Widespread recombination, reassortment, and transmission of unbalanced compound viral genotypes in natural arenavirus infections.

Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential

Gravitating Chern-Simons vortices

The construction of self-dual vortex solutions to the Chern-Simons-Higgs model (with a suitable eighth-order potential) coupled to Einstein gravity in (2 + 1) dimensions is reconsidered. We show that the self-duality condition may be derived from the sole assumption $g_{00} = 1$. Next, we derive a family of exact, doubly self-dual vortex solutions, which interpolate between the symmetrical and asymmetrical vacua. The corresponding spacetimes have two regions at spatial infinity. The eighth-order Higgs potential is positive definite, and closed timelike curves are absent, if the gravitational constant is chosen to be negative.Comment: 11 pages, LaTe

Incidence of Plasmodium falciparum malaria infection in 6-month to 45-year-olds on selected areas of Bioko Island, Equatorial Guinea

BACKGROUND: Extensive malaria control measures have been implemented on Bioko Island, Equatorial Guinea over the past 16 years, reducing parasite prevalence and malaria-related morbidity and mortality, but without achieving elimination. Malaria vaccines offer hope for reducing the burden to zero. Three phase 1/2 studies have been conducted successfully on Bioko Island to evaluate the safety and efficacy of whole Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccines. A large, pivotal trial of the safety and efficacy of the radiation-attenuated Sanaria((R)) PfSPZ Vaccine against P. falciparum is planned for 2022. This study assessed the incidence of malaria at the phase 3 study site and characterized the influence of socio-demographic factors on the burden of malaria to guide trial design. METHODS: A cohort of 240 randomly selected individuals aged 6 months to 45 years from selected areas of North Bioko Province, Bioko Island, was followed for 24 weeks after clearance of parasitaemia. Assessment of clinical presentation consistent with malaria and thick blood smears were performed every 2 weeks. Incidence of first and multiple malaria infections per person-time of follow-up was estimated, compared between age groups, and examined for associated socio-demographic risk factors. RESULTS: There were 58 malaria infection episodes observed during the follow up period, including 47 first and 11 repeat infections. The incidence of malaria was 0.25 [95% CI (0.19, 0.32)] and of first malaria was 0.23 [95% CI (0.17, 0.30)] per person per 24 weeks (0.22 in 6-59-month-olds, 0.26 in 5-17-year-olds, 0.20 in 18-45-year-olds). Incidence of first malaria with symptoms was 0.13 [95% CI (0.09, 0.19)] per person per 24 weeks (0.16 in 6-59-month-olds, 0.10 in 5-17-year-olds, 0.11 in 18-45-year-olds). Multivariate assessment showed that study area, gender, malaria positivity at screening, and household socioeconomic status independently predicted the observed incidence of malaria. CONCLUSION: Despite intensive malaria control efforts on Bioko Island, local transmission remains and is spread evenly throughout age groups. These incidence rates indicate moderate malaria transmission which may be sufficient to support future larger trials of PfSPZ Vaccine. The long-term goal is to conduct mass vaccination programmes to halt transmission and eliminate P. falciparum malaria

Improving the health of Native Hawaiians.

Overall, the evaluations of the conference were excellent and the speakers received high scores. Many participants were deeply moved and eager to share what they learned with colleagues and family. The negative comments centered on the large number of topics covered in a short time. Requests that the organizers decrease the number of speakers and increase the amount of time for discussion will be addressed in the planning of what will hopefully be another similar program next year. In summary, based on this experience, pairing a didactic curriculum with three days of immersion--that is, employing Hawaiian cultural values in daily living routines--promotes learning on several levels. Culture is learned, but also felt-physically, emotionally and spiritually. The result is a group of providers who are more culturally attuned to Hawaiian values and hopefully, better able to care for the needs of the Kanaka Maoli

The effect of an anti-malarial herbal remedy, Maytenus senegalensis, on electrocardiograms of healthy Tanzanian volunteers

Abstract Background The emergence of resistance to artemisinin-based combination therapy necessitates the search for new, more potent antiplasmodial compounds, including herbal remedies. The whole extract of Maytenus senegalensis has been scientifically investigated for potential biological activities both in vitro and in vivo, demonstrating strong antimalarial activity. However, there is a lack of data on the electrocardiographic effects of M. senegalensis in humans, which is a crucial aspect in the investigation of malaria treatment. Assessing the electrocardiographic effects of M. senegalensis is essential, as many anti-malarial drugs can inadvertently prolong the QT interval on electrocardiograms. Therefore, the study's objective was to evaluate the electrocardiographic effects of M. senegalensis in healthy adult volunteers. Methods This study is a secondary analysis of an open-label single-arm dose escalation. Twelve healthy eligible Tanzanian males, aged 18 to 45, were enrolled in four study dose groups. A single 12-lead electrocardiogram (ECG) was performed at baseline and on days 3, 7, 14, 28, and 56. Results No QTcF adverse events occurred with any drug dose. Only one volunteer who received the highest dose (800 mg) of M. senegalensis experienced a moderate transient change (△QTcF > 30 ms; specifically, the value was 37 ms) from baseline on day 28. There was no difference in maximum QTcF and maximum △QTcF between volunteers in all four study dose groups. Conclusions A four-day regimen of 800 mg every 8 h of M. senegalensis did not impact the electrocardiographic parameters in healthy volunteers. This study suggests that M. senegalensis could be a valuable addition to malaria treatment, providing a safer alternative and potentially aiding in the battle against artemisinin-resistant malaria. The results of this study support both the traditional use and the modern therapeutic potential of M. senegalensis. They also set the stage for future research involving larger and more diverse populations to explore the safety profile of M. senegalensis in different demographic groups. This is especially important considering the potential use of M. senegalensis as a therapeutic agent and its widespread utilization as traditional medicine. Trial registration ClinicalTrials.gov, NCT04944966. Registered 30 June 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04944966?term=kamaka&draw=2&rank=

Concerning trends in allopathic medical school faculty rank for Indigenous people: 2014–2016

Background: Trends in faculty rank according to racial and ethnic composition have not been reviewed in over a decade. Objective: To study trends in faculty rank according to racial and ethnicity with a specific focus on Indigenous faculty, which has been understudied. Methods: Data from the Association of American Medical Colleges’ Faculty Administrative Management Online User System was used to study trends in race/ethnicity faculty composition and rank between 2014 and 2016, which included information on 481,753 faculty members from 141 US allopathic medical schools. Results: The majority of medical school faculty were White, 62.4% (n = 300,642). Asian composition represented 14.7% (n = 70,647). Hispanic, Latino, or of Spanish Origin; Multiple Race-Hispanic; Multiple Race-Non-Hispanic; and Black/African American faculty represented 2.2%, 2.3%, 3.0%, and 3.0%, respectively. Indigenous faculty members, defined as American Indian/Alaska Native (AIAN), Native Hawaiian or Other Pacific Islander (NHPI), represented the smallest percentage of faculty at 0.11% and 0.18%, respectively. White faculty predominated the full professor rank at 27.5% in 2016 with a slight decrease between 2014 and 2016. Indigenous faculty represented the lowest percent of full professor faculty at 5.2% in 2016 for AIAN faculty and a decline from 4.6% to 1.6% between 2014 and 2016 for NHPI faculty (p < 0.001). Conclusions: While US medical school faculty are becoming more racially and ethnically diverse, representation of AIAN faculty is not improving and is decreasing significantly among NHPI faculty. Little progress has been made in eliminating health disparities among Indigenous people. Diversifying the medical workforce could better meet the needs of communities that historically and currently experience a disproportionate disease burden