Tyrosinase is a multifunctional, glycosylated and copper-containing oxidase enzyme that can be found in animals, plants, and fungi. It is involved in several biological processes such as melanin biosynthesis. In this work, a series of isobenzofuran-1(3H)-ones was evaluated as tyrosinase inhibitors. It was found that compounds phthalaldehydic acid (1), 3-(2,6-dihydroxy-4-isopropylphenyl)isobenzofuran-1(3H)-one (7), and 2-(3-oxo-1,3-dihydroisobenzofuran-1-yl)-1,3-phenylene diacetate (9) were the most potent compounds inhibiting tyrosinase activity in a concentration dependent manner. Ligand-enzyme NMR studies and docking investigations allowed to map the atoms of the ligands involved in the interaction with the copper atoms present in the active site of the tyrosinase. This behaviour is similar to kojic acid, a well know tyrosinase inhibitor and used as positive control in the biological assays. The findings herein described pave the way for future rational design of new tyrosinase inhibitors.Augmentation of cAMP signaling through inhibition of phosphodiesterases (PDE) is known to enhance plasticity and memory. Inhibition of PDE4 enhances consolidation into memory, but less is known about the role of other cAMP specific PDEs. Here, we tested the effects of oral treatment with a selective inhibitor of PDE7 of nanomolar potency on spatial and contextual memory. In an object location task, doses of 0.3-3 mg/kg administered 3 h after training dose-dependently attenuated time-dependent forgetting in rats. Significant enhancement of memory occurred at a dose of 3 mg/kg with corresponding brain levels consistent with PDE7 inhibition. The same dose given prior to training augmented contextual fear conditioning. In mice, daily dosing before training enhanced spatial memory in two different incremental learning paradigms in the Barnes Maze. Drug treated mice made significantly less errors locating the escape in a probe-test 24 h after the end of training, and they exhibited hippocampal-dependent spatial search strategies more frequently than controls, which tended to show serial sampling of escape locations.  https://www.selleckchem.com/  Acquisition and short-term memory, in contrast, were unaffected. Our data provide evidence for a role of PDE7 in the consolidation of hippocampal-dependent memory. We suggest that targeting PDE7 for memory enhancement may provide an alternative to PDE4 inhibitors, which tend to have undesirable gastrointestinal side-effects.
  Transcranial direct current stimulation (tDCS) has previously been shown to improve fear extinction learning and retention when administered prior to or during extinction learning. This study investigates whether tDCS immediately following extinction learning improves efficacy of extinction memory retention.
 
  30 participants completed a 2-day fear learning and extinction paradigm, where they acquired fear of a stimulus conditioned to an aversive electric shock on day 1. Extinction learning occurred on day 1, with tDCS or sham tDCS administered immediately following the learning phase. Participants returned for a second day test of extinction memory recall. Skin conductance was measured as the primary outcome.
 
  Participants in the tDCS group showed impaired fear extinction retention on day 2, marked by significant generalisation of fear to the safety stimulus. This contrasts with earlier studies showing improved extinction retention when stimulation occurred during encoding of extinction learning, compared to immediate consolidation as in our study. These findings may have important implications for the use of tDCS during exposure therapy for anxiety and trauma disorders.
 Participants in the tDCS group showed impaired fear extinction retention on day 2, marked by significant generalisation of fear to the safety stimulus. This contrasts with earlier studies showing improved extinction retention when stimulation occurred during encoding of extinction learning, compared to immediate consolidation as in our study. These findings may have important implications for the use of tDCS during exposure therapy for anxiety and trauma disorders.
  Increased infection risk after total knee arthroplasty (TKA) in patients with a higher body mass index (BMI), particularly a BMI ≥40kg/m
  , suggests that BMI reduction (through weight loss) prior to TKA may be important. However, the impact of weight loss on TKA risk reduction is unclear. Furthermore, weight loss could have detrimental consequences with respect to muscle loss and development of sarcopenic obesity, whereby a potential weight loss paradox in adults with advanced knee OA and obesity may be present. Using a critical review approach, we examined the current evidence supporting weight loss in adults with obesity and advanced knee osteoarthritis (OA). We focused on three key areas (1) TKA complication risk with severe obesity compared to obesity (BMI ≥40kg/m
  versus 30.0-39.9kg/m
  ); (2) weight loss recommendations for individuals with advanced knee OA; and (3) TKA outcomes after pre-surgical weight loss.
 
  Medline and CINAHL databases were examined from Jan 2010 to May 2020 to identify high-leve benefit of weight loss prior to TKA is lacking. Until knowledge gaps are clarified, it is recommended that practitioners consider individual patient needs and risk before recommending weight loss (and therefore BMI reduction).
  To evaluate salivary gland (SG) involvement in patients with systemic sclerosis (SSc) using SG ultrasound (SGUS).
 
  Patients with SSc (n=62), primary Sjögren's syndrome (pSS) (n=59), and idiopathic Sicca syndrome (n=43) were evaluated using the outcome measures in rheumatology clinical trial (OMERACT) definitions of the SGUS scoring system. The hyperechogenic bands using the 0-3 scoring system, intraglandular power Doppler signal (PDS), and SG volumes were also assessed.
 
  The proportion of patients with OMERACT grades (≥2) among the four SGs was significantly higher in SSc (51.6%) and pSS (62.7%) groups than those in the idiopathic Sicca syndrome group (4.7%). Patients with SSc and pSS had significantly higher total fibrosis grades than controls. No difference in fibrosis grades was observed between SSc and pSS groups. The PDS scores of SGs were higher in the SSc group than in the idiopathic Sicca syndrome group. SG volumes did not differ between the groups. SSc patients with SGUS grades ≥2 had more anti-centromere antibodies (ACA) (65.