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United States healthcare outcomes, including avoidable mortality rates, are among the worst of high-income countries despite the highest healthcare spending per capita. While community pharmacies contribute to chronic disease management and preventive medicine, they also offer consumer products that increase mortality risks and the prevalence of cardiovascular diseases, diabetes, cancer, and depression. To resolve these contradictions, our perspective article describes opportunities for major pharmacy chains (e.g., CVS Pharmacy and Walgreens) to introduce digital health aisles dedicated to prescription and over-the-counter digital therapeutics (DTx), together with mobile apps and wearables that support disease self-management, wellness, and well-being. We provide an evidence-based rationale for digital health aisles to replace spaces devoted to sugar-sweetened beverages and other unhealthy commodities (alcohol, tobacco) that may increase risks for premature death. We discuss how digital health aisles can serve as marketing and patient education resources, informing customers about commercially available DTx and other technologies that support healthy lifestyles. Since pharmacy practice requires symbiotic balancing between profit margins and patient-centered, value-based care, replacing health-harming products with health-promoting technologies could positively impact prevention of chronic diseases, as well as the physical and mental health of patients and caregivers who visit neighborhood pharmacies in order to pick up medicines. [ABSTRACT FROM AUTHOR]

Limitations of pharmaceutical drugs and biologics for chronic diseases (e.g., medication non-adherence, adverse effects, toxicity, or inadequate efficacy) can be mitigated by mobile medical apps, known as digital therapeutics (DTx). Authorization of adjunct DTx by the US Food and Drug Administration and draft guidelines on "prescription drug use-related software" illustrate opportunities to create drug + digital combination therapies, ultimately leading towards drug–device combination products (DTx has a status of medical devices). Digital interventions (mobile, web-based, virtual reality, and video game applications) demonstrate clinically meaningful benefits for people living with Alzheimer's disease, dementia, rheumatoid arthritis, cancer, chronic pain, epilepsy, depression, and anxiety. In the respective animal disease models, preclinical studies on environmental enrichment and other non-pharmacological modalities (physical activity, social interactions, learning, and music) as surrogates for DTx "active ingredients" also show improved outcomes. In this narrative review, we discuss how drug + digital combination therapies can impact translational research, drug discovery and development, generic drug repurposing, and gene therapies. Market-driven incentives to create drug–device combination products are illustrated by Humira® (adalimumab) facing a "patent-cliff" competition with cheaper and more effective biosimilars seamlessly integrated with DTx. In conclusion, pharma and biotech companies, patients, and healthcare professionals will benefit from accelerating integration of digital interventions with pharmacotherapies. [ABSTRACT FROM AUTHOR]

The successful chemical synthesis and oxidative folding of [mu]O-conotoxin MrVIB is described. The synthetic MrVIB blocks rat Na(sub v)1.8 sodium channels and also propagation of action potentials in A- and C-fibers in sciatic nerve as well as skeletal muscle and MrVIB has potent and long lasting local anesthetic effect.

Four novel mu-conotoxins CnIIIA, CnIIIB, CIIIA and MIIIA are identified by molecular cloning, and a comparison of their sequences with those of previously characterized mu-conotoxins suggest that the new mu-conotoxins are likely to target tetrodotoxin-resistant (TTX-r) sodium channels. The four peptides are chemically synthesized and their biological activities, their structural and functional diversities are most comprehensively characterized.

Results demonstrate that the mu-conotoxin SmIIIAfrom Conus stercusmuscarum inhibits irreversibly the tetrodotoxin-resistant sodium channels in frog neurons, indicating to its unique ligand property for voltage-gated sodium channels. The peptide differs from other mu-conotoxins by lacking hydroxyproline.

Research has been conducted on the omega-conotoxin native disulfides. The identification of one-disulfide intermediates in their folding and the determination of the equilibrium constants for forming the species with disulfide bonds have been carried out and the results indicate that the cooperativity of this protein folding is expressed only when the chain is constrained.

Research shows that cladistic analysis method is useful in identifying critical amino acids involved in the biological activity of delta-conotoxin Conus peptides. Data indicate that conotoxin possesses three large hydrophobic amino acids which are conserved and required for its activity.

The rates of reaction of four disulfide reagents with the cysteine (Cys) thiols from 16 different peptides have been measured. Reactions between thiols and disulfides are needed in the folding of disulfide-bonded proteins, electron transfer and regulatory mechanisms of cell metabolism. The measurements reveal the relationship between nucleophile pKa and reactivity depends on the net charge of the disulfide reagent used. This shows that interactions between reagents and peptides are important in determining the rate of exchange between thiols and disulfides.

Analysis of Curcurbita maxima trypsin inhibitor I (CMTII) involved a study of porcine pepsin hydrolysis of the Leu7-Met8 (P2'-P3') peptide bond. Similar Gibbs energies are evident for intact MTI and its cleaved form. Ionization constants of any preexistent groups are affected by peptide bond hydrolysis. Hydrolysis reaction catalytic rate constants resemble those of resynthesis reactions.