Putting Public Safety First: 13 Strategies for Successful Supervision and Reentry

Outlines organizational- and case management-level strategies to reduce recidivism through risk reduction and behavior change, such as by aligning resources with risk factors. Describes each practice's benefits, evidence base, and examples from the field

Activity Coefficients at Infinite Dilution for Organic Compounds Dissolved in 1-Alkyl-1-methylpyrrolidinium Bis(trifluoromethylsulfonyl)imide Ionic Liquids Having Six-, Eight-, and Ten-Carbon Alkyl Chains

International audienceActivity coefficients at infinite dilution (gamma(proportional to)(1,2)) for 40 diverse probe solutes, including various (cyclo)alkanes, alkenes, alkynes, aromatic hydrocarbons, alcohols, thiophene, ethers, nitroalkanes, and ketones, were measured by inverse gas chromatography at temperatures from 323 to 343 K in three homologous 1-alkyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide ionic liquids (ILs), bearing hexyl, octyl, and decyl side chains. The retention data were further converted to gas-to-IL and water-to-IL partition coefficients using the corresponding gas-to-water partition coefficients. Both sets of partition coefficients were analyzed using the modified Abraham solvation parameter model, with the derived equations tightly correlating the experimental gas-to-IL and water-to-IL partition coefficient data to within average standard deviations of 0.088 and 0.111 log units, respectively

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Fyn tyrosine kinase increases Apolipoprotein E Receptor 2 levels and phosphorylation.

Apolipoprotein E Receptor 2 (ApoER2) and the tyrosine kinase Fyn are both members of the Reelin pathway, a signaling pathway essential for the laminar formation of the cortex during development and proper dendritic spine density and long-term potential (LTP) in the adult brain. In the presence of extracellular Reelin, ApoER2 binds the intracellular protein Dab1, an adaptor protein that is phosphorylated by Fyn. However, direct interactions between ApoER2 and Fyn are not well defined. Here, we show that total levels of ApoER2 and surface levels of ApoER2 are increased by active Fyn. Via a separate mechanism, ApoER2 is also phosphorylated by Fyn, an event that peaks in the postnatal cortex at day 5 and can occur at multiple ApoER2 tyrosine residues. Dab1 is also involved in this phosphorylation, promoting the phosphorylation of ApoER2 by Fyn when it is itself phosphorylated. These results elucidate some of the intracellular mechanisms that give rise to a functional Reelin pathway

Fyn phosphorylation of ApoER2 is increased in the presence of Dab1.

<p>A. COS7 cells were transfected with untagged ApoER2 and either empty vector, Fyn, Dab1-WT, or Fyn and Dab1-WT together. Lysates were collected in IP buffer and immunoprecipitated (IP) with either 4G10 or mouse IgG, run on a Western blot, and probed for ApoER2. Input refers to the starting material that was not subjected to IP. Below are Western blots showing total levels of ApoER2, Dab1, Fyn, and β–actin. B–C. COS7 cells were transfected and analyzed as in A, but with Dab1-ab (B) or Dab1-cd (C) instead of Dab1-WT.</p

Fyn phosphorylates ApoER2.

<p>A. COS7 cells were co-transfected with untagged ApoER2 and Fyn or empty vector. Lysates were collected in IP buffer and immunoprecipitated (IP) with either 4G10 or mouse IgG, and analyzed for ApoER2. Input refers to the starting material that was not subjected to IP. Lane numbers are indicated for clarity. B. Schematic of WT ApoER2 and the mutant with all three intracellular tyrosines mutated to phenylalanines (tYF). The signal peptide (SP), N-terminal HA tag, and C-terminal myc tag are indicated. C. COS7 cells were co-transfected with different ApoER2 mutants (2 single mutants on left, 1 single mutant and triple mutant on right) and Fyn or empty vector and immunoprecipitated as in A, and analyzed for myc. Below are Western blots showing total levels of ApoER2, Fyn, and β–actin. D. Quantification of the upper-phosphorylated ApoER2 band (indicated by arrow in boxed example) over total ApoER2 from C. **<i>p<0.01,</i> ***<i>p<0.001 vs empty vector (Bonferroni’s Multiple Comparisons test). Data are mean +/− SD. N = 3.</i></p