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Zika virus (ZIKV) outbreaks occur sporadically in tropical and subtropical regions. At present, there are no licensed vaccines or specific treatments available for ZIKV. Ivermectin is approved for use in humans as an antiparasitic drug. In this study, we conducted in vitro cell culture and in vivo experiments in rhesus macaque hosts and Aedes aegypti vectors to investigate the potential of ivermectin as an inhibitor of ZIKV infection. In LLC-MK2 mammalian cells, ivermectin inhibited ZIKV growth in vitro with 50% inhibitory concentration (IC50) values in the ranges of 7.4-21.3 µM and 4.0-11.6 µM for African and Asian genotypes, respectively. In C6/36 mosquito cells, ivermectin inhibited ZIKV growth in vitro with IC50 values in the ranges of 10.1-17.4 µM and 8.0-15.6 µM for the African and Asian genotypes, respectively. Despite these in vitro results, high-dose ivermectin prophylaxis (1.2 mg/kg for 3 consecutive days) failed to prevent ZIKV infection in rhesus macaque and did not alter ZIKV IgM antibody production. The secondary transfer of ivermectin from nonhuman primate blood to mosquito vectors at 3 days post-ZIKV inoculation and after the last dose of ivermectin administration showed no reduction in ZIKV replication in mosquitoes. However, mosquito survival rates were significantly (P <0.0001) lower after exposure to ivermectin, thereby potentially impacting ZIKV transmission through increased vector mortality. However, further investigation is needed to determine dosing regimens that may realize these effects in vivo.

Objectives: To study the population structure and genomic characteristics, including antimicrobial resistance genes, plasmid types and surface polysaccharide type, of the globally distributed Acinetobacter baumannii belonging to ST32 (Institut Pasteur scheme)., Methods: Antibiotic resistance phenotype for 19 antibiotics was determined using Vitek 2. Whole-genome sequencing was performed using the Illumina MiSeq platform. Genomes were assembled using Newbler. Phylogenetic analysis was done by determining the core-genome alignments using Panaroo v1.3, analysed in IQ-Tree2 v2.2.0.3 to construct Maximum Likelihood trees using the RaxML software. Resistance genes and IS were identified using the Abricate programme, and ISFinder databases., Results: One hundred and thirty-three (n = 133) ST32 A. baumannii isolates were analysed in this study. These genomes originated mainly from US military treatment facilities (n = 113), but also included additional publicly available genomes in GenBank (n = 20) recovered from a broad geographic distribution extending to Asia and South America. Phylogenetic analysis of all 133 genomes revealed at least four clades, with over 80 genomes forming a tightly clustered branch, suggesting they are likely to represent outbreak strains. Analysis of the ampC region showed that ST32 strains played a significant role in the formation of the widely distributed ampC transposon, Tn6168, and supplying DNA segments containing an ISAba1-ampC from ST32s via homologous recombination., Conclusions: ST32 strains played a significant role in the evolution of antibiotic resistance in several widely distributed sequence types including ST1 (global clone 1) and ST3., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Well-tolerated and novel antimalarials that can combat multiple stages of the parasite life cycle are desirable but challenging to discover and develop. Herein, we report results for natural product-inspired novel tambjamine antimalarials. We show that they are potent against liver, asexual erythrocytic, and sexual erythrocytic parasite life cycle stages. Notably, our lead candidate 1 (KAR425) displays excellent oral efficacy with complete clearance of parasites within 72 h of treatment in the humanized Plasmodium falciparum (NOD-scid) mouse model at 50 mg/kg × 4 days. Profiling of compound 1 demonstrated a fast in vitro killing profile. In addition, several other tambjamine analogues cured erythrocytic Plasmodium yoelii infections after oral doses of 30 and 50 mg/kg × 4 days in a murine model while exhibiting good safety and metabolic profiles. This study presents the first account of multiple-stage antiplasmodial activities with rapid killing profile in the tambjamine family.

We describe the genomes of five lytic Klebsiella pneumoniae myophages, therapeutic candidates, that belong to the family Straboviridae and genus Jiaodavirus . The genomes ranged from 165,574 to 169,768 bp, with ca. 40% GC content, contained 289-300 coding sequences, had 15-16 tRNA genes, and no terminal repeats., Competing Interests: The authors declare no conflict of interest.

Dengue virus (DENV) is an increasingly important human pathogen, with already half of the globe's population living in environments with transmission potential. Since only a minority of cases are captured by direct detection methods (RT-PCR or antigen tests), serological assays play an important role in the diagnostic process. However, individual assays can suffer from low sensitivity and specificity and interpreting results from multiple assays remains challenging, particularly because interpretations from multiple assays may differ, creating uncertainty over how to generate finalized interpretations. We develop a Bayesian mixture model that can jointly model data from multiple paired serological assays, to infer infection events from paired serological data. We first test the performance of our model using simulated data. We then apply our model to 677 pairs of acute and convalescent serum collected as a part of illness and household investigations across two longitudinal cohort studies in Kamphaeng Phet, Thailand, including data from 232 RT-PCR confirmed infections (gold standard). We compare the classification of the new model to prior standard interpretations that independently utilize information from either the hemagglutination inhibition assay (HAI) or the enzyme-linked immunosorbent assay (EIA). We find that additional serological assays improve accuracy of infection detection for both simulated and real world data. Models incorporating paired IgG and IgM data as well as those incorporating IgG, IgM, and HAI data consistently have higher accuracy when using PCR confirmed infections as a gold standard (87-90% F1 scores, a combined metric of sensitivity and specificity) than currently implemented cut-point approaches (82-84% F1 scores). Our results provide a probabilistic framework through which multiple serological assays across different platforms can be leveraged across sequential serum samples to provide insight into whether individuals have recently experienced a DENV infection. These methods are applicable to other pathogen systems where multiple serological assays can be leveraged to quantify infection history.

Adjuvant therapy with bacteriophage (phage) cocktails in combination with antibiotics is a therapeutic approach currently considered for treatment of infections with encapsulated, biofilm forming, and multidrug-resistant Klebsiella pneumoniae (Kp). Klebsiella phage are highly selective in targeting a bacterial capsule type. Considering the numerous Kp capsule types and other host restriction factors, phage treatment could be facilitated when generating phages with a broad host range. A modified 'Appelmans protocol' was used to create phages with an extended host range via in vitro forced DNA recombination. Three T7-like Kp phages with highly colinear genomes were subjected to successive propagation on their susceptible host strains representing the capsule types K64, K27, and K23, and five Kp isolates of the same capsule types initially unsusceptible for phage lysis. After 30 propagation cycles, five phages were isolated via plaque assay. Four output phages represented the original input phages, while the fifth lysed a previously non-permissible Kp isolate, which was not lysed by any of the input phages. Surprisingly, sequence analysis revealed a novel N15/phiKO2-like phage genome (vB&#95;KpnS&#95;KpLi5) lacking substantial homologies to any of the used T7-like phages. This phage is not a chimeric recombinant of the applied T7-like phages, but represents a temperate phage that was induced from Kp due to the application of the input phages phages (cocktail), but not by any of them individually. Adapted phages with chimeric genomes and extended host range derived from input phages were not observed. Induction of temperate phages may be a stress response caused by using multiple phages simultaneously (i.e., by destabilization of the cell wall due to an unspecific binding of the phages). Successive use of different phages for therapeutic purposes may be preferable over simultaneous application in cocktail formulations to avoid undesired induction of temperate phages., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Visceral leishmaniasis (VL), known as Kala-azar on the Indian subcontinent, is a parasitic disease caused by the flagellated protozoa Leishmania donovani and can be fatal if left untreated. The sand fly Phlebotomus argentipes is the only proven vector of VL in the Southeast Asia region, and VL control in this region has relied on the use of synthetic insecticides for indoor residual spraying (IRS). The use of DDT in VL control programmes has led to the development of resistance to this insecticide in sand flies, resulting in DDT being replaced with the insecticide alpha-cypermethrin. However, alpha-cypermethrin has a similar mode of action as DDT and, therefore, the risk of resistance development in sand flies increases under the pressure of regular exposure to this insecticide. In the present study we assessed the susceptibility status of wild-caught sand flies and F1 progeny using the CDC bottle bioassay., Methods: Sand flies were collected from 10 villages in Muzaffarpur District, Bihar, India. Eight of these villages are receiving continuous IRS with alpha-cypermethrin, one village had discontinued IRS with alpha-cypermethrin and one village had never received IRS with alpha-cypermethrin. The collected sand flies were exposed to a pre-determined diagnostic dose for a specific time duration (3 µg/ml for 40 min), and knockdown and mortality at 24 h post-exposure were recorded., Results: Knockdown ranged from 91.19% to 99.47% for wild-caught sand flies and from 91.70% to 98.89% for their F1 progeny. At 24 h post-exposure, mortality ranged from 89.34% to 98.93% for wild-caught sand flies and from 90.16% to 98.33% for F1 progeny., Conclusions: The results of this study showed that P. argentipes is potentially developing resistance, signalling the need for continuous monitoring and vigilance to sustain the validation of elimination once achieved., Competing Interests: Declarations. Ethical approval and consent to participant: This work was conducted with ethical approval (Letter No. CAEC/DEAN/2014/CAEC/615) obtained from Institutional Review Committees of Banaras Hindu University, Varanasi, India. Informed verbal consent was obtained from the household and cattle shed owners before the installation of light traps for sand fly collection. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) represent a significant global threat. The emergence of dual CP-CRE is particularly alarming, as they can potentially compromise the efficacy of newer antibiotics, further decreasing therapeutic alternatives. Herein, we report the emergence of multiple species of CP-CRE recovered from invasive infections in Chile that simultaneously harbor bla KPC and provide an in-depth genomic characterization of these worrisome pathogens. We collected carbapenem-resistant Enterobacterales (CRE) isolates from invasive infections over a 4-year period, across 11 healthcare centers in Chile. Bacterial species and the presence of carbapenemase genes were confirmed using MALDI-TOF and PCR assays, respectively. Antimicrobial susceptibility testing was conducted through disk diffusion and broth microdilution methods. Dual CP-CRE isolates were subjected to short- and long-read whole genome sequencing to perform a detailed genomic characterization of the isolates and of the mobile genetic elements harboring the enzymes. From a total of 1,335 CRE isolates, we observed an increase in the prevalence of CP-CRE, from 11% in 2019 to 38% in 2022. A total of 11 dual CP-CRE isolates were recovered, all of them harboring bla NDM and provide an in-depth genomic characterization of these worrisome pathogens. We collected carbapenem-resistant Enterobacterales (CRE) isolates from invasive infections over a 4-year period, across 11 healthcare centers in Chile. Bacterial species and the presence of carbapenemase genes were confirmed using MALDI-TOF and PCR assays, respectively. Antimicrobial susceptibility testing was conducted through disk diffusion and broth microdilution methods. Dual CP-CRE isolates were subjected to short- and long-read whole genome sequencing to perform a detailed genomic characterization of the isolates and of the mobile genetic elements harboring the enzymes. From a total of 1,335 CRE isolates, we observed an increase in the prevalence of CP-CRE, from 11% in 2019 to 38% in 2022. A total of 11 dual CP-CRE isolates were recovered, all of them harboring bla KPC and bla NDM . Species corresponded to Escherichia coli ( n = 6), Klebsiella pneumoniae ( n = 2), Klebsiella oxytoca ( n = 2), and Citrobacter freundii ( n was only found on fairly conserved IncX3 plasmids. We report that a rapid increase of CP-CRE in Chile, alongside with the emergence of multiple bacterial species of CP-CRE co-harboring bla KPC , underscores a critical public health challenge. Our data suggest that the dissemination of bla was predominantly facilitated by IncX3 plasmids, whereas the spread of NDM involved multiple plasmid backbones. Active surveillance and genomic monitoring are critical to inform public policy and curtail the spread of these highly resistant pathogens.bla KPC were diverse and included IncN, IncF, and IncFIB plasmids. In contrast, bla NDM-7 was only found on fairly conserved IncX3 plasmids. We report that a rapid increase of CP-CRE in Chile, alongside with the emergence of multiple bacterial species of CP-CRE co-harboring bla KPC-2/3 and bla NDM-7 , underscores a critical public health challenge. Our data suggest that the dissemination of bla NDM-7 was predominantly facilitated by IncX3 plasmids, whereas the spread of bla KPC involved multiple plasmid backbones. Active surveillance and genomic monitoring are critical to inform public policy and curtail the spread of these highly resistant pathogens.

Background: Sexual and gender minorities (SGM) bear a high burden of HIV. The age of anal sexual debut may influence HIV care engagement. Our objective was to evaluate this relationship to help healthcare providers promote and anticipate future HIV care engagement among at-risk SGM., Methods: The TRUST/RV368 study provided HIV testing and treatment at SGM-friendly clinics in Abuja and Lagos, Nigeria. Self-reported age of sexual debut was dichotomized as <16 or ≥16 years. Multivariable logistic models estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the association of sexual debut with 1) prior HIV testing history, 2) HIV testing at the clinics, 3) initiation of antiretroviral therapy (ART) within 6 months of a clinic diagnosis, 4) viral suppression within 12 months of ART initiation., Results: Of the 2,680 participants, 30% (n=805) reported a sexual debut <16 years. Those with an <16-year debut had significantly more receptive sex partners, condomless sex, and transactional sex (all p<0.01) and were 24% less likely to have tested for HIV before enrollment (aOR: 0.76; CI: 0.62-0.93). However, <16-year debut was not associated with HIV testing, receiving ART or achieving viral suppression once engaged with TRUST/RV368 (all p>0.05)., Conclusions: SGM with <16-year debut engaged in behaviors that could increase HIV risk and were less likely to have a history of HIV testing. However, once enrolled in SGM-friendly clinics, uptake of HIV care was not associated with <16-year debut, suggesting that SGM-friendly care models may promote HIV care engagement., Competing Interests: Conflicts of Interest and Source of Funding: All authors declare no potential conflicts of interest. The content is solely the responsibility of the authors and should not be construed to represent the positions of the National Institutes of Health or other funders. This work was supported by the National Cancer Institute [1K07CA225403, 5T32CA009314-40;]; Maryland Department of Health’s Cigarette Restitution Fund Program [CH-649-CRF], National Institutes of Health [R01 MH099001, R01 AI120913, R01 MH110358]; the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense [W81XWH-11-2-0174, W81XWH-18-2-0040]; Fogarty Epidemiology Research Training for Public Health Impact in Nigeria program [D43TW010051]; and the President’s Emergency Plan for AIDS Relief through a cooperative agreement between the Department of Health and Human Services/Centers for Disease Control and Prevention, Global AIDS Program, and the Institute for Human Virology-Nigeria [NU2GGH002099]., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Rehabilitation from musculoskeletal injuries (MSKI) complicate healing dynamics typically by sustained disuse of bone and muscles. Microgravity naturally allows limb disuse and thus an effective model to understand MSKI. The current study examined epigenetic changes in a segmental bone defect (SBD) mouse model in a prolonged unloading condition after spaceflight (FLT). We further connected potential miRNA-mRNA regulatory pathways impacting bone healing. Here, SBD surgery was performed on nine-week-old male mice that were launched into space for approximately 4 weeks. Sham with no surgery and ground controls were included in the study. The midshaft of the ipsilateral femur (with callus on the surgical mice) as well as the ipsilateral quadriceps tissue were used for analysis. Femur and quadriceps had a distinct miRNA profile. There was a stronger surgery effect as observed by miRNA expression when compared to microgravity effects. Leukopoiesis, granulopoiesis, myelopoiesis of leukocytes, differentiation of myeloid leukocytes, and differentiation of progenitor cells were all altered because of surgery in the femur. The biological functions such as apoptosis, necrosis, and activation of cell migration and viability were altered because of surgery in quadriceps. Integrating the transcriptome and microRNA data indicated pronounced changes because of microgravity. According to pathway analysis, microgravity had a greater impact on the quadriceps tissue than the bone tissue in the absence of surgery. The altered biological functions resulting from microgravity were validated by integrating limited proteomics data to miRNA-mRNA. Thus, this study highlights the importance of dynamic interplay of gene-epigene regulations as they appear to be intrinsically interconnected and influence in combination for the biological outcome., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

This review discusses findings on the use of behavioral nudges in both the Canadian and U.S. military. To date, most of this research has focused on improving recruitment and healthy eating behaviors in military personnel. The current review also highlights important areas of future research, focusing on the role behavioral nudges could potentially play in curbing three pressing issues in the U.S. military: 1) recruitment, 2) health-related readiness of the military, and 3) suicide prevention. The review concludes with an overview of unique challenges this work may face in the military context as well as unique resources available for this research and implementation not likely accessible in civilian communities., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: We examined the added value of serologic testing for estimating influenza virus infection incidence based on illness surveillance with molecular testing versus periodic serologic testing., Methods: Pregnant persons unvaccinated against influenza at <28 weeks gestation were enrolled before the 2017 and 2018 influenza seasons in Peru and Thailand. Blood specimens were collected at enrollment and ≤14 days postpartum for testing by hemagglutination inhibition assay for antibodies against influenza reference viruses. Seroconversion was defined as a ≥4-fold rise in antibody titers from enrollment to postpartum with the second specimen's titer of ≥40. Throughout pregnancy, participants responded to twice weekly surveillance contacts asking about influenza vaccination and influenza-like symptoms (ILS). A mid-turbinate swab was collected with each ILS episode for influenza real-time reverse transcription polymerase chain reaction (rRT-PCR)., Results: Of 1,466 participants without evidence of influenza vaccination during pregnancy, 296 (20.2%) had evidence of influenza virus infections. Fifteen (5.1%) were detected by rRT-PCR only, 250 (84.4%) by serologic testing only, and 31 (10.5%) by both methods., Conclusions: Influenza virus infections during pregnancy occurred in 20% of cohort participants; >80% were not detected by a broad illness case definition coupled with rRT-PCR., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Given the large number and diverse types of PTSD symptoms, examination of subtypes within the comprehensive PTSD criteria is necessary. This is especially true for subpopulations of active-duty service members such as specialized military units that undergo assessment and selection, receive extensive training, and have significant operational experience and trauma exposure. The current study identified PTSD subtypes in 16,284 U.S. Special Operations Forces (SOF) personnel who completed the Preservation of the Force and Family Needs Assessment Survey. Results identified a 4-profile solution. When stratifying the sample by occupation type (Operator vs Support), findings suggest that SOF Support personnel symptom presentations are primarily characterized by dysphoric and negative alterations in cognitions and mood symptoms. In contrast, SOF Operator personnel symptoms are best characterized by traditional profiles, consistent with the existing PTSD subtype literature. Results provide support for pursuing precision medicine approaches based on PTSD symptom profiles., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

It is well established that individuals differ in their response to sleep loss. However, existing methods to predict an individual's sleep-loss phenotype are not scalable or involve effort-dependent neurobehavioural tests. To overcome these limitations, we sought to predict an individual's level of resilience or vulnerability to sleep loss using electroencephalographic (EEG) features obtained from routine night sleep. To this end, we retrospectively analysed five studies in which 96 healthy young adults (41 women) completed a laboratory baseline-sleep phase followed by a sleep-loss challenge. After classifying subjects into sleep-loss phenotypic groups, we extracted two EEG features from the first sleep cycle (median duration: 1.6 h), slow-wave activity (SWA) power and SWA rise rate, from four channels during the baseline nights. Using these data, we developed two sets of logistic regression classifiers (resilient versus not-resilient and vulnerable versus not-vulnerable) to predict the probability of sleep-loss resilience or vulnerability, respectively, and evaluated model performance using test datasets not used in model development. Consistently, the most predictive features came from the left cerebral hemisphere. For the resilient versus not-resilient classifiers, we obtained an average testing performance of 0.68 for the area under the receiver operating characteristic curve, 0.72 for accuracy, 0.50 for sensitivity, 0.84 for specificity, 0.61 for positive predictive value, and 3.59 for likelihood ratio. We obtained similar performance for the vulnerable versus not-vulnerable classifiers. These results indicate that logistic regression classifiers based on SWA power and SWA rise rate from routine night sleep can largely predict an individual's sleep-loss phenotype., (© 2024 European Sleep Research Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Recent outbreaks between 2015-17 and production delays have led to a yellow fever vaccine shortage. Therefore, there is an urgent need for new yellow fever vaccines with improved production scalability. A next-generation live-attenuated yellow fever vaccine candidate (vYF), produced in a Vero cell line has shown similar immunogenicity to licensed yellow fever vaccines in preclinical studies. In this study, we aimed to report the safety and immunogenicity of vYF in human clinical trial participants., Methods: In this first in-human, phase 1 randomised, observer-blind, active-controlled, dose-ranging clinical trial conducted at a single centre in the USA (Walter Reed Army Institute of Research, Silver Spring, MD, USA), 72 healthy adults (aged 18-60 years), without a known history of flavivirus infection or vaccination were randomly assigned (1:1:1:1) using interactive response technology to receive one dose of either vYF at 4, 5 or 6 Log CCID 50 or the licensed YF-VAX (18 individuals per group). The primary outcomes were safety, neutralising antibody (NAb) titres through D180 post-vaccination in the per-protocol analysis set (comprised of yellow fever-naive participants who received their intended vaccine and provided a valid post-vaccination blood sample), and occurrence, and level of yellow fever viraemia in each vaccine group through D14 post-vaccination., Findings: All vYF doses had a safety and tolerability profile similar to YF-VAX. The most frequently reported solicited injection site reactions (vYF groups vs YF-VAX group) were pain (22% [12 of 54 participants, 95% CI 12-36] vs 28% [five of 18 participants, 10-54]), and erythema (13% [seven of 54 participants, 5-25] vs 39% [seven of 18 participants, 17-64]), with headache (32% [17 of 54 participants, 20-46] vs 44% [eight of 18 participants, 22-69]) and malaise (26% [14 of 54 participants, 15-40] vs 33% [six of 18 participants, 13-59]) as the most frequently reported solicited systemic reactions. One grade 3 solicited reaction (erythema) reported in the YF-VAX group resolved spontaneously. No serious unsolicited adverse events or deaths were reported. Viraemia was transiently detected in 50 participants between D4 and D10 in all groups and was observed in more participants or for a longer time in the vYF 6 Log CCID 50 and YF-VAX groups. All yellow fever-naive vaccine recipients across the study groups seroconverted yielding four-fold increase from baseline in yellow fever NAb titres measured by yellow fever microneutralisation assay by D28 and were seroprotected with yellow fever NAb titres of at least 10 [1/dil]). Overall, 100% (18 of 18 participants, 95% CI 82-100), 89% (16 participants, 65-99), 100% (18 participants, 82-100), and 94% (17 participants, 73-100) of participants in the vYF 4 Log, vYF 5 Log, vYF 6 Log CCID 50 groups, and YF-VAX group, respectively, remained seroprotected through D180., Interpretation: vYF has a similar safety and immunogenicity profile to YF-VAX. In general, the vYF 5 Log CCID 50 dose appeared to show optimal viraemia, safety, and immunogenicity, and was chosen for subsequent development., Funding: Sanofi., Competing Interests: Declaration of interests A-MM, HA, YW, ARP, VD, NM, MV, and EF are Sanofi employees and hold shares and stock options in the company. KM and PTS were employed by the Walter Reed Army Institute of Research at the time of this study. MM, BO-S, ES, MFA, APP, BO, MNM, KSK, MEM, IG, MEG, JMD, MAK, MJH, CEL, JNH, SAP, and MLR received funds from Sanofi through their institutions to support their work in the VYF01 trial (NCT04142086)., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

SARS-CoV-2 has caused over 6.9 million deaths and continues to produce lasting health consequences. COVID-19 manifests broadly from no symptoms to death. In a retrospective cross-sectional study, we developed personalized risk assessment models that predict clinical outcomes for individuals with COVID-19 and inform targeted interventions. We sequenced viruses from SARS-CoV-2-positive nasopharyngeal swab samples between July 2020 and July 2022 from 4450 individuals in Missouri and retrieved associated disease courses, clinical history, and urban-rural classification. We integrated this data to develop machine learning-based predictive models to predict hospitalization, ICU admission, and long COVID.The mean age was 38.3 years (standard deviation = 21.4) with 55.2% ( N  = 2453) females and 44.8% ( N  = 1994) males (not reported, N  = 4). Our analyses revealed a comprehensive set of predictors for each outcome, encompassing human, environment, and virus genome-wide genetic markers. Immunosuppression, cardiovascular disease, older age, cardiac, gastrointestinal, and constitutional symptoms, rural residence, and specific amino acid substitutions were associated with hospitalization. ICU admission was associated with acute respiratory distress syndrome, ventilation, bacterial co-infection, rural residence, and non-wild type SARS-CoV-2 variants. Finally, long COVID was associated with hospital admission, ventilation, and female sex.Overall, we developed risk assessment models that offer the capability to identify patients with COVID-19 necessitating enhanced monitoring or early interventions. Of importance, we demonstrate the value of including key elements of virus, host, and environmental factors to predict patient outcomes, serving as a valuable platform in the field of personalized medicine with the potential for adaptation to other infectious diseases.

Identification of the diverse animal hosts responsible for spill-over events from animals to humans is crucial for comprehending the transmission patterns of emerging infectious diseases, which pose significant public health risks. To better characterize potential animal hosts of Lassa virus (LASV), we assessed domestic and non-domestic animals from 2021-2022 in four locations in southern Nigeria with reported cases of Lassa fever (LF). Birds, lizards, and domestic mammals (dogs, pigs, cattle and goats) were screened using RT-qPCR, and whole genome sequencing was performed for lineage identification on selected LASV positive samples. Animals were also screened for exposure to LASV by enzyme-linked immunosorbent assay (ELISA). Among these animals, lizards had the highest positivity rate by PCR. Genomic sequencing of samples in most infected animals showed sub-lineage 2 g of LASV. Seropositivity was highest among cattle and lowest in pigs. Though the specific impact these additional hosts may have in the broader virus-host context are still unknown - specifically relating to pathogen diversity, evolution, and transmission - the detection of LASV in non-rodent hosts living in proximity to confirmed human LF cases suggests their involvement during transmission as potential reservoirs. Additional epidemiological data comparing viral genomes from humans and animals, as well as those circulating within the environment will be critical in understanding LASV transmission dynamics and will ultimately guide the development of countermeasures for this zoonotic health threat.

Multiple accidents in nuclear power plants and the growing concerns about the misuse of radiation exposure in warfare have called for the rapid determination of absorbed radiation doses (RDs). The latest findings about circulating microRNA (miRNAs) using several animal models revealed considerable promises, although translating this knowledge to clinics remains a major challenge. To address this issue, we randomly divided 36 nonhuman primates (NHPs) into six groups and exposed these groups to six different radiation doses ranging from 6.0-8.5 Gy in increments of 0.5 Gy. Serum samples were collected pre-irradiation as well as three post-irradiation timepoints, namely 1, 2 and 6 days post-total body irradiation (TBI). Generated from a deep sequencing platform, the miRNA reads were multi-variate analyzed to find the differentially expressed putative biomarkers that were linked to RDs, time since irradiation (TSI) and sex. To increase these biomarkers' translational potential, we aligned the NHP-miRNAs' sequences and their functional responses to humans following an in-silico routine. Those miRNAs, which were sequentially and functionally conserved between NHPs and humans, were down selected for further analysis. A linear regression model identified miRNA markers that were consistently regulated with increasing RD but independent TSI. Likewise, a set of potential TSI-markers were identified that consistently shifted with increasing TSI, but independent of RD. Additional molecular analysis found a considerable gender bias in the low-ranges of doses when the risk to radiation-induced fatality was low. Bionetworks linked to cell quantity and cell invasion were significantly altered between the survivors and decedents. Using these biomarkers, an assay could be developed to retrospectively determine the RD and TSI with high translational potential. Ultimately, this knowledge can lead to precise and personalized medicine., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

During the last two decades, wound invasive fungal diseases (WIFDs) have reemerged as important causes of mortality and morbidity in military personnel and civilian casualties in war areas. Historically, mycotic infections acquired in combat operations during Vietnam War and were associated with burn wounds. Modern combat related WIFDs are almost exclusively associated with severe traumatic events which encompass blast exposure as the primary mechanism of injury and subsequent extremity amputation and extensive blood loss. Such infections often lead to deep tissue necrosis, long hospitalizations, extensive surgeries, and more severe amputation. Studies of combat related WIFDs among U.S. military personnel in Operation Enduring Freedom (Afghanistan) demonstrated incidence rates of approximately 7% and crude mortality of 8.5%. WIFDs were also seen in U.K. military personnel returning from Afghanistan and are common in the current Ukraine and Gaza conflicts. Mucorales, Aspergillus and Fusarium species are the predominant causes of WIFDs. These molds are opportunistic pathogens which thrive in patients with immune system imbalances following traumatic injury. They are ubiquitous environmental fungi found in a variety of soils but there are significant regional differences depending on the local soil type, vegetation, and climate. The management of WIFDs is complicated by the limited efficacy of current antifungals on many of these environmental species and by emerging antifungal resistance globally. This review provides an overview of the global burden, epidemiology, and clinical features of combat-related fungal infections with the aim to provide a better understanding of the threat posed for wounded Service Members and civilians., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethical Approval: This is a review article. No ethical approval is required., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Hypothermia in combination with infection presents a complex challenge in clinical and battlefield medicine. Multifaceted physiological and immunological consequences of hypothermia drastically change the risk, progression, and treatment of a concomitant infection. Managing hypothermia and infection in extreme cold settings is particularly relevant in an era with increased risk of military operations in Polar climates. Here, we discuss the elevated instance of infection during accidental and therapeutic hypothermia and speculate how a compromised immune system may contribute. We focus on skin and soft tissue infections and sepsis, which are among the serious infectious complications of hypothermia and battlefield injuries. We also present the challenges associated with treating infections under hypothermic conditions. Finally, we advocate for a renewed focus on identifying causal relationships between hypothermia and infection risk and assessing established infection treatment regiments in hypothermic patients to enhance trauma management and survival outcomes in hypothermia-related injuries., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CPT Richard Kevorkian reports financial support was provided by US Department of Defense JPC-6 Combat Casualty Care Research Program. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Achieving bone union remains a significant clinical dilemma. The use of osteoinductive agents, specifically bone morphogenetic proteins (BMPs), has gained wide attention. However, multiple side effects, including increased incidence of cancer, has renewed interest in investigating alternatives that provide safer, yet effective bone regeneration. Here we demonstrate the robust bone healing capabilities of the main megakaryocyte growth factor, thrombopoietin (TPO) and second generation TPO agents using multiple animal models including mice, rats, and pigs. This bone healing activity is shown in two fracture models (critical sized defect [CSD] and closed fracture) and with local or systemic administration. Our transcriptomic analyses, cellular studies, and protein arrays demonstrate that TPO enhances multiple cellular processes important to fracture healing, particularly angiogenesis, which is required for bone union. Finally, the therapeutic potential of thrombopoietic agents is high since they are used in the clinic for other indications (e.g., thrombocytopenia) with established safety profiles and act upon a narrowly defined population of cells., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Objectives: Although studies have addressed food insecurity among veterans, few have focused on active-duty soldiers or on variables associated with the military occupational context. We examined the link between marginal food insecurity (defined as anxiety over food sufficiency or shortage of food in the house) among US soldiers and demographic, behavioral health, and unit-related factors., Methods: We analyzed survey data from 6343 active-duty soldiers using χ 2 tests, generalized linear mixed-effect models, and adjusted odds ratios (AORs) to identify significant differences between soldiers categorized as marginally food insecure versus those who were not., Results: In a fully adjusted model taking unit into account, marginal food insecurity was associated with preferring not to report gender (vs reporting being male) (AOR = 1.39; 95% CI, 1.08-1.78), being married/in a relationship (vs being single) (AOR = 1.22; 95% CI, 1.06-1.40), junior enlisted rank (vs noncommissioned officer: AOR = 0.45; 95% CI, 0.37-0.54; and vs officer: AOR = 0.13; 95% CI, 0.09-0.19), less time in unit (vs more time) (AOR = 0.99; 95% CI, 0.99-1.00), screening positive for depression (vs not) (AOR = 2.67; 95% CI, 2.30-3.11), screening positive for hazardous drinking (vs not) (AOR = 1.34; 95% CI, 1.11-1.63), and lack of reported unit-related social support (vs support) (AOR = 0.52; 95% CI, 0.45-0.59)., Conclusions: In this sample, more than 1 in 5 US soldiers reported marginal food insecurity. In addition to supporting households with financial and food assistance and targeting junior enlisted personnel, policy makers and leaders should prioritize soldiers who are married or in a relationship, who are new to their unit, and who screen positive for depression and hazardous drinking, and they should encourage units to take care of unit members who need support. Policy makers and leaders can use these study results to direct prevention and early intervention initiatives., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, we show that neutralization titers and breadth of matched human and hamster pre-Omicron variant primary infection sera correlate well and generate similar antigenic maps. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with fivefold to sixfold antigenic differences between these variants and XBB.1.5. Compared to sera following only ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, XBB.1.5 booster sera had the broadest neutralization against XBB sub-lineage variants, although a fivefold titer difference was still observed between JN.1 and XBB.1.5 variants. These findings suggest that antibody coverage of antigenically divergent JN.1 could be improved with a matched vaccine antigen.IMPORTANCEUpdates to COVID-19 vaccine antigens depend on assessing how much vaccine antigens differ antigenically from newer SARS-CoV-2 variants. Human sera from single variant infections are ideal for discriminating antigenic differences among variants, but such primary infection sera are now rare due to high population immunity. It remains unclear whether sera from experimentally infected animals could substitute for human sera for antigenic assessments. This report shows that neutralization titers of variant-matched human and hamster primary infection sera correlate well and recognize variants similarly, indicating that hamster sera can be a proxy for human sera for antigenic assessments. We further show that human sera following an XBB.1.5 booster vaccine broadly neutralized XBB sub-lineage variants but titers were fivefold lower against the more recent JN.1 variant. These findings support updating the current COVID-19 vaccine variant composition and developing a framework for assessing antigenic differences in future variants using hamster primary infection sera., Competing Interests: The authors declare no conflict of interest.

Hantaan virus (HTNV) and Puumala virus (PUUV) are pathogenic zoonoses found in Asia and Europe, respectively. We conducted a randomized Phase 1 clinical trial of individual HTNV and PUUV DNA vaccines targeting the envelope glycoproteins (GnGc), as well as a combined HTNV/PUUV DNA vaccine delivered at varying doses using the PharmaJet Stratis® needle-free injection system (NCT02776761). Cohort 1 and 2 vaccines consisted of 2 mg/vaccination of HTNV or PUUV plasmid, respectively. Cohort 3 vaccine consisted of 2 mg/vaccination of 1:1 mixture of HTNV and PUUV vaccines. Vaccinations were administered on Days 0, 28, 56, and 168. The vaccines were safe and well tolerated. Neutralizing antibody responses were elicited in 7/7 (100%) subjects who received the HTNV DNA (Cohort 1) and 6/6 (100%) subjects who received the PUUV DNA (Cohort 2) vaccines alone. The combination vaccine resulted in 4/9 (44%) seroconversion against both viruses. After the first two vaccinations, the seroconversion rates for the HTNV and PUUV vaccines were >80%., Competing Interests: Competing interests J.W.H. is an inventor of hantavirus DNA vaccine patents (United States Patent Numbers 8183358, 8852598, and 7217812) that are assigned to the U.S. Army and declare no competing interests. Other authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Elimination of latent HIV-1 is a major goal of AIDS research but the host factors determining the size of these reservoirs are poorly understood. Here, we investigated whether differences in host gene expression modulate the size of the HIV-1 reservoir during suppressive ART. Peripheral blood mononuclear cells (PBMC) from fourteen individuals initiating ART during acute infection who demonstrated effective viral suppression but varying magnitude of total HIV-1 DNA were characterized by single-cell RNA sequencing (scRNA-seq). Differentially expressed genes and enriched pathways demonstrated increased monocyte activity in participants with undetectable HIV-1 reservoirs. IL1B expression in CD14+ monocytes showed the greatest fold difference. The inverse association of IL1B with reservoir size was validated in an independent cohort comprised of 38 participants with different genetic backgrounds and HIV-1 subtype infections, and further confirmed with intact proviral DNA assay (IPDA ® ) measurements of intact HIV-1 proviruses in a subset of the samples. Modeling interactions with cell population frequencies showed that monocyte IL1B expression associated inversely with reservoir size in the context of higher frequencies of central memory CD4+ T cells, implicating an indirect effect of IL1B via the cell type well established to be a reservoir for persistent HIV-1. Signatures consisting of co-expressed genes including IL1B were highly enriched in the "TNFα signaling via NF-κB" geneset. Functional analyses in cell culture revealed that IL1B activates NF-κB, thereby promoting productive HIV-1 infection while simultaneously suppressing viral spread, suggesting a natural latency reversing activity to deplete the reservoir in ART treated individuals. Altogether, unbiased high throughput scRNA-seq analyses revealed that monocyte IL1B variation could decrease HIV-1 proviral reservoirs in individuals initiating ART during acute infection.

Background: Dengue virus (DENV) nonstructural protein 1 (NS1) has multiple functions within infected cells, on the cell surface, and in secreted form, and is highly immunogenic. Immunity from previous DENV infections is known to exert both positive and negative effects on subsequent DENV infections, but the contribution of NS1-specific antibodies to these effects is incompletely understood., Methods: We investigated the functions of NS1-specific antibodies and their significance in DENV infection. We analyzed plasma samples collected in a prospective cohort study prior to symptomatic or subclinical secondary DENV infection. We measured binding to purified recombinant NS1 protein and to NS1-expressing CEM cells, antibody-mediated natural killer (NK) cell activation by plate-bound NS1 protein, and antibody-dependent cellular cytotoxicity (ADCC) of NS1-expressing target cells., Results: We found that antibody responses to NS1 were highly serotype cross-reactive and that subjects who experienced subclinical DENV infection had significantly higher antibody responses to NS1 in preinfection plasma than subjects who experienced symptomatic infection. We observed strong positive correlations between antibody binding and NK activation., Conclusions: These findings demonstrate the involvement of NS1-specific antibodies in ADCC and provide evidence for a protective effect of NS1-specific antibodies in secondary DENV infection., Competing Interests: Potential conflicts of interest. A. F. received support for conference registration and travel from Janssen Pharmaceuticals. K. A. received payments for service on a Data and Safety Monitoring Board from AstraZeneca and an advisory board from Emergent Biosolutions. J. C. is coinventor on a patent for “IgA Monoclonal Antibodies for Treating Flavivirus Infection”. A. L. R. received payments from Takeda (consulting and Advisory Board) and Moderna (consulting); and support for travel from Takeda. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: In Thailand, HIV transmission is well characterized in large urban centers such as Bangkok and Chiang Mai but less so outside of these areas. The main purpose of this study was to assess HIV incidence and associated risk factors in Nakhon Ratchasima and Ratchaburi., Methods: Participants assigned male sex at birth were enrolled in this prospective observational cohort study between November 2017 and July 2018. HIV and syphilis testing and sociobehavioral questionnaires were administered over 18 months. HIV incidence rates and 95% confidence intervals (CIs) were estimated using a Poisson distribution. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios (aHRs) and 95% CIs for associations between potential risk factors and HIV seroconversion., Results: A total of 1003 participants were enrolled. Overall HIV incidence was 1.56 per 100 person-years (95% CI:1.02-2.44) and similar at both sites. In the fully adjusted model, sex with a sex worker in the past six months was associated with reduced risk of seroconversion (aHR:0.10, 95% CI:0.01-0.77). In the reduced adjusted model, receptive anal sex (aHR:3.40, 95% CI:1.32-8.74) and STI diagnosis in the past six months (aHR:3.58, 95% CI:1.19-10.76) were associated with seroconversion, while sex with a sex worker in the past six months was associated with reduced risk of seroconversion (aHR:0.11, 95% CI:0.02-0.67). Additionally, 56% reported interest in taking PrEP and 82% reported willingness to participate in a hypothetical future vaccine trial., Conclusions: Recent receptive anal sex practices were associated with HIV acquisition in these populations, highlighting the continued need for interventions encouraging safer anal sex practices to reduce HIV incidence., Competing Interests: NO authors have competing interests., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Malaria has been a deadly enemy of mankind throughout history, affecting over 200 million people annually, along with approximately half a million deaths. Resistance to current therapies is of great concern, and there is a dire need for novel and well-tolerated antimalarials that operate by clinically unexploited mechanisms. We have previously reported that both tambjamines and prodiginines are highly potent novel antiplasmodial agents, but they required rigor optimizations to enhance the oral efficacy, safety, and physicochemical properties. Here, we launched a comprehensive structure-activity relationship study for B-ring-functionalized tambjamines and prodiginines with 54 novel analogues systematically designed and synthesized. A number of compounds exhibited remarkable antiplasmodial activities against asexual erythrocytic Plasmodium parasites, with improved safety and metabolic profiles. Notably, several prodiginines cured erythrocytic Plasmodium yoelii infections after oral 25 mg/kg × 4 days in a murine model and provided partial protection against liver stage Plasmodium berghei sporozoite-induced infection in mice.

The genomes of three Pseudomonas aeruginosa Phikzvirus bacteriophages isolated in Kenya are described. The genomes of phages vB&#95;PaePAO1-KEN19, vB&#95;Pae3705-KEN49, and vB&#95;Pae10145-KEN51, respectively, had lengths of 278,921, 280,231, and 280,173 bp, with 36.93%, 36.84%, and 36.86% GC content, containing 419, 417, and 417 coding sequences (including seven tRNAs in each genome)., Competing Interests: The authors declare no conflict of interest.

Emerging evidence suggests a significant role of gut microbiome in bone health. Aging is well recognized as a crucial factor influencing the gut microbiome. In this study, we investigated whether age-dependent microbial change contributes to age-related bone loss in CB6F1 mice. The bone phenotype of 24-month-old germ-free (GF) mice was indistinguishable compared to their littermates colonized by fecal transplant at 1-month-old. Moreover, bone loss from 3 to 24-month-old was comparable between GF and specific pathogen-free (SPF) mice. Thus, GF mice were not protected from age-related bone loss. 16S rRNA gene sequencing of fecal samples from 3-month and 24-month-old SPF males indicated an age-dependent microbial shift with an alteration in energy and nutrient metabolism potential. An integrative analysis of 16S predicted metagenome function and LC-MS fecal metabolome revealed an enrichment of protein and amino acid biosynthesis pathways in aged mice. Microbial S-adenosyl methionine metabolism was increased in the aged mice, which has previously been associated with the host aging process. Collectively, aging caused microbial taxonomic and functional alteration in mice. To demonstrate the functional importance of young and old microbiome to bone, we colonized GF mice with fecal microbiome from 3-month or 24-month-old SPF donor mice for 1 and 8 months. The effect of microbial colonization on bone phenotypes was independent of the microbiome donors' age. In conclusion, our study indicates age-related bone loss occurs independent of gut microbiome., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Deep vein thrombosis and pulmonary embolism prophylaxis is an important part of trauma care. Despite an increased risk of thrombotic complications, the use of venous thrombosis chemoprophylaxis in penetrating traumatic brain injury (pTBI) patients is met with reluctance from neurosurgeons because of concern for the exacerbation of intracerebral hemorrhage. The objective of this study was to provide initial pre-clinical evidence of the effects of Lovenox (LVX) administration following pTBI with significant intracerebral hemorrhage. Sprague-Dawley rats received a penetrating ballistic-like brain injury. Animals were randomly divided into two groups following injury: LVX (25 mg/kg) or vehicle (VEH, saline). LVX or vehicle was administered subcutaneously beginning 24 h after the injury and continued daily for 7 days post-injury. A neurological assessment was performed daily and magnetic resonance imaging (MRI) was performed at baseline, 1, 2, 3, and 7 days post-injury. Following the final MRI, brains were isolated and prepared for histological analysis. Thromboelastography demonstrated dramatic anticoagulation effects which were confirmed by significant increases in partial thromboplastin time ( p < 0.001). Daily neurological assessment revealed no worsening of functional deficits following LVX treatment. MRI analysis demonstrated no differences in cerebral edema or intracranial hemorrhage volumes between treatment groups at any tested post-injury time points. However, LVX elicited a significant reduction in fibrin deposition in the ipsilateral striatum and lesion site at 7 days post-injury ( p < 0.05). Serum levels of beta-amyloid were decreased at 7 days following LVX treatment ( p < 0.05) which may indicate neuroprotective effects but was not correlated to brain levels. The results presented indicate that administration of LVX at a dose capable of inducing anticoagulation is safe in a rodent model of pTBI without exacerbation of intracerebral hemorrhage within the first 7 days of injury.

The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among DoD organizations and to facilitate resource, material and information sharing among consortium members, which includes collaborators in academia and industry. The 2023 annual symposium was a hybrid meeting held in Washington DC on 26-27 September 2023 concurrent with the virtual attendance, with oral and poster presentations and discussions centered on microbiome-related topics within five broad thematic areas: 1) Environmental Microbiome Characterization; 2) Microbiome Analysis; 3) Human Microbiome Characterization; 4) Microbiome Engineering; and 5) In Vitro and In Vivo Microbiome Models. Collectively, the symposium provided an update on the scope of current DoD and DoD-affiliated microbiome research efforts and fostered collaborative opportunities. This report summarizes the presentations and outcomes of the 7th annual TSMC symposium., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Genomic surveillance detected clonal Escherichia coli sequence type-361 isolates carrying bla NDM-5 , bla KPC-3 , bla CTX-M-15 , and rmtB1 from a patient in Ukraine and four wounded foreign soldiers evacuated to Germany. Isolates were non-susceptible to carbapenems, aminoglycosides, and cefiderocol and aztreonam/avibactam due to a PBP3 YRIN insertion and the bla CMY-145 AmpC β-lactamase. Coordinated surveillance efforts across civilian, military, and veteran healthcare systems are essential to prevent further spread as international volunteers return home after medical evacuation from Ukraine., Competing Interests: The authors declare no conflict of interest.

Introduction: The National Guard (NG) served as a critical component of the U.S. response to the coronavirus disease 2019 pandemic. Understanding the impact of types of pandemic-related disaster work on mental health responses can aid in sustaining NG service members' health and preparation for subsequent activations and future pandemics., Materials and Methods: We surveyed 1,363 NG unit (NGU) service members (88% Army; 80% enlisted; 32% 30 to 39 years old; 84% male) following activation in response to the pandemic. Surveys were administered between August and December 2020, which was approximately 2 to 3 months post-activation. Surveys assessed overall activation stress, participation in different types of disaster work, probable post-traumatic stress disorder (PTSD), anxiety and depression, and anger. A disaster work stress scale assessed different types of disaster work during activation and associated stress levels. For each individual, we calculated an overall work task stress (WTS) scaled score, with a maximum score of 100. Logistic regression analyses were conducted to examine the relationship of high-stress disaster work tasks to post-activation PTSD, anxiety and depression, and anger, adjusting for socio-demographic and service-related variables. The study was approved by the Institutional Review Board of the Uniformed Services University (USU) in Bethesda, MD., Results: Among NGU service members, 12.7% (n = 172) described their activation as very/extremely stressful. The work tasks with the highest scaled scores were as follows: (1) Patient transportation (WTS scaled score = 100); (2) working with the dead (WTS = 82.2); and (3) working with families of coronavirus disease 2019 patients (WTS = 72.7). For each individual's work tasks, we identified the work task associated with the highest WTS score. The top one-third of WTS scores were classified as the high-stress group. Approximately 9% of participants (n = 111) had probable PTSD, 6.7% (n = 85) had clinically significant anxiety and depression, and 12.3% (n = 156) had high anger. Multivariable logistic regression analyses, adjusting for covariates, found that NGU service members exposed to the highest level of disaster WTS were more likely to report PTSD (odds ratio [OR] = 1.48 [95% confidence interval [CI] = 1.13-1.94], χ2 = 7.98), anxiety and depression (OR = 1.91 [95% CI = 1.17-3.13]; χ2 = 6.67), and anger (OR = 1.63 [95% CI = 1.13-2.37]; χ2 = 6.66) post-activation., Conclusions: Identifying work tasks associated with high levels of stress can help detect individuals at risk for adverse mental health responses post-exposure. Distinguishing features of high-stress work conditions can be generalized to other types of work conditions and disaster response and are important targets for planning and preventive efforts., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Subconcussive blast exposure has been shown to alter neurological functioning. However, the extent to which neurological dysfunction persists after blast exposure is unknown. This longitudinal study examined the potential short- and long-term effects of repeated subconcussive blast exposure on neuromotor performance from heavy weapons training in military personnel. A total of 214 participants were assessed; 137 were exposed to repeated subconcussive blasts and 77 were not exposed to blasts (controls). Participants completed a short stepping-in-place task while an Android smartphone app placed on their thigh recorded movement kinematics. We showed acute suppression of neuromotor variability 6 h after subconcussive blast exposure, followed by a rebound to levels not different from baseline at the 72 h, 2-week, and 3-month post-tests. It is postulated that this suppression of neuromotor variability results from a reduction in the functional degrees of freedom from the subconcussive neurological insult. It is important to note that this change in behavior is short-lived, with a return to pre-blast exposure movement kinematics within 72 h.

Toscana virus (TOSV) is an emerging arthropod-borne virus (arbovirus) of medical importance that is increasing its range across much of the Mediterranean Basin, Europe and the Middle East. Transmitted by Phlebotomus spp. sand flies, it is the most clinically relevant sand fly-borne phlebovirus. Initially isolated in the Tuscany region of Central Italy, it has now been detected in multiple countries that surround this geographical area. Infection of the vertebrate host can cause fever and neurological disease, following the dissemination of the virus to the brain. The prevalence is high in some regions, with a notable percentage of individuals showing seroconversion. TOSV can be a leading cause of acute meningitis and encephalitis (AME) during the summer months. In this comprehensive review, we will focus on several key topics. We discuss how TOSV has spread to establish outbreaks of infection in both humans and animals around the Mediterranean and the wider region. Clinical aspects of TOSV infection in humans are described, along with the best standards in diagnosis. Finally, we focus our discussion on the role of the sand fly vector, describing their biology, vector competency, implications for putative vertebrate reservoirs, the effect of the climate emergency on sand fly distribution and the putative role that sand fly-derived salivary factors may have on modulating host susceptibility to TOSV infection.