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When a virus crosses from one host species to another, the consequences can be devastating. However, animal models to empirically evaluate cross-species transmission can fail to recapitulate natural transmission routes, physiologically relevant doses of pathogens, and population structures of naturally circulating viruses. Here, we present a new model of cross-species transmission where deer mice ( Peromyscus maniculatus ) are exposed to the natural virome of pet store mice ( Mus musculus ). Using RNA sequencing, we tracked viral transmission via fecal-oral routes and found the evidence of transmission of murine astroviruses, coronaviruses, and picornaviruses. Deep sequencing of murine kobuvirus revealed tight bottlenecks during transmission and purifying selection that leaves limited diversity present after transmission from Mus to Peromyscus . This work provides a structure for studying viral bottlenecks across species while keeping natural variation of viral populations intact and a high resolution look at within-host dynamics that occur during the initial stages of cross-species viral transmission.IMPORTANCEViral spillover events can have devastating public health consequences. Tracking cross-species transmission in real-time and evaluating viral evolution during the initial spillover event are useful for understanding how viruses adapt to new hosts. Using our new animal model and next generation sequencing, we develop a framework for understanding intrahost viral evolution and bottleneck events, which are very difficult to study in natural transmission settings., Competing Interests: The authors declare no conflict of interest.

Objectives: This study aimed to analyse the influence of the continuum of care during pregnancy and neonatal periods on the risk of intergenerational cycle of stunting., Design: This study was a cross-sectional study, with data analysed from the 2018 Basic Health Research in Indonesia., Settings: Basic Health Research 2018 was conducted throughout 513 cities/regencies in 34 provinces in Indonesia. The households were selected through two-stage sampling methods. First, census blocks (CB) were selected using probability proportional to size methods in each urban/rural stratum from each city/regency. Ten households were then selected from each CB using systematic sampling methods. All family members of the selected households were measured and interviewed., Participants: This study analyses 31 603 children aged 0-24 months., Outcomes Measures: The dependent variable was the risk of the intergenerational cycle of stunting. Mothers who had a height less than 150.1 cm (short stature mothers) and had children (≤ 24 months of age) with length-for-age Z-score less than -2 Standard Deviation (SD) of the WHO Child Growth Standard (stunted children) were defined as at risk of the intergenerational cycle of stunting., Results: Mothers with incomplete maternal and neonatal care visits were 30% more likely to be at risk on the intergenerational cycle of stunting (OR (95% CI): 1.3 (1.00 to 1.63)) after adjusting for economic status., Conclusion: The continuum of maternal and neonatal healthcare visits could potentially break the intergenerational cycle of stunting, especially in populations where stunted mothers are prevalent., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Specific pathogen-free (SPF) laboratory mice dominate preclinical studies for immunology and vaccinology. Unfortunately, SPF mice often fail to accurately model human responses to vaccination and other immunological perturbations. Several groups have taken different approaches to introduce additional microbial experience to SPF mice to better model human immune experience. How these different models compare is unknown. Here, we directly compare three models: housing SPF mice in a microbe-rich barn-like environment (feralizing), adding wild-caught mice to the barn-like environment (fer-cohoused), or cohousing SPF mice with pet store mice in a barrier facility (pet-cohoused); the two latter representing different murine sources of microbial transmission. Pet-cohousing mice resulted in the greatest microbial exposure. Feralizing alone did not result in the transmission of any pathogens tested, while fer-cohousing resulted in the transmission of several picornaviruses. Murine astrovirus 2, the most common pathogen from pet store mice, was absent from the other two model systems. Previously, we had shown that pet-cohousing reduced the antibody response to vaccination compared with SPF mice. This was not recapitulated in either the feralized or fer-cohoused mice. These data indicate that not all dirty mouse models are equivalent in either microbial experience or immune responses to vaccination. These disparities suggest that more cross model comparisons are needed but also represent opportunities to uncover microbe combination-specific phenotypes and develop more refined experimental models. Given the breadth of microbes encountered by humans across the globe, multiple model systems may be needed to accurately recapitulate heterogenous human immune responses.IMPORTANCEAnimal models are an essential tool for evaluating clinical interventions. Unfortunately, they can often fail to accurately predict outcomes when translated into humans. This failure is due in part to a lack of natural infections experienced by most laboratory animals. To improve the mouse model, we and others have exposed laboratory mice to microbes they would experience in the wild. Although these models have been growing in popularity, these different models have not been specifically compared. Here, we directly compare how three different models of microbial experience impact the immune response to influenza vaccination. We find that these models are not the same and that the degree of microbial exposure affects the magnitude of the response to vaccination. These results provide an opportunity for the field to continue comparing and contrasting these systems to determine which models best recapitulate different aspects of the human condition., Competing Interests: The authors declare no conflict of interest.

Background: Epidemiological studies show that the height-for-age Z-scores (HAZ) falter dramatically shortly after birth until the end of the first two years. Understanding these changes in linear growth in the first two years can help us understand the critical period of child linear growth and propose interventions., Objectives: This study objectives were to describe the pattern of linear growth faltering and analyze the changes in length-for-age Z-scores (LAZs) throughout the first two years based on birthweight and length status., Methods: This study analyzed 408 children, participants in Longitudinal Study on Child Growth and Development in Bogor, Indonesia. The linear growth pattern was described based on birthweight and length status. Birthweight and length status was categorized into normal and Small for Gestational Age (SGA). Changes in LAZs (Δ LAZs) in 0-6 months, 6-12 months, and 12-23 months were calculated. General Linear Model Univariate analysis was conducted to analyze the difference of Δ LAZ between SGA and normal children., Results: Though full-term SGA children have significantly higher linear growth velocity during the first 6 months of the infancy period, full-term SGA children could not catch up with the attained growth/height of normal children throughout the first two years. Thus, full-term SGA children ended up with a higher prevalence of stunted. Both in SGA and normal children, the substantial loss of LAZ occurred between 0-6 months., Conclusion: The finding in this study showed that the first 1000 days of life is still the best period in stunting prevention; however, the stunting prevention program should start earlier, focusing on the first 500 days of life, and potentially the prenatal period., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kumala Putri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Emerging viruses threaten global health, but few experimental models can characterize the virus and host factors necessary for within- and cross-species transmission. Here, we leverage a model whereby pet store mice or rats-which harbor natural rodent pathogens-are cohoused with laboratory mice. This "dirty" mouse model offers a platform for studying acute transmission of viruses between and within hosts via natural mechanisms. We identified numerous viruses and other microbial species that transmit to cohoused mice, including prospective new members of the Coronaviridae, Astroviridae, Picornaviridae, and Narnaviridae families, and uncovered pathogen interactions that promote or prevent virus transmission. We also evaluated transmission dynamics of murine astroviruses during transmission and spread within a new host. Finally, by cohousing our laboratory mice with the bedding of pet store rats, we identified cross-species transmission of a rat astrovirus. Overall, this model system allows for the analysis of transmission of natural rodent viruses and is a platform to further characterize barriers to zoonosis., Competing Interests: Disclosures:   S.V. Kotenko reported a patent to IFN-λ polypeptides and compositions issued, a patent to IFN-λ1 polypeptides issued, a patent to method for increasing IFN activity in an individual issued, a patent to methods for increasing levels of IFN activity with an IFN-λ3 polypeptide issued, and a patent to type I and type III IFN fusion molecules and methods for use thereof pending. No other disclosures were reported., (© 2021 Fay et al.)

Human cytomegalovirus (HCMV) infects the placenta, and these placental infections can cause fetal injury and/or demise. The timing of maternal HCMV infection during pregnancy is a determinant of fetal outcomes, but how development affects the placenta's susceptibility to infection, the likelihood of placental injury post-infection, and the frequency of transplacental HCMV transmission remains unclear. In this study, guinea pig cytomegalovirus (GPCMV) was used to model primary maternal infection and compare the effects of infection at two different times on the placenta. When guinea pigs were infected with GPCMV at either 21- or 35-days gestation (dGA), maternal and placental viral loads, as determined by droplet digital PCR, were not significantly affected by the timing of maternal infection. However, when the transcriptomes of gestational age-matched GPCMV-infected and control placentas were compared, significant infection-associated changes in gene expression were only observed after maternal infection at 35 dGA. Notably, transcripts associated with immune activation (e.g. Cxcl10 , Ido1 , Tgtp1 , and Tlr8 ) were upregulated in the infected placenta. A GPCMV-specific in situ hybridization assay detected rare infected cells in the main placenta after maternal infection at either time, and maternal infection at 35 dGA also caused large areas of GPCMV-infected cells in the junctional zone. As GPCMV infection after mid-gestation is known to cause high rates of stillbirth and/or fetal growth restriction, our results suggest that the placenta becomes sensitized to infection-associated injury late in gestation, conferring an increased risk of adverse pregnancy outcomes after cytomegalovirus infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Berkebile, Putri, Abrahante, Seelig, Schleiss and Bierle.)

Tetrahydropentagamavunon-0 (THPGV-0) is a curcumin metabolite analog which known has a higher antioxidant activity than Vitamin E. This compound has been formulated in lotion as antiaging cosmetics, but the irritation effect is unknown yet. This study aims to analyze the effect of variation of THPGV-0 concentration in lotion and emulgel formula toward acute dermal irritation. The concentrations of THPGV-0 varied to 0.1%, 0.2%, and 0.4% in lotion/emulgel and tested for their physical properties such as organoleptic, homogeneity, pH, spreadability, and adhesion. Acute dermal irritation test is done in accordance with the In vivo Nonclinical Toxicity Test Guidelines by the Indonesian Food and Drug Administration (BPOM). This study showed that Primary Irritation Index (PII) value concentrations of 0.1%, 0.2%, and 0.4% THPGV-0 in lotion formula are 0.014, 0.014, and 0.028 (close to 0) and in emulgel formula are 0.08 at concentration of 0.1%, 0.33 at concentration of 0.2%, and 0.25 at concentration of 0.4%. PII of 0.1%, 0.2%, and 0.4% THPGV-0 in lotion and emulgel is included in negligible irritation response. Hence, the both of THPGV-0 formula in lotion and emulgel are considered safe to use on skin according to this study., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Advanced Pharmaceutical Technology & Research.)

Human cytomegalovirus (HCMV) infects the chorioamnion, but whether these infections cause fetal membrane dysfunction remains poorly understood. We sought to assess whether guinea pig cytomegalovirus (GPCMV) infects amnion-derived cells in vitro, compare the inflammatory response of amnion cells to GPCMV and HCMV, and determine if GPCMV infects the amnion in vivo. We found that GPCMV replicates in primary guinea pig amnion derived cells and HPV16 E6/E7-transduced amniotic epithelial cells (AEC[E6/E7]s). HCMV and GPCMV infection of amnion cells increased the transcription of the chemokines CCL5/Ccl5, CXCL8/Cxcl8, and CXCL10/Cxcl10. Myd88-knockdown decreased Ccl5 and Cxc8 transcription in GPCMV-infected AEC[E6/E7]s. GPCMV was detected in the guinea pig amnion after primary maternal infection, revealing that guinea pigs are an appropriate model to study fetal membrane physiology after cytomegalovirus infection. As inflammation is known to cause fetal membrane weakening, the amnion's response to cytomegalovirus infection may cause preterm birth and other adverse pregnancy outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Primary Zika virus (ZIKV) infections that occur during pregnancy can cause spontaneous abortion and profoundly disrupt fetal development. While the full range of developmental abnormalities associated with congenital Zika syndrome is not yet known, severe cases of the syndrome can present with microcephaly, extensive neurologic and ocular damage, and pronounced joint malformations. Animal models that accurately recapitulate congenital Zika syndrome are urgently needed for vaccine development and for the study of ZIKV pathogenesis. As guinea pigs have successfully been used to model transplacental infections by cytomegalovirus, syphilis, and Listeria monocytogenes, we sought to test whether ZIKV could productively infect guinea pigs and whether viral transmission with attendant fetal pathology would occur after a mid-gestation viral challenge. We found that guinea pig cells supported ZIKV replication in vitro. Experimental infection of non-pregnant animals did not result in overt disease but low-level, detectable viremia was observed. When pregnant guinea pigs were challenged with ZIKV at between 18 and 21 days gestational age, ZIKV was not detected in maternal or pup blood, plasma, or tissues and no significant differences in maternal weight gain or pup size were observed following challenge. Nonetheless, a robust antibody response against ZIKV was detected in both the pups and dams. These results suggest that, while guinea pigs can model aspects of the immune response to ZIKV infection during pregnancy, naturally circulating ZIKV strains are not pathogenic during the pregnancy of immunocompetent guinea pigs and do not interfere with normal pup development.