Recent advances in addressing vaccine hesitancy.

PURPOSE OF REVIEW: To offer healthcare providers current, evidence-based approaches for addressing vaccine hesitancy to increase vaccine coverage and reduce the frequency of vaccine-preventable disease outbreaks. RECENT FINDINGS: Vaccine hesitancy is a growing problem with profound societal, economic, and medical consequences. Understanding the complexity of vaccine hesitancy can inform approaches to increasing vaccine uptake on both the individual and population levels. Notably, pediatricians play a critical role in increasing vaccine uptake due to their relationships with families. This doctor-patient relationship establishes trust and allows evidence-based intervention strategies to be effective in the office. Understanding potential solutions outside the office, such as media campaigns and policy changes, also provide insight into vaccine hesitancy and potential directions for future research. While pediatricians' attempts in the clinic to increase coverage remain crucial, vaccine hesitancy remains a formidable public health problem that requires attention on both the micro and macro levels to be addressed successfully. SUMMARY: Providers have an opportunity to increase both confidence in and uptake of vaccines. Public health interventions would effectively complement strategies in the clinic to increase overall coverage.

Diastereoselective 1,3-dipolar cycloaddition of nitrones to donor-acceptor cyclopropanes catalyzed by a calcium(II) complex.

Calcium triflate has been identified as an efficient catalyst for the cycloaddition of nitrones to donor-acceptor cyclopropanes. The reaction proceeds with good to excellent yields of the corresponding tetrahydro-1,2-oxazines with high levels of diastereoselectivity. The generality of the reaction allowed for the synthesis of tetrahydro-1,2-oxazines bearing alkyl, aryl, and heteroaromatic substitution.

Multicopper oxidase-1 is a ferroxidase essential for iron homeostasis in Drosophila melanogaster.

Multicopper ferroxidases catalyze the oxidation of ferrous iron to ferric iron. In yeast and algae, they participate in cellular uptake of iron; in mammals, they facilitate cellular efflux. The mechanisms of iron metabolism in insects are still poorly understood, and insect multicopper ferroxidases have not been identified. In this paper, we present evidence that Drosophila melanogaster multicopper oxidase-1 (MCO1) is a functional ferroxidase. We identified candidate iron-binding residues in the MCO1 sequence and found that purified recombinant MCO1 oxidizes ferrous iron. An association between MCO1 function and iron homeostasis was confirmed by two observations: RNAi-mediated knockdown of MCO1 resulted in decreased iron accumulation in midguts and whole insects, and weak knockdown increased the longevity of flies fed a toxic concentration of iron. Strong knockdown of MCO1 resulted in pupal lethality, indicating that MCO1 is an essential gene. Immunohistochemistry experiments demonstrated that MCO1 is located on the basal surfaces of the digestive system and Malpighian tubules. We propose that MCO1 oxidizes ferrous iron in the hemolymph and that the resulting ferric iron is bound by transferrin or melanotransferrin, leading to iron storage, iron withholding from pathogens, regulation of oxidative stress, and/or epithelial maturation. These proposed functions are distinct from those of other known ferroxidases. Given that MCO1 orthologues are present in all insect genomes analyzed to date, this discovery is an important step toward understanding iron metabolism in insects.

A Descriptive Study of Maternal Vaccination Uptake, Attitudes, and Beliefs in Pregnancy Among Persons Delivering at an Urban Safety Net Hospital.

Objective: To estimate uptake of influenza, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap), and COVID-19 vaccines during pregnancy and describe vaccine attitudes and beliefs among predominantly racial and ethnic minority individuals delivering at a publicly funded hospital. Methods: We collected survey and electronic medical record data for English-speaking postpartum individuals who delivered a live-born infant from July 7, 2022, through August 21, 2022, and agreed to participate in our study. The 58-item survey included questions about general vaccine attitudes and beliefs as well as vaccine-specific questions. We calculated rates of influenza, Tdap, and COVID-19 vaccinations and compared distributions of survey responses by number (no vaccines, one vaccine, or two or three of the recommended vaccines) and type of vaccines received during pregnancy. Results: Of the 231 eligible individuals, 125 (54.1%) agreed to participate. Rates of influenza, Tdap, and COVID-19 vaccination were 18.4%, 48.0%, and 5.6% respectively. A total of 61 (48.8%) did not receive any recommended vaccines during pregnancy, 40 (32.0%) received one vaccine, and 24 (19.0%) received two or three vaccines. Approximately 66.1% of the no vaccine group, 81.6% of the one vaccine group, and 87.5% of the two or three vaccine group strongly agreed or agreed that they trusted the vaccine information provided by their obstetrician or midwife. While most (>69.2%) agreed that the vaccine-preventable diseases were dangerous for pregnant women, only 24.0%, 29.3%, and 40.3% agreed that they were worried about getting influenza, whooping cough, or COVID-19, respectively, while pregnant. Discussion: Vaccine uptake in our population was low and may be due, in part, to low perceived susceptibility to vaccine-preventable diseases. Obstetricians and midwives were trusted sources of vaccine information, suggesting that enhanced communication strategies could be critical for addressing maternal vaccine hesitancy, particularly in communities of color justifiably affected by medical mistrust.

Multicopper oxidase-1 orthologs from diverse insect species have ascorbate oxidase activity.

Members of the multicopper oxidase (MCO) family of enzymes can be classified by their substrate specificity; for example, ferroxidases oxidize ferrous iron, ascorbate oxidases oxidize ascorbate, and laccases oxidize aromatic substrates such as diphenols. Our previous work on an insect multicopper oxidase, MCO1, suggested that it may function as a ferroxidase. This hypothesis was based on three lines of evidence: RNAi-mediated knock down of Drosophila melanogaster MCO1 (DmMCO1) affects iron homeostasis, DmMCO1 has ferroxidase activity, and DmMCO1 has predicted iron binding residues. In our current study, we expanded our focus to include MCO1 from Anopheles gambiae, Tribolium castaneum, and Manduca sexta. We verified that MCO1 orthologs have similar expression profiles, and that the MCO1 protein is located on the basal surface of cells where it is positioned to oxidize substrates in the hemolymph. In addition, we determined that RNAi-mediated knock down of MCO1 in A. gambiae affects iron homeostasis. To further characterize the enzymatic activity of MCO1 orthologs, we purified recombinant MCO1 from all four insect species and performed kinetic analyses using ferrous iron, ascorbate and two diphenols as substrates. We found that all of the MCO1 orthologs are much better at oxidizing ascorbate than they are at oxidizing ferrous iron or diphenols. This result is surprising because ascorbate oxidases are thought to be specific to plants and fungi. An analysis of three predicted iron binding residues in DmMCO1 revealed that they are not required for ferroxidase or laccase activity, but two of the residues (His374 and Asp380) influence oxidation of ascorbate. These two residues are conserved in MCO1 orthologs from insects and crustaceans; therefore, they are likely to be important for MCO1 function. The results of this study suggest that MCO1 orthologs function as ascorbate oxidases and influence iron homeostasis through an unknown mechanism.