Challenges and opportunities in current vaccine technology and administration: A comprehensive survey examining oral vaccine potential in the United States.

This study provides a snapshot of the current vaccine business ecosystem, including practices, challenges, beliefs, and expectations of vaccine providers. Our team focused on providers' firsthand experience with administering vaccines to determine if an oral vaccine (e.g. pill or oral-drop) would be well-received. We interviewed 135 healthcare providers and vaccine specialists across the US, focusing questions on routine vaccinations, not COVID-19 vaccines. Improving workflow efficiency is a top concern among vaccine providers due to shrinking reimbursement rates-determined by pharmacy benefit managers (PBMs)-and the time-intensiveness of injectable vaccines. Administering injectable vaccines takes 23 minutes/patient on average, while dispensing pills takes only 5 minutes/patient. An average of 24% of patients express needle-fear, which further lengthens the processing time. Misaligned incentives between providers and PBMs could reduce the quality and availability of vaccine-related care. The unavailability of single-dose orders prevents some rural providers from offering certain vaccines. Most interviewees (74%) believe an oral vaccine would improve patient-provider experience, patient-compliance, and workflow efficiency, while detractors (26%) worry about the taste, vaccine absorption, and efficacy. Additional research could investigate whether currently non-vaccinating pharmacies would be willing to offer oral vaccines, and the impact of oral vaccines on vaccine acceptance.

Methamphetamine causes anorexia in Drosophila melanogaster, exhausting metabolic reserves and contributing to mortality.

Methamphetamine (MA) appears to produce neurotoxic effects, in part, through disruptions of energy metabolism. A recent study of the whole-body proteome of Drosophila melanogaster showed many changes in energy metabolism-related proteins, leading us to hypothesize that MA toxicity may cause whole-body disruptions of energy metabolism. To test this, we monitored the response of energy reserves and other metabolites to MA-exposure with and without the addition of dietary glucose. We also monitored changes in feeding behavior, locomotor activity and respiration rates associated with MA-exposure to investigate how MA affects energy balance. We observed that glycogen and triglyceride levels decreased dramatically within 48 hr of MA-exposure, indicating a strongly negative caloric balance. Behavioral assays revealed that MA-treated flies decreased food consumption by 60-80% and exhibited a 2-fold increase in locomotion. Caloric expenditure decreased with MA-exposure, apparently due to a compensatory decrease in resting metabolism, showing that anorexia was the primary driver of the negative caloric balance. Additionally, we observed that glucose supplementation of MA-containing diet increased glycogen reserves by 44% at 48 hr, leading to a commensurate increase in survivorship. We conclude that dietary sugar supplementation enhances survivorship by partially compensating for decreased caloric intake resulting from MA-induced anorexia. The observation that MA produces similar behavioral changes in Drosophila and humans, i.e. increased locomotor activity and anorexia, further supports the use of Drosophila as a model organism for the study of the effects of MA.

Leucine or carbohydrate supplementation reduces AMPK and eEF2 phosphorylation and extends postprandial muscle protein synthesis in rats.

Muscle protein synthesis (MPS) increases after consumption of a protein-containing meal but returns to baseline values within 3 h despite continued elevations of plasma amino acids and mammalian target of rapamycin (mTORC1) signaling. This study evaluated the potential for supplemental leucine (Leu), carbohydrates (CHO), or both to prolong elevated MPS after a meal. Male Sprague-Dawley rats (∼270 g) trained to consume three meals daily were food deprived for 12 h, and then blood and gastrocnemius muscle were collected 0, 90, or 180 min after a standard 4-g test meal (20% whey protein). At 135 min postmeal, rats were orally administered 2.63 g of CHO, 270 mg of Leu, both, or water (sham control). Following test meal consumption, MPS peaked at 90 min and then returned to basal (time 0) rates at 180 min, although ribosomal protein S6 kinase and eIF4E-binding protein-1 phosphorylation remained elevated. In contrast, rats administered Leu and/or CHO supplements at 135 min postmeal maintained peak MPS through 180 min. MPS was inversely associated with the phosphorylation states of translation elongation factor 2, the "cellular energy sensor" adenosine monophosphate-activated protein kinase-α (AMPKα) and its substrate acetyl-CoA carboxylase, and increases in the ratio of AMP/ATP. We conclude that the incongruity between MPS and mTORC1 at 180 min reflects a block in translation elongation due to reduced cellular energy. Administering Leu or CHO supplements ∼2 h after a meal maintains cellular energy status and extends the postprandial duration of MPS.