Cathepsin B Processing Is Required for the Efficacy of Albumin-Drug Conjugates.

Targeted drug delivery approaches that selectively and preferentially deliver therapeutic agents to specific tissues are of great interest for safer and more effective pharmaceutical treatments. We investigated whether cathepsin B cleavage of a valine-citrulline [VC()]-containing linker is required for the release of monomethyl auristatin E (MMAE) from albumin-drug conjugates. In this study, we used an engineered version of human serum albumin, Veltis High Binder II (HBII), which has enhanced binding to the neonatal Fc (fragment crystallizable) receptor (FcRn) to improve drug release upon binding and FcRn-mediated recycling.

Expanding Transition Metal-Mediated Bioorthogonal Decaging to Include C-C Bond Cleavage Reactions.

The ability to control the activation of prodrugs by transition metals has been shown to have great potential for controlled drug release in cancer cells. However, the strategies developed so far promote the cleavage of C-O or C-N bonds, which limits the scope of drugs to only those that present amino or hydroxyl groups. Here, we report the decaging of an -quinone prodrug, a propargylated β-lapachone derivative, through a palladium-mediated C-C bond cleavage.

The Epidemiology and Costs of Disease Intervention Specialist Retention.

Background: The COVID-19 pandemic changed the environment in which disease intervention specialists (DISs) operate, as their skills were in demand beyond sexually transmitted disease (STD) control programs. Workforce conditions generally have changed in the last 2 years, imposing additional challenges. Retaining STD DIS has become more difficult in the changed environment.

Strategies for Conditional Regulation of Proteins.

Design of the next-generation of therapeutics, biosensors, and molecular tools for basic research requires that we bring protein activity under control. Each protein has unique properties, and therefore, it is critical to tailor the current techniques to develop new regulatory methods and regulate new proteins of interest (POIs). This perspective gives an overview of the widely used stimuli and synthetic and natural methods for conditional regulation of proteins.

Controlled masking and targeted release of redox-cycling ortho-quinones via a C-C bond-cleaving 1,6-elimination.

Natural products that contain ortho-quinones show great potential as anticancer agents but have been largely discarded from clinical development because their redox-cycling behaviour results in general systemic toxicity. Here we report conjugation of ortho-quinones to a carrier, which simultaneously masks their underlying redox activity. C-benzylation at a quinone carbonyl forms a redox-inactive benzyl ketol.

Photo-transformation of aqueous nitroguanidine and 3-nitro-1,2,4-triazol-5-one: Emerging munitions compounds.

Two major components of insensitive munition formulations, nitroguanidine (NQ) and 3-nitro-1,2,4-triazol-5-one (NTO), are highly water soluble and therefore likely to photo-transform while in solution in the environment. The ecotoxicities of NQ and NTO solutions are known to increase with UV exposure, but a detailed accounting of aqueous degradation rates, products, and pathways under different exposure wavelengths is currently lacking. Here, we irradiated aqueous solutions of NQ and NTO over a 32-h period at three ultraviolet wavelengths (254 nm, 300 nm, and 350 nm) and analyzed their degradation rates and transformation products.

Going social: Success in online recruitment of men who have sex with men for prevention HIV vaccine research.

Objective: To compare the use of four different social media sites to recruit men who have sex with men (MSM) and transgender women to a phase 2b HIV prevention vaccine trial, HVTN 505.

Design: Retrospective, observational study.

Methods: The University of Pennsylvania HIV Vaccine Trials Unit (Penn HVTU) employed street outreach and online recruitment methods to recruit participants for HVTN 505 using a combination of national recruitment images/messages with Philadelphia-specific language and imagery.

Photo-degradation of 2,4-dinitroanisole (DNAN): An emerging munitions compound.

The US military is developing insensitive munitions (IM) that are less sensitive to shock and high temperatures to minimize unintentional detonations. DNAN (2,4-dinitroanisole) is one of the main ingredients of these IM formulations. During live-fire training, chunks of IM formulations are scattered by partial detonations and, once on the soil, they weather and dissolve.

Racial disparities in HIV prevalence and risk behaviors among injection drug users and members of their risk networks.

In the United States, racial differences in the prevalence and incidence of HIV infection and AIDS diagnoses are dramatic. These differences are large, have been recognized for nearly 20 years, and are as yet not well investigated. These disparities show no signs of diminishing and, in fact, are widening, particularly among drug users and women.

Early data from Project Engage: a program to identify and transition medically hospitalized patients into addictions treatment.

Background: Patients with untreated substance use disorders (SUDs) are at risk for frequent emergency department visits and repeated hospitalizations. Project Engage, a US pilot program at Wilmington Hospital in Delaware, was conducted to facilitate entry of these patients to SUD treatment after discharge. Patients identified as having hazardous or harmful alcohol consumption based on results of the Alcohol Use Disorders Identification Test-Primary Care (AUDIT-PC), administered to all patients at admission, received bedside assessment with motivational interviewing and facilitated referral to treatment by a patient engagement specialist (PES).

A randomized trial of extended telephone-based continuing care for alcohol dependence: within-treatment substance use outcomes.

Objective: The study tested whether adding up to 18 months of telephone continuing care, either as monitoring and feedback (TM) or longer contacts that included counseling (TMC), to intensive outpatient programs (IOPs) improved outcomes for alcohol-dependent patients.

Method: Participants (N = 252) who completed 3 weeks of IOP were randomized to up to 36 sessions of TM (M = 11.5 sessions), TMC (M = 9.