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Uncovering conserved 3D protein-ligand binding patterns on the basis of functional groups (FGs) shared by a variety of small molecules can greatly expand our knowledge of protein-ligand interactions. Despite that conserved binding patterns for a few commonly used FGs have been reported in the literature, large-scale identification and evaluation of FG-based 3D binding motifs are still lacking. Here, we propose a computational method for automatic mapping of 3D motifs to different FGs of a specific ligand. Applying our method to 233 naturally-occurring ligands, we defined 481 FG-binding motifs that are highly conserved across different ligand-binding pockets. Systematic analysis further reveals four main classes of binding motifs corresponding to distinct sets of FGs. Combinations of FG-binding motifs facilitate the binding of proteins to a wide spectrum of ligands with various binding affinities. Finally, we showed that our FG-motif map can be used to nominate FGs that potentially bind to specific drug targets, thus providing useful insights and guidance for rational design of small-molecule drugs.
Noninvasive tests (NITs) of liver fibrosis have been suggested to be less accurate in type 2 diabetes mellitus (T2DM). We aimed to compare the accuracy of 6 NITs between patients with or without T2DM, explain any differences, and adapt diagnostic algorithms for clinical practice accordingly.
We included 1051 patients with nonalcoholic fatty liver disease with liver biopsy, blood fibrosis tests (Nonalcoholic Fatty Liver Disease Fibrosis Score, FIB4, Fibrotest, FibroMeter), vibration-controlled transient elastography (VCTE), and the combinatory elasto-blood test FibroMeter
. The study endpoint was advanced fibrosis on liver biopsy.
NIT areas under the receiver operating characteristic curve were significantly lower in patients with T2DM, mostly because of a decrease in specificity. For FIB4, this decrease in specificity was only related to the higher age of patients with T2DM enrolled. For Fibrotest, FibroMeter, and FibroMeter
, the decrease in specificity was related to age but also to higher alpha2-maould be used first-line to diagnose advanced liver fibrosis in T2DM.We investigated and forecasted the impact of diabetes mellitus (DM) on tuberculosis (TB) epidemiology in Indonesia between 2020 and 2050. A recently-developed age-structured TB-DM dynamic mathematical model was utilized to assess the impact of DM on TB epidemiology. Model parameters were informed by systematic reviews and meta-analyses. selleck Sensitivity and uncertainty analyses were conducted to assess robustness of predictions. The proportion of TB incident cases attributed to DM increased from 18.8% (95% uncertainty interval (UI) 12.6%-24.3%) in 2020, to 20.9% (95% UI 14.7%-27.1%) in 2030, and 25.8% (95% UI 17.7%-32.2%) in 2050. The proportion of TB-related deaths attributed to DM increased from 24.3% (95% UI 18.7%-29.1%) in 2020, to 27.7% (95% UI 22.4%-32.4%) in 2030, and 34.3% (95% UI 27.6%-38.0%) in 2050. Most of the impact of DM on TB transmission has risen because of faster progression to TB disease, increased risk of reinfection, and increased infectiousness, with higher bacterial loads. Sensitivity and uncertainty analyses affirmed the predictions. TB-DM synergy is projected to increase in Indonesia over the next three decades with DM becoming a major driver of TB incidence and deaths. Joint TB-DM management and programs could offer significant reductions in TB incidence and mortality, making post-2015 End TB targets more feasible.
Postoperative pain has become one of the major obstacles to postoperative recovery and can lead to increasing demand for opioids. So far, a wide variety of drugs is used for regional block anesthesia, but which one is the best remains unclear. Thus, this study aims to obtain the best drug for thyroid surgery regional block based on their efficacy and side effects through Bayesian network meta-analysis.
Systemically searched MEDLINE, CENTRAL, Embase, and web of science on July 3, 2021 to obtain randomized controlled trials (RCTs) focusing on adults who underwent open thyroidectomy and regional blocks, and took opioids requirement, and the postoperative pain level as outcomes. The "Gemtc" package of R-4.1.1 was used for Bayesian network meta-analysis based on extracted data.
We retrieved 398 articles, and finally included 31 RCTs, which included a total of 2221 patients. Patients received levobupivacaine had the lowest requirement rate for opioids and lowest pain score at T6 and T12. Non-steroidal anti-inflammatory drugs show significant superiority neither in the opioids requirement nor the pain score. Clonidine has a better potential to act as a qualified anesthetic adjuvant compared to adrenaline. The ranking results of the subgroup analysis were consistent with the integrated analysis.
Levobupivacaine has a relatively greater advantage in reducing opioids requirement and decreasing the pain score of patients, and bilateral superficial cervical plexus blockade and pre thyroidectomy intervention have more advantages than local wound infiltration and post thyroidectomy intervention in alleviating patients' pain.
Levobupivacaine has a relatively greater advantage in reducing opioids requirement and decreasing the pain score of patients, and bilateral superficial cervical plexus blockade and pre thyroidectomy intervention have more advantages than local wound infiltration and post thyroidectomy intervention in alleviating patients' pain.
The objective of this study was to compare cup survival and the incidence of adverse events associated with the use of trabecular metal (TM) and non-TM cups for acetabular revision surgery.
The MEDLINE, EMBASE, and Cochrane Library databases were searched for comparative studies that reported cup survival and the incidence of adverse events associated with the use of TM and non-TM cups for acetabular revision surgery. Primary outcomes included cup survival, aseptic loosening, dislocation, and infection.
The meta-analysis included 6 studies that involved 13,864 total hip arthroplasty (THA) revisions who underwent acetabular revision surgery with TM (n=5,619) or non-TM (n=8,245) cups. The meta-analysis demonstrated no significant difference in cup survival using re-revision for any reason or aseptic loosening as the endpoint following acetabular revision surgery with TM or non-TM cups (HR=0.96; [95% CI, 0.84-1.09]; HR=1.29; [95% CI, 0.70-2.38]). Pooled data indicated that the overall incidence of adverse st to use reconstructed time-to-event data to find that there was no difference in survival of TM and non-TM cups in acetabular revision surgery. Overall, fewer adverse events were associated with the use of TM compared to non-TM cups, but the difference was not significant. The incidence of aseptic loosening and infection were significantly lower and the incidence of dislocation was significantly higher for TM compared to non-TM cups. This information is expected to guide orthopedic surgeons in the selection of appropriate acetabular components for THA revision.Spironolactone, a potassium-sparing diuretic and aldosterone antagonist, is a mineralocorticoid hormone commonly prescribed to patients suffering from heart failure, hirsutism, dermatological afflictions, and hypertension. Interestingly, relatively little work has been done on the development of vertebrate embryos after exposure to this compound. Here, we treat zebrafish embryos with spironolactone at 10-6 M, 10-7 M, or 10-8 M, and observe them after three to seven days of exposure. While no effect was observed in mortality, we did detect differences in cardiovascular development at 3 dpf and craniofacial development at 5 dpf. At 10-6 M, smaller atria, ventricles, and blood vessels were observed. The highest concentrations also caused a longer ceratohyal/Meckel's distance, longer palatoquadrate, and smaller angles between the palatoquadrate and both the ceratohyal and Meckel's. Further research of spironolactone's effects on embryonic development could lead to a better understanding of the compound resulting in improved public and environmental health.Environmental contamination by heavy metals (HMs) has impelled searching for stabilization strategies, where the use of zero-valent iron nanoparticles (nZVI) is considered a promising option. We have evaluated the combined effect of Cu(II)-Cr(VI) on two Caenorhabditis elegans strains (N2 and RB1072 sod-2 mutant) in aqueous solutions and in a standard soil, prior and after treatment with nZVI (5% w/w). The results showed that HMs aqueous solutions had an intense toxic effect on both strains. Production of reactive oxygen species and enhanced expression of the heat shock protein Hsp-16.2 was observed, indicating increased HM-mediated oxidative stress. Toxic effects of HM-polluted soil on worms were higher for sod-2 mutant than for N2 strain. However, nZVI treatment significantly diminished all these effects. Our findings highlighted C. elegans as a sensitive indicator for HMs pollution and its usefulness to assess the efficiency of the nanoremediation strategy to decrease the toxicity of Cu(II)-Cr(VI) polluted environments.
Clinicians use both global and point-wise information from visual fields to assess the rate of glaucomatous functional progression. We asked which objective, quantitative measures best correlated with subjective assessment by glaucoma experts. In particular, we aimed to determine how much that judgment was based on localized rates of change vs. on global indices reported by the perimeter.
Prospective cohort study.
Eleven academic, expert glaucoma specialists independently scored the rate of functional progression, from 1 (improvement) to 7 (very rapid progression), for a series of 5 biannual clinical printouts from 100 glaucoma or glaucoma suspect eyes of 51 participants, 20 of which were scored twice to assess repeatability.
Regression models were used to predict the average of the 11 clinicians' scores based on objective rates of change of mean deviation (MD), visual field index (VFI), pattern standard deviation (PSD), the Nth fastest progressing location, and the Nth fastest progressing of 10 anatoFI rates, except in eyes with a VFI near the ceiling of 100%. Sensitivities averaged within clusters of locations have been shown to detect change sooner, but the experts' opinions correlated more closely with global VFI. This could be because it is currently the only index for which the perimeter automatically provides a quantitative estimate of the rate of functional progression.
Expert academic glaucoma specialists' assessment of the rate of change correlated best with VFI rates, except in eyes with a VFI near the ceiling of 100%. Sensitivities averaged within clusters of locations have been shown to detect change sooner, but the experts' opinions correlated more closely with global VFI. This could be because it is currently the only index for which the perimeter automatically provides a quantitative estimate of the rate of functional progression.
To investigate the association between the intensity and cumulative dose of cigarette smoking and incidence risk of metabolic syndrome (MetS) in a longitudinal prospective study over 12 years of follow-up.
This study included 3151 men aged 40 to 69 years from the Korean Genome and Epidemiology Study. MetS was defined as proposed by the Joint Interim Statement of the Circulation 2009 report. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incidence risk of MetS were calculated from 2 separate perspectives (1) number of cigarettes smoked per day (intensity) and (2) total number of cigarettes smoked over a person's lifetime (cumulative dose) using multiple logistic regression analyses.
In comparison with never smokers, the HRs (95% CIs) were 0.97 (0.78-1.21) for former smokers and 1.50 (1.07-2.01) with 0 to 9 cigarettes per day, 1.66 (1.34-2.06) with 10 to 19 cigarettes per day, and 1.75 (1.34-2.29) with ≥20 cigarettes per day for current smokers after adjusting for confounding variables.
Homepage: https://www.selleckchem.com/products/bromopyruvic-acid.html
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