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The shear strength of materials under shock-loading conditions has long been recognized as being of the utmost importance, as this can be related to deformation mechanisms and ballistic performance. As such, a number of experimental techniques have been developed to study this component of shock loading, and in this paper, we concentrate on the embedded lateral stress gauge. We acknowledge that as the requirements of the target assembly necessitate that the target be sectioned, the gauge glued in place, and the target reassembled, it is possible that the gauge response is dominated by its local environment. As a consequence, we have, therefore, asked three questions—can the gauge be placed in a known stress condition and measure the correct lateral stress and shear strengths; do the results from the lateral stress gauge agree with other non-invasive techniques; and finally, if we do trust the results from lateral gauges, can they be placed in context with other known shock-induced materials responses. In all three cases, we believe that the answer is yes, and we present evidence for all three situations. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants known to pose significant risks to human and wildlife health. Freshwater turtles (Emydura macquarii macquarii), as long-lived species inhabiting aquatic ecosystems, are particularly vulnerable to PFAS bioaccumulation. This study investigated the multifaceted impact of PFAS contamination on these turtles, focusing on metabolic disruptions, reproductive success, hatchling health, and population impacts. Comprehensive analyses, including proteomics, lipidomics, metabolomics, and histopathology, were conducted on turtles from PFAS-impacted, control, and reference sites. The findings reveal significant metabolic disruptions in PFAS-exposed turtles, with alterations in amino acid and lipid metabolism, energy production, and oxidative stress responses. Proteomic analysis identified several health biomarkers indicative of early disease progression. Despite high levels of PFAS in tissues and organs, no gross or histopathological phenotypical abnormalities were directly linked to PFAS exposure. Gravid females from contaminated sites exhibited altered egg composition, particularly in magnesium to calcium ratios, potentially affecting eggshell strength. Biochemical profiles of egg albumin and yolk indicated significant differences in metabolites and lipids between contaminated and reference sites, suggesting potential impacts on embryo development. Hatchling deformities were notably higher and with increased frequency in terms of the types of deformities at the PFAS-impacted sites, with common defects including abnormal intergular scale shapes and marginal scale counts. Furthermore, the demographic profile of the turtle population showed a lack of juvenile turtles at contaminated sites, indicating reduced recruitment and potential long-term population declines. This indicates a field-based demonstration of an Adverse Outcome Pathway, from elevated levels of PFAS in the turtles, to biochemical perturbations within the animals, and finally population effects. These findings underscore the urgent need for regulatory measures to address PFAS contamination and its detrimental effects on wildlife., Competing Interests: Declaration 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 Authors. Published by Elsevier B.V. All rights reserved.)

Ebola virus (EBOV) is one of three filovirus members of the Orthoebolavirus genus that can cause severe Ebola disease (EBOD) in humans. Transmission predominantly occurs from spillover events from wildlife but has also happened between humans with infected bodily fluids. Specifically, the sexual route through infectious male survivors could be the origin of flare up events leading to the deaths of multiple women. More studies are needed to comprehend this route of infection which has recently received more focus. The use of microbicides prior to intercourse is of interest if neither of the Ebola vaccines are an option. These experimental products have been used against sexually transmitted diseases, and recently polyphenylene carboxymethylene (PPCM) showed efficacy against EBOV in vitro. Shortly after, the first animal model of EBOV sexual transmission was established using type I interferon receptors (IFNAR -/- ) knockout female mice in which mortality endpoint could be achieved. Here, we investigated PPCM efficacy against a mouse-adapted (ma)EBOV isolate in IFNAR -/- mice and demonstrated that 4% PPCM gel caused a 20% reduction in mortality in two distinct groups compared to control groups when inoculated prior to virus challenge. Among animals that succumbed to disease despite PPCM treatment, we report an increase in median survival time as well as a less infectious virus, and fewer virus positive vaginal swabs compared to those from vehicle-treated animals, altogether indicating the beneficial effect of using PPCM prior to exposure. A post-study analysis of the different gel formulations tested indicated that buffering the gels would have prevented an increase in acidity seen only in vehicles, suggesting that PPCM antiviral efficacy against EBOV was suboptimal in our experimental set-up. These results are encouraging and warrant further studies using optimized stable formulations with the goal of providing additional safe protective countermeasures from sexual transmission of EBOV in humans.

Chikungunya virus (CHIKV) a mosquito-borne alphavirus is the causative agent of Chikungunya (CHIK), a disease with low mortality but high acute and chronic morbidity resulting in a high overall burden of disease. After the acute disease phase, chronic disease including persistent arthralgia is very common, and can cause fatigue and pain that is severe enough to limit normal activities. On average, around 40% of people infected with CHIKV will develop chronic arthritis, which may last for months or years. Recommendations for protection from CHIKV focus on infection control through preventing mosquito proliferation. There is currently no licensed antiviral drug or vaccine against CHIKV. Therefore, one of the most important public health impacts of vaccination would be to decrease burden of disease and economic losses in areas impacted by the virus, and prevent or reduce chronic morbidity associated with CHIK. This benefit would particularly be seen in Low and Middle Income Countries (LMIC) and socio-economically deprived areas, as they are more likely to have more infections and more severe outcomes. This 'Vaccine Value Profile' (VVP) for CHIK is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of vaccines in the development pipeline and vaccine-like products.This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships, and multi-lateral organizations. All contributors have extensive expertise on various elements of the CHIK VVP and collectively aimed to identify current research and knowledge gaps.The VVP was developed using only existing and publicly available information., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Following completion of the drafting of this document, David Beasley assumed responsibility for a Research Testing Agreement at the University of Texas Medical Branch funded by Valneva. SE related to evaluation of Chikungunya vaccine. All other authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

CD4 + and CD8 + tissue resident memory cells (TRM) express many shared anti-viral activities upon re-exposure to virus. CD4 + T cells were depleted from HSV-immune guinea pigs to identify CD4-dependent functions in the vaginal mucosa following HSV-2 challenge. The incidence of animals shedding HSV-2 fell rapidly after challenge in control animals but remained significantly higher through day four post infection in CD4-depleted animals. Genes encoding CD14, IFN-γ, CCL2, and CCL5 were up-regulated in the vaginal mucosa of both groups following challenge. However, significantly higher expression of CD107b, IL-15, and TLR9 but lower expression of CD20, IL-21, and CCL5 was detected in CD4-depleted- compared to control-treated animals. Further, antigen stimulation of CD4 + TRM increased the expression of IFN-γ, IL-2, IL-21, IL-17A, and CCL5. The impact of these gene expression patterns on the recruitment and maintenance of the cellular milieu of the vaginal mucosa upon virus challenge is discussed., Competing Interests: Declaration 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 © 2023 Elsevier Inc. All rights reserved.)

Boosting herpes simplex virus (HSV)-specific immunity in the genital tissues of HSV-positive individuals to increase control of HSV-2 recurrent disease and virus shedding is an important goal of therapeutic immunization and would impact HSV-2 transmission. Experimental therapeutic HSV-2 vaccines delivered by a parenteral route have resulted in decreased recurrent disease in experimental animals. We used a guinea pig model of HSV-2 infection to test if HSV-specific antibody and cell-mediated responses in the vaginal mucosa would be more effectively increased by intravaginal (Ivag) therapeutic immunization compared to parenteral immunization. Therapeutic immunization with HSV glycoproteins and CpG adjuvant increased glycoprotein-specific IgG titers in vaginal secretions and serum to comparable levels in Ivag- and intramuscular (IM)-immunized animals. However, the mean numbers of HSV glycoprotein-specific antibody secreting cells (ASCs) and IFN-γ SCs were greater in Ivag-immunized animals demonstrating superior boosting of immunity in the vaginal mucosa compared to parenteral immunization. Therapeutic Ivag immunization also resulted in a significant decrease in the cumulative mean lesion days compared to IM immunization. There was no difference in the incidence or magnitude of HSV-2 shedding in either therapeutic immunization group compared to control-treated animals. Collectively, these data demonstrated that Ivag therapeutic immunization was superior compared to parenteral immunization to boost HSV-2 antigen-specific ASC and IFN-γ SC responses in the vagina and control recurrent HSV-2 disease. These results suggest that novel antigen delivery methods providing controlled release of optimized antigen/adjuvant combinations in the vaginal mucosa would be an effective approach for therapeutic HSV vaccines. IMPORTANCE HSV-2 replicates in skin cells before it infects sensory nerve cells where it establishes a lifelong but mostly silent infection. HSV-2 occasionally reactivates, producing new virus which is released back at the skin surface and may be transmitted to new individuals. Some HSV-specific immune cells reside at the skin site of the HSV-2 infection that can quickly activate and clear new virus. Immunizing people already infected with HSV-2 to boost their skin-resident immune cells and rapidly control the new HSV-2 infection is logical, but we do not know the best way to administer the vaccine to achieve this goal. In this study, a therapeutic vaccine given intravaginally resulted in significantly better protection against HSV-2 disease than immunization with the same vaccine by a conventional route. Immunization by the intravaginal route resulted in greater stimulation of vaginal-resident, virus-specific cells that produced antibody and produced immune molecules to rapidly clear virus., Competing Interests: The authors declare no conflict of interest

Ebola virus (EBOV) causes Ebola virus disease (EVD), which is characterized by hemorrhagic fever with high mortality rates in humans. EBOV sexual transmission has been a concern since the 2014-2016 outbreak in Africa, as persistent infection in the testis and transmission to women was demonstrated. The only study related to establishing an intravaginal small animal infection model was recently documented in IFNAR -/- mice using wild-type and mouse-adapted EBOV (maEBOV), and resulted in 80% mortality, supporting epidemiological data. However, this route of transmission is still poorly understood in women, and the resulting EVD from it is understudied. Here, we contribute to this field of research by providing data from immunocompetent BALB/c mice. We demonstrate that progesterone priming increased the likelihood of maEBOV vaginal infection and of exhibiting the symptoms of disease and seroconversion. However, our data suggest subclinical infection, regardless of the infective dose. We conclude that maEBOV can infect BALB/c mice through vaginal inoculation, but that this route of infection causes significantly less disease compared to intraperitoneal injection at a similar dose, which is consistent with previous studies using other peripheral routes of inoculation in that animal model. Our data are inconsistent with the disease severity described in female patients, therefore suggesting that BALB/c mice are unsuitable for modeling typical EVD following vaginal challenge with maEBOV. Further studies are required to determine the mechanisms by which EVD is attenuated in BALB/c mice, using maEBOV via the vaginal route, as in our experimental set-up.

Dengue is a major health threat and the number of symptomatic infections caused by the four dengue serotypes is estimated to be 96 million 1 with annually around 10,000 deaths 2 . However, no antiviral drugs are available for the treatment or prophylaxis of dengue. We recently described the interaction between non-structural proteins NS3 and NS4B as a promising target for the development of pan-serotype dengue virus (DENV) inhibitors 3 . Here we present JNJ-1802-a highly potent DENV inhibitor that blocks the NS3-NS4B interaction within the viral replication complex. JNJ-1802 exerts picomolar to low nanomolar in vitro antiviral activity, a high barrier to resistance and potent in vivo efficacy in mice against infection with any of the four DENV serotypes. Finally, we demonstrate that the small-molecule inhibitor JNJ-1802 is highly effective against viral infection with DENV-1 or DENV-2 in non-human primates. JNJ-1802 has successfully completed a phase I first-in-human clinical study in healthy volunteers and was found to be safe and well tolerated 4 . These findings support the further clinical development of JNJ-1802, a first-in-class antiviral agent against dengue, which is now progressing in clinical studies for the prevention and treatment of dengue., (© 2023. The Author(s).)

The aim of this systematic review and meta-analysis was to determine whether differences in reported fall rates exist between different ethnic groups. Searches were carried out on four databases: Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Web of Science. Only English language studies with community-dwelling participants aged 60 + years were included. Studies also needed to compare fall prevalence for at least two or more ethnic groups. Two reviewers independently screened all articles and evaluated study quality. Twenty-three articles were included for systematic review, and meta-analyses were carried out on the 16 retrospective studies that reported falls in the previous 12 months. The Asian group demonstrated significantly lower fall prevalence than all other ethnic groups at 13.89% (10.87, 16.91). The Hispanic group had a fall prevalence of 18.54% (12.95, 24.13), closely followed by the Black group at 18.60% (13.27, 23.93). The White group had the highest prevalence at 23.77% (18.66, 28.88). Some studies provided adjusted estimates of effect statistics for the odds/risk of falls, which showed that differences still existed between some ethnic groups even after adjusting for other risk factors. Overall, differences in fall prevalence do appear to exist between different ethnic groups, although the reasons for these differences currently remain undetermined and require further investigation. These findings highlight the need to provide more ethnically tailored responses to public health challenges, which could potentially increase the adherence to prevention interventions, and allow for a more targeted use of resources., (© 2021. The Author(s).)

Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic contaminants that are pervasive in the environment. Toxicity resulting from elevated PFAS concentrations in wildlife has been studied, yet evidence of their accumulation, developmental toxicity and maternal offloading in egg-laying species is limited. Here we show the maternal offloading of PFAS in freshwater short-necked turtles (Emydura macquarii macquarii) exposed to elevated PFAS and the resulting biological impact on oviducal eggs. Total PFAS concentrations were determined in serum from adult females and harvested oviducal eggs collected from euthanised turtles exposed to low and high levels of PFAS and compared against turtle serum and eggs collected from a suitable reference site. Multi-omics assays were utilised to explore the biochemical impact of elevated PFAS on egg albumen, yolk and eggshell using a range of metabolomics, lipidomics, and proteomics techniques. Eggshells were also screened for metals by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Analysis of the serum collected from adult female turtles and their oviducal eggs demonstrated PFAS offloading and transference that is 1.6 and 5.3 times higher in the low and high PFAS impacted eggs, respectively, compared to maternal serum concentrations. Oviducal egg yolk comprised >90% of the bioaccumulated PFAS load. Multi-omic analysis of the dissected egg fractions illustrated PFAS impacted eggs are significantly elevated in purine metabolism metabolites, which are tied to potential biological dysfunctional processes. The yolks were significantly depleted in lipids and lipid quality tied to growth and development. The high PFAS impacted oviducal eggshells were lower in calcium, important developmental and immune response proteins, and higher in glycerophosphoethanolamines (PE) lipids and histidine metabolism metabolites that are tied to a weakened physical structure. Further investigation is needed to establish the rate of PFAS offloading and quantify the developmental impact on hatchling and hatchling success to fully demonstrate PFAS-developmental toxicity linkages., Competing Interests: Declaration 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 © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

The envelope (E) protein of flaviviruses is functionally associated with viral tissue tropism and pathogenicity. For yellow fever virus (YFV), viscerotropic disease primarily involving the liver is pathognomonic for wild-type (WT) infection. In contrast, the live-attenuated vaccine (LAV) strain 17D does not cause viscerotropic disease and reversion to virulence is associated with neurotropic disease. The relationship between structure-function of the E protein for WT strain Asibi and its LAV derivative 17D strain is poorly understood; however, changes to WT and vaccine epitopes have been associated with changes in virulence. Here, a panel of Asibi and 17D infectious clone mutants were generated with single-site mutations at the one membrane residue and each of the eight E protein amino acid substitutions that distinguish the two strains. The mutants were characterized with respect to WT-specific and vaccine-specific monoclonal antibodies (mAbs) binding to virus plus binding of virus to brain, liver, and lung membrane receptor preparations (MRPs) generated from AG129 mice. This approach shows that amino acids in the YFV E protein domains (ED) I and II contain the WT E protein epitope, which overlap with those that mediate YFV binding to mouse liver. Furthermore, amino acids in EDIII associated with the vaccine epitope overlap with those that facilitate YFV binding mouse brain MRPs. Taken together, these data suggest that the YFV E protein is a key determinant in the phenotype of WT and 17D vaccine strains of YFV., (© 2022. The Author(s).)

Oropouche virus (OROV) is an arthropod-borne orthobunyavirus found in South America and causes Oropouche fever, a febrile infection similar to dengue. It is the second most prevalent arthropod-borne viral disease in South America after dengue. Over 500,000 cases have been diagnosed since the virus was first discovered in 1955; however, this is likely a significant underestimate given the limited availability of diagnostics. No fatalities have been reported to date, however, up to 60% of cases have a recurrent phase of disease within one month of recovery from the primary disease course. The main arthropod vector is the biting midge Culicoides paraensis, which has a geographic range as far north as the United States and demonstrates the potential for OROV to geographically expand. The transmission cycle is incompletely understood and vertebrate hosts include both non-human primates and birds further supporting the potential ability of the virus to spread. A number of candidate antivirals have been evaluated against OROV in vitro but none showed antiviral activity. Surprisingly, there is only one report in the literature on candidate vaccines. We suggest that OROV is an undervalued pathogen much like chikungunya, Schmallenberg, and Zika viruses were before they emerged. Overall, OROV is an important emerging disease that has been under-investigated and has the potential to cause large epidemics in the future. Further research, in particular candidate vaccines, is needed for this important pathogen., (© 2022. The Author(s).)