Natural hazard insurance outcomes at national, regional and local scales: A comparison between Sweden and Portugal.

This study addresses the role of natural hazard insurance in two European countries with different insurance markets and socioeconomic conditions: Sweden and Portugal. The analyses were conducted at the national, regional (Southern Sweden and Lisbon Metropolitan Area - LMA), and local (Malmö and Lisbon cities) scales. Most damage caused by weather and climate-related (WCR) hazards during the 1980-2019 period was not covered by insurance companies in Sweden (71%) and Portugal (91%). An insurance affordability analysis was performed using income for the national and regional scales. Unaffordability is higher in Southern Sweden than in LMA, implying that better socioeconomic conditions do not necessarily mean a higher average capacity to pay for insurance. At the local scale, urban flooding was analysed for Malmö (1996-2019) and Lisbon (2000-2011) using insurance databases, in which the most relevant 21st century rainfall events for each city are included (2014 and 2008, respectively). The influence of terrain features on flooding claims and payouts was determined using Geographic Information Systems (GIS) spatial analyses. The flat Malmö favours ponding and extensive flooding, while the distance to the drainage network and flow accumulation are key factors to promote flooding along valley bottoms in the hilly Lisbon. Flooding hotspots tend to result from a combination of higher depths/lower velocities (accumulation of floodwaters and ponding) and not from a pattern of lower depths/higher velocities (shallow overland flow). More detailed data on insurance, flooding, and socioeconomic conditions, at regional and mainly local scales, is needed to improve affordability and urban flooding risk assessments.

Pre-pregnancy maternal BMI classification is associated with preschool childhood diet quality and childhood obesity in the Avon Longitudinal Study of Parents and Children.

OBJECTIVE: To explore the effect of maternal BMI class pre-pregnancy (overweight/obese v. healthy weight/underweight) on childhood diet quality and on childhood overweight/obesity risk. DESIGN: Dietary data were collected using 3-d parental-completed food records for their children at ages 18 and 43 months. An index of diet quality was derived by classification of food items into core and non-core foods. Adjusted multiple linear regression analyses were used to explore the effect of maternal BMI class on diet quality in their children. SETTING: Avon, UK. PARTICIPANTS: A 10% subsample of the Avon Longitudinal Study of Parents and Children. Nine-hundred and eighty children provided complete dietary data at 18 months and 769 at 43 months. RESULTS: Children with overweight/obese mothers consumed greater amounts of energy from non-core foods than children with healthy weight/underweight mothers (0·20 MJ (48 kcal)/d more at 18 months (P < 0·001); 0·19 MJ (45 kcal)/d more at 43 months (P = 0·008)) in adjusted models. Diet quality deteriorated between 18 and 43 months (children reduced their dietary energy intake from core foods (P < 0·001) and increased intake from non-core foods (P < 0·001)). However, this change was not associated with maternal BMI class in adjusted models. Having an overweight/obese mother was associated with an increased odds of the child being overweight/obese at 43 months (OR 1·74 (1·17, 2·58)). CONCLUSIONS: Children aged 18 and 43 months with overweight/obese mothers are likely to have a poorer quality diet than those with healthy/underweight mothers. Parents should be supported in discouraging the consumption of non-core foods in children at these ages.

The Affordability of Flood Risk Property-Level Adaptation Measures.

The affordability of property-level adaptation measures against flooding is crucial due to the movement toward integrated flood risk management, which requires the individuals threatened by flooding to actively manage flooding. It is surprising to find that affordability is not often discussed, given the important roles that affordability and social justice play regarding flood risk management. This article provides a starting point for investigating the potential rate of unaffordability of flood risk property-level adaptation measures across Europe using two definitions of affordability, which are combined with two different affordability thresholds from within flood risk research. It uses concepts of investment and payment affordability, with affordability thresholds based on residual income and expenditure definitions of unaffordability. These concepts, in turn, are linked with social justice through fairness concerns, in that, all should have equal capability to act, of which affordability is one avenue. In doing so, it was found that, for a large proportion of Europe, property owners generally cannot afford to make one-time payment of the cost of protective measures. These can be made affordable with installment payment mechanisms or similar mechanisms that spread costs over time. Therefore, the movement toward greater obligations for flood-prone residents to actively adapt to flooding should be accompanied by socially accessible financing mechanisms.

Using Panel Data to Understand the Dynamics of Human Behavior in Response to Flooding.

Insights into the dynamics of human behavior in response to flooding are urgently needed for the development of effective integrated flood risk management strategies, and for integrating human behavior in flood risk modeling. However, our understanding of the dynamics of risk perceptions, attitudes, individual recovery processes, as well as adaptive (i.e., risk reducing) intention and behavior are currently limited because of the predominant use of cross-sectional surveys in the flood risk domain. Here, we present the results from one of the first panel surveys in the flood risk domain covering a relatively long period of time (i.e., four years after a damaging event), three survey waves, and a wide range of topics relevant to the role of citizens in integrated flood risk management. The panel data, consisting of 227 individuals affected by the 2013 flood in Germany, were analyzed using repeated-measures ANOVA and latent class growth analysis (LCGA) to utilize the unique temporal dimension of the data set. Results show that attitudes, such as the respondents' perceived responsibility within flood risk management, remain fairly stable over time. Changes are observed partly for risk perceptions and mainly for individual recovery and intentions to undertake risk-reducing measures. LCGA reveal heterogeneous recovery and adaptation trajectories that need to be taken into account in policies supporting individual recovery and stimulating societal preparedness. More panel studies in the flood risk domain are needed to gain better insights into the dynamics of individual recovery, risk-reducing behavior, and associated risk and protective factors.

Defining the role of a genetic counselor within pediatric hematology and oncology comprehensive care teams: Perspectives of the provider team and patients.

As genetic testing is increasingly integrated into medical care, the genetic counselor (GC) has emerged as a key member of multidisciplinary (MD) teams. Prior research has demonstrated the importance of role clarification when subspecialties are introduced to these teams given the potential differences in team member expectations regarding the division of responsibilities in clinic. To assess perceptions of a GC's role in four pediatric hematology/oncology clinics, Accreditation Council for Genetic Counseling (ACGC) competencies were used to develop two separate surveys for providers and patients and their caregivers. Providers (n = 25) perceived roles related to genetic expertise and coordination of care to be primarily the role of a GC significantly more often than psychosocial roles (p < .0001). Several potential GC roles were perceived as a shared role or the role of another provider, such as eliciting psychosocial history. Patients/caregivers (n = 70) perceived genetic-centric roles as significantly more important than roles related to coordination of care (p = .03) and psychosocial skills (p < .0001). Our findings from a pediatric specialty department suggest that GCs may maximize their potential in MD clinics by functioning as genetic subject matter experts with care coordination responsibilities related to genetic testing. Further communication between team members may be indicated to clarify the division of responsibilities.

Early identification and management of the unstable adult patient in the emergency department.

AIMS AND OBJECTIVES: The focus of this research was to standardise an emergency observation chart, the Adult Emergency Department Flow Chart, which incorporates elements designed to allow clinicians to more readily recognise the trends of patient deterioration. BACKGROUND: Patients present to the Emergency Department with some form of instability. Core skills and principles of Emergency Department care are to rapidly and continually assess the clinical condition of the patient, prioritise their care and treat accordingly. Often, however, deterioration of these patients is missed. The incidence of missed deterioration is set within a background of increasing presentations to Emergency Departments, greater complexity of the patient health status, longer length of stay within the Emergency Department and an ageing population. DESIGN: This quantitative research study comprised a retrospective medical record audit. Only those records containing notes relating to an Emergency Department admission were included. METHODS: An online data collection tool based on the Adult Emergency Department Flow Chart was developed. A total of 181 medical records were reviewed: 80 during the pre-implementation audit and 101 during the post-implementation audit. RESULTS: The Adult Emergency Department Flow Chart enabled clinicians to better identify deteriorating patients, with a higher number of abnormal vital signs being identified at the post-implementation audit. Identification of pain also dramatically increased at the post-implementation audit. Documentation of notification to Medical Officers also increased, as did documentation of the number of patients receiving medication to help treat the abnormal vital sign. CONCLUSION: The introduction of the Adult Emergency Department Flow Chart facilitated the essential role of nurses in the identification, documentation and monitoring of the unstable or deteriorating patient in the Emergency Department. Further research is required with larger samples to determine the impact of the Adult Emergency Department Flow Chart on the timely management of abnormal vital signs. RELEVANCE TO CLINICAL PRACTICE: The Adult Emergency Flow Chart provides a valuable tool for the early identification and subsequent management of an unstable / deteriorating adult in the emergency department, particularly for clinicians with limited experience.

Antibody inhibition of a viral type 1 interferon decoy receptor cures a viral disease by restoring interferon signaling in the liver.

Type 1 interferons (T1-IFNs) play a major role in antiviral defense, but when or how they protect during infections that spread through the lympho-hematogenous route is not known. Orthopoxviruses, including those that produce smallpox and mousepox, spread lympho-hematogenously. They also encode a decoy receptor for T1-IFN, the T1-IFN binding protein (T1-IFNbp), which is essential for virulence. We demonstrate that during mousepox, T1-IFNs protect the liver locally rather than systemically, and that the T1-IFNbp attaches to uninfected cells surrounding infected foci in the liver and the spleen to impair their ability to receive T1-IFN signaling, thus facilitating virus spread. Remarkably, this process can be reversed and mousepox cured late in infection by treating with antibodies that block the biological function of the T1-IFNbp. Thus, our findings provide insights on how T1-IFNs function and are evaded during a viral infection in vivo, and unveil a novel mechanism for antibody-mediated antiviral therapy.

Blood Culture Ordering After Sepsis Alerts and Subsequent Patient Outcomes: An Electronic Health Record-Based Study.

Sepsis is a global health priority associated with high mortality. Clinical decision support systems have been developed to support clinicians with sepsis management. Ordering blood cultures (BCs) for suspected sepsis patients are strongly recommended by clinical guidelines. However, limited evidence exists investigating BC ordering following sepsis alerts and subsequent patient outcomes. This study aimed to investigate this issue using electronic health record data from an acute care hospital in Australia. Of 4,092 patients, only 16.6% had a BC ordered following a sepsis alert. The median time from the first sepsis alert to a BC order was 15.3 hours. Patients had 5.89 times higher odds of being diagnosed with sepsis if a BC was ordered following a sepsis alert than those without BC ordered (p<0.0001). Further investigation is needed to understand reasons behind the delay or failure to order a BC despite receiving electronic sepsis alerts and how decision support can be optimized to improve patient outcomes.

Contribution of antibody-based protein profiling to the human Chromosome-centric Proteome Project (C-HPP).

A gene-centric Human Proteome Project has been proposed to characterize the human protein-coding genes in a chromosome-centered manner to understand human biology and disease. Here, we report on the protein evidence for all genes predicted from the genome sequence based on manual annotation from literature (UniProt), antibody-based profiling in cells, tissues and organs and analysis of the transcript profiles using next generation sequencing in human cell lines of different origins. We estimate that there is good evidence for protein existence for 69% (n = 13985) of the human protein-coding genes, while 23% have only evidence on the RNA level and 7% still lack experimental evidence. Analysis of the expression patterns shows few tissue-specific proteins and approximately half of the genes expressed in all the analyzed cells. The status for each gene with regards to protein evidence is visualized in a chromosome-centric manner as part of a new version of the Human Protein Atlas ( www.proteinatlas.org ).

Efficacy of tecovirimat (ST-246) in nonhuman primates infected with variola virus (Smallpox).

Naturally occurring smallpox has been eradicated but remains a considerable threat as a biowarfare/bioterrorist weapon (F. Fleck, Bull. World Health Organ. 81:917-918, 2003). While effective, the smallpox vaccine is currently not recommended for routine use in the general public due to safety concerns (http://www.bt.cdc.gov/agent/smallpox/vaccination). Safe and effective countermeasures, particularly those effective after exposure to smallpox, are needed. Currently, SIGA Technologies is developing the small-molecule oral drug, tecovirimat (previously known as ST-246), as a postexposure therapeutic treatment of orthopoxvirus disease, including smallpox. Tecovirimat has been shown to be efficacious in preventing lethal orthopoxviral disease in numerous animal models (G. Yang, D. C. Pevear, M. H. Davies, M. S. Collett, T. Bailey, et al., J. Virol. 79:13139-13149, 2005; D. C. Quenelle, R. M. Buller, S. Parker, K. A. Keith, D. E. Hruby, et al., Antimicrob. Agents Chemother., 51:689-695, 2007; E. Sbrana, R. Jordan, D. E. Hruby, R. I. Mateo, S. Y. Xiao, et al., Am. J. Trop. Med. Hyg. 76:768-773, 2007). Furthermore, in clinical trials thus far, the drug appears to be safe, with a good pharmacokinetic profile. In this study, the efficacy of tecovirimat was evaluated in both a prelesional and postlesional setting in nonhuman primates challenged intravenously with 1 × 10(8) PFU of Variola virus (VARV; the causative agent of smallpox), a model for smallpox disease in humans. Following challenge, 50% of placebo-treated controls succumbed to infection, while all tecovirimat-treated animals survived regardless of whether treatment was started at 2 or 4 days postinfection. In addition, tecovirimat treatment resulted in dramatic reductions in dermal lesion counts, oropharyngeal virus shedding, and viral DNA circulating in the blood. Although clinical disease was evident in tecovirimat-treated animals, it was generally very mild and appeared to resolve earlier than in placebo-treated controls that survived infection. Tecovirimat appears to be an effective smallpox therapeutic in nonhuman primates, suggesting that it is reasonably likely to provide therapeutic benefit in smallpox-infected humans.

Extreme weather events and farmer adaptation in Zeeland, the Netherlands: A European climate change case study from the Rhine delta.

Global climate change is manifest by local-scale changes in precipitation and temperature patterns, including the frequency of extreme weather events (EWEs). EWEs are associated with a myriad range of adverse environmental and societal consequences, including negative impacts to agriculture and food production. This study focuses on EWEs and their effect on adaptation strategies by potato and onion farmers in Zeeland, a Dutch coastal province in the Rhine delta that can serve as a model for other intensive agricultural landscapes in industrialized nations impacted by extreme weather events. The research approach combines quantitative trend analysis of long-term climatic data (temperature, precipitation) with a formal survey of Zeelandic farmers to statistically test four specific hypotheses regarding the frequency of EWEs in the Netherlands and farmer awareness and adaptation. Trend analyses reveal a strong (statistically significant) increase in extreme heat, a small increase in extreme rainfall and drought, and a strong decrease in frost occurrence. Survey results indicate Zeelandic farmers perceive high risk and awareness of changes to the frequency of EWEs. Many farmers have experienced financial losses from EWEs, particularly between 2017 and 2020. For extreme heat, droughts, and frost, the proportion of farmers that incurred financial damages annually is statistically correlated to the actual occurrence of EWEs. Farmers who incurred more financial losses between 2000 and 2020 due to heat and lack of frost had a higher risk perception of these extremes. Further, almost all farmers have already implemented one or more adaptation strategies. A third of surveyed farmers reduced or stopped with potato and onion cultivation in response to climate change and EWEs. Awareness, exposure to, and risk perception of EWEs contribute to adaptation support by farmers. The high perceived risk of climate change and EWEs among respondents and the high incidence of financial losses from extremes in the past two decades highlights the importance of adaptation in the agricultural sector, including in temperate regions where growing seasons are expanding. Study results support the current 'Rural Development Program' and future 'National Strategic Plan' policies in the Netherlands, both part of the European Union's Common Agricultural Policy (CAP), that provides accessibility to adaptation measures for farmers to avoid financial loss.

Poxvirus complement control proteins are expressed on the cell surface through an intermolecular disulfide bridge with the viral A56 protein.

The vaccinia virus (VACV) complement control protein (VCP) is an immunomodulatory protein that is both secreted from and expressed on the surface of infected cells. Surface expression of VCP occurs though an interaction with the viral transmembrane protein A56 and is dependent on a free N-terminal cysteine of VCP. Although A56 and VCP have been shown to interact in infected cells, the mechanism remains unclear. To investigate if A56 is sufficient for surface expression, we transiently expressed VCP and A56 in eukaryotic cell lines and found that they interact on the cell surface in the absence of other viral proteins. Since A56 contains three extracellular cysteines, we hypothesized that one of the cysteines may be unpaired and could therefore form a disulfide bridge with VCP. To test this, we generated a series of A56 mutants in which each cysteine was mutated to a serine, and we found that mutation of cysteine 162 abrogated VCP cell surface expression. We also tested the ability of other poxvirus complement control proteins to bind to VACV A56. While the smallpox homolog of VCP is able to bind VACV A56, the ectromelia virus (ECTV) VCP homolog is only able to bind the ECTV homolog of A56, indicating that these proteins may have coevolved. Surface expression of poxvirus complement control proteins may have important implications in viral pathogenesis, as a virus that does not express cell surface VCP is attenuated in vivo. This suggests that surface expression of VCP may contribute to poxvirus pathogenesis.

The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon.

Variola virus (VARV) caused smallpox, one of the most devastating human diseases and the first to be eradicated, but its deliberate release represents a dangerous threat. Virulent orthopoxviruses infecting humans, such as monkeypox virus (MPXV), could fill the niche left by smallpox eradication and the cessation of vaccination. However, immunomodulatory activities and virulence determinants of VARV and MPXV remain largely unexplored. We report the molecular characterization of the VARV- and MPXV-secreted type I interferon-binding proteins, which interact with the cell surface after secretion and prevent type I interferon responses. The proteins expressed in the baculovirus system have been purified, and their interferon-binding properties characterized by surface plasmon resonance. The ability of these proteins to inhibit a broad range of interferons was investigated to identify potential adaptation to the human immune system. Furthermore, we demonstrate by Western blot and activity assays the expression of the type I interferon inhibitor during VARV and MPXV infections. These findings are relevant for the design of new vaccines and therapeutics to smallpox and emergent virulent orthopoxviruses because the type I interferon-binding protein is a major virulence factor in animal models, vaccination with this protein induces protective immunity, and its neutralization prevents disease progression.

Safety and efficacy of dual-axis rotational coronary angiography vs. standard coronary angiography.

OBJECTIVE: To determine the safety and efficacy of dual-axis rotational coronary angiography (DARCA) by directly comparing it to standard coronary angiography (SA). BACKGROUND: Standard coronary angiography (SA) requires numerous fixed static images of the coronary tree and has multiple well-documented limitations. Dual-axis rotational coronary angiography (DARCA) is a new rotational acquisition technique that entails simultaneous LAO/RAO and cranial/caudal gantry movement. This technological advancement obtains numerous unique images of the left or right coronary tree with a single coronary injection. We sought to assess the safety and efficacy of DARCA as well as determine DARCA's adequacy for CAD screening and assessment. METHODS: Thirty patients underwent SA following by DARCA. Contrast volume, radiation dose (DAP) and procedural time were recorded for each method to assess safety. For DARCA acquisitions, blood pressure (BP), heart rate (HR), symptoms and any arrhythmias were recorded. All angiograms were reviewed for CAD screening adequacy by two independent invasive cardiologists. RESULTS: Compared to SA, use of DARCA was associated with a 51% reduction in contrast, 35% less radiation exposure, and 18% shorter procedural time. Both independent reviewers noted DARCA to be at least equivalent to SA with respect to the ability to screen for CAD. CONCLUSION: DARCA represents a new angiographic technique which is equivalent in terms of image quality and is associated with less contrast use, radiation exposure, and procedural time than SA.

Clinical outcomes following predilation with a novel 1.25-mm diameter angioplasty catheter.

OBJECTIVE: An unmet need is represented in angioplasty catheters that permit the predilation stage of treating complex coronary anatomy oftentimes not amenable to conventional device therapies. BACKGROUND: Lesion preparation with balloon angioplasty prior to stent placement remains the most common method of percutaneous coronary revascularization. METHODS: Clinical and angiographic outcomes were evaluated following a treatment strategy of coronary artery disease that included predilation with a low-profile, 1.25-mm angioplasty catheter prior to stent placement. The study primary end point of procedural success was defined as successful device delivery and lesion treatment, including the absence of clinically significant perforation, arrhythmia, flow-limiting dissection, or reduction in baseline Thrombolysis In Myocardial Infarction (TIMI) grade with final achievement of TIMI 3 flow. RESULTS: Among 51 patients (54 lesions), predilation using a 1.25 mm angioplasty catheter was associated with procedural and device-related success rates of 100%. In-hospital target lesion failure occurred in one patient (2.0%) related to postprocedural myocardial infarction. Patient and angiographic characteristics included diabetes, 43.1%; lesion length ≥ 20 mm, 20.4%; bifurcation lesion, 31.5%; lesion classification B2/C, 74.1%; and baseline TIMI 0/1 flow, 13.0%. No subsequent in-hospital adverse events occurred. CONCLUSIONS: Percutaneous coronary revascularization involving a predilation strategy with a low profile, 1.25-mm angioplasty catheter is associated with favorable procedural safety and efficacy and may represent an effective initial treatment for complex coronary anatomy.

Association of prior coronary artery bypass graft surgery with quality of care of patients with non-ST-segment elevation myocardial infarction: a report from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines.

BACKGROUND: The American College of Cardiology/American Health Association guidelines recommend both an early invasive strategy and administration of antiplatelet/anticoagulant therapy for high-risk patients in the absence of contraindications. Little is known about adherence to guideline recommendations in patients with prior coronary artery bypass graft (CABG) surgery presenting with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: We analyzed 47,557 patients with NSTEMI in the 2007-2008 National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines. Treatment patterns were compared between patients with and without prior CABG surgery. Multivariable regression with generalized estimating equations evaluated the association between prior CABG and in-hospital outcomes. RESULTS: In this study, 8,790 NSTEMI patients (18.5%) had a history of CABG surgery. Prior CABG surgery was associated with a significantly lower adjusted likelihood of early cardiac catheterization (adjusted odds ratio [OR] 0.88, 95% CI 0.83-0.92), higher rates of short-term clopidogrel use (adjusted OR 1.08, 95% CI 1.02-1.14), and comparable use of anticoagulant therapy (adjusted OR 0.96, 95% CI 0.88-1.04). Adjusted risks of bleeding and in-hospital mortality did not differ significantly between the 2 groups (adjusted ORs 1.00, 95% CI 0.92-1.11 and 0.99, 95% CI 0.87-1.11, respectively). CONCLUSIONS: Patients with prior CABG surgery presenting with NSTEMI are often felt to be at high risk for adverse outcomes and therefore require aggressive treatment. Our study indicates that they are less likely to undergo guideline-recommended early cardiac catheterization but equally or more likely to receive guideline-recommended antiplatelet and anticoagulant therapy. This risk-treatment paradox, however, does not appear to negatively influence short-term clinical outcomes.

Spontaneous left main coronary artery dissection and the role of intravascular ultrasonography.

OBJECTIVE: Spontaneous left main coronary artery (LMCA) dissection is a rare event with an unknown incidence and high risk of sudden cardiac death. The diagnosis of LMCA dissection is often challenging given the limitations of 2-dimensional angiography. The 3-dimensional perspective of intravascular ultrasonography (IVUS) is often indispensable in confirming or excluding the diagnosis of spontaneous LMCA dissection. We report 2 cases of spontaneous LMCA dissection with unique angiographic presentations wherein IVUS was essential in defining the extent of LMCA involvement and facilitated the subsequent referral for emergent coronary artery bypass grafting. METHODS: Two patients presented to our facility with acute coronary syndrome prompting coronary angiography, which was notable for an unusual angiographic appearance of the LMCA. Intravascular ultrasonography was performed in each case, revealing spontaneous LMCA dissection. RESULTS: Intravascular ultrasonography permitted the prompt diagnosis and aided in definitive surgical intervention in our 2 cases of spontaneous LMCA dissection. CONCLUSIONS: Intravascular ultrasonography is a useful adjunctive imaging modality in the diagnosis and management of spontaneous LMCA dissection.

Use of live Variola virus to determine whether CAST/EiJ mice are a suitable surrogate animal model for human smallpox.

Numerous animal models of systemic orthopoxvirus disease have been developed to evaluate therapeutics against variola virus (VARV), the causative agent of smallpox. These animal models do not resemble the disease presentation in human smallpox and most used surrogate Orthopoxviruses. A rodent model using VARV has a multitude of advantages, and previous investigations identified the CAST/EiJ mouse as highly susceptible to monkeypox virus infection, making it of interest to determine if these rodents are also susceptible to VARV infection. In this study, we inoculated CAST/EiJ mice with a range of VARV doses (102-106 plaque forming units). Some animals had detectable viable VARV from the oropharynx between days 3 and 12 post inoculation. Despite evidence of disease, the CAST/EiJ mouse does not provide a model for clinical smallpox due to mild signs of morbidity and limited skin lesions. However, in contrast to previous rodent models using VARV challenge (i.e. prairie dogs and SCID mice), a robust immune response was observed in the CAST/EiJ mice (measured by Immunoglobulin G enzyme-linked immunosorbent assay). This is an advantage of this model for the study of VARV and presents a unique potential for the study of the immunomodulatory pathways following VARV infection.

Analgesia during Monkeypox Virus Experimental Challenge Studies in Prairie Dogs (Cynomys ludovicianus).

Because human patients with monkeypox virus (MPXV) infection report painful symptoms, it is reasonable to assume that animals infected with MPXV experience some degree of pain. Understanding whether and how analgesics affect MPXV disease progression is crucial when planning in vivo challenge experiments. In the current study, we challenged prairie dogs with a low dose (4 ×10³ pfu) of MPXV and treated with meloxicam (NSAID) or buprenorphine (opioid); control animals did not receive analgesia or received analgesia without MPXV challenge. Subsets of animals from each group were serially euthanized during the course of the study. Disease progression and viral kinetics were similar between groups, but MXPVinfected, meloxicam-treated animals showed increasing trends of morbidity and mortality compared with other groups. Differences between no-analgesia MPXV-infected control animals and MPXV-infected animals treated with buprenorphine were minimal. The findings in the current study allow more informed decisions concerning the use of analgesics during experimental MPXV challenge studies, thereby improving animal welfare. In light of these findings, we have modified our pain scale for this animal model to include the use of buprenorphine for pain relief when warranted after MPXV challenge.