We are interested in the free energies of transferring nonpolar solutes into aqueous NaCl solutions with salt concentrations upwards of 2 M, the Hofmeister regime. We use the semi-explicit assembly (SEA) computational model to represent these electrolyte solutions. We find good agreement with experiments (Setschenow coefficients) on 43 nonpolar and polar solutes and with TIP3P explicit-solvent simulations. Besides being much faster than explicit solvent calculations, SEA is more accurate than the PB models we tested, successfully capturing even subtle salt effects in both the polar and nonpolar components of solvation. We find that the salt effects are mainly due to changes in the cost of forming nonpolar cavities in aqueous NaCl solutions, and not mainly due to solute-ion electrostatic interactions.

The basic amino acids lysine (Lys) and arginine (Arg) play important roles in membrane protein activity, the sensing of membrane voltages, and the actions of antimicrobial, toxin, and cell-penetrating peptides. These roles are thought to stem from the strong interactions and disruptive influences of these amino acids on lipid membranes. In this study, we employ fully atomistic molecular dynamics simulations to observe, quantify, and compare the interactions of Lys and Arg with saturated phosphatidylcholine membranes of different thickness. We make use of both charged (methylammonium and methylguanidinium) and neutral (methylamine and methylguanidine) analogue molecules, as well as Lys and Arg side chains on transmembrane helix models. We find that the free energy barrier experienced by a charged Lys crossing the membrane is strikingly similar to that of a charged Arg (to within 2 kcal/mol), despite the two having different chemistries, H-bonding capability, and hydration free energies that differ by ∼10 kcal/mol. In comparison, the barrier for neutral Arg is higher than that for neutral Lys by around 5 kcal/mol, being more selective than that for the charged species. This can be explained by the different transport mechanisms for charged or neutral amino acid side chains in the membrane, involving membrane deformations or simple dehydration, respectively. As a consequence, we demonstrate that Lys would be deprotonated in the membrane, whereas Arg would maintain its charge. Our simulations also reveal that Arg attracts more phosphate and water in the membrane, and can form extensive H-bonding with its five H-bond donors to stabilize Arg-phosphate clusters. This leads to enhanced interfacial binding and membrane perturbations, including the appearance of a trans-membrane pore in a thinner membrane. These results highlight the special role played by Arg as an amino acid to bind to, disrupt, and permeabilize lipid membranes, as well as to sense voltages for a range of peptide and protein activities in nature and in engineered bionanodevices.

Hippocampal pyramidal cells possess elaborate dendritic arbors with distinct domains that are targeted with input-specific synaptic sites. This synaptic arrangement is facilitated by synaptic cell-adhesion molecules that act as recognition elements to connect presynaptic and postsynaptic neurons. In this study, we investigate the organization of the synaptic recognition molecule latrophilin-2 at the surface of pyramidal neurons classified by spatial positioning and action potential firing patterns. Surveying two hippocampal neurons that highly express latrophilin-2, late-bursting CA1 pyramidal cells and early-bursting subiculum pyramidal cells, we found the molecule to be differentially positioned on their respective dendritic compartments. Investigating this latrophilin-2 positioning at the synaptic level, we found that the molecule is not present within either the pre- or postsynaptic terminal but rather is tightly coupled to synapses at a perisynaptic location. Together these findings indicate that hippocampal latrophilin-2 distribution patterning is cell-type specific, and requires multiple postsynaptic neurons for its synaptic localization.

This study examines perceived neighborhood characteristics associated with successful outcome among mothers 10 years after being treated for substance use disorders. Data were obtained from 713 mothers first studied at admission to drug treatment in California in 2000-2002 and followed up in 2009-2011. At follow-up, 53.6% of mothers had a successful outcome (i.e., no use of illicit drugs and not involved with the criminal justice system). Perceived neighborhood safety almost doubled the odds of success. Perceived neighborhood safety interacted with social involvement, decreasing the odds of success among mothers who reported more versus less neighborhood social involvement. Perceived neighborhood climate is associated with long-term outcomes among mothers with substance use disorders independent of individual-level characteristics, underscoring the need for further efforts to understand its interaction with recovery capital in ways that promote and impede health.

Background

California treats the largest population of opioid dependent individuals in the USA and is among a small group of states that applies regulations for opioid treatment that are more stringent than existing federal regulations. We aim to characterize changes in patient characteristics and treatment utilization over time, and identify determinants of successful completion of detoxification and MMT retention in repeated attempts.

Methods

State-wide administrative data was obtained from California Outcome Measurement System during the period: January 1st, 1991-March 31st, 2012. Short-term detoxification treatment and long-term maintenance treatment, primarily with methadone, was available to study participants. Mixed effects regression models were used to define determinants of successful completion of the detoxification treatment protocol (as classified by treatment staff) and duration of maintenance treatment.

Results

The study sample consisted of 237,709 unique individuals and 885,971 treatment episodes; 837% were detoxification treatment episodes in 1994, dropping to 40.5% in 2010. Among individuals accessing only detoxification, the adjusted odds of success declined with each successive attempt (vs. 1st attempt: 2nd: OR: 0.679; 95% CI (0.610, 0.755); 3rd: 0.557 (0.484, 0.641); 4th: 0.526 (0.445, 0.622); 5th: 0.407 (0.334, 0.497); ≥6th: 0.339 (0.288, 0.399). For those ever accessing maintenance treatment, later subsequent attempts were longer in duration, and those with two or more prior attempts at detoxification had marginally longer subsequent maintenance episodes (hazard ratio: 0.97; 95% CI: 0.95, 0.99). Finally, only 10.9% of all detoxification episodes were followed by admission into maintenance treatment within 14 days.

Conclusions

This study has revealed high rates of detoxification treatment for opioid dependence in California throughout the study period, and decreasing odds of success in repeated attempts at detoxification.