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Western equine encephalitis virus (WEEV) is a mosquitoborne alphavirus that causes central nervous system (CNS) infection in humans and equids in the United States, Canada, and the southern cone of [...]

IntroductionLimited data exist on factors associated with concurrent use patterns of electronic nicotine delivery systems (ENDS) and cigarettes. We examined longitudinally perceptions and experiences with ENDS in relationship to concurrent use patterns among established, recent smokers who recently initiated ENDS.MethodsParticipant recruitment took place using paid digital advertisements on social media. Between December 2020 and October 2021, 303 adults aged ≥21 years from across the US who currently or recently smoked and had initiated ENDS use within the past 30 days or reinitiated ENDS use after more than one year of non-use were surveyed. Multinomial logistic regressions were conducted to analyze association between the outcome of current use pattern at follow-up at 1 month [rejectors (discontinued ENDS, continued smoking), primary smokers (concurrent users, mostly smoke), dual user (similar smoking and ENDS use), primary vapers (concurrent users, mostly vape), and switchers (discontinued smoking, continued using ENDS) or quitters (discontinued both smoking and ENDS] and perceptions of and experiences with ENDS predictors at baseline.ResultsAt follow-up at 1 to 2 months after initiating ENDS, 20% were rejectors, 31% were primary smokers, 13% were dual users, 19% were primary vapers, and 17% were switchers/quitters. Perceiving ENDS as less harmful than smoking or being uncertain and as equally or more enjoyable smoking, experiencing a lot or complete reduction in cravings to smoking and in irritability with ENDS use, liking the taste of ENDS, and being satisfied with vaping were associated with higher odds of quitting smoking compared to rejecting ENDS or mostly smoking at follow-up at 1 month.ConclusionsFindings highlight the importance of initial ENDS perceptions and experiences when examining tobacco outcomes and potentially for developing policies and interventions targeting smoking cessation. ENDS initiators are differentiating into distinct use patterns based on these factors within a short period of time.

Mayaro virus (MAYV) is an endemic and neglected mosquitoborne alphavirus that causes acute and chronic debilitating arthritogenic disease in Latin America and the Caribbean (1). MAYV infection can cause fever, [...]

Kedougou, Senegal's southeastern region, is a substantial arbovirus hotspot (1,2). Decades of comprehensive surveillance have existed through both a nationwide Syndromic Sentinel Surveillance Network (3) and passive surveillance in several [...]

Chikungunya virus (CHIKV) is a mosquitoborne alphavirus that has caused >10 million cases in >125 countries and territories in the past 2 decades. Chikungunya disease is characterized by acute and [...]

Understanding the molecular basis of innate immune evasion by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important consideration for designing the next wave of therapeutics. Here, we investigate the role of the nonstructural protein 16 (NSP16) of SARS-CoV-2 in infection and pathogenesis. NSP16, a ribonucleoside 2'-O-methyltransferase (MTase), catalyzes the transfer of a methyl group to mRNA as part of the capping process. Based on observations with other CoVs, we hypothesized that NSP16 2'-O-MTase function protects SARS-CoV-2 from cap-sensing host restriction. Therefore, we engineered SARS-CoV-2 with a mutation that disrupts a conserved residue in the active site of NSP16. We subsequently show that this mutant is attenuated both in vitro and in vivo, using a hamster model of SARS-CoV-2 infection. Mechanistically, we confirm that the NSP16 mutant is more sensitive than wild-type SARS-CoV-2 to type I interferon (IFN-I) in vitro. Furthermore, silencing IFIT1 or IFIT3, IFN-stimulated genes that sense a lack of 2'-O-methylation, partially restores fitness to the NSP16 mutant. Finally, we demonstrate that sinefungin, an MTase inhibitor that binds the catalytic site of NSP16, sensitizes wild-type SARS-CoV-2 to IFN-I treatment and attenuates viral replication. Overall, our findings highlight the importance of SARS-CoV-2 NSP16 in evading host innate immunity and suggest a target for future antiviral therapies. IMPORTANCE Similar to other coronaviruses, disruption of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) NSP16 function attenuates viral replication in a type I interferon-dependent manner. In vivo, our results show reduced disease and viral replication at late times in the hamster lung, but an earlier titer deficit for the NSP16 mutant (dNSP16) in the upper airway. In addition, our results confirm a role for IFIT1 but also demonstrate the necessity of IFIT3 in mediating dNSP16 attenuation. Finally, we show that targeting NSP16 activity with a 2'-O-methyltransferase inhibitor in combination with type I interferon offers a novel avenue for antiviral development.

The objective of this study was to determine the etiology of febrile illnesses among patients from October 1, 1993 through September 30, 1999, in the urban community of Iquitos in the Amazon River Basin of Peru. Epidemiological and clinical data as well as blood samples were obtained from consenting patients at hospitals, health clinics and private residences. Samples were tested for arboviruses in cell cultures and for IgM and IgG antibodies by ELISA. Blood smears were examined for malaria, and sera were tested for antibodies to Leptospira spp. by ELISA and microscopic agglutination. Among 6,607 febrile patients studied, dengue viruses caused 14.6% of the cases, and Venezuelan equine encephalitis virus caused 2.5%, Oropouche virus 1.0%, Mayaro virus 0.4%, and other arboviruses caused 0.2% of the cases. Also, 22.9% of 4,844 patients tested were positive for malaria, and of 400 samples tested, 9% had evidence of acute leptospirosis. Although the study was not designed to assess the importance of these pathogens as a cause of human morbidity in the total population, these results indicate that arboviruses, leptospirosis, and malaria were the cause of approximately 50% of the febrile cases. Although the arboviruses that were diagnosed can produce asymptomatic infections, our findings increased the overall understanding of the relative health burden of these infections, as well as baseline knowledge needed for designing and implementing further studies to better assess the health impact and threat of these pathogens in the Amazon Basin of Peru.

Chikungunya (CHIKV) is an emerging worldwide viral threat. The immune response to infection can lead to protection and convalescence or result in long-term sequelae such as arthritis. Early innate immune events during acute infection have been characterized for some cell types, but more must be elucidated with respect to cellular responses of monocytes and other myeloid lineage cells. In addition to their roles in protection and inflammation resolution, monocytes and macrophages are sites for viral replication and may also act as viral reservoirs. These cells are also found in joints postinfection, possibly playing a role in long-term CHIKV-induced pathology. We examined kinetic and phenotypic changes in myeloid lineage cells, including monocytes, in cynomolgus macaques early after experimental infection with CHIKV. We found increased proliferation of monocytes and decreased proliferation of myeloid dendritic cells early during infection, with an accompanying decrease in absolute numbers of both cell types, as well as a simultaneous increase in plasmacytoid dendritic cell number. An increase in CD16 and CD14 was seen along with a decrease in monocyte Human Leukocyte Antigen-DR isotype expression within 3 days of infection, potentially indicating monocyte deactivation. A transient decrease in T cells, B cells, and natural killer cells correlated with lymphocytopenia observed during human infections with CHIKV. CD4+ T cell proliferation decreased in blood, indicating relocation of cells to effector sites. These data indicate CHIKV influences proliferation rates and kinetics of myeloid lineage cells early during infection and may prove useful in development of therapeutics and evaluation of infection-induced pathogenesis.

ObjectivesIn this study, we used a discrete choice experiment (DCE) conducted August-October 2017 to examine electronic nicotine delivery systems (ENDS) product preferences in a national sample of adult smokers (N = 1154) who were also using ENDS or had not ruled out future use.MethodsThe DCE evaluated 5 ENDS attributes: relative harm; effectiveness for helping smokers quit; nicotine strength; flavor; and price. We asked participants to choose among their own cigarettes, 2 ENDS products whose attributes varied across tasks, or none. We analyzed ENDS preferences using multinomial, nested, and mixed logit regressions.ResultsSmokers preferred ENDS that are less harmful than cigarettes, are effective in helping smokers quit, are lower priced, and are not menthol-flavored. The marginal willingness to pay for an ENDS product was $8.40 when less harmful than cigarettes, $4.13 when of unknown effectiveness in helping quitting ($13.90 when effective), and $3.37 when ENDS are not menthol-flavored. Furthermore, the overall flavor preference is driven by tobacco smokers, not by menthol cigarette smokers who do prefer menthol-flavored ENDS.ConclusionsPolicies that affect perceptions of ENDS effectiveness in promoting cessation and their relative harm may alter smokers' ENDS preferences. Regulating flavors and price also may influence adult smokers' ENDS preference.

This study focuses on potential impacts of climate change on the early spring (March-April) temperature and its extremes in the mid-latitudes of North America, discriminated between the 1.5 °C and 2 °C levels of global warming, as projected by a suit of numerical experiments. The results suggest relatively mild seasonal average warming (0.25 °C-1.5 °C), but also an intensification of both warm and cold temperature extremes. The derived changes feature much stronger warming over the West of the United States and weak to no warming to the East, which is congruent with the ventilating effect of the intensified northerly wind over central Canada and the East of the United States. The intensified northerly component of the mid-latitude jet is likely a contributing factor to the derived increased seasonal variability of March-April temperatures over parts of Manitoba and Ontario in Canada, and the Midwest of the United States. The projected changes in temperature extremes agree to some extent with the previous studies: Warm extremes intensify especially over southern mid-latitudes, while cold extremes are weakening over the north mid-to high-latitudes. However, high-resolution simulations with the Community Atmospheric Model 5 (CAM5) indicate much sharper spatial gradients, which translate into higher magnitudes and also more complex patterns of changes. Particularly, cold extremes feature not only reductions north of ∼45°N latitudes, but also a very strong intensification of cold extremes (by-4 °C for 20 year return values) in the band 25°-45°N, centered in the Midwest of the United States. While general warming and intensification of the warm extremes may accelerate the arrival of early spring, the intensifying cold extremes may increase the risk of early spring frost damage, and hence may yield a profound impact on the regional agriculture of North America. Combined with reliable information on expected temperature variability at interannual-to-decadal timescales, the background longer-term projections can help inform decision makers in the food security sector.

In the Anthropocene, in which we now live, climate change is impacting most life on Earth. Microorganisms support the existence of all higher trophic life forms. To understand how humans and other life forms on Earth (including those we are yet to discover) can withstand anthropogenic climate change, it is vital to incorporate knowledge of the microbial 'unseen majority'. We must learn not just how microorganisms affect climate change (including production and consumption of greenhouse gases) but also how they will be affected by climate change and other human activities. This Consensus Statement documents the central role and global importance of microorganisms in climate change biology. It also puts humanity on notice that the impact of climate change will depend heavily on responses of microorganisms, which are essential for achieving an environmentally sustainable future.

The clinical outcomes associated with Zika virus (ZIKV) in the Americas have been well documented, but other aspects of the pandemic, such as attack rates and risk factors, are poorly understood. We prospectively followed a cohort of 1453 urban residents in Salvador, Brazil, and, using an assay that measured immunoglobulin G3 (IgG3) responses against ZIKV NS1 antigen, we estimated that 73% of individuals were infected during the 2015 outbreak. Attack rates were spatially heterogeneous, varying by a factor of 3 within a community spanning 0.17 square kilometers. Preexisting high antibody titers to dengue virus were associated with reduced risk of ZIKV infection and symptoms. The landscape of ZIKV immunity that now exists may affect the risk for future transmission.

There is an increasing global burden from chikungunya virus (CHIKV). Bangladesh reported a major epidemic in 2017, but it was unclear whether there had been prior widespread transmission. We conducted a nationally representative seroprevalence survey in 70 randomly selected communities immediately before the epidemic. We found that 69 of 2938 sampled individuals (2.4%) were seropositive to CHIKV. Seropositivity to dengue virus (adjusted odds ratio, 3.13 [95% confidence interval, 1.86–5.27]), male sex (0.59 [.36–.99]), and community presence of Aedes aegypti mosquitoes (1.80 [1.05–3.0]7) were significantly associated with CHIKV seropositivity. Using a spatial prediction model, we estimated that across the country, 4.99 (95% confidence interval, 4.89–5.08) million people had been previously infected. These findings highlight high population susceptibility before the major outbreak and that previous outbreaks must have been spatially isolated. [ABSTRACT FROM AUTHOR]

Severe winter storms in combination with precipitation extremes pose a serious threat to Europe. Located at the southeastern exit of the North Atlantic's storm track, European coastlines are directly exposed to impacts by high wind speeds, storm floods and coastal erosion. In this study we analyze potential changes in simulated winter storminess and extreme precipitation, which may occur under 1.5 or 2°C warming scenarios. Here we focus on a first simulation suite of the atmospheric model CAM5 performed within the HAPPI project and evaluate how changes of the horizontal model resolution impact the results regarding atmospheric pressure, storm tracks, wind speed and precipitation extremes. The comparison of CAM5 simulations with different resolutions indicates that an increased horizontal resolution to 0.25° not only refines regional-scale information but also improves large-scale atmospheric circulation features over the Euro-Atlantic region. The zonal bias in monthly pressure at mean sea level and wind fields, which is typically found in low-resolution models, is considerably reduced. This allows us to analyze potential changes in regional- to local-scale extreme wind speeds and precipitation in a more realistic way. Our analysis of the future response for the 2°C warming scenario generally confirms previous model simulations suggesting a poleward shift and intensification of the meridional circulation in the Euro-Atlantic region. Additional analysis suggests that this shift occurs mainly after exceeding the 1.5°C global warming level, when the midlatitude jet stream manifests a strengthening northeastward. At the same time, this northeastern shift of the storm tracks allows an intensification and northeastern expansion of the Azores high, leading to a tendency of less precipitation across the Bay of Biscay and North Sea. Regions impacted by the strengthening of the midlatitude jet, such as the northwestern coasts of the British Isles, Scandinavia and the Norwegian Sea, and over the North Atlantic east of Newfoundland, experience an increase in the mean as well as daily and sub-daily precipitation, wind extremes and storminess, suggesting an important influence of increasing storm activity in these regions in response to global warming.