combatting age-related NMJ and skeletal muscle degradation.
  Adult patients are considered the best reporters of their own health-related quality of life (HRQOL). Self-report in pediatrics has been challenged by a limited array of valid measures. Caregiver report is therefore often used as a proxy for child report.
 
  To examine the degree of alignment between child and caregiver proxy report for Patient-Reported Outcomes Measurement Information System (PROMIS) HRQOL domains among children with cancer and to identify factors associated with better child and caregiver-proxy congruence.
 
  In this multicenter cohort study, children with a first cancer diagnosis and their caregivers completed surveys at 2 time points within 72 hours preceding treatment initiation (T1) and during follow-up (T2), when symptom burden was expected to be higher (eg, 7-17 days later for chemotherapy). Data were collected from October 26, 2016, to October 5, 2018, at 9 pediatric oncology hospitals. Five hundred eighty children (aged 7-18 years) and their caregivers were approached; 482 child-car's own report should be pursued whenever possible.
 This study found that caregivers consistently overestimated symptoms and underestimated mobility relative to the children themselves. These results suggest that elicitation of the child's own report should be pursued whenever possible.
  The purpose of this study was to determine whether genipin-induced crosslinked cell-derived matrix (XCDM) precipitates fibrotic phenotypes in human trabecular meshwork (hTM) cells by dysregulating β-catenin and Yes-associated protein (YAP)/ transcriptional coactivator with PDZ-binding motif (TAZ) signaling pathways.
 
  Cell-derived matrices were treated with control or genipin for 5 hours to obtain respective uncrosslinked (CDM) and XCDMs and characterized. hTM cells were seeded on these matrices with/without Wnt pathway modulators in serum-free media for 24 hours. Elastic modulus, gene, and protein (whole cell and subcellular fractions) expressions of signaling mediators and targets of Wnt/β-catenin and YAP/TAZ pathways were determined.
 
  At the highest genipin concentration (10% XCDM), XCDM had increased immunostaining of N-ε(γ-glutamyl)-lysine crosslinks, appeared morphologically fused, and was stiffer (5.3-fold, P < 0.001). On 10% XCDM, hTM cells were 7.8-fold (P < 0.001) stiffer, total β-catenin wenotypes induced by crosslinked ECM.
 Increased cytoplasmic TAZ may inhibit β-catenin from its nuclear shuttling or regulating cadherin 11 important for aqueous homeostasis. Elevated cytoplasmic TAZ may inhibit YAP's probable homeostatic function in the nucleus. Together, TAZ's cytoplasmic localization may be an important downstream event of how increased TM extracellular matrix (ECM) crosslinking may cause increased stiffness and ocular hypertension in vivo. However, Wnt pathway activation may ameliorate ocular hypertensive phenotypes induced by crosslinked ECM.
  To determine the effects of narrowband light exposure on choroidal thickness and the pupil response in humans.
 
  Twenty subjects, ages 21 to 43 years, underwent 1 hour of exposure to broadband, short wavelength "blue," or long wavelength "red" light, or darkness. Choroidal thickness, imaged with spectral domain optical coherence tomography, axial length, determined from biometry, and rod/cone- and intrinsically photosensitive retinal ganglion cell-driven pupil responses were measured before and after exposure. Pupil stimuli were six 1 second alternating red (651 nm) and blue (456 nm) stimuli, 60 seconds apart. Pupil metrics included maximum constriction and the 6 second post-illumination pupil response (PIPR).
 
  Compared with before exposure, the choroid significantly thinned after broadband light, red light, and dark exposure (all P < 0.05), but not after blue light exposure (P = 0.39). The maximum constriction to 1 second red stimuli significantly decreased after all light exposures (all P < 0.001), but increased after dark exposure (P = 0.