An Analysis of COVID-19 Vaccine Hesitancy in the U.S. at the County Level

Reluctance or refusal to get vaccinated, referred to as vaccine hesitancy (VH), has hindered the efforts of COVID-19 vaccination campaigns. It is important to understand what factors impact VH behavior. This information can help design public health interventions that could potentially increase vaccine uptake. We develop a random forest (RF) classification model that uses a wide variety of data to determine what factors affected VH at the county level during 2021. We consider static factors (such as gender, race, political affiliation, etc.) and dynamic factors (such as Google searches, social media postings, Stringency Index, etc.). Our model found political affiliation and the number of Google searches to be the most relevant factors in determining VH behavior. The RF classification model grouped counties of the U.S. into 5 clusters. VH is lowest in cluster 1 and highest in cluster 5. Most of the people who live in cluster 1 are democrat, are more internet-inquisitive (are more prone to seek information from multiple sources on the internet), have the longest life expectancy, have a college degree, have the highest income per capita, live in metropolitan areas. Most people who live in cluster 5 are republicans, are the least internet-inquisitive, have the shortest life expectancy, do not have a college degree, have the lowest income per capita, and live in non-metropolitan areas. Our model found that counties in cluster 1 were most responsive to vaccination-related policies and COVID-19 restrictions. These strategies did not have an impact on the VH of counties in cluster 5.Comment: 28 pages, 12 figures, 4 table

Acute Arterial Thrombosis after Covered Stent Exclusion of Bleeding Mycotic Pseudoaneurysm: Treatment Using Catheter-Directed Thrombolysis

Conventional absolute contraindications to catheter-directed thrombolysis include active or recent hemorrhage and the presence of local vascular infection, both of which increase the risk of procedure-related complications such as bleeding and systemic sepsis. For this reason, lytic therapy of arterial thromboembolism under these circumstances is generally precluded. Herein, we describe a unique case of safe catheter-directed lysis of an acutely thrombosed iliac artery following covered stent placement for treatment of an actively bleeding infected pseudoaneurysm. Our management approach is discussed

Assessing the Impact of Substandard and Falsified Antimalarials in Benin

Substandard and falsified antimalarials contribute to the global malaria burden by increasing the risk of treatment failures, adverse events, unnecessary health expenditures, and avertable deaths. Yet no study has examined this impact in Western Francophone Africa to date. In Benin, where malaria remains endemic and is the leading cause of mortality among children under age five, there is a lack of robust data to combat the issue effectively and inform policy decisions. We adapted the Substandard and Falsified Antimalarial Research Impact (SAFARI) model to assess the health and economic impact of poor-quality antimalarials in this population. The model simulated population characteristics, malaria infection, care-seeking behavior, disease progression, treatment outcomes, and associated costs of malaria. We estimated approximately 1.8 million cases of malaria in Benin among children under age five, which cost $177 million (95$176 – $178 million) in treatment costs and productivity losses annually. Substandard and falsified antimalarials were responsible for 2.8$4.9 million in annual costs. Moreover, we found that replacing all antimalarials with quality-assured artemisinin combination therapies (ACTs) could result in $13.6 million in cost-savings, and increasing pediatric malaria care-seeking by 20$19.4 million in cost-savings. These results highlight the value of improving access to quality-assured ACTs for malaria treatment and increasing care-seeking in Benin. Policymakers and key stakeholders should use these findings to advocate for increased access to quality-assured antimalarials, inform policies and interventions to improve healthcare access and quality, and reduce the burden of malaria.Doctor of Pharmac

Updated molecular phylogenetic data for Opisthorchis spp. (Trematoda: Opisthorchioidea) from ducks in Vietnam

Background: An opisthorchiid liver fluke was recently reported from ducks (Anas platyrhynchos) in Binh Dinh Province of Central Vietnam, and referred to as "Opisthorchis viverrini-like". This species uses common cyprinoid fishes as second intermediate hosts as does Opisthorchis viverrini, with which it is sympatric in this province. In this study, we refer to the liver fluke from ducks as "Opisthorchis sp. BD2013", and provide new sequence data from the mitochondrial (mt) genome and the nuclear ribosomal transcription unit. A phylogenetic analysis was conducted to clarify the basal taxonomic position of this species from ducks within the genus Opisthorchis (Digenea: Opisthorchiidae). Methods: Adults and eggs of liver flukes were collected from ducks, metacercariae from fishes (Puntius brevis, Rasbora aurotaenia, Esomus metallicus) and cercariae from snails (Bithynia funiculata) in different localities in Binh Dinh Province. From four developmental life stage samples (adults, eggs, metacercariae and cercariae), the complete cytochrome b (cob), nicotinamide dehydrogenase subunit 1 (nad1) and cytochrome c oxidase subunit 1 (cox1) genes, and near-complete 18S and partial 28S ribosomal DNA (rDNA) sequences were obtained by PCR-coupled sequencing. The alignments of nucleotide sequences of concatenated cob + nad1 + cox1, and of concatenated 18S + 28S were separately subjected to phylogenetic analyses. Homologous sequences from other trematode species were included in each alignment. Results: Phylogenetic trees were inferred from concatenated (cob + nad1 + cox1) nucleotide sequences and combined 18S + 28S nucleotide sequences of five Opisthorchis sp. BD2013 samples and additional reference taxa. Both trees demonstrated the anticipated clustering of taxa within the superfamily Opisthorchioidea, the paraphyly of the genus Opisthorchis and the sister-species relationship of Opisthorchis sp. BD2013 with O. viverrini. Conclusions: While it is likely that Opisthorchis sp. BD2013 is distinct from O. viverrini, it is clearly a sister taxon of O. viverrini within the limited number of Opisthorchis species for which appropriate sequence data are available. The new sequences provided here will assist the diagnosis and the taxonomic clarification of the opisthorchiid species

Generalist and Specialist Mite Herbivores Induce Similar Defense Responses in Maize and Barley but Differ in Susceptibility to Benzoxazinoids

While substantial progress has been made in understanding defense responses of cereals to insect herbivores, comparatively little is known about responses to feeding by spider mites. Nevertheless, several spider mite species, including the generalist Tetranychus urticae and the grass specialist Oligonychus pratensis, cause damage on cereals such as maize and wheat, especially during drought stress. To understand defense responses of cereals to spider mites, we characterized the transcriptomic responses of maize and barley to herbivory by both mite species, and included a wounding control against which modulation of defenses could be tested. T. urticae and O. pratensis induced highly correlated changes in gene expression on both maize and barley. Within 2 h, hundreds of genes were upregulated, and thousands of genes were up- or downregulated after 24 h. In general, expression changes were similar to those induced by wounding, including for genes associated with jasmonic acid biosynthesis and signaling. Many genes encoding proteins involved in direct defenses, or those required for herbivore-induced plant volatiles, were strongly upregulated in response to mite herbivory. Further, biosynthesis genes for benzoxazinoids, which are specialized compounds of Poaceae with known roles in deterring insect herbivores, were induced in maize. Compared to chewing insects, spider mites are cell content feeders and cause grossly different patterns of tissue damage. Nonetheless, the gene expression responses of maize to both mite herbivores, including for phytohormone signaling pathways and for the synthesis of the benzoxazinoid 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one glucoside, a known defensive metabolite against caterpillars, resembled those reported for a generalist chewing insect, Spodoptera exigua. On maize plants harboring mutations in several benzoxazinoid biosynthesis genes, T. urticae performance dramatically increased compared to wild-type plants. In contrast, no difference in performance was observed between mutant and wild-type plants for the specialist O. pratensis. Collectively, our data provide little evidence that maize and barley defense responses differentiate herbivory between T. urticae and O. pratensis. Further, our work suggests that the likely route to specialization for O. pratensis involved the evolution of a robust mechanism to cope with the benzoxazinoid defenses of its cereal hosts

The History and Future of the “Neglected Tropical Diseases” – Integrating Qualitative and Quantitative Research to Improve Public Health Outcomes

"We propose a new, multidisciplinary research team to explore historical and ongoing dynamics that have influenced the scientific priorities, funding resources, and research capacities focused on the “neglected tropical diseases” (NTDs). The NTDs are a suite of high-morbidity, low-mortality illnesses, generally affecting impoverished populations, that have animated significant financial, human, and technical resources toward their elimination or eradication in the past several decades. Little is known about the historical evolution of this fundamental category in global health research, or of how the designation of an illness as an NTD has impacted the development of new knowledge, diagnostic tools, vaccines, treatments, or laws and policies. A successful Dietrich School Social Science Research Initiative (SSRI)-funded project (2018-19) began to explore the evolution and impact of NTD strategies on global health. Awarded to Professors Dietrich, Sirleaf, and Webel, that SSRI grant funded the development of a comprehensive new database of NTD publications and research trends from 1945 to the present, from which we have identified several crucial inflection points for further research. We have started to analyze preliminary data on a single NTD test case (onchocerciasis), for which we will incorporate additional geographical data on researchers, institutional affiliations, and origins of research samples, as well as funding sources and country-level data on disease prevalence, in order to map and visualize how research and research capacity of this NTD changed over time.   We now seek to expand and formalize collaboration with colleagues in Public Health and Medicine. This new collaboration will allow us to marry quantitative and qualitative analysis of NTD publications data and real-world observational data to explore how comprehensive knowledge of the origins, development, and trajectory of the NTD category can shape future policy and research. Understanding historical inflection points in NTD research, as well as their long-term outcomes in new policies, drugs, or interventions, will clarify how different funding strategies, new and changing collaborative networks, and complementarities and tensions in research have impacted NTD research since the 1970s. This new understanding of the NTDs will allow our research team to connect global political agendas to research funding and public health outcomes in unprecedented ways.  The team’s goal is the development of a major grant application suitable for the Bill and Melinda Gates Foundation, and/or a proposal for co-application with the WHO’s Programme in Tropical Diseases Research to private funders.

Association of soluble markers of inflammation with peri-coronary artery inflammation in people with and without HIV infection and without cardiovascular disease

BACKGROUND: Inflammation is linked to elevated cardiovascular disease (CVD) risk in people with HIV (PWH) on antiretroviral therapy (ART). Fat attenuation index (FAI) is a measure of peri-coronary inflammation that independently predicts CVD risk in HIV-uninfected persons. Whether FAI is associated with soluble inflammatory markers is unknown. METHODS: Plasma levels of inflammatory markers were measured in 58 PWH and 16 controls without current symptoms or prior known CVD who underwent coronary computed tomography angiography and had FAI measurements. A cross-sectional analysis was performed, and associations of markers with FAI values of the right coronary artery (RCA) and left anterior descending artery (LAD) were assessed using multivariable regression models adjusted for the potential confounders age, sex, race, low-density lipoprotein cholesterol, body mass index, and use of lipid-lowering medication. RESULTS: Several inflammatory markers had significant associations with RCA or LAD FAI in adjusted models, including sCD14, sCD163, TNFR-I, and TNFR-II, CCL5, CX3CL1, IP-10. CONCLUSIONS: The associations between indices of systemic and peri-coronary inflammation are novel and suggest that these systemic markers and FAI together are promising noninvasive biomarkers that can be applied to assess asymptomatic CVD in people with and without HIV; they also may be useful tools to evaluate effects of anti-inflammatory interventions

Generalist and Specialist Mite Herbivores Induce Similar Defense Responses in Maize and Barley but Differ in Susceptibility to Benzoxazinoids

While substantial progress has been made in understanding defense responses of cereals to insect herbivores, comparatively little is known about responses to feeding by spider mites. Nevertheless, several spider mite species, including the generalist Tetranychus urticae and the grass specialist Oligonychus pratensis, cause damage on cereals such as maize and wheat, especially during drought stress. To understand defense responses of cereals to spider mites, we characterized the transcriptomic responses of maize and barley to herbivory by both mite species, and included a wounding control against which modulation of defenses could be tested. T. urticae and O. pratensis induced highly correlated changes in gene expression on both maize and barley. Within 2 h, hundreds of genes were upregulated, and thousands of genes were up- or downregulated after 24 h. In general, expression changes were similar to those induced by wounding, including for genes associated with jasmonic acid biosynthesis and signaling. Many genes encoding proteins involved in direct defenses, or those required for herbivore-induced plant volatiles, were strongly upregulated in response to mite herbivory. Further, biosynthesis genes for benzoxazinoids, which are specialized compounds of Poaceae with known roles in deterring insect herbivores, were induced in maize. Compared to chewing insects, spider mites are cell content feeders and cause grossly different patterns of tissue damage. Nonetheless, the gene expression responses of maize to both mite herbivores, including for phytohormone signaling pathways and for the synthesis of the benzoxazinoid 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one glucoside, a known defensive metabolite against caterpillars, resembled those reported for a generalist chewing insect, Spodoptera exigua. On maize plants harboring mutations in several benzoxazinoid biosynthesis genes, T. urticae performance dramatically increased compared to wild-type plants. In contrast, no difference in performance was observed between mutant and wild-type plants for the specialist O. pratensis. Collectively, our data provide little evidence that maize and barley defense responses differentiate herbivory between T. urticae and O. pratensis. Further, our work suggests that the likely route to specialization for O. pratensis involved the evolution of a robust mechanism to cope with the benzoxazinoid defenses of its cereal hosts