One-step in vivo gene knock-out in porcine embryos using recombinant adeno-associated viruses.

Introduction: Gene-edited pigs have become prominent models for studying human disease mechanisms, gene therapy, and xenotransplantation. CRISPR (clustered regularly interspaced short palindromic repeats)/CRISPR-associated 9 (CRISPR/Cas9) technology is a widely employed tool for generating gene-edited pigs. Nevertheless, delivering CRISPR/Cas9 to pre-implantation embryos has traditionally posed challenges due to its reliance on intricate micromanipulation equipment and specialized techniques, resulting in high costs and time-consuming procedures. This study aims to introduce a novel one-step approach for generating genetically modified pigs by transducing CRISPR/Cas9 components into pre-implantation porcine embryos through oviductal injection of recombinant adeno-associated viruses (rAAV). Methods: We first used rAAV-1, rAAV-6, rAAV-8, rAAV-9 expressing EGFP to screen for rAAV serotypes that efficiently target porcine embryos, and then, to achieve efficient expression of CRISPR/Cas9 in vivo for a short period, we packaged sgRNAs targeting the GHR genes to self-complementary adeno-associated virus (scAAV), and Cas9 proteins to single-stranded adeno-associated virus (ssAAV). The efficiency of porcine embryos -based editing was then validated in vitro. The feasibility of this one-step method to produce gene-edited pigs using rAAV-CRISPR/Cas9 oviductal injection into sows within 24 h of conception was then validated. Results: Our research firstly establishes the efficient delivery of CRISPR/Cas9 to pig zygotes, both in vivo and in vitro, using rAAV6. Successful gene editing in pigs was achieved through oviductal injection of rAAV-CRISPR/Cas9. Conclusion: This method circumvents the intricate procedures involved in in vitro embryo manipulation and embryo transfers, providing a straightforward and cost-effective approach for the production of gene-edited pigs.

Optimizing sweet potato production: insights into the interplay of plant sanitation, virus influence, and cooking techniques for enhanced crop quality and food security.

This study investigates the impact of sweet potato plant sanitation on the yield and external and internal quality root storage exploring the nutritional content affected by various cooking methods (raw, boiled, and oven-cooked). The presence of viruses, and concretely of the sweet potato leaf curl virus (SPLCV), in sweet potato propagation material is shown to significantly reduce yield and modify storage root quality. Notably, the research reveals a substantial improvement in crop yield and external quality, reinforcing the efficacy of plant sanitation methods, specifically apical meristem culture, in preserving the overall productivity of sweet potato crops. Furthermore, the investigation identifies a noteworthy decrease in starch content, suggesting a dynamic interaction between plant sanitation and starch metabolism in response to viral diseases. The study also delves into the alteration of mineral absorption patterns, shedding light on how plant sanitation influences the uptake of essential minerals in sweet potato storage roots. While the health status of the plants only slightly affected magnesium (Mg) and manganese (Mn) accumulation, indicating a potential resilience of mineral balance under virus-infected conditions. Moreover, the research identifies significant modifications in antioxidant levels, emphasizing the role of plant sanitation in enhancing the nutritional quality of sweet potatoes. Heat-treated storage roots, subjected to various cooking methods such as boiling and oven-cooking, exhibit notable differences in internal quality parameters. These differences include increased concentrations of total soluble solids (SS) and heightened levels of antioxidant compounds, particularly phenolic and flavonoid compounds. The observed increase in antioxidant capacity underscores the potential health-promoting benefits associated with plant sanitation practices. Overall, the study underscores the critical importance of plant sanitation in enhancing sweet potato production sustainability, contributing to food security, and supporting local agricultural economies. The results emphasize the need for further research to optimize plant sanitation methods and promote their widespread adoption globally, providing valuable insights into the complex relationships in food quality.

Arsenic trioxide impacts hepatitis B virus core nuclear localization and efficiently interferes with HBV infection.

The key to a curative treatment of hepatitis B virus (HBV) infection is the eradication of the intranuclear episomal covalently closed circular DNA (cccDNA), the stable persistence reservoir of HBV. Currently, established therapies can only limit HBV replication but fail to tackle the cccDNA. Thus, novel therapeutic approaches toward curative treatment are urgently needed. Recent publications indicated a strong association between the HBV core protein SUMOylation and the association with promyelocytic leukemia nuclear bodies (PML-NBs) on relaxed circular DNA to cccDNA conversion. We propose that interference with the cellular SUMOylation system and PML-NB integrity using arsenic trioxide provides a useful tool in the treatment of HBV infection. Our study showed a significant reduction in HBV-infected cells, core protein levels, HBV mRNA, and total DNA. Additionally, a reduction, albeit to a limited extent, of HBV cccDNA could be observed. Furthermore, this interference was also applied for the treatment of an established HBV infection, characterized by a stably present nuclear pool of cccDNA. Arsenic trioxide (ATO) treatment not only changed the amount of expressed HBV core protein but also induced a distinct relocalization to an extranuclear phenotype during infection. Moreover, ATO treatment resulted in the redistribution of transfected HBV core protein away from PML-NBs, a phenotype similar to that previously observed with SUMOylation-deficient HBV core. Taken together, these findings revealed the inhibition of HBV replication by ATO treatment during several steps of the viral replication cycle, including viral entry into the nucleus as well as cccDNA formation and maintenance. We propose ATO as a novel prospective treatment option for further pre-clinical and clinical studies against HBV infection. IMPORTANCE: The main challenge for the achievement of a functional cure for hepatitis B virus (HBV) is the covalently closed circular DNA (cccDNA), the highly stable persistence reservoir of HBV, which is maintained by further rounds of infection with newly generated progeny viruses or by intracellular recycling of mature nucleocapsids. Eradication of the cccDNA is considered to be the holy grail for HBV curative treatment; however, current therapeutic approaches fail to directly tackle this HBV persistence reservoir. The molecular effect of arsenic trioxide (ATO) on HBV infection, protein expression, and cccDNA formation and maintenance, however, has not been characterized and understood until now. In this study, we reveal ATO treatment as a novel and innovative therapeutic approach against HBV infections, repressing viral gene expression and replication as well as the stable cccDNA pool at low micromolar concentrations by affecting the cellular function of promyelocytic leukemia nuclear bodies.

Comparing RT-PCR of individual samples with high throughput sequencing of pooled plant samples for field-level surveillance of viruses in blackberry and wild Rubus.

Blackberry production is increasing in the southeastern U.S. with the availability of new cultivars. In addition to high production costs, growers are challenged by virus diseases. Blackberry yellow vein disease (BVYD) significantly limits blackberry production. BYVD is associated with the crinivirus blackberry yellow vein-associated virus (BYVaV) in mixed infections with other viruses. The specific disease etiology and ecological factors underlying BYVD are not well understood and rely on the effective diagnosis of several viruses involved in the complex. In 2021, we collected samples from blackberry plants showing BYVD symptoms, asymptomatic blackberry plants, and wild Rosaceae spp. from nine farms across South Carolina, for a total of 372 individual plant samples. RNA from individual samples was isolated and pooled into sample groups (i.e., symptomatic, asymptomatic, and wild) from each farm for a total of 24 pooled samples. We sequenced the pooled RNA using Illumina and analyzed sequence profiles using the Virtool bioinformatics application. We also tested each plant for six viruses by RT-PCR or RT-qPCR and compared plant (PCR)-level and field (high throughput sequencing (HTS))-level data. Virtool detected 17 known viruses in the pooled samples, including 11 blackberry viruses. PCR testing was mostly consistent with HTS, with some notable disagreements for specific viruses. Our study demonstrates that HTS could be used as an efficient tool to detect viruses in bulked samples in blackberry fields, though limitations to using HTS for field-level surveillance are also discussed here.

Low-dose decitabine enhances the efficacy of viral cancer vaccines for immunotherapy.

Cancer immunotherapy requires a specific antitumor CD8+ T cell-driven immune response; however, upon genetic and epigenetic alterations of the antigen processing and presenting components, cancer cells escape the CD8+ T cell recognition. As a result, poorly immunogenic tumors are refractory to conventional immunotherapy. In this context, the use of viral cancer vaccines in combination with hypomethylating agents represents a promising strategy to prevent cancer from escaping immune system recognition. In this study, we evaluated the sensitivity of melanoma (B16-expressing ovalbumin) and metastatic triple-negative breast cancer (4T1) cell lines to FDA-approved low-dose decitabine in combination with PeptiCRAd, an adenoviral anticancer vaccine. The two models showed different sensitivity to decitabine in vitro and in vivo when combined with PeptiCRAd. In particular, mice bearing syngeneic 4T1 cancer showed higher tumor growth control when receiving the combinatorial treatment compared to single controls in association with a higher expression of MHC class I on cancer cells and reduction in Tregs within the tumor microenvironment. Furthermore, remodeling of the CD8+ T cell infiltration and cytotoxic activity toward cancer cells confirmed the effect of decitabine in enhancing anticancer vaccines in immunotherapy regimens.

Detection of Beet curly top virus in Solanum jamesii, Artemisia tridentata, Helianthus annuus, and Cannabis sativa in Utah.

Historically, beet curly top virus (BCTV; Geminiviridae, Curtovirus) is known for destroying the sugar beet industry in Utah and has been a persistent problem in the state since then (Ball, 1917). Starting in June of 2022, we began identifying plants in San Juan County, Utah with chlorosis and leaf curling. Of note, Solanum jamesii, the Four Corners potato, Artemisia tridentata, big sagebrush, and Helianthus annuus, common sunflower, were found with general chlorosis, severe leaf curling and in the case of the sage brush, completely lacking in smell whereas nearby sage plants without the yellowing were intensely fragrant. In August 2023, Cannabis sativa plants for hemp production were found with severe leaf curling in Juab County, Utah. Samples were collected and stored at -80°C for future work. DNA was extracted using the IBI Genomic Plant DNA kit (IBI Scientific, Dubuque, IA) and subjected to rolling circle amplification using Phi29 polymerase (NEB, Ipswich, MA). The primer set BCTV2 (Strausbaugh et al. 2008) for BCTV detection was then used on a subset of the RCA-positive samples for either one (A. tridentata, H. annus, and S. jamesii) or two (C. sativa) plants displaying classic BCTV symptoms, to amplify a 518 bp region. This amplicon was then sequenced by the Sanger method to a 4x coverage. The resulting sequences (accession nos. OR698900 to OR698904) share 98.94 to 99.80% nucleotide identity to the Worland strain (accession no. KU892789.1) for all samples. To confirm the detection, a triple antibody sandwich ELISA kit from Nano Diagnostics (San Jose, CA) was used on these, and other plants of similar species and symptoms from across the state. Samples that tested positive include 3/3 symptomatic H. annuus plants, 1/1 symptomatic S. jamesii, 3/3 symptomatic A. tridentata. The A. tridentata samples were collected from Juab, San Juan, and Utah Counties. None of three asymptomatic A. tridentata plants tested were ELISA positive. Of the C. sativa plants tested by ELISA, 9/9 of the plants displaying classic BCTV symptoms in that host were positive and 6/6 of the plants without classic BCTV symptoms were ELISA positive. The findings of these novel hosts indicate the need for increased testing and analysis of economically relevant crops and native flora across the state. These findings represent a concern for conservation in the case of S. jamesii and a potential threat to the growing hemp industry in the state due to the severity of BCTV symptoms on these plants. Additionally, the finding of A. tridentata as a host may represent a significant finding for the epidemiology of BCTV in the Mountain West region as A. tridentata is distributed from Mexico to Canada along the Rocky Mountain range and is found in much of the Western US in arid regions. This is the first report, to our knowledge, of S. jamesii and A. tridentata as hosts for BCTV and the first peer reviewed reports for H. annuus and C. sativa as hosts for BCTV in Utah.

Use of FTA card for the detection of two RNA (CSFV and SV-A) and two DNA viruses (ASFVand SuHV-1) of importance in veterinary medicine.

The FTA card has emerged as a promising alternative for nucleic acid extraction. The FTA card is a filter paper impregnated with chemicals that preserve and stabilize the genetic material present in the sample, allowing for its storage and transport at room temperature. The aim of this study was to test the card for the detection of RNA and DNA nucleic acids. Two RNA viruses (Senecavirus A and classical swine fever virus) and two DNA viruses (African swine fever virus and suid alphaherpesvirus 1) were tested, and in all cases, there was a decrease in sensitivity. The methods exhibited good repeatability and demonstrated a rapid and practical use for sample transport and nucleic acid extraction.

Recent Progress in Human Milk Oligosaccharides and Its Antiviral Efficacy.

Gastrointestinal (GI)-associated viruses, including rotavirus (RV), norovirus (NV), and enterovirus, usually invade host cells, transmit, and mutate their genetic information, resulting in influenza-like symptoms, acute gastroenteritis, encephalitis, or even death. The unique structures of human milk oligosaccharides (HMOs) enable them to shape the gut microbial diversity and endogenous immune system of human infants. Growing evidence suggests that HMOs can enhance host resistance to GI-associated viruses but without a systematic summary to review the mechanism. The present review examines the lactose- and neutral-core HMOs and their antiviral effects in the host. The potential negative impacts of enterovirus 71 (EV-A71) and other GI viruses on children are extensive and include neurological sequelae, neurodevelopmental retardation, and cognitive decline. However, the differences in the binding affinity of HMOs for GI viruses are vast. Hence, elucidating the mechanisms and positive effects of HMOs against different viruses may facilitate the development of novel HMO derived oligosaccharides.

Inhibition of influenza A virus and SARS-CoV-2 infection or co-infection by griffithsin and griffithsin-based bivalent entry inhibitor.

Outbreaks of acute respiratory viral diseases, such as influenza and COVID-19 caused by influenza A virus (IAV) and SARS-CoV-2, pose a serious threat to global public health, economic security, and social stability. This calls for the development of broad-spectrum antivirals to prevent or treat infection or co-infection of IAV and SARS-CoV-2. Hemagglutinin (HA) on IAV and spike (S) protein on SARS-CoV-2, which contain various types of glycans, play crucial roles in mediating viral entry into host cells. Therefore, they are key targets for the development of carbohydrate-binding protein-based antivirals. This study demonstrated that griffithsin (GRFT) and the GRFT-based bivalent entry inhibitor GL25E (GRFT-L25-EK1) showed broad-spectrum antiviral effects against IAV infection in vitro by binding to HA in a carbohydrate-dependent manner and effectively protected mice from lethal IAV infection. Although both GRFT and GL25E could inhibit infection of SARS-CoV-2 Omicron variants, GL25E proved to be significantly more effective than GRFT and EK1 alone. Furthermore, GL25E effectively inhibited in vitro co-infection of IAV and SARS-CoV-2 and demonstrated good druggability, including favorable safety and stability profiles. These findings suggest that GL25E is a promising candidate for further development as a broad-spectrum antiviral drug for the prevention and treatment of infection or co-infection from IAV and SARS-CoV-2.IMPORTANCEInfluenza and COVID-19 are highly contagious respiratory illnesses caused by the influenza A virus (IAV) and SARS-CoV-2, respectively. IAV and SARS-CoV-2 co-infection exacerbates damage to lung tissue and leads to more severe clinical symptoms, thus calling for the development of broad-spectrum antivirals for combating IAV and SARS-CoV-2 infection or co-infection. Here we found that griffithsin (GRFT), a carbohydrate-binding protein, and GL25E, a recombinant protein consisting of GRFT, a 25 amino acid linker, and EK1, a broad-spectrum coronavirus inhibitor, could effectively inhibit IAV and SARS-CoV-2 infection and co-infection by targeting glycans on HA of IAV and spike (S) protein of SARS-CoV-2. GL25E is more effective than GRFT because GL25E can also interact with the HR1 domain in SARS-CoV-2 S protein. Furthermore, GL25E possesses favorable safety and stability profiles, suggesting that it is a promising candidate for development as a drug to prevent and treat IAV and SARS-CoV-2 infection or co-infection.

Cost-utility analysis of palivizumab for preventing respiratory syncytial virus in preterm neonates and infants in Colombia.

AIM: Palivizumab has proven effective in reducing hospitalizations, preventing severe illness, improving health outcomes, and reducing healthcare costs for infants at risk of respiratory syncytial virus (RSV) infection. We aim to assess the value of palivizumab in preventing RSV infection in high-risk infants in Colombia, where RSV poses a significant threat, causing severe respiratory illness and hospitalizations. METHODS: We conducted a decision tree analysis to compare five doses of palivizumab with no palivizumab. The study considered three population groups: preterm neonates (≤ 35 weeks gestational age), infants with bronchopulmonary dysplasia (BPD), and infants with hemodynamically significant congenital heart disease (CHD). We obtained clinical efficacy data from IMpact-RSV and Cardiac Synagis trials, while we derived neonatal hospitalization risks from the SENTINEL-1 study. We based hospitalization and recurrent wheezing management costs on Colombian analyses and validated them by experts. We estimated incremental cost-effectiveness ratios and performed 1,000 Monte Carlo simulations for probabilistic sensitivity analyses. RESULTS: Palivizumab is a dominant strategy for preventing RSV infection in preterm neonates and infants with BPD and CHD. Its high efficacy (78% in preventing RSV in preterm infants), the substantial risk of illness and hospitalization, and the high costs associated with hospitalization, particularly in neonatal intensive care settings, support this finding. The scatter plots and willingness-to-pay curves align with these results. CONCLUSION: Palivizumab is a cost-saving strategy in Colombia, effectively preventing RSV infection in preterm neonates and infants with BPD and CHD by reducing hospitalizations and lowering healthcare costs.

Synthesis of LAVR-289, a new [(Z)-3-(acetoxymethyl)-4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl]phosphonic acid prodrug with pronounced antiviral activity against DNA viruses.

New acyclic pyrimidine nucleoside phosphonate prodrugs with a 4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl]phosphonic acid skeleton (O-DAPy nucleobase) were prepared through a convergent synthesis by olefin cross-metathesis as the key step. Several acyclic nucleoside 4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl]phosphonic acid prodrug exhibited in vitro antiviral activity in submicromolar or nanomolar range against varicella zoster virus (VZV), human cytomegalovirus (HCMV), human herpes virus type 1 (HSV-1) and type 2 (HSV-2), and vaccinia virus (VV), with good selective index (SI). Among them, the analogue 9c (LAVR-289) proved markedly inhibitory against VZV wild-type (TK+) (EC50 0.0035 µM, SI 740) and for thymidine kinase VZV deficient strains (EC50 0.018 µM, SI 145), with a low morphological toxicity in cell culture at 100 µM and acceptable cytostatic activity resulting in excellent selectivity. Compound 9c exhibited antiviral activity against HCMV (EC50 0.021 µM) and VV (EC50 0.050 µM), as well as against HSV-1 (TK-) (EC50 0.0085 µM). Finally, LAVR-289 (9c) deserves further (pre)clinical investigations as a potent candidate broad-spectrum anti-herpesvirus drug.

A retrospective cohort study of Paxlovid efficacy depending on treatment time in hospitalized COVID-19 patients.

Paxlovid, a SARS-CoV-2 antiviral, not only prevents severe illness but also curtails viral shedding, lowering transmission risks from treated patients. By fitting a mathematical model of within-host Omicron viral dynamics to electronic health records data from 208 hospitalized patients in Hong Kong, we estimate that Paxlovid can inhibit over 90% of viral replication. However, its effectiveness critically depends on the timing of treatment. If treatment is initiated three days after symptoms first appear, we estimate a 17% chance of a post-treatment viral rebound and a 12% (95% CI: 0%-16%) reduction in overall infectiousness for non-rebound cases. Earlier treatment significantly elevates the risk of rebound without further reducing infectiousness, whereas starting beyond five days reduces its efficacy in curbing peak viral shedding. Among the 104 patients who received Paxlovid, 62% began treatment within an optimal three-to-five-day day window after symptoms appeared. Our findings indicate that broader global access to Paxlovid, coupled with appropriately timed treatment, can mitigate the severity and transmission of SARS-Cov-2.

Health Belief Model to Assess Mpox Knowledge, Attitudes, and Practices among Residents and Staff, Cook County Jail, Illinois, USA, July-August 2022.

In summer 2022, a case of mpox was confirmed in a resident at the Cook County Jail (CCJ) in Chicago, Illinois, USA. We conducted in-depth interviews with CCJ residents and staff to assess mpox knowledge, attitudes, and practices; hygiene and cleaning practices; and risk behaviors. We characterized findings by using health belief model constructs. CCJ residents and staff perceived increased mpox susceptibility but were unsure about infection severity; they were motivated to protect themselves but reported limited mpox knowledge as a barrier and desired clear communication to inform preventive actions. Residents expressed low self-efficacy to protect themselves because of contextual factors, including perceived limited access to cleaning, disinfecting, and hygiene items. Our findings suggest correctional facilities can support disease prevention by providing actionable and tailored messages; educating residents and staff about risk and vaccination options; and ensuring access to and training for hygiene, cleaning, and disinfecting supplies.

COVID-19 Vaccination in Patients with Inborn Errors of Immunity Reduces Hospitalization and Critical Care Needs Related to COVID-19: a USIDNET Report.

BACKGROUND: The CDC and ACIP recommend COVID-19 vaccination for patients with inborn errors of immunity (IEI). Not much is known about vaccine safety in IEI, and whether vaccination attenuates infection severity in IEI. OBJECTIVE: To estimate COVID-19 vaccination safety and examine effect on outcomes in patients with IEI. METHODS: We built a secure registry database in conjunction with the US Immunodeficiency Network to examine vaccination frequency and indicators of safety and effectiveness in IEI patients. The registry opened on January 1, 2022, and closed on August 19, 2022. RESULTS: Physicians entered data on 1245 patients from 24 countries. The most common diagnoses were antibody deficiencies (63.7%). At least one COVID-19 vaccine was administered to 806 patients (64.7%), and 216 patients received vaccination prior to the development of COVID-19. The most common vaccines administered were mRNA-based (84.0%). Seventeen patients were reported to seek outpatient clinic or emergency room care for a vaccine-related complication, and one patient was hospitalized for symptomatic anemia. Eight hundred twenty-three patients (66.1%) experienced COVID-19 infection. Of these, 156 patients required hospitalization (19.0%), 47 required ICU care (5.7%), and 28 died (3.4%). Rates of hospitalization (9.3% versus 24.4%, p < 0.001), ICU admission (2.8% versus 7.6%, p = 0.013), and death (2.3% versus 4.3%, p = 0.202) in patients who had COVID-19 were lower in patients who received vaccination prior to infection. In adjusted logistic regression analysis, not having at least one COVID-19 vaccine significantly increased the odds of hospitalization and ICU admission. CONCLUSION: Vaccination for COVID-19 in the IEI population appears safe and attenuates COVID-19 severity.

Seasonal variation of asymptomatic viral and bacterial nasopharyngeal carriage in rural Senegal.

BACKGROUND: The surveillance of respiratory pathogens in rural areas of West Africa has, to date, largely been focussed on symptoms. In this prospective study conducted prior to the COVID-19 pandemic, we aimed to assess the asymptomatic prevalence of respiratory pathogen carriage in a group of individuals living in a rural area of Senegalese. METHODS: Longitudinal follow up was performed through monthly nasopharyngeal swabbing during the dry season and weekly swabbing during the rainy season. We enrolled 15 individuals from the village of Ndiop. A total of 368 nasopharyngeal swabs were collected over a one-year period. We investigated the prevalence of 18 respiratory viruses and eight respiratory bacteria in different age groups using singleplex and multiplex PCR. RESULTS: In total, 19.56% of the samples (72/368) were positive for respiratory viruses and 13.60% of the samples (50/368) were positive for respiratory bacteria. Coronaviruses (19/72, 26.39%), adenoviruses (17/72, 23.61%), rhinoviruses (14/72, 19.44%), Streptococcus pneumoniae (17/50, 34%), and Moraxella catarrhalis (15/50, 30%) were the most frequently detected viruses. Interestingly, the carriage of respiratory pathogens was shown to be more frequent during the rainy season, as pluviometry was shown to be positively associated with the occurrence of respiratory viruses such as influenza (P = .0078, r2 =.523) and RSV (P = .0055, r2 =.554). CONCLUSIONS: Our results show a non-negligible circulation of respiratory pathogens in a rural area in Senegal (West Africa) with an underestimated proportion of asymptomatic individuals. This study highlights the fact that the circulation of viruses and bacteria in the community has been overlooked.

An explicit review and proposal of an integrated framework system to mitigate the baffling complexities induced by road dust-associated contaminants.

Road dust-associated contaminants (RD-AC) are gradually becoming a much thornier problem, as their monotonous correlations render them carcinogenic, mutagenic, and teratogenic. While many studies have examined the harmful effects of road dust on both humans and the environment, few studies have considered the co-exposure risk and gradient outcomes given the spatial extent of RD-AC. In this spirit, this paper presents in-depth elucidation into the baffling complexities induced by both major and emerging contaminants of road dust through a panorama-to-profile up-to-date review of diverse studies unified by the goal of advancing innovative methods to mitigate these contaminants. The paper thoroughly explores the correlations between RD-AC and provides insights to understand their potential in dispersing saprotrophic microorganisms. It also explores emerging challenges and proposes a novel integrated framework system aimed at thermally inactivating viruses and other pathogenic micro-organisms commingled with RD-AC. The main findings are: (i) the co-exposure risk of both major and emerging contaminants add another layer of complexity, highlighting the need for more holistic framework strategies, given the geospatial morphology of these contaminants; (ii) road dust contaminants show great potential for extended prevalence and severity of viral particles pollution; (iii) increasing trend of environmentally persistent free radicals (EPFRs) in road dust, with studies conducted solely in China thus far; and (iv) substantial hurdle exists in acquiring data concerning acute procedural distress and long-term co-exposure risk to RD-ACs. Given the baffling complexities of RD-ACs, co-exposure risk and the need for innovative mitigation strategies, the study underscore the significance of establishing robust systems for deep road dust contaminants control and future research efforts while recognizing the interconnectivity within the contaminants associated with road dust.

Lessons Learned from COVID-19 Response in Correctional and Detention Facilities.

The COVID-19 pandemic disproportionately affected persons held in and working in correctional and detention facilities, causing facilities' traditional priorities to shift when healthcare and public health needs temporarily drove many aspects of operations. During July-August 2022, we interviewed members of health departments and criminal justice organizations to document lessons learned from the COVID-19 response in correctional settings. Participants valued enhanced partnerships, flexibility, and innovation, as well as real-time data and corrections-specific public health guidance. Challenges included cross-sector collaborations, population density, scarcity of equipment and supplies, and mental health. Most participants reported improved relationships between criminal justice and public health organizations during the pandemic. Lessons from COVID-19 can be applied to everyday public health preparedness and emergency response in correctional facilities by ensuring representation of correctional health in public health strategy and practice and providing timely, data-driven, and partner-informed guidance tailored to correctional environments when public health needs arise.

Lessons Learned from Cross-Systems Approach to COVID-19 Pandemic Response in Juvenile Justice System, Colorado, USA.

The global COVID-19 pandemic illustrates the importance of a close partnership between public health and juvenile justice systems when responding to communicable diseases. Many setting-specific obstacles must be navigated to respond effectively to limit disease transmission and negative health outcomes while maintaining necessary services for youth in confinement facilities. The response requires multidisciplinary expertise and collaboration to address unique considerations. Public health mitigation strategies must balance the risk for disease against the negative effects of restrictions. Key aspects of the COVID-19 response in the juvenile justice system of Colorado, USA, involved establishing robust communication and data reporting infrastructures, building a multidisciplinary response team, adapting existing infection prevention guidelines, and focusing on a whole-person health approach to infection prevention. We examine lessons learned and offer recommendations on pandemic emergency response planning and managing a statewide public health emergency in youth confinement settings that ensure ongoing readiness.

Correlation of SARS-CoV-2 in Wastewater and Individual Testing Results in a Jail, Atlanta, Georgia, USA.

Institution-level wastewater-based surveillance was implemented during the COVID-19 pandemic, including in carceral facilities. We examined the relationship between COVID-19 diagnostic test results of residents in a jail in Atlanta, Georgia, USA (average population ≈2,700), and quantitative reverse transcription PCR signal for SARS-CoV-2 in weekly wastewater samples collected during October 2021‒May 2022. The jail offered residents rapid antigen testing at entry and periodic mass screenings by reverse transcription PCR of self-collected nasal swab specimens. We aggregated individual test data, calculated the Spearman correlation coefficient, and performed logistic regression to examine the relationship between strength of SARS-CoV-2 PCR signal (cycle threshold value) in wastewater and percentage of jail population that tested positive for COVID-19. Of 13,745 nasal specimens collected, 3.9% were COVID-positive (range 0%-29.5% per week). We observed a strong inverse correlation between diagnostic test positivity and cycle threshold value (r = -0.67; p<0.01). Wastewater-based surveillance represents an effective strategy for jailwide surveillance of COVID-19.