In recent years, there has been a significant increase in detection of Enterovirus D-68 (EV-D68) among patients with severe respiratory infections worldwide. EV-D68 is now recognized as a re-emerging ...pathogen; however, due to lack of a permissive animal model for EV-D68, a comprehensive understanding of the pathogenesis and immune response against EV-D68 has been hampered. Recently, it was shown that EV-D68 has a strong affinity for α2,6-linked sialic acids (SAs) and we have shown previously that α2,6-linked SAs are abundantly present in the respiratory tract of cotton rats (Sigmodon hispidus). Thus, we hypothesized that cotton rats could be a potential model for EV-D68 infection. Here, we evaluated the ability of two recently isolated EV-D68 strains (VANBT/1 and MO/14/49), along with the historical prototype Fermon strain (ATCC), to infect cotton rats. We found that cotton rats are permissive to EV-D68 infection without virus adaptation. The different strains of EV-D68 showed variable infection profiles and the ability to produce neutralizing antibody (NA) upon intranasal infection or intramuscular immunization. Infection with the VANBT/1 resulted in significant induction of pulmonary cytokine gene expression and lung pathology. Intramuscular immunization with live VANBT/1 or MO/14/49 induced strong homologous antibody responses, but a moderate heterologous NA response. We showed that passive prophylactic administration of serum with high content of NA against VANBT/1 resulted in an efficient antiviral therapy. VANBT/1-immunized animals showed complete protection from VANBT/1 challenge, but induced strong pulmonary Th1 and Th2 cytokine responses and enhanced lung pathology, indicating the generation of exacerbated immune response by immunization. In conclusion, our data illustrate that the cotton rat is a powerful animal model that provides an experimental platform to investigate pathogenesis, immune response, anti-viral therapies and vaccines against EV-D68 infection.
Penguins are highly specialized divers that are expected to reflect environmental variation by adjusting their foraging behavior. We performed a comprehensive analysis of the at-sea distribution, ...diving, and foraging performance of Magellanic penguins (
Spheniscus magellanicus
) during the early chick-rearing period over two consecutive breeding seasons. The study was conducted at Cabo dos Bahías, (44° 54′ 50″ S; 65° 32′ 37″ W) a breeding colony located south of the latitudinal range of penguins’ main prey item Argentine anchovies (
Engraulis anchoita
). We also linked penguin foraging behavior to sea surface temperature (SST) to examine how birds cope with differences in oceanographic conditions. For this, we instrumented 37 adult penguins (18 in 2015 and 19 in 2016) with data loggers. In addition, we recorded chick growth in body mass during the first 12 days of life. Overall, the diving patterns of adult Magellanic penguins were similar in both breeding seasons. However, during 2015, adult breeders spent more time at the sea surface between foraging dives and performed more foraging dives per hour. The time spent foraging was higher in 2016 than in 2015. Foraging penguins also expanded their foraging range more than 100 km during 2016. Temperature records gathered by diving penguins during 2016 showed significantly higher temperatures, both at the sea surface as well as at the bottom of dives. Adults performed a higher foraging effort and chicks gained weight faster during 2016. Site-specific variability in prey distribution and abundance may be responsible for inter-seasonal discrepancies in the foraging and diving patterns. We reasoned that any environmental change could cause a shift in the distribution of anchovies, which would change the foraging behavior of penguins as they attempted to optimize their chick growth. Penguins from Cabo dos Bahías appear to face this environmental challenge with a highly sensitive at-sea foraging performance by increasing foraging effort when necessary.
Heterogeneity of COVID-19 manifestations in human population is vast, for reasons unknown. Cotton rats are a clinically relevant small animal model of human respiratory viral infections. Here, we ...demonstrate for the first time that SARS-CoV-2 infection in cotton rats affects multiple organs and systems, targeting species- and age-specific biological processes. Infection of S. fulviventer, which developed a neutralizing antibody response and were more susceptible to SARS-CoV-2 replication in the upper respiratory tract, was accompanied by hyperplasia of lacrimal drainage-associated lymphoid tissue (LDALT), a first known report of mucosa-associated lymphoid tissue activation at the portal of SARS-CoV-2 entry. Although less permissive to viral replication, S. hispidus showed hyperplasia of bone marrow in the facial bones and increased pulmonary thrombosis in aged males. Augmentation of these features by SARS-CoV-2 infection suggests a virus-induced breach in regulatory mechanisms which could be devastating for people of all ages with underlying conditions and in particular for elderly with a multitude of ongoing disorders.
Gestational Diabetes Mellitus (GDM) and obesity affect the functioning of multiple maternal systems and influence colonization of the newborn gastrointestinal through the breastmilk microbiota (BMM). ...It is currently unclear how GDM and obesity affect the human BMM composition. Here, we applied 16S-rRNA high-throughput sequencing to human colostrum milk to characterize BMM taxonomic changes in a cohort of 43 individuals classified in six subgroups according to mothers patho-physiological conditions (healthy control (n = 18), GDM (n = 13), or obesity (n = 12)) and newborn gender. Using various diversity indicators, including Shannon/Faith phylogenetic index and UniFrac/robust Aitchison distances, we evidenced that BMM composition was influenced by the infant gender in the obesity subgroup. In addition, the GDM group presented higher microbial diversity compared to the control group. Staphylococcus, Corynebacterium 1, Anaerococcus and Prevotella were overrepresented in colostrum from women with either obesity or GDM, compared to control samples. Finally, Rhodobacteraceae was distinct for GDM and 5 families (Bdellovibrionaceae, Halomonadaceae, Shewanellaceae, Saccharimonadales and Vibrionaceae) were distinct for obesity subgroups with an absolute effect size greater than 1 and a q-value ≤ 0.05. This study represents the first effort to describe the impact of maternal GDM and obesity on BMM.
Background Time in therapeutic range (TTR) of international normalized ratio (INR) of 2.0 to 3.0 is important for the safety and effectiveness of warfarin anticoagulation. There are few data on TTR ...among patients with atrial fibrillation (AF) in community-based clinical practice. Methods Using the US Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), we examined TTR (using a modified Rosendaal method) among 5,210 patients with AF on warfarin and treated at 155 sites. Patients were grouped into quartiles based on TTR data. Multivariable logistic regression modeling with generalized estimating equations was used to determine patient and provider factors associated with the lowest (worst) TTR. Results Overall, 59% of the measured INR values were between 2.0 and 3.0, with an overall mean and median TTR of 65% ± 20% and 68% (interquartile range IQR 53%-79%). The median times below and above the therapeutic range were 17% (IQR 8%-29%) and 10% (IQR 3%-19%), respectively. Patients with renal dysfunction, advanced heart failure, frailty, prior valve surgery, and higher risk for bleeding (ATRIA score) or stroke (CHA2 DS2 -VASc score) had significantly lower TTR ( P < .0001 for all). Patients treated at anticoagulation clinics had only slightly higher median TTR (69%) than those not (66%) ( P < .0001). Conclusions Among patients with AF in US clinical practices, TTR on warfarin is suboptimal, and those at highest predicted risks for stroke and bleeding were least likely to be in therapeutic range.
The present study evaluated the effect of the Fenton process as pretreatment for metronidazole (MNZ) removal coupled with a phytoremediation system using Scirpus lacustris as macrophyte. Initial ...concentrations of 0.5, 5, 10, 15, and 20 mg MNZ/L were studied in batch cultures. Results obtained in the MNZ removal by phytoremediation showed efficiencies of 93 ± 2%, 81 ± 4%, 85 ± 1%, 84 ± 2%, and 87 ± 6%, respectively. The metronidazole pretreated by the Fenton process and subsequently fed to the phytoremediation system increased the removal efficiencies up to 93 ± 3%, 99 ± 1%, 99 ± 4%, 94 ± 2%, and 94 ± 3%, respectively. Individual studies with Scirpus lacustris in touch with metronidazole displayed relative growth rates of 0.02-0.04 d
−1
, showing the not toxic effect of the antibiotic on the macrophyte growth. On the other hand, the BMG kinetic model best describes the removal of MNZ by phytoremediation. Finally, applying the Fenton process as a pretreatment makes the MNZ more assimilable for the phytoremediation system, converting the integration of Fenton with the phytoremediation like other attractive technology to be considered in removing emerging compounds.
Rest homes for the elderly have been particularly hit during the crisis due the current COVID-19 pandemic. At the time of writing this article, more than 17,500 elderly people that lived in Care ...Homes have died due to coronavirus, more than 66% of the deaths. The infection and mortality rates in the institutionalised population are high. This is due to the advanced age, immune system deficit, and the presence of comorbidities, as well as because there are frail, because they live with other residents and carers in a closed institution, and transmission is easy in the context of a highly contagious and virulent virus. The elderly often have more severe forms of the disease. Atypical presentations are more frequent in the elderly and can delay the diagnosis. The Polymer Chain Reaction (PCR) test in the first 7 days for the detection of SARS-CoV-2 viral RNA is considered the test of reference ('Gold standard'). The criteria for referring to a hospital site from Care Homes should take into account an assessment of comorbidity, the severity, the presence of severe cognitive impairment, and the dependency or necessity of ventilatory support in seriously ill patients. The social-health centres should have contingency plans available in order to offer a response when cases of COVID-19 appear. Isolation during pandemics may have important physical and psychosocial consequences in the residents. It is necessary to reflect and claim a new residential model from a person-centered care approach that seeks the integration of health and social services.
The cotton rat (Sigmodon) is the gold standard pre-clinical small animal model for respiratory viral pathogens, especially for respiratory syncytial virus (RSV). However, without a reference genome ...or a published transcriptome, studies requiring gene expression analysis in cotton rats are severely limited. The aims of this study were to generate a comprehensive transcriptome from multiple tissues of two species of cotton rats that are commonly used as animal models (Sigmodon fulviventer and Sigmodon hispidus), and to compare and contrast gene expression changes and immune responses to RSV infection between the two species. Transcriptomes were assembled from lung, spleen, kidney, heart, and intestines for each species with a contig N50 > 1600. Annotation of contigs generated nearly 120,000 gene annotations for each species. The transcriptomes of S. fulviventer and S. hispidus were then used to assess immune response to RSV infection. We identified 238 unique genes that are significantly differentially expressed, including several genes implicated in RSV infection (e.g., Mx2, I27L2, LY6E, Viperin, Keratin 6A, ISG15, CXCL10, CXCL11, IRF9) as well as novel genes that have not previously described in RSV research (LG3BP, SYWC, ABEC1, IIGP1, CREB1). This study presents two comprehensive transcriptome references as resources for future gene expression analysis studies in the cotton rat model, as well as provides gene sequences for mechanistic characterization of molecular pathways. Overall, our results provide generalizable insights into the effect of host genetics on host-virus interactions, as well as identify new host therapeutic targets for RSV treatment and prevention.
In the context of increasing global efforts to migrate towards more sustainable energy systems, Paraguay is notable for boosting a power system based entirely on renewable sources. Paradoxically it ...has one of the lowest rates of electricity consumption in Latin America. Hence, a carefully crafted energy transition policy aimed at maximizing its energy resources could be the cornerstone of the country's long-term development strategy. The process of crafting public policy, particularly for emerging countries, entails an intricate decision problem involving several policy options with the potential to influence the country's welfare and all dimensions of socio-economic development. Thus, we present a policy-making tool applied to the multi-criteria decision energy policy problem in Paraguay, based on an Analytic Hierarchy Process model, which can aid in the crafting of more nuanced decisions. Here, four policy options are considered based on economic, technical, social, environmental and political criteria. Our findings are significant for the on-going policy debate on the “surplus question” in Paraguay and suggest that, considering the model employed, a policy oriented at directing the surplus to leverage the industrial cluster development is the best option. Additionally, we believe the proposed model could benefit other emerging economies for addressing similar policy dilemmas.
•Policies for increasing the social welfare of a country with hydropower surplus.•New case study highlighting an energy transition in an emerging economy.•Four alternatives for the hydropower surplus use are analyzed under five criteria.•An AHP model assess the alternatives under different criteria weights.•Industrial sector development is the best alternative under the analyzed conditions.
Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Maternal immunization is an option to increase maternal antibody levels and protect infants from infection. ...Here we assess the efficacy of virus-like particle (VLP) vaccine candidates containing stabilized pre-fusion (pre-F) or post-fusion (post-F) conformations of the RSV F protein and the attachment RSV G protein in a maternal immunization model using cotton rats. VLP vaccines containing RSV F and G proteins strongly boost pre-existing RSV immunity in dams preventing their perinatal drop in immunity. Boosting is stronger for the pre-F VLP than for the post-F VLP or purified subunit F protein vaccines, giving an advantage on mothers' protection. VLP immunization of dams provides significant protection to pups from RSV challenge and reduced pulmonary inflammation. Collectively, our results show that a VLP vaccine with RSV F and G proteins is safe and effective for maternal and adult vaccination.
PDF
