Plasmon-assisted delivery of single nano-objects in an optical hot spot.

Fully exploiting the capability of nano-optics to enhance light-matter interaction on the nanoscale is conditioned by bringing the nano-object to interrogate within the minuscule volume where the field is concentrated. There currently exists several approaches to control the immobilization of nano-objects but they all involve a cumbersome delivery step and require prior knowledge of the "hot spot" location. Herein, we present a novel technique in which the enhanced local field in the hot spot is the driving mechanism that triggers the binding of proteins via three-photon absorption. This way, we demonstrate exclusive immobilization of nanoscale amounts of bovine serum albumin molecules into the nanometer-sized gap of plasmonic dimers. The immobilized proteins can then act as a scaffold to subsequently attach an additional nanoscale object such as a molecule or a nanocrystal. This universal technique is envisioned to benefit a wide range of nano-optical functionalities including biosensing, enhanced spectroscopy like surface-enhanced Raman spectroscopy or surface-enhanced infrared absorption spectroscopy, as well as quantum optics.

Daily telephone monitoring compared with retrospective recall of alcohol use among patients in early recovery.

Most studies comparing frequent self-monitoring protocols and retrospective assessments of alcohol use find good correspondence, but have excluded participants with significant comorbidity and/or social instability, and some have included abstainers. We evaluated the correspondence between measures of alcohol use based on daily interactive voice response (IVR) telephone monitoring and a 28-day modification of the Form-90 (Form-28). Participants were 25 outpatients with alcohol use disorder and significant PTSD symptomatology . Overall correlations between the IVR and Form-28 on days drinking and total standard drink units (SDUs) were strong for the entire sample and the subsample of drinkers (n = 7). Day-to-day correspondence between IVR and Form-28 was modest, but much stronger for the most recent week assessed than for the prior 3 weeks. Finally, the drinkers reported significantly greater total SDUs and heavy drinking days on the Form-28 than via IVR. The results indicate a need for further refinement of IVR methodology for treatment seeking populations as well as caution when retrospectively assessing drinking over time periods longer than a week among these individuals.

Cefiderocol, a Siderophore Cephalosporin for Gram-Negative Bacterial Infections: Pharmacokinetics and Safety in Subjects With Renal Impairment.

Cefiderocol, a new injectable siderophore cephalosporin antibiotic, has promising in vitro and in vivo activity against Gram-negative bacteria including multidrug-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. Cefiderocol is mainly renally eliminated. The pharmacokinetics and safety of cefiderocol in subjects with renal impairment were assessed following a single 1000-mg intravenous 1-hour infusion of cefiderocol. Subjects with mild, moderate, or severe renal impairment and end-stage renal disease (ESRD) requiring hemodialysis were compared with demographically (age, body mass index, and sex) matched healthy subjects with normal renal function. The effect of hemodialysis on the clearance of cefiderocol was also assessed. Total drug clearance from plasma (CL) and terminal half-life (t1/2 ) correlated with renal function. Ratios (90% confidence intervals) of area under the plasma concentration-time curve from 0 to infinity (AUC) in mild, moderate, severe, and ESRD groups compared to those with normal renal function were 1.0 (0.8-1.3), 1.5 (1.2-1.9), 2.5 (2.0-3.3), and 4.1 (3.3-5.2), respectively. Maximum plasma concentration (Cmax ) was similar between renal-impairment groups and the normal-renal-function group. Approximately 60% of cefiderocol was removed by hemodialysis for 3 to 4 hours. The plasma-protein-unbound fraction was similar between various renal function groups. The incidence of adverse events did not appear to have any correlation with the degree of renal impairment. Single 1000-mg intravenous doses of cefiderocol were generally well tolerated in subjects with impaired renal function except for 1 subject who discontinued due to urticaria. In conclusion, renal impairment impacted AUC, CL, and t1/2 without affecting Cmax . Cefiderocol was significantly removed by intermittent hemodialysis.

Coping motives as a moderator of daily mood-drinking covariation.

OBJECTIVE: The current study examines the extent to which college students' reports of drinking to cope (DTC) with negative affect moderate the daily covariation between specific types of negative mood (sadness, fear, hostility, shyness and boredom) and alcohol use. METHOD: Participants were full-time college students, aged 18-20, attending a large Southeastern university (N = 72; 50% male). These individuals completed an experience-sampling protocol over a 1-month interval, to assess daily mood and alcohol use. RESULTS: A series of Hierarchical General Linear Models found that individuals who reported low motives to cope through drinking showed an expected absence of daily mood and drinking covariation. For those reporting high coping motives, a complex and somewhat counterintuitive series of findings were found; students high in DTC drank less on days in which they experienced greater sadness. Analyses on the quadratic effects of mood revealed that when experiencing moderate to high levels of fear and shyness, individuals high in DTC were more likely to drink. For those low in coping motivations, fear and shyness did not predict daily drinking. CONCLUSIONS: Findings highlight the need to better our understanding of the exact meaning of DTC measures. In addition, there is a need to study how the context of college drinking influences self-medication and students' self-reports of DTC.

Pharmacokinetics of hepatitis C virus NS5A inhibitor JNJ-56914845 (GSK2336805) in subjects with hepatic impairment.

JNJ-56914845 (GSK2336805) is a hepatitis C virus nonstructural protein 5A inhibitor under development for the treatment of chronic hepatitis C (CHC) infection. This open-label, parallel-group, 2-part study evaluated the pharmacokinetics and safety of a single oral 60 mg dose of JNJ-56914845 in 4 cohorts: healthy, mild, moderate, and severe hepatic impairment (n = 8/cohort). Severity of hepatic impairment was categorized using Child-Pugh score, and the healthy subjects were matched for age, sex, body mass index, and smoking status to the moderate hepatic impairment cohort. JNJ-56914845 plasma AUC0-∞ was 26%, 52%, and 45% lower in subjects with mild, moderate, and severe hepatic impairment, respectively, relative to healthy subjects with no difference in half-life among the groups. The apparent oral clearance and volume of distribution were higher in subjects with hepatic impairment. The lower plasma concentrations were largely explained by decreased plasma protein binding in hepatically impaired subjects. One subject with severe hepatic impairment had 2 non-drug-related serious adverse events: an esophageal bleed requiring hospitalization, encephalopathy. Although hepatically impaired subjects have lower exposures than healthy matched controls, they had similar or slightly higher exposures than those observed in past studies of noncirrhotic, CHC patients, suggesting that no dose adjustments for hepatic impairment will be needed.