Resistant and susceptible chicken lines show distinctive responses to Newcastle disease virus infection in the lung transcriptome.

BACKGROUND: Newcastle disease virus (NDV) is a threat to poultry production worldwide. A better understanding of mechanisms of resistance and susceptibility to this virus will improve measures for NDV prevention and control. Males and females from resistant Fayoumi and susceptible Leghorn lines were either challenged with a lentogenic strain of the virus or given a mock infection at 3 weeks of age. The lung transcriptomes generated by RNA-seq were studied using contrasts across the challenged and nonchallenged birds, the two lines, and three time points post-infection, and by using Weighted Gene Co-expression Network Analysis (WGNCA). RESULTS: Genetic line and sex had a large impact on the lung transcriptome. When contrasting the challenged and nonchallenged birds, few differentially expressed genes (DEG) were identified within each line at 2, 6, and 10 days post infection (dpi), except for the more resistant Fayoumi line at 10 dpi, for which several pathways were activated and inhibited at this time. The interaction of challenge and line at 10 dpi significantly impacted 131 genes (False Discovery Rate (FDR) <0.05), one of which was PPIB. Many DEG were identified between the Fayoumi and Leghorns. The number of DEG between the two lines in the challenged birds decreased over time, but increased over time in the nonchallenged birds. The nonchallenged Fayoumis at 10 dpi showed enrichment of immune type cells when compared to 2 dpi, suggesting important immune related development at this age. These changes between 10 and 2 dpi were not identified in the challenged Fayoumis. The energy allocated to host defense may have interrupted normal lung development. WGCNA identified important modules and driver genes within those modules that were associated with traits of interest, several of which had no known associated function. CONCLUSIONS: The lines' unique response to NDV offers insights into the potential means of their resistance and susceptibility. The lung transcriptome shows a unique response to lentogenic NDV compared to a previous study on the trachea of the same birds. It is important to analyze multiple tissues in order to best understand the chicken's overall response to NDV challenge and improve strategies to combat this devastating disease.

Increased Mortality of Black Incarcerated and Hospitalized People: a Single State Cohort Analysis.

OBJECTIVE: To quantify racial disparities in mortality and post-hospitalization outcomes among incarcerated individuals that were hospitalized during their incarceration period. METHODS: We designed a retrospective cohort study using administrative and hospital data collected from a preferred healthcare referral center for all Massachusetts jails and prisons between January 2011 and December 2018 with linkage to Massachusetts Vital Records and Statistics. We identified 4260 incarcerated individuals with complete data on race/ethnicity that were hospitalized during the study period. The primary study indicators were age, race, ethnicity, length of hospital stay, Elixhauser comorbidity score, incarceration facility type, and number of hospital admissions. The primary outcome was time to death. RESULTS: Of the incarcerated individuals that were hospitalized, 2606 identified as White, 1214 identified as Black, and 411 people who identified as some other race. The hazard of death significantly increased by 3% (OR: 1.03; 95% CI: 1.02-1.03) for each additional yearly increase in age. After adjusting for the interaction between race and age, Black race was significantly associated with 3.01 increased hazard (95% CI: 1.75-5.19) of death for individuals hospitalized while incarcerated compared to White individuals hospitalized while incarcerated. Hispanic ethnicity and being incarcerated in a prison facility was not associated with time to mortality, while increased mean Elixhauser score (HR: 1.07; 95% CI: 1.06-1.08) and ≥ 3 hospital admissions (HR: 2.47; 95% CI: 2.07-2.95) increased the hazard of death. CONCLUSIONS: Our findings suggest disparities exist in the mortality outcomes among Black and White individuals who are hospitalized during incarceration, with an increased rate of death among Black individuals. Despite hypothesized equal access to healthcare within correctional facilities, our findings suggest that incarcerated and hospitalized Black individuals may experience worse disparities than their White counterparts, which has not been previously explored or reported in the literature. In addition to decarceration, advocacy, and political efforts, increased efforts to support research access to datasets of healthcare outcomes, including hospitalization and death, for incarcerated people should be encouraged. Further research is needed to identify and address the implicit and explicit sources of these racial health disparities across the spectrum of healthcare provision.

Disparities in patient engagement with video telemedicine among high-video-use providers during the COVID-19 pandemic.

Aims: Known racial, ethnic, age, and socioeconomic disparities in video telemedicine engagement may widen existing health inequities. We assessed if telemedicine disparities were alleviated among patients of high-video-use providers at a large cardiovascular practice. Methods and results: All telemedicine visits from 16 March to 31 October 2020 and patient demographics were collected from an administrative database. Providers in the upper quintile of video use were classified as high-video-use providers. Descriptive statistics and a multivariable logistic model were calculated to determine the distribution and predictors of a patient ever having a video visit vs. only phone visits. A total of 24 470 telemedicine visits were conducted among 18 950 patients by 169 providers. Video visits accounted for 48% of visits (52% phone). Among telemedicine visits conducted by high-video-use providers (n = 33), ever video patients were younger (P < 0.001) and included 78% of Black patients vs. 86% of White patients (P < 0.001), 74% of Hispanic patients vs. 86% of non-Hispanic patients (P < 0.001), and 79% of public insurance patients vs. 91% of private insurance patients (P < 0.001). High-video-use provider patients had 9.4 (95% confidence interval 8.4-10.4) times the odds of having video visit compared to low-video-use provider patients. Conclusion: These results suggest that provider-focused solutions alone, including promoting provider adoption of video visits, may not adequately reduce disparities in telemedicine engagement. Even in the presence of successful clinical infrastructure for telemedicine, individuals of Black race, Hispanic ethnicity, older age, and with public insurance continue to have decreased engagement. To achieve equity in telemedicine, patient-focused design is needed.

Detection and prevention of highly pathogenic avian influenza in communities with high poultry disease burdens.

The implementation of strategies to detect, prevent, and control highly pathogenic avian influenza (HPAI) in developing countries presents several challenges, one of which is the presence of other diseases in poultry populations. Training workshops in developing countries using the Avian Flu School have revealed that in areas with heavy Newcastle disease burdens, smallholder poultry keepers do not recognize HPAI as an immediate threat. We have developed a strategy to address the more proximal needs and priorities of communities with free-ranging poultry flocks as a means to create value in poultry, and thus to improve disease detection and prevention overall. To this end, we have created the Poultry Health and Well-Being for Development project, which trains graduate veterinarians and paraprofessionals in poultry disease diagnosis, control, and treatment. These trainees then serve their local communities to improve poultry health and to implement disease detection and management programs.

Avian flu school: a training approach to prepare for H5N1 highly pathogenic avian influenza.

Since the reemergence of highly pathogenic avian influenza (H5N1 HPAI) in 2003, a panzootic that is historically unprecedented in the number of infected flocks, geographic spread, and economic consequences for agriculture has developed. The epidemic has affected a wide range of birds and mammals, including humans. The ineffective management of outbreaks, mainly due to a lack of knowledge among those involved in detection, prevention, and response, points to the need for training on H5N1 HPAI. The main challenges are the multidisciplinary approach required, the lack of experts, the need to train at all levels, and the diversity of outbreak scenarios. Avian Flu School addresses these challenges through a three-level train-the-trainer program intended to minimize the health and economic impacts of H5N1 HPAI by improving a community's ability to prevent and respond, while protecting themselves and others. The course teaches need-to-know facts using highly flexible, interactive, and relevant materials.

Awareness and Practices Relating to Zoonotic Diseases Among Smallholder Farmers in Nepal.

Increasing livestock production to meet growing demands has resulted in greater interactions at the livestock-wildlife-human interface and more opportunities for zoonotic disease spread. Zoonoses impose enormous burdens on low-income countries like Nepal, where populations are largely dependent on livestock production and access to shared grazing lands, often near protected areas, due to population pressures. Several livestock-associated zoonoses have been reported in Nepal; however, little is known regarding Nepali farmers' knowledge of zoonoses and opportunities for disease management. We conducted a cross-sectional study to investigate Nepali farmers' awareness of zoonoses, assess current health challenges, and evaluate disease prevention and control practices. We found that awareness of zoonotic pathogens was limited, especially in informally educated and illiterate farmers; the majority of which were women. Further, farmers' preventive herd health, food safety, and sanitation practices were not associated with their awareness. Several farmers reported high-risk practices despite being aware of zoonotic diseases, suggesting a disconnect between the farmers' awareness and practice. Our study highlights the need for improving Nepali farmers' knowledge of zoonoses and disease prevention measures. Closing these awareness-practice gaps will require an improved understanding of risk and effective drivers of behavior change, alongside engagement of farmers in development of zoonotic disease prevention programs that encourage participation of both male and female farmers across all levels of education.

Novel analysis of the Harderian gland transcriptome response to Newcastle disease virus in two inbred chicken lines.

Behind each eye of the chicken resides a unique lymph tissue, the Harderian gland, for which RNA sequencing (RNA-seq) analysis is novel. We characterized the response of this tissue to Newcastle disease virus (NDV) in two inbred lines with different susceptibility to NDV across three time points. Three-week-old relatively resistant (Fayoumi) and relatively susceptible (Leghorn) birds were inoculated with a high-titered (107EID50) La Sota strain of NDV via an oculonasal route. At 2, 6, and 10 days post infection (dpi) Harderian glands were collected and analyzed via RNA-seq. The Fayoumi had significantly more detectable viral transcripts in the Harderian gland at 2 dpi than the Leghorn, but cleared the virus by 6 dpi. At all three time points, few genes were declared differentially expressed (DE) between the challenged and nonchallenged birds, except for the Leghorns at 6 dpi, and these DE genes were predicted to activate an adaptive immune response. Relative to the Leghorn, the Fayoumi was predicted to activate more immune pathways in both challenged and nonchallenged birds suggesting a more elevated immune system in the Fayoumis under homeostatic conditions. Overall, this study helped characterize the function of this important tissue and its response to NDV.

Transcriptome Analysis in Spleen Reveals Differential Regulation of Response to Newcastle Disease Virus in Two Chicken Lines.

Enhancing genetic resistance of chickens to Newcastle Disease Virus (NDV) provides a promising way to improve poultry health, and to alleviate poverty and food insecurity in developing countries. In this study, two inbred chicken lines with different responses to NDV, Fayoumi and Leghorn, were challenged with LaSota NDV strain at 21 days of age. Through transcriptome analysis, gene expression in spleen at 2 and 6 days post-inoculation was compared between NDV-infected and control groups, as well as between chicken lines. At a false discovery rate <0.05, Fayoumi chickens, which are relatively more resistant to NDV, showed fewer differentially expressed genes (DEGs) than Leghorn chickens. Several interferon-stimulated genes were identified as important DEGs regulating immune response to NDV in chicken. Pathways predicted by IPA analysis, such as "EIF-signaling", "actin cytoskeleton organization nitric oxide production" and "coagulation system" may contribute to resistance to NDV in Fayoumi chickens. The identified DEGs and predicted pathways may contribute to differential responses to NDV between the two chicken lines and provide potential targets for breeding chickens that are more resistant to NDV.

Novel Mechanisms Revealed in the Trachea Transcriptome of Resistant and Susceptible Chicken Lines following Infection with Newcastle Disease Virus.

Newcastle disease virus (NDV) has a devastating impact on poultry production in developing countries. This study examined the transcriptome of tracheal epithelial cells from two inbred chicken lines that differ in NDV susceptibility after challenge with a high-titer inoculum of lentogenic NDV. The Fayoumi line had a significantly lower NDV load postchallenge than the Leghorn line, demonstrating the Fayoumi line's classification as a relatively NDV-resistant breed. Examination of the trachea transcriptome showed a large increase in immune cell infiltration in the trachea in both lines at all times postinfection. The pathways conserved across lines and at all three time points postinfection included iCOS-iCOSL signaling in T helper cells, NF-κB signaling, the role of nuclear factor of activated T cells in the regulation of the immune response, calcium-induced T lymphocyte apoptosis, phospholipase C signaling, and CD28 signaling in T helper cells. Although shared pathways were seen in the Fayoumi and Leghorn lines, each line showed unique responses as well. The downregulation of collagen and the activation of eukaryotic translation initiation factor 2 signaling in the Fayoumis relative to the Leghorns at 2 days postinfection may contribute to the resistance phenotype seen in the Fayoumis. This study provides a further understanding of host-pathogen interactions which could improve vaccine efficacy and, in combination with genome-wide association studies, has the potential to advance strategies for breeding chickens with enhanced resistance to NDV.

Eggs: the uncracked potential for improving maternal and young child nutrition among the world's poor.

Eggs have been consumed throughout human history, though the full potential of this nutritionally complete food has yet to be realized in many resource-poor settings around the world. Eggs provide essential fatty acids, proteins, choline, vitamins A and B12 , selenium, and other critical nutrients at levels above or comparable to those found in other animal-source foods, but they are relatively more affordable. Cultural beliefs about the digestibility and cleanliness of eggs, as well as environmental concerns arising from hygiene practices and toxin exposures, remain as barriers to widespread egg consumption. There is also regional variability in egg intake levels. In Latin American countries, on average, greater proportions of young children consume eggs than in Asian or African countries. In China and Indonesia, nutrition education and social marketing have been associated with greater amounts of eggs in the diets of young children, though generally, evidence from interventions is minimal. Homestead chicken-and-egg production with appropriate vaccination, extension service, and other supports can simultaneously address poverty and nutrition in very poor rural households. With undernutrition remaining a significant problem in many parts of the world, eggs may be an uncracked part of the solution.

Modeling highly pathogenic avian influenza transmission in wild birds and poultry in West Bengal, India.

Wild birds are suspected to have played a role in highly pathogenic avian influenza (HPAI) H5N1 outbreaks in West Bengal. Cluster analysis showed that H5N1 was introduced in West Bengal at least 3 times between 2008 and 2010. We simulated the introduction of H5N1 by wild birds and their contact with poultry through a stochastic continuous-time mathematical model. Results showed that reducing contact between wild birds and domestic poultry, and increasing the culling rate of infected domestic poultry communities will reduce the probability of outbreaks. Poultry communities that shared habitat with wild birds or those indistricts with previous outbreaks were more likely to suffer an outbreak. These results indicate that wild birds can introduce HPAI to domestic poultry and that limiting their contact at shared habitats together with swift culling of infected domestic poultry can greatly reduce the likelihood of HPAI outbreaks.