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Feline infectious peritonitis (FIP) is a devastating and often fatal disease caused by feline coronavirus (FCoV). Currently, there is no widely used vaccine for FIP, and many attempts using a variety of platforms have been largely unsuccessful due to the disease's highly complicated pathogenesis. One such complication is antibody-dependent enhancement (ADE) seen in FIP, which occurs when sub-neutralizing antibody responses to viral surface proteins paradoxically enhance disease. A novel vaccine strategy is presented here that can overcome the risk of ADE by instead using a lipid nanoparticle-encapsulated mRNA encoding the transcript for the internal structural nucleocapsid (N) FCoV protein. Both wild type and, by introduction of silent mutations, GC content-optimized mRNA vaccines targeting N were developed. mRNA durability in vitro was characterized by quantitative reverse-transcriptase PCR and protein expression by immunofluorescence assay for one week after transfection of cultured feline cells. Both mRNA durability and protein production in vitro were improved with the GC-optimized construct as compared to wild type. Immune responses were assayed by looking at N-specific humoral (by ELISA) and stimulated cytotoxic T cell (by flow cytometry) responses in a proof-of-concept mouse vaccination study. These data together demonstrate that an LNP-mRNA FIP vaccine targeting FCoV N is stable in vitro, capable of eliciting an immune response in mice, and provides justification for beginning safety and efficacy trials in cats.
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Head-up displays (HUDs) have the potential to change work in operation environments by providing hands-free information to wearers. However, these benefits may be accompanied by trade-offs, primarily by increasing cognitive load due to dividing attention. Previous studies have attempted to understand the trade-offs of HUD usage; however, all of which were focused on land-based tasks. A gap in understanding exists when examining HUD use in aquatic environments as immersion introduces unique environmental and physiological factors that could affect multitasking. In this study, we investigated multitasking performance associated with swimming with a HUD. Eighteen participants completed three tasks: swimming only, a HUD-administered word recall task, and a dual-task combining both tasks. Results revealed significant dual-task interference in both tasks, though possibly less pronounced than in land-based tasks. These findings enhance not only help characterise dual-task performance, but also offer valuable insights for HUD design for aquatic settings.
HUDs have become an increasingly popular tool to present information to users in complex working environments. However, past research examining HUD task performance has been restricted to land-based contexts. The current study examines HUD use while swimming and provides characterisation of multitasking performance within aquatic environments.
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The roster of amdoparvoviruses (APVs) in small carnivores is growing rapidly, but in most cases, the consequences of infection are poorly understood. Red panda amdoparvovirus (RPAV) is highly prevalent in zoo-housed red pandas and has been detected in both healthy and sick animals. Clarifying the clinical impact of RPAV in this endangered species is critical, and zoological collections offer a unique opportunity to examine viral disease association in carefully managed populations. We evaluated the potential impact of RPAV in captive red pandas with a combination of prospective and retrospective analyses. First, we collected feces from 2 healthy animals from one collection over a 6-year period and detected virus in 72/75 total samples, suggesting that RPAV can be a long-term subclinical infection. We next investigated the infections using a retrospective study of infection status and tissue distribution in a cohort of necropsied animals. We performed polymerase chain reaction and in situ hybridization on 43 necropsy cases from 4 zoo collections (3 from the United States, 1 from Europe, 1997-2022). RPAV was present in these populations for at least 2 decades before its discovery and is detectable in common and significant lesions of zoo-housed red pandas, including myocarditis (3/3 cases), nephritis (9/10), and interstitial pneumonia (2/4). RPAV is also detectable in sporadic lesions, including multisystemic pyogranulomatous inflammation, oral/pharyngeal mucosal inflammation, and dermatitis. The colocalization of virus with lesions supports a role in causation, suggesting that despite the apparently persistent and subclinical carriage of most infections, RPAV may have a significant impact in zoo collections.
Subject(s)
Ailuridae , Humans , Animals , Retrospective Studies , Prospective Studies , Endangered Species , Inflammation/veterinaryABSTRACT
BACKGROUND: Psychogenic nonepileptic seizures (PNES) are a common type of functional neurological disorder in which patients experience seizurelike episodes. Health disparities based on race and socioeconomics, documented in children with epilepsy and adults with PNES, have not been reported in children and adolescents with PNES. We hypothesize that disparities exist in this population, which impact overall care and therefore influence outcomes. METHODS: We retrospectively analyzed youth referred to our multidisciplinary clinic from 2018 to 2020. All patient charts were screened by social work before the visit to identify potential barriers to care, and a nurse conducted follow-up calls. Patients' race was identified from the electronic health record and compared with several variables. Outcomes were collected via phone follow-up. Descriptive statistics were produced, and comparisons between white patients and patients of other races were completed using Fisher exact tests and multivariable logistic regressions. RESULTS: During the study period, 237 patients were eligible for the analysis. Sixty-eight patients (29%) identified as a race other than white. Only 60%, 56%, and 40% of the cohort were reached for follow-up at one, three, and 12 months, respectively. In general, outcomes were similar between racial groups; however, we found that patients of nonwhite race were more likely to receive support from social work due to barriers identified in screening (P = 0.045). CONCLUSIONS: Health disparities based on race may exist in youth with PNES. A multidisciplinary clinic including social work may help mitigate barriers leading to more equitable care and similar outcomes for white and nonwhite youth with PNES.
Subject(s)
Conversion Disorder , Epilepsy , Adult , Child , Humans , Adolescent , Seizures/diagnosis , Retrospective Studies , Psychogenic Nonepileptic Seizures , Epilepsy/diagnosis , ElectroencephalographyABSTRACT
During metastasis, tumor cells invade through the basement membrane and intravasate into blood vessels and then extravasate into distant organs to establish metastases. Here, we report a critical role of a transmembrane serine protease fibroblast activation protein (FAP) in tumor metastasis. Expression of FAP and TWIST1, a metastasis driver, is significantly correlated in several types of human carcinomas, and FAP is required for TWIST1-induced breast cancer metastasis to the lung. Mechanistically, FAP is localized at invadopodia and required for invadopodia-mediated extracellular matrix degradation independent of its proteolytic activity. Live cell imaging shows that association of invadopodia precursors with FAP at the cell membrane promotes the stabilization and growth of invadopodia precursors into mature invadopodia. Together, our study identified FAP as a functional target of TWIST1 in driving tumor metastasis via promoting invadopodia-mediated matrix degradation and uncovered a proteolytic activity-independent role of FAP in stabilizing invadopodia precursors for maturation.
Subject(s)
Breast Neoplasms , Podosomes , Humans , Female , Podosomes/metabolism , Cell Line, Tumor , Peptide Hydrolases/metabolism , Neoplasm Invasiveness/pathology , Breast Neoplasms/pathology , Membrane Proteins/metabolism , Serine Endopeptidases/metabolism , Fibroblasts/metabolism , Extracellular Matrix/metabolism , Melanoma, Cutaneous MalignantABSTRACT
OBJECTIVE: This article evaluates the risk (defined here as incidence per 1,000 infants) of developmental dysplasia of the hip (DDH) in premature infants undergoing hip ultrasound (HUS) for breech presentation only compared with other indications. STUDY DESIGN: Retrospective study of infants born between January 1, 2009 and December 31, 2018 at <37 weeks' gestation with a HUS obtained in the first year of life, at Nationwide Children's Hospital, the only available facility for pediatric radiology and orthopaedic services in central Ohio. We calculated risk differences and odds ratios of DDH by the indication of HUS. RESULTS: From 2,397 infants reviewed, 89% underwent HUS for breech presentation only. The local incidence of DDH for infants undergoing HUS for breech-only indication was 15 per 1,000 compared with 155 per 1,000 for infants undergoing HUS for other indications. The odds ratio of DDH diagnosis was 12.1 (95% confidence interval: 7.5, 19.6) for infants undergoing HUS for an indication other than breech presentation only relative to infants undergoing HUS for the indication of breech presentation only. CONCLUSION: The risk of DDH diagnosis in premature infants undergoing HUS for breech presentation is much lower than those undergoing HUS for clinical concerns and other risk factors. Screening these infants with physical examination may be sufficient. KEY POINTS: · Breech presentation is the most common indication for hip ultrasound in premature infants.. · The risk of DDH is lower in premature infants with breech presentation compared with premature infants with other clinical concerns.. · The risk of DDH is higher in infants born at 33 to 36 weeks of gestation compared with those born at an earlier gestation..
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STUDY OBJECTIVE: To describe satisfaction with and preference for subcutaneous depot medroxyprogesterone acetate (DMPA-SC), along with adherence and feasibility, in adolescents and young adults (AYAs) METHODS: Survey of a sample of AYA patients who received DMPA-SC prescription and injection RESULTS: Of 108 eligible patients, 34 completed the survey, and 29 respondents received at least 1 DMPA-SC injection. The mean age was 16.9 years. Seventy-nine point three percent used it for gynecologic reasons, 27.6% for gender dysphoria, and 20.7% for contraception (multiple responses allowed); 93.1% were satisfied with DMPA-SC; 78.6% gave DMPA-SC on time; 88.9% reported that giving the injection was easy; 89.7% reported no problems with administration; 89.3% reported no problems obtaining DMPA-SC; and 76.9% plan to continue using DMPA-SC. CONCLUSION: In this small sample of patients within a children's hospital, the overall experience with DMPA-SC was favorable. Clinicians caring for adolescents should consider including DMPA-SC in counseling when depot medroxyprogesterone acetate (DMPA) is indicated.
Subject(s)
Contraceptive Agents, Female , Medroxyprogesterone Acetate , Child , Humans , Female , Young Adult , Adolescent , Medroxyprogesterone Acetate/adverse effects , Contraceptive Agents, Female/adverse effects , Pilot Projects , Injections, Subcutaneous , Self AdministrationABSTRACT
Clinical evidence of vascular dysfunction and hypercoagulability as well as pulmonary vascular damage and microthrombosis are frequently reported in severe cases of human coronavirus disease 2019 (COVID-19). Syrian golden hamsters recapitulate histopathologic pulmonary vascular lesions reported in patients with COVID-19. Herein, special staining techniques and transmission electron microscopy further define vascular pathologies in a Syrian golden hamster model of human COVID-19. The results show that regions of active pulmonary inflammation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are characterized by ultrastructural evidence of endothelial damage with platelet marginalization and both perivascular and subendothelial macrophage infiltration. SARS-CoV-2 antigen/RNA was not detectable within affected blood vessels. Taken together, these findings suggest that the prominent microscopic vascular lesions in SARS-CoV-2-inoculated hamsters likely occur due to endothelial damage followed by platelet and macrophage infiltration.
Subject(s)
COVID-19 , Vascular Diseases , Cricetinae , Animals , Humans , Mesocricetus , SARS-CoV-2 , COVID-19/pathology , Lung/pathology , Vascular Diseases/pathology , Disease Models, AnimalABSTRACT
The purpose of this study was to 1) examine whether frequency of positive and negative interactions (manipulated via reliability) with a computer agent had an impact on an individual's trust resilience after a major error occurs and 2) empirically test the notion of relationship equity, which encompasses the total accumulation of positive and negative interactions and experiences between two actors, on user trust on a separate transfer task. Participants were randomized into one of four groups, differing in agent positivity and frequency of interaction, and completed both a pattern recognition task and transfer task with the aid of the same computer agent. Subjective trust ratings, performance data, compliance, and agreement were collected and analyzed. Results demonstrated that frequency of positive and negative interactions did have an impact on user trust and trust resilience after a major error. Additionally, it was shown that relationship equity has an impact on user trust and trust resilience. This is the first empirical demonstration of relationship equity's impact on user trust in an automated teammate.
Subject(s)
Computers , Trust , Humans , Reproducibility of Results , Automation , Man-Machine SystemsABSTRACT
BACKGROUND: Ulceration is an important complication in infantile hemangiomas (IHs). Prior to the use of ß-blockers, the estimated incidence of this complication in a referral population was between 15% and 30%. The incidence and factors associated with ulceration have not been systematically studied since the emergence of ß-blocker therapy. OBJECTIVE: Examine the incidence and clinical predictors for ulceration in IHs. METHODS: Retrospective study at tertiary referral centers. RESULTS: Compared with a previous large pre-propranolol cohort study, ulceration occurred at a significantly lower incidence of 11.4%. Clinical factors associated with ulceration included partial segmental morphology, location in the diaper area, and size greater than 5 cm. Higher risk of ulceration in Black patients was observed, suggesting barriers to care including delayed diagnosis and referral to specialty care. LIMITATIONS: Retrospective design at tertiary referral centers. CONCLUSION: Compared with reports before the use of ß-blockers became widespread, the incidence of ulceration in IHs has decreased. However, it continues to be a relatively frequent complication of IH.
Subject(s)
Hemangioma, Capillary , Skin Neoplasms , Humans , Infant , Retrospective Studies , Cohort Studies , Incidence , Hemangioma, Capillary/complications , Hemangioma, Capillary/epidemiology , Hemangioma, Capillary/drug therapy , Adrenergic beta-Antagonists/therapeutic use , Skin Neoplasms/drug therapyABSTRACT
BACKGROUND: Lack of access to reliable transportation is a barrier to timely receipt of prenatal care. OBJECTIVES: We aimed to assess the impact of modernisation of non-emergency medical transportation services on patient satisfaction, prenatal care utilisation, and preterm delivery. METHODS: We conducted a randomised controlled pilot trial among pregnant Medicaid recipients in Franklin County, Ohio, a county with high rates of infant mortality. Individuals were randomly assigned to usual non-emergency medical transportation services or enhanced smart transportation (EST) services (i.e. on-demand transportation with access to a mobile application and trips to the grocery store, food bank or pharmacy). The primary outcome was satisfaction with transportation services. Secondary outcomes included adequacy of prenatal care utilisation (APNCU) and preterm delivery <37 weeks. RESULTS: Women were screened between 31 May 2019 and 30 June 2020, with 143 being eligible and enrolling. Evidence of increased satisfaction with transportation was observed in the intervention group compared to usual transportation, with 83.8% and 68.8% reporting being somewhat satisfied or very satisfied respectively (risk difference [RD] 14.8%, 95% confidence interval [CI] 0.5, 29.1). There were no meaningful differences in APNCU or preterm delivery between groups (APNCU: RD 2.1%, 95% CI -14.0, 18.2 and preterm delivery: RD -3.9%, 95% CI -17.0, 9.3). CONCLUSIONS: We found evidence of increased transportation satisfaction among pregnant women randomly assigned to EST versus usual transportation. It remains unclear whether the provision of EST increases prenatal care utilisation or decreases preterm delivery.
Subject(s)
Premature Birth , Transportation , Female , Humans , Infant , Infant, Newborn , Pregnancy , Medicaid , Patient Acceptance of Health Care , Personal Satisfaction , Premature Birth/epidemiology , Prenatal Care , Health Services AccessibilityABSTRACT
The operational costs of multitasking are more pressing given the increase in wearable technologies (head-up displays; HUDs) that facilitate multitasking. Often multitasking comes with performance costs, where the addition of more tasks impairs the performance of the tasks. The current study explored the extent to which multitasking interference can be characterised in simulated environments, as opposed to risky and harsh environments in real operational contexts. Forty-eight participants completed several trials where they performed a visual search task while navigating a simulated environment. There were three conditions: a standalone memory task, a standalone search task, and both tasks simultaneously. Results revealed significant dual-task interference when comparing the dual-task to each of the single-tasks. Results were corroborated by subjective workload and stress metrics. The results could prove useful for designing systems for individuals who routinely multitask in operational environments. Specifically, by furthering the understanding of their performance capabilities and trade-offs due to multitasking.Practitioner summary: Due to the demands of multitasking in operational environments, quantifying the degree of information lost on each task individually will aid in the understanding of the deficits of multitasking performance. This study shows that deficits in multi-tasking (via a HUD) can be understood in simulated environments to a similar degree as real-world tasks.
Subject(s)
Smart Glasses , Task Performance and Analysis , Humans , Memory , WorkloadABSTRACT
BACKGROUND: Greater than 50% of neonates with Down Syndrome (DS) have perinatal complications that require admission to the neonatal intensive care unit (NICU) at birth. Previous studies have shown increased morbidity and mortality rates in neonates without DS delivered prior to 39 weeks of completed gestation. OBJECTIVE: To determine if an association exists between gestational age at delivery and adverse outcomes in neonates with DS. STUDY DESIGN: Neonates with DS admitted to a large, tertiary care center NICU from 2010 to 2020 were evaluated. Gestational age (GA) was stratified into 4 groups: <34 (preterm), 34-36 (late-preterm), 37-38 (early-term) and ≥39 (term + post-term) completed weeks. Fisher's exact tests were used to evaluate morbidity and mortality rates between groups. RESULT: Of the 314 neonates with DS, 10% (N = 31) were <34 weeks, 22% (N = 68) 34-36 weeks, 40% (N = 127) 37-38 weeks, and 28% (N = 88) ≥39 completed weeks at birth. Baseline characteristics were similar between groups. GA at birth <34 weeks was associated with a higher in-hospital mortality rate when compared to those born 37-38 (19% vs. 0%, P < 0.001) and ≥39 (19% vs. 3%, P = 0.01). Neonates with DS born <34 weeks had a higher likelihood of oxygen requirement at time of discharge compared to 34-36, 37-38, and ≥39 groups (P = 0.01; P < 0.001; P < 0.001 respectively). Neonates with DS < 34 weeks were more likely to develop necrotizing enterocolitis (P = 0.02) and require nitric oxide (P = 0.014) compared to neonates with DS ≥ 39. We observed no differences in the need for surgical interventions between groups aside from the rate of gastrostomy/jejunostomy tube placement between 34-36 weeks and 37-38 weeks GA. CONCLUSION: Neonates with DS born preterm (<34 weeks) represent a highly vulnerable subgroup. Multidisciplinary strategies are needed to address their higher rates of morbidity and mortality.
Subject(s)
Down Syndrome , Infant, Premature , Pregnancy , Female , Infant, Newborn , Humans , Gestational Age , Down Syndrome/complications , Pregnancy Outcome , Morbidity , Retrospective StudiesABSTRACT
Simulated environments have become better able to replicate the real world and can be used for a variety of purposes, such as testing new technology without any of the costs or risks associated with working in the real world. Because of this, it is now possible to gain a better understanding of cognitive demands when working in operational environments, where individuals are often required to multitask. Multitasking often results in performance decrements, where adding more tasks can cause a decrease in performance in each of the individual tasks. However, little research investigated multitasking performance in simulated environments. In the current study we examined how multitasking affects performance in simulated environments. Forty-eight participants performed a dual visual search and word memory task where participants were navigated through a simulated environment while being presented with words. Performance was then compared to single-task performance (visual search and word memory alone). Results showed that participants experienced significant dual-task interference when comparing the dual-tasks to the single-tasks and subjective measures confirmed these findings. These results could provide useful insight for the design of technology in operational environments, but also serve as an evaluation of MRT in simulated environments.
Subject(s)
Ergonomics , Task Performance and Analysis , HumansABSTRACT
OBJECTIVE: To evaluate serum creatinine (SCr) patterns and the development of acute kidney injury (AKI), as potential biomarkers of necrotizing enterocolitis (NEC). STUDY DESIGN: Retrospective chart review of preterm infants with and without NEC born 23-32 weeks gestation admitted to Nationwide Children's Hospital NICU. Medical versus surgical NEC was determined by radiographic and clinical findings. Available inpatient SCr levels obtained on days 8 through 365 were included. RESULT: In this cohort, 77 NEC and a randomly selected group of 82 non-NEC infants met inclusion criteria. Fifteen of the 70 (21.4%) with NEC met criteria for AKI versus 0 of 43 (0.0%) without NEC. One of the 13 with AKI had AKI within 7 days prior to NEC diagnosis (7.7%). CONCLUSION: AKI is more prevalent in infants with NEC. The temporal association between AKI and NEC could not be evaluated due to inconsistent SCr surveillance and should be evaluated in future studies.
Subject(s)
Acute Kidney Injury , Enterocolitis, Necrotizing , Infant, Newborn, Diseases , Child , Infant, Newborn , Humans , Infant , Infant, Premature , Enterocolitis, Necrotizing/epidemiology , Retrospective Studies , Creatinine , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiologyABSTRACT
Feline calicivirus (FCV) is a major cause of upper respiratory disease in cats and is often used as a model for human norovirus, making it of great veterinary and human medical importance. However, questions remain regarding the route of entry of FCV in vivo. Increasing work has shown that extracellular vesicles (EVs) can be active in viral infectivity, yet there is no work examining the role of EVs in FCV infection. Here, we begin to address this knowledge gap by characterizing EVs produced by a feline mammary epithelial cell line (FMEC). We have confirmed that EVs are produced by infected and mock-infected FMECs and that both virions and EVs are coisolated with standard methods of virus purification. We also show that they can be enriched differentially by continuous iodixanol density gradient. EVs were enriched at a density of 1.10 g/mL confirmed by tetraspanin expression, size profile, and transmission electron microscopy (TEM). Maximum enrichment of FCV at a density of 1.18 g/mL was confirmed by titration, quantitative reverse transcriptase PCR (q-RT PCR), and TEM. However, infectious virus was recovered from nearly all samples. When used to infect in vitro epithelium, both EV-rich and virus-rich fractions had the same levels of infectiousness as determined by percentage of wells infected or titer achieved postinfection. These findings highlight the importance of coisolates during viral purification, showing that EVs may represent a parallel route of entry that has previously been overlooked. Additional experiments are necessary to explore the role of EVs in FCV infection. IMPORTANCE Feline calicivirus (FCV) is a common cause of upper respiratory infection in cats. Both healthy and infected cells produce small particles called extracellular vesicles (EVs), which are nanoparticles that act as messengers between cells and can be hijacked during viral infection. Historically, the role of EVs in viral infection has been overlooked, and subsequently no group has studied the role of EVs in FCV infection. We hypothesized that EVs may play a role in FCV infection. Here, we show that EVs are copurified with FCV when collecting virus. To study their individual effects, we successfully enrich for viral particles and EVs separately by taking advantage of their different densities. Our initial studies show that EV-enriched versus virus-enriched fractions are equally able to infect cells in culture. These findings highlight the need to both consider the purity of virus after purification and to further study EVs' role in natural FCV infection.
Subject(s)
Caliciviridae Infections , Calicivirus, Feline , Cat Diseases , Communicable Diseases , Extracellular Vesicles , Respiratory Tract Infections , Animals , Caliciviridae Infections/veterinary , Calicivirus, Feline/metabolism , Cats , HumansABSTRACT
Raccoons (Procyon lotor) are abundant in urban/wildland interfaces and are key sources of canine distemper virus (CDV) outbreaks in domestic, zoo, and free-ranging wildlife species. CDV is pantropic, which provides multiple potential routes of transmission (urine, respiratory secretions, feces), but the specific role of skin as a target of infection, as a diagnostic sample, or as a potential source of environmental persistence and transmission is unknown. We have characterized the distribution of CDV and its known receptor, nectin-4, in skin samples of 36 raccoons. Even with skin samples that were grossly and histologically normal, immunohistochemistry of skin was useful in the diagnosis of CDV infection, which was found in both epithelium and endothelium. Nectin-4 was codistributed with cellular targets of viral infection. Skin secretions, shed keratinocytes, and hair of CDV infected raccoons are all potential environmental fomites.
Subject(s)
Distemper Virus, Canine , Distemper , Dog Diseases , Animals , Animals, Wild , Dogs , Nectins , RaccoonsABSTRACT
OBJECTIVE: To describe changes in neonatal use of acute care services during the coronavirus disease 2019 (COVID-19) pandemic. We hypothesized neonatal visits would decrease and the degree of decline would vary by condition. METHODS: We conducted a retrospective cohort study of neonatal visits to the urgent cares, emergency departments, inpatient units, and intensive care units at a free-standing pediatric healthcare system during the COVID-19 pandemic and a comparator period. We included visits of infants presenting for acute care within the first 30 days of life. Transfers from a referring nursery, inpatient unit, or ICU were excluded. Data collected included demographics, patient characteristics, and visit characteristics. Descriptive statistics and χ2 tests were used for analyses and to determine statistically significant differences. RESULTS: We identified 4439 neonatal acute care visits, of which 2677 occurred in the prepandemic period and 1762 in the COVID-19 pandemic period, representing a 34.2% decline. Urgent cares and emergency departments experienced the greatest decline in visits for infectious conditions (49%) and the proportion of these visits also significantly decreased. Similarly, the largest clinically significant declines in hospitalizations were for infectious and respiratory diagnoses (48% and 52%, respectively) and the proportions of these hospitalizations also significantly decreased. Despite a small decline in hospitalizations for jaundice, the proportion of jaundice hospitalizations significantly increased by 5.7% (P = .02). CONCLUSIONS: The COVID-19 pandemic was associated with a significant reduction in neonatal visits across a spectrum of acute care settings. The impact on use varied by diagnosis with the most notable decline in visits for infectious conditions.
Subject(s)
COVID-19 , Communicable Diseases , COVID-19/epidemiology , Child , Emergency Service, Hospital , Hospitalization , Humans , Infant , Infant, Newborn , Pandemics , Retrospective StudiesABSTRACT
Striped skunks (Mephitis mephitis) densely populate the human-animal interface of suburbia throughout North America. Skunks share that habitat with numerous related mesocarnivores, where increased contact, competition for shared food and water sources and other stressors contribute to increased exposure and susceptibility to viral infection. The recently identified skunk amdoparvovirus (SKAV) has been detected at high prevalence in skunks and occasionally in mink, but its distribution in North America is unknown. To understand the impact of SKAV in striped skunks and the risk posed to related species, we investigated the geographic distribution of SKAV, analysed its genetic diversity and evolutionary dynamics and evaluated viral distribution in tissues of infected animals to identify possible mechanisms of transmission. SKAV was detected in 72.5% (37/51) skunks and was present at high rates at all locations tested across North America. Analysis of the complete genomic sequence of 29 strains showed a clear geographic segregation, frequent recombination and marked differences in the evolutionary dynamics of the major structural (VP2) and non-structural (NS1) proteins. NS1 was characterized by a higher variability and a higher percentage of positively selected codons. This could indicate that antibody-mediated enhancement of infection occurs in SKAV, an infection strategy that may be conserved across amdoparvoviruses. Finally, in situ hybridization revealed virus in epithelium of the gastrointestinal tract, urinary tract and skin, indicating that viral transmission could occur via oronasal, faecal and/or urinary secretions, as well as from skin and hair. The endemicity of SKAV over large geographic distances and its high genetic diversity suggest a long-term virus-host association. Persistent shedding and high environmental stability likely contribute to efficient viral spread, simultaneously offering opportunities for cross-species transmission with consequent risk to sympatric species, including domestic animals and wildlife.
Subject(s)
Animals, Wild , Mephitidae , Animals , Feces , Humans , Mink , North America/epidemiologyABSTRACT
Red pandas (Ailurus fulgens) are a globally endangered small carnivoran species and subjects of a robust ex situ conservation effort that includes animals housed in zoos. In 2018, red panda amdoparvovirus (RPAV) was discovered by metagenomics analyses of tissues from two geriatric red pandas, and in one case it was associated with significant lesions. Because RPAV was discovered in a single zoo cohort, it was unclear whether these infections represented a widely distributed, enzootic virus of red pandas or a localized 'spillover' from a different host species into this collection. The first goal of this study was to estimate the prevalence of RPAV in US zoos. The authors amplified RPAV from feces of 104 individual red pandas from 37 US zoos, and the virus was detected in 52/104 samples (50.0%). Next, to establish persistence of infection in individual animals, the authors tested serial samples in a single cohort over a 4.5-yr period, and virus was consistently shed by infected animals throughout the sampling period. Finally, full viral coding sequences were amplified and sequenced from three cases, and partial sequences of both the nonstructural and capsid genes were obtained for an additional 19 cases. RPAV is a genetically diverse but monophyletic viral species, and multiple viral lineages are present in US zoo-housed red pandas. The authors do not know how red pandas were originally infected, but RPAV is very common in red pandas in the United States, and infections are persistent-presumably for the lifetime of the animal.