Severe Acute Respiratory Syndrome Coronavirus 2 Vasculopathy in a Syrian Golden Hamster Model.

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.

Sylvatic Transmission of Chikungunya Virus among Nonhuman Primates in Myanmar.

Nonhuman primates living in proximity to humans increase risks for sylvatic arbovirus transmission. We collected serum samples from nonhuman primates in Hlawga National Park near Yangon, Myanmar, and detected antibodies against chikungunya (33%) and Japanese encephalitis (4%) viruses. Buffer zones between primate and human communities might reduce cross-species arbovirus transmission.

Respiratory Tract Explant Infection Dynamics of Influenza A Virus in California Sea Lions, Northern Elephant Seals, and Rhesus Macaques.

To understand susceptibility of wild California sea lions and Northern elephant seals to influenza A virus (IAV), we developed an ex vivo respiratory explant model and used it to compare infection kinetics for multiple IAV subtypes. We first established the approach using explants from colonized rhesus macaques, a model for human IAV. Trachea, bronchi, and lungs from 11 California sea lions, 2 Northern elephant seals, and 10 rhesus macaques were inoculated within 24 h postmortem with 6 strains representing 4 IAV subtypes. Explants from the 3 species showed similar IAV infection kinetics, with peak viral titers 48 to 72 h post-inoculation that increased by 2 to 4 log10 PFU/explant relative to the inoculum. Immunohistochemistry localized IAV infection to apical epithelial cells. These results demonstrate that respiratory tissue explants from wild marine mammals support IAV infection. In the absence of the ability to perform experimental infections of marine mammals, this ex vivo culture of respiratory tissues mirrors the in vivo environment and serves as a tool to study IAV susceptibility, host range, and tissue tropism. IMPORTANCE Although influenza A virus can infect marine mammals, a dearth of marine mammal cell lines and ethical and logistical challenges prohibiting experimental infections of living marine mammals mean that little is known about IAV infection kinetics in these species. We circumvented these limitations by adapting a respiratory tract explant model first to establish the approach with rhesus macaques and then for use with explants from wild marine mammals euthanized for nonrespiratory medical conditions. We observed that multiple strains representing 4 IAV subtypes infected trachea, bronchi, and lungs of macaques and marine mammals with variable peak titers and kinetics. This ex vivo model can define infection dynamics for IAV in marine mammals. Further, use of explants from animals euthanized for other reasons reduces use of animals in research.

Reconsidering the Role of Design Standards in Developing Effective Safety Labeling: Monolithic Recipes or Collections of Separable Features?

OBJECTIVE: This research investigated whether safety labeling design guidelines, such as the American National Standards Institute (ANSI) Z535 series, contribute to better warnings. BACKGROUND: Studies investigating the impact of safety label formatting on warning effectiveness have produced mixed findings. Additionally, research has failed to find a consistent relationship between measures of predicted and actual compliance. One commonality is that all of these studies have investigated the ANSI Z535 guidelines as a binary variable rather than as an integrative system of separable features. METHOD: We measured predicted compliance using both a within-subjects and a between-subjects design, but actual compliance using only a between-subjects design. Data were analyzed using both analysis of variance and linear/probit regressions to test the relationships between warning features recommended in the ANSI Z535 guidelines and measures of behavioral compliance. RESULTS: Predicted compliance assessed via a within-subjects design differed greatly from predicted compliance assessed via a between-subjects design. Levels of predicted and actual compliance were most similar when both measures were assessed using a between-subjects design. Consistent with previous research, location had a strong relationship with actual compliance, but surprisingly, presence of an ANSI-style orange warning header had a negative relationship with compliance. CONCLUSION: The choice of experimental design and analytical methods can dramatically influence a study's results and conclusions drawn. This research identified several aspects of experimental design that should be considered in future research on warning effectiveness. APPLICATION: Testing features recommended in the ANSI Z535 guidelines under varying conditions can contribute to the development of more effective warnings.

Role of Place in Explaining Racial Heterogeneity in Cognitive Outcomes among Older Adults.

Racially patterned disadvantage in Southern states, especially during the formative years of primary school, may contribute to enduring disparities in adult cognitive outcomes. Drawing on a lifecourse perspective, we examine whether state of school attendance affects cognitive outcomes in older adults and partially contributes to persistent racial disparities. Using data from older African American and white participants in the national Health and Retirement Study (HRS) and the New York based Washington Heights Inwood Cognitive Aging Project (WHICAP), we estimated age-and gender-adjusted multilevel models with random effects for states predicting years of education and cognitive outcomes (e.g., memory and vocabulary). We summarized the proportion of variation in outcomes attributable to state of school attendance and compared the magnitude of racial disparities across states. Among WHICAP African Americans, state of school attendance accounted for 9% of the variance in years of schooling, 6% of memory, and 12% of language. Among HRS African Americans, state of school attendance accounted for 13% of the variance in years of schooling and also contributed to variance in cognitive function (7%), memory (2%), and vocabulary (12%). Random slope models indicated state-level African American and white disparities in every Census region, with the largest racial differences in the South. State of school attendance may contribute to racial disparities in cognitive outcomes among older Americans. Despite tremendous within-state heterogeneity, state of school attendance also accounted for some variability in cognitive outcomes. Racial disparities in older Americans may reflect historical patterns of segregation and differential access to resources such as education.

The impact of neighborhood park access and quality on body mass index among adults in New York City.

OBJECTIVE: To evaluate the association between adult individuals' body mass index (BMI) and characteristics of parks (size and cleanliness) in an urban environment taking into account the physical and social environments of the neighborhood. METHODS: Cross-sectional, hierarchical linear models were used to determine whether park effects were associated with BMI using self-reported height and weight data obtained from the Community Health Survey in New York City (2002-2006). RESULTS: Both the proportion of the residential zip code that was large park space and the proportion that was small park space had significant inverse associations with BMI after controlling for individual socio-demographic and zip code built environment characteristics (-0.20 BMI units across the inter-quartile range (IQR) for large parks, 95% CI -0.32, -0.08; -0.21 BMI units across the IQR for small parks, 95% CI -0.31, -0.10, respectively). Poorer scores on the park cleanliness index were associated with higher BMI, 0.18 BMI units across the IQR of the park cleanliness index (95% CI 0.05, 0.30). CONCLUSIONS: This study demonstrated that proportion of neighborhoods that was large or small park space and park cleanliness were associated with lower BMI among NYC adults after adjusting for other neighborhood features such as homicides and walkability, characteristics that could influence park usage.

Developing a competency framework for U.S. state food and feed testing laboratory personnel.

A competency-based training curriculum framework for U.S. state food and feed testing laboratories personnel is being developed by the International Food Protection Training Institute (IFPTI) and three partners. The framework will help laboratories catalog existing training courses/modules, identify training gaps, inform training curricula, and create career-spanning professional development learning paths, ensuring consistent performance expectations and increasing confidence in shared test results. Ultimately, the framework will aid laboratories in meeting the requirements of ISO/IEC 17025 (2005) international accreditation and the U.S. Food Safety Modernization Act (U.S. Public Law 111-353). In collaboration with the Association of Food and Drug Officials, the Association of Public Health Laboratories, and the Association of American Feed Control Officials, IFPTI is carrying out the project in two phases. In 2013, an expert panel of seven subject matter experts developed competency and curriculum frameworks for five professional levels (entry, mid-level, expert, supervisor/manager, and senior administration) across four competency domains (technical, communication, programmatic, and leadership) including approximately 80 competencies. In 2014 the expert panel will elicit feedback from peers and finalize the framework.

Neighborhood walkability and active travel (walking and cycling) in New York City.

Urban planners have suggested that built environment characteristics can support active travel (walking and cycling) and reduce sedentary behavior. This study assessed whether engagement in active travel is associated with neighborhood walkability measured for zip codes in New York City. Data were analyzed on engagement in active travel and the frequency of walking or biking ten blocks or more in the past month, from 8,064 respondents to the New York City 2003 Community Health Survey (CHS). A neighborhood walkability scale that measures: residential, intersection, and subway stop density; land use mix; and the ratio of retail building floor area to retail land area was calculated for each zip code. Data were analyzed using zero-inflated negative binomial regression incorporating survey sample weights and adjusting for respondents' sociodemographic characteristics. Overall, 44 % of respondents reported no episodes of active travel and among those who reported any episode, the mean number was 43.2 episodes per month. Comparing the 75th to the 25th percentile of zip code walkability, the odds ratio for reporting zero episodes of active travel was 0.71 (95 % CI 0.61, 0.83) and the exponentiated beta coefficient for the count of episodes of active travel was 1.13 (95 % CI 1.06, 1.21). Associations between lower walkability and reporting zero episodes of active travel were significantly stronger for non-Hispanic Whites as compared to non-Hispanic Blacks and to Hispanics and for those living in higher income zip codes. The results suggest that neighborhood walkability is associated with higher engagement in active travel.

Socio-economic status, neighbourhood food environments and consumption of fruits and vegetables in New York City.

OBJECTIVE: Recommendations for fruit and vegetable consumption are largely unmet. Lower socio-economic status (SES), neighbourhood poverty and poor access to retail outlets selling healthy foods are thought to predict lower consumption. The objective of the present study was to assess the interrelationships between these risk factors as predictors of fruit and vegetable consumption. DESIGN: Cross-sectional multilevel analyses of data on fruit and vegetable consumption, socio-demographic characteristics, neighbourhood poverty and access to healthy retail food outlets. SETTING: Survey data from the 2002 and 2004 New York City Community Health Survey, linked by residential zip code to neighbourhood data. SUBJECTS: Adult survey respondents (n 15 634). RESULTS: Overall 9?9% of respondents reported eating $5 servings of fruits or vegetables in the day prior to the survey. The odds of eating $5 servings increased with higher income among women and with higher educational attainment among men and women. Compared with women having less than a high-school education, the OR was 1?12 (95% CI 0?82, 1?55) for high-school graduates, 1?95 (95% CI 1?43, 2?66) for those with some college education and 2?13 (95% CI 1?56, 2?91) for college graduates. The association between education and fruit and vegetable consumption was significantly stronger for women living in lower- v. higher-poverty zip codes (P for interaction,0?05). The density of healthy food outlets did not predict consumption of fruits or vegetables. CONCLUSIONS: Higher SES is associated with higher consumption of produce, an association that, in women, is stronger for those residing in lower-poverty neighbourhoods.

The development of a standards-based national curriculum framework for regulatory food safety training in the United States.

In response to the recognized need for a training system to support an integrated food safety system in the U.S., the International Food Protection Training Institute (IFPTI) in Battle Creek, Michigan, designed a career-spanning curriculum framework. IFPTI collaborated with a national curriculum team consisting of regulatory officials and university academics. The curriculum framework encompasses and organizes existing professional development for the estimated 45,000 federal, state, and local food regulators in the U.S. into efficient, standards-driven learning paths. This article describes the development process leading to an integrated national food protection training curriculum framework.

Acute bone loss following SARS-CoV-2 infection in mice.

The novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has infected more than 650 million people worldwide. Approximately 23% of these patients developed lasting "long-haul" COVID symptoms, including fatigue, joint pain, and systemic hyperinflammation. However, the direct clinical impact of SARS-CoV-2 infection on the skeletal system including bone and joint health has not been determined. Utilizing a humanized mouse model of COVID-19, this study provides the first direct evidence that SARS-CoV-2 infection leads to acute bone loss, increased osteoclast number, and thinner growth plates. This bone loss could decrease whole-bone mechanical strength and increase the risk of fragility fractures, particularly in older patients, while thinner growth plates may create growth disturbances in younger patients. Evaluating skeletal health in patients that have recovered from COVID-19 will be crucial to identify at-risk populations and develop effective countermeasures.

N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2.

The rapid emergence and global dissemination of SARS-CoV-2 that causes COVID-19 continues to cause an unprecedented global health burden resulting in nearly 7 million deaths. While multiple vaccine countermeasures have been approved for emergency use, additional treatments are still needed due to sluggish vaccine rollout, vaccine hesitancy, and inefficient vaccine-mediated protection. Immunoadjuvant compounds delivered intranasally can guide non-specific innate immune responses during the critical early stages of viral replication, reducing morbidity and mortality. N-dihydrogalactochitosan (GC) is a novel mucoadhesive immunostimulatory polymer of ß-0-4-linked N-acetylglucosamine that is solubilized by the conjugation of galactose glycans with current applications as a cancer immunotherapeutic. We tested GC as a potential countermeasure for COVID-19. GC was well-tolerated and did not produce histopathologic lesions in the mouse lung. GC administered intranasally before and after SARS-CoV-2 exposure diminished morbidity and mortality in humanized ACE2 receptor expressing mice by up to 75% and reduced infectious virus levels in the upper airway. Fluorescent labeling of GC shows that it is confined to the lumen or superficial mucosa of the nasal cavity, without involvement of adjacent or deeper tissues. Our findings demonstrate a new application for soluble immunoadjuvants such as GC for preventing disease associated with SARS-CoV-2 and may be particularly attractive to persons who are needle-averse.

Exposure to diverse sarbecoviruses indicates frequent zoonotic spillover in human communities interacting with wildlife.

BACKGROUND: Sarbecoviruses are a subgenus of Coronaviridae that mostly infect bats with known potential to infect humans (SARS-CoV and SARS-CoV-2). Populations in Southeast Asia, where these viruses are most likely to emerge, have been undersurveyed to date. METHODS: We surveyed communities engaged in extractive industries and bat guano harvesting from rural areas in Myanmar. Participants were screened for exposure to sarbecoviruses, and their interactions with wildlife were evaluated to determine the factors associated with exposure to sarbecoviruses. RESULTS: Of 693 people screened between July 2017 and February 2020, 12.1% were seropositive for sarbecoviruses. Individuals were significantly more likely to have been exposed to sarbecoviruses if their main livelihood involved working in extractive industries (logging, hunting, or harvesting of forest products; odds ratio [OR] = 2.71, P = 0.019) or had been hunting/slaughtering bats (OR = 6.09, P = 0.020). Exposure to a range of bat and pangolin sarbecoviruses was identified. CONCLUSION: Exposure to diverse sarbecoviruses among high-risk human communities provides epidemiologic and immunologic evidence that zoonotic spillover is occurring. These findings inform risk mitigation efforts needed to decrease disease transmission at the bat-human interface, as well as future surveillance efforts warranted to monitor isolated populations for viruses with pandemic potential.

Individual- and school-level sociodemographic predictors of obesity among New York City public school children.

To identify student- and school-level sociodemographic characteristics associated with overweight and obesity, the authors conducted cross-sectional analyses of data from 624,204 public school children (kindergarten through 12th grade) who took part in the 2007-2008 New York City Fitnessgram Program. The overall prevalence of obesity was 20.3%, and the prevalence of overweight was 17.6%. In multivariate models, the odds of being obese as compared with normal weight were higher for boys versus girls (odds ratio (OR) = 1.39, 95% confidence interval (CI): 1.36, 1.42), for black (OR = 1.11, 95% CI: 1.07, 1.15) and Hispanic (OR = 1.48, 95% CI: 1.43, 1.53) children as compared with white children, for children receiving reduced-price (OR = 1.17, 95% CI: 1.13, 1.21) or free (OR = 1.12, 95% CI: 1.09, 1.15) school lunches as compared with those paying full price, and for US-born students (OR = 1.54, 95% CI: 1.50, 1.58) as compared with foreign-born students. After adjustment for individual-level factors, obesity was associated with the percentage of students who were US-born (across interquartile range (75th percentile vs. 25th), OR = 1.10, 95% CI: 1.07, 1.14) and the percentage of students who received free or reduced-price lunches (across interquartile range, OR = 1.13, 95% CI: 1.10, 1.18). The authors conclude that individual sociodemographic characteristics and school-level sociodemographic composition are associated with obesity among New York City public school students.

Mucosal administration of a live attenuated recombinant COVID-19 vaccine protects nonhuman primates from SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 is an enveloped RNA virus that relies on its trimeric surface glycoprotein spike for entry into host cells. Here we describe the COVID-19 vaccine candidate MV-014-212, a live, attenuated, recombinant human respiratory syncytial virus expressing a chimeric SARS-CoV-2 spike as the only viral envelope protein. MV-014-212 was attenuated and immunogenic in African green monkeys (AGMs). One mucosal administration of MV-014-212 in AGMs protected against SARS-CoV-2 challenge, reducing by more than 200-fold the peak shedding of SARS-CoV-2 in the nose. MV-014-212 elicited mucosal immunoglobulin A in the nose and neutralizing antibodies in serum that exhibited cross-neutralization against virus variants of concern Alpha, Beta, and Delta. Intranasally delivered, live attenuated vaccines such as MV-014-212 entail low-cost manufacturing suitable for global deployment. MV-014-212 is currently in Phase 1 clinical trials as an intranasal COVID-19 vaccine.

Geographic distribution of dementia mortality: elevated mortality rates for black and white Americans by place of birth.

We hypothesized that patterns of elevated stroke mortality among those born in the United States Stroke Belt (SB) states also prevailed for mortality related to all-cause dementia or Alzheimer Disease. Cause-specific mortality (contributing cause of death, including underlying cause cases) rates in 2000 for United States-born African Americans and whites aged 65 to 89 years were calculated by linking national mortality records with population data based on race, sex, age, and birth state or state of residence in 2000. Birth in a SB state (NC, SC, GA, TN, AR, MS, or AL) was cross-classified against SB residence at the 2000 Census. Compared with those who were not born in the SB, odds of all-cause dementia mortality were significantly elevated by 29% for African Americans and 19% for whites born in the SB. These patterns prevailed among individuals who no longer lived in the SB at death. Patterns were similar for Alzheimer Disease-related mortality. Some non-SB states were also associated with significant elevations in dementia-related mortality. Dementia mortality rates follow geographic patterns similar to stroke mortality, with elevated rates among those born in the SB. This suggests important roles for geographically patterned childhood exposures in establishing cognitive reserve.

Reconsidering access: park facilities and neighborhood disamenities in New York City.

With increasing concern about rising rates of obesity, public health researchers have begun to examine the availability of parks and other spaces for physical activity, particularly in cities, to assess whether access to parks reduces the risk of obesity. Much of the research in this field has shown that proximity to parks may support increased physical activity in urban environments; however, as yet, there has been limited consideration of environmental impediments or disamenities that might influence individuals' perceptions or usage of public recreation opportunities. Prior research suggests that neighborhood disamenities, for instance crime, pedestrian safety, and noxious land uses, might dissuade people from using parks or recreational facilities and vary by neighborhood composition. Motivated by such research, this study estimates the relationship between neighborhood compositional characteristics and measures of park facilities, controlling for variation in neighborhood disamenities, using geographic information systems (GIS) data for New York City parks and employing both kernel density estimation and distance measures. The central finding is that attention to neighborhood disamenities can appreciably alter the relationship between neighborhood composition and spatial access to parks. Policy efforts to enhance the recreational opportunities in urban areas should expand beyond a focus on availability to consider also the hazards and disincentives that may influence park usage.

Neighbourhood immigrant acculturation and diet among Hispanic female residents of New York City.

OBJECTIVE: To identify predominant dietary patterns among Hispanic women and to determine whether adherence to dietary patterns is predicted by neighbourhood-level factors: linguistic isolation, poverty rate and the retail food environment. DESIGN: Cross-sectional analyses of predictors of adherence to dietary patterns identified from principal component analysis of data collected using the Study of Women's Health Across the Nation FFQ. Census data were used to measure poverty rates and the percentage of Spanish-speaking families in the neighbourhood in which no person aged ≥14 years spoke English very well (linguistic isolation) and the retail food environment was measured using business listings data. SETTING: New York City. SUBJECTS: A total of 345 Hispanic women. RESULTS: Two major dietary patterns were identified: a healthy dietary pattern loading high for vegetables, legumes, potatoes, fish and other seafood, which explained 17 % of the variance in the FFQ data and an energy-dense dietary pattern loading high for red meat, poultry, pizza, french fries and high-energy drinks, which explained 9 % of the variance in the FFQ data. Adherence to the healthy dietary pattern was positively associated with neighbourhood linguistic isolation and negatively associated with neighbourhood poverty. Presence of more fast-food restaurants per square kilometre in the neighbourhood was significantly associated with lower adherence to the healthy diet. Adherence to the energy-dense dietary pattern was inversely, but not significantly, associated with neighbourhood linguistic isolation. CONCLUSIONS: These results are consistent with the hypothesis that living in immigrant enclaves is associated with healthy dietary patterns among Hispanics.

Operationalizing diagnostic criteria for Alzheimer's disease and other age-related cognitive impairment-Part 1.

In this article, the challenges faced by several noted population studies for Alzheimer dementia in operationalizing current clinical diagnostic criteria for Alzheimer's disease (AD) have been reviewed. Differences in case ascertainment, methodological biases, cultural and educational influences on test performance, inclusion of special populations such as underrepresented minorities and the oldest old, and detection of the earliest symptomatic stages of underlying AD have been considered. Classification of Alzheimer dementia may be improved by the incorporation of biomarkers for AD if the sensitivity, specificity, and predictive value of the biomarkers are established and if they are appropriate for epidemiological studies, as may occur should a plasma biomarker be developed. Biomarkers for AD could also facilitate studies of the interactions of various forms of neurodegenerative disorders with cerebrovascular disease, resulting in "mixed dementia".

Big school, small school: (re)testing assumptions about high school size, school engagement and mathematics achievement.

In an effort to increase both adolescents' engagement with school and academic achievement, school districts across the United States have created small high schools. However, despite the widespread adoption of size reduction reforms, relatively little is known about the relationship between size, engagement and outcomes in high school. In response, this article employs a composite measure of engagement that combines organizational, sociological, and psychological theories. We use this composite measure with the most recent nationally-representative dataset of tenth graders, Educational Longitudinal Study: 2002, (N = 10,946, 46% female) to better assess a generalizable relationship among school engagement, mathematics achievement and school size with specific focus on cohort size. Findings confirm these measures to be highly related to student engagement. Furthermore, results derived from multilevel regression analysis indicate that, as with school size, moderately sized cohorts or grade-level groups provide the greatest engagement advantage for all students and that there are potentially harmful changes when cohorts grow beyond 400 students. However, it is important to note that each group size affects different students differently, eliminating the ability to prescribe an ideal cohort or school size.