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We tested the predictive validity of the Progress Assessment (PA), a brief counselor administered tool for use in measurement-based care for substance use disorders. The PA includes 5 items assessing relapse risk and 5 items assessing factors protective against relapse. Data were drawn from a completed study of continuing care for cocaine dependence (McKay et al., 2013) and includes 12 months of follow-up on158 participants (76% male) who received brief telephone or face-to-face sessions. Each session began with the administration of the PA, followed by cognitive-behavioral counseling tied to the results of the PA and anticipated risky situations. Outcome was assessed via urine toxicology every 3 months. As administered in an effectiveness trial, average PA risk and protective scales within each 3-month segment of the study predicted urine toxicology results at the end of that period, with higher risk scores and lower protective scores predicting greater rates of cocaine positive urine drug screens. PA scores did not predict dropout from continuing care participation. The 10-item PA shows promise as a pragmatic clinical tool for ongoing monitoring during continuing care for substance dependence. There is controversy regarding surgical margins in the management of early oral squamous cell carcinoma (OSCC). The main objectives of this study were to assess the relevance of the margin independent of tumour variables; threshold for a safe margin; relevance of dysplasia at the margin. UK based retrospective multicenter cohort study of patients with previously untreated and clinically early OSCC between 1998 and 2016. All patients had surgery as the primary modality and had surgical staging of the neck. Minimum follow-up was 2 years. Margins were classified as clear ≥5.0 mm; close 1.0-4.9 mm; involved not cut-through (INC-T) 0.1-0.9 mm; cut-through (C-T) 0 mm. 669 patients were included. After adjusting for tumour variables Cox multivariate regression analysis demonstrated that close margins had similar survival outcomes to clear margins (Hazard Ratio(HR) 0.99 (95%CI 0.50-1.95) for Local Recurrence Free Survival (LRFS); HR 1.08 (95%CI 0.7-1.66) for Disease Free Survival (DFS); HR 0.74 (95%CI 0.44-1.25) for Disease Specific Survival (DSS); HR 0.80 (95%CI 0.58-1.11) for Overall Survival (OS)). C-T margins had significantly worse LRFS (HR 5.01 (95%CI 2.02-12.39)) and DFS (HR 2.58 (95%CI 1.28-5.20)). INC-T margins had significantly worse DFS (HR 1.98 (95% CI 1.01-3.87)). Time dependent receiver operating characteristic curve analysis did not demonstrate a clear margin threshold for LRFS within 24 months (AUC = 0.53 (95%CI 0.41-0.64)). Dysplasia at the margin did not influence LRFS or DFS. Only resection margins <1 mm independently affected survival outcomes. This should be considered when making decisions regarding adjuvant treatment. Only resection margins less then 1 mm independently affected survival outcomes. This should be considered when making decisions regarding adjuvant treatment.Staphylococcus epidermidis is a common causative of nosocomial infections associated with indwelling medical devices. To date, the mechanisms of the pathogenicity and drug resistance of S. epidermidis have not been clearly elucidated. AbfR has been previously identified as an oxidation-sensing regulator that regulates bacterial aggregation and biofilm formation by responding to oxidative stress in S. epidermidis; however, the regulatory pathways of AbfR are underexplored. In this study, we investigated the oxidation-sensing regulatory mechanism of AbfR using TMT10-plex labelling quantitative proteomic and untargeted metabolomic approaches. Integrated analysis of two omics datasets indicated that abfR depletion influenced nucleic acid metabolism and activated the DNA mismatch repair pathway. In addition, several energy-related metabolic pathways, including tricarboxylic acid (TCA) cycle, glycolysis, and arginine metabolism, were remarkably impacted by the deletion of abfR. This study revealed the regulatory networks of the transcription factor AbfR from a multi-omics view and demonstrated that AbfR played a broad role in not only mismatch repair but also energy metabolism, enabling S. epidermidis to constantly sense and adapt to environmental stress. SIGNIFICANCE Staphylococcus epidermidis has emerged as a major nosocomial infection causing pathogen. AbfR, a transcription factor of S. epidermidis, plays an important role in oxidative stress, cell aggregation, and biofilm formation; however, the regulatory mechanism of AbfR is unknown. Using proteomic and metabolomic approaches, this study unveils the global regulatory networks of AbfR, and demonstrates that AbfR not only regulates the DNA mismatch repair pathway by an oxidation sensing mechanism but also affects energy metabolism. This study expands the body of knowledge related to regulatory transcription factors in staphylococci and lays a foundation for future research on clinical infections caused by S. epidermidis.This work aimed to evaluate the modifications on the proteome profile of Saccharomyces cerevisiae T73™ strain as a consequence of its adaptive response to the presence of tetraconazole molecules in the fermentation medium. Pasteurised grape juices were separately supplemented with tetraconazole or a commercial formulation containing 12.5% w/v of tetraconazole at two concentration levels. In addition, experiments without fungicides were developed for comparative purposes. Proteome profiles of yeasts cultured in the presence or absence of fungicide molecules were different. Independently of the fungicide treatment applied, the highest variations concerning the control sample were observed for those proteins involved in metabolic processes, especially in the metabolism of nitrogen compounds. Tetraconazole molecules altered the abundance of several enzymes involved in the biosynthesis of amino acids, purines, and ergosterol. https://www.selleckchem.com/CDK.html Moreover, differences in the abundance of several enzymes of the TCA cycle were found. Changes observed were different between the active substance and the commercial formulation. SIGNIFICANCE The presence of fungicide residues in grape juice has direct implications on the development of the aromatic profile of the wine. These alterations could be related to changes in the secondary metabolism of yeasts. However, the molecular mechanisms involved in the response of yeasts to fungicide residues remains quite unexplored. Through this exhaustive proteomic study, alterations in the amino acids biosynthesis pathways due to the presence of the tetraconazole molecules were observed. Amino acids are precursors of some important higher alcohols and ethyl acetates (such as methionol, 2-phenylethanol, isoamyl alcohol or 2-phenylacetate). Besides, the effect of tetraconazole on the ergosterol biosynthesis pathway could be related to a higher production of medium-chain fatty acids and their corresponding ethyl acetates.
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