Our aim was to obtain knowledge of how meteorological conditions affect community epidemics of respiratory syncytial virus (RSV) infection. To this end we recorded year-round RSV activity in nine ...cities that differ markedly in geographic location and climate. We correlated local weather conditions with weekly or monthly RSV cases. We reviewed similar reports from other areas varying in climate. Weekly RSV activity was related to temperature in a bimodal fashion, with peaks of activity at temperatures above 24–30°C and at 2–6°C. RSV activity was also greatest at 45–65% relative humidity. RSV activity was inversely related to UVB radiance at three sites where this could be tested. At sites with persistently warm temperatures and high humidity, RSV activity was continuous throughout the year, peaking in summer and early autumn. In temperate climates, RSV activity was maximal during winter, correlating with lower temperatures. In areas where temperatures remained colder throughout the year, RSV activity again became nearly continuous. Community activity of RSV is substantial when both ambient temperatures and absolute humidity are very high, perhaps reflecting greater stability of RSV in aerosols. Transmission of RSV in cooler climates is inversely related to temperature possibly as a result of increased stability of the virus in secretions in the colder environment. UVB radiation may inactivate virus in the environment, or influence susceptibility to RSV by altering host resistance.
Human respiratory syncytial virus (hRSV) is an important cause of lower respiratory tract infections in the pediatric and the geriatric population worldwide. There is a substantial economic burden ...resulting from hRSV disease during winter. Although no vaccines have been approved for human use, prophylactic therapies are available for high-risk populations. Choosing the proper animal models to evaluate different vaccine prototypes or pharmacological treatments is essential for developing efficient therapies against hRSV.
This article describes the relevance of using different animal models to evaluate the effect of antiviral drugs, pharmacological molecules, vaccine prototypes, and antibodies in the protection against hRSV. The animal models covered are rodents, mustelids, bovines, and nonhuman primates. Animals included were chosen based on the available literature and their role in the development of the drugs discussed in this manuscript.
Choosing the correct animal model is critical for exploring and testing treatments that could decrease the impact of hRSV in high-risk populations. Mice will continue to be the most used preclinical model to evaluate this. However, researchers must also explore the use of other models such as nonhuman primates, as they are more similar to humans, prior to escalating into clinical trials.
•Inclusion of high crude glycerin levels (210g/kg) in the diet decreased 4.1% of dry matter intake.•High levels (210g/kg) of crude glycerin decreased milk yield.•Dietary crude glycerin reduced ...neutral detergent fiber digestibility.•Crude glycerin at 210g/kg in the diet increased ruminal propionate proportions.
The objective of the current study was to evaluate the effects of increasing levels of crude glycerin on dry matter intake, nutrient digestibility, ruminal parameters, blood metabolites, milk yield and composition of dairy cows fed corn silage-based diets. Twenty-four Holstein cows (16 non-cannulated and 8 rumen-cannulated; 184±50 days in milk DIM and 594±39kg of body weight BW) were assigned to a replicated 4×4 Latin square design experiment, consisting of 14 days for adaptation to diets and 7 days for sampling. Cows were assigned to receive one of the diets: 0 (Control), 70, 140 or 210g of crude glycerin/kg of diet dry matter (DM). Dry matter intake and milk yield linearly decreased with the inclusion of crude glycerin. However, crude glycerin did not affect milk composition. Total-tract digestibility of DM, crude protein (CP) and ether extract (EE) linearly increased, and neutral detergent fiber (NDF) digestibility linearly decreased according to dietary inclusion of crude glycerin. Feeding crude glycerin changed volatile fatty acid concentrations: linearly increased propionate, quadratically affected butyrate, and linearly decreased acetate concentrations, resulting in lower acetate to propionate ratio. Total volatile fatty acid was not affected by crude glycerin. Ruminal NH3-N linearly decreased according to crude glycerin dietary levels. Crude glycerin linearly increased blood glucose concentration. Inclusion of high levels of crude glycerin (210g/kg) in diets of mid-lactating cows, increased dry matter digestibility and ruminal propionate concentrations, but negatively affected dry matter intake and milk yield.
The investigation focuses on an on-off protocol for relieving the COVID-19 widespread. The protocol establishes a working period of 4 days for all the citizens, followed by 8 days of lock-down. We ...further propose splitting people into smaller groups that accomplish the on-off protocol, but shifted in time. This procedure is expected to regularize the overall economic activity. Our results show that either the protocol and the splitting procedure relieve the spreading. However, the latter seems to be better for economic reasons. Our simulations further show that the start-up time is a key issue for the success of the implementation.
A síndrome mielodisplásica pediátrica (SMD-p) é rara, sua etiopatologia é complexa e ainda não se sabe a causa de seu surgimento. Embora avanços rápidos tenham sido feitos na SMD no adulto, a ...genética e epigenética da SMD-p ainda são pouco compreendidas. Nesse sentido, o objetivo deste trabalho foi caracterizar as alterações citogenéticas e epigenéticas em SMD-p para verificar sua associação com seu desenvolvimento e evolução para LMA, buscando identificar marcadores de diagnóstico e prognóstico.
A análise citogenética foi realizada por bandeamento GTG e FISH. O estudo de expressão dos genes da maquinaria de metilação (DNMTs) e desmetilação (TET2/APOBEC3B) foram realizados por PCR quantitativa em tempo real. O perfil de metilação do gene p15INK4B foi estudado por pirosequenciamento.
Dos 200 pacientes estudados citogeneticamente 50,5% apresentaram cariótipo anormal, sendo as alterações mais frequentes: -7, del(11)(q23), cariótipos complexos e +8. Essas alterações também estiveram associadas com a evolução da doença, que foi observada em 29% dos casos. O estudo epigenético mostrou uma super-expressão das DNMTS em relação aos controles (DNMT1 (p < 0,01); DNMT3A (p < 0,02) e DNMT3B (p < 0,01). Esse aumento de expressão esteve associado ao desenvolvimento e evolução para LMA (DNMT1 p < 0,03, DNMT3A p < 0,02, DNMT3B p < 0,004). A expressão de TET2 e APOBEC3B nos pacientes não apresentou diferenças significativas em relação aos controles. A hipermetilação do gene p15INK4B foi observada em 35% (15/43) dos pacientes, estando mais presente em SMD-EB/SMD-EB-t (60%). A hipermetilação do gene p15INK4B foi associada ao aumento de expressão em DNMT1 (p < 0,001), assim como os cariótipos anormais (p < 0,006), sendo as principais alterações: -7/del7q (p < 0,003).
Nossos resultados mostraram que a CRI foi o subtipo mais comum, sendo as alterações associadas à evolução: -7, cariótipos complexos corroborando com a literatura. No entanto, diferente do esperado pela classificação do IPSS-R pacientes com del(11)(q23) e +8, também estiveram associados com a evolução da doença. Alterações epigenéticas na SMD-p são sutis sendo raras mutações DNMT3A e TET2. No entanto, observamos um aumento de expressão das DNMTs associada com a evolução da doença e a hipermetilação em p15INK4B. Enquanto a expressão dos genes da maquinaria de desmetilação foi semelhante aos controles. Estudos mostram que o envelhecimento está associação há uma maior desregulação na maquinaria de metitilação e desmetilação do DNA dos pacientes com SMD, contudo podemos observar que essas alterações tentem a acentuar com a evolução da doença para alguns genes importantes como o p15INK4B.
Nossos resultados mostraram que durante o desenvolvimento e evolução de SMD-p para LMA há um desbalanço progressivo na maquinaria de metilação com aumento de expressão das DNMTs. A hipermetilação em p15INK4B foi um evento mais tardio associado à progressão da SMD, principalmente nos pacientes que apresentaram -7/del(7q). Em conjunto nossos resultados sugerem um modelo de evolução de SMD para LMA.
INCA – Ministério da Saúde, FAPERJ.
Thanks to tremendous experimental efforts, galactic cosmic-ray fluxes are being measured up to the unprecedented percent precision level. The logarithmic slope of these fluxes is a crucial quantity ...that promises us information on the diffusion properties and the
primary
or
secondary
nature of the different species. However, these measured slopes are sometimes interpreted in the pure diffusive regime, guiding to misleading conclusions. In this paper, we have studied the propagation of galactic cosmic rays by computing the fluxes of species between H and Fe using the USINE code and considering all the relevant physical processes and an updated set of cross-section data. We show that the slope of the well-studied secondary-to-primary B/C ratio is distinctly different from the diffusion coefficient slope, by an offset of
∼
0.2
in the rigidity range in which the AMS-02 data reach their best precision (several tens of GV). Furthermore, we have demonstrated that none of the species from H to Fe follows the expectations of the pure-diffusive regime. We argue that these differences arise from propagation processes such as fragmentation, convection, and reacceleration, which cannot be neglected. On this basis, we also provide predictions for the spectral slope of elemental fluxes not yet analysed by the AMS collaboration.
Studying the isotopic composition of single-charge cosmic rays (CRs) provides essential data to investigate the CR propagation processes in our Galaxy. While current measurements are rare above 4 ...GeV/nucleon, the Alpha Magnetic Spectrometer (AMS-02) is able to measure the isotopic fluxes up to 10 GeV/n by combining the momentum measured by the silicon tracker with the precise measurements of the velocity provided by its Ring Imaging Cherenkov Detector (RICH). The correct measurement of the particles’ velocity is essential for identifying isotopes through their mass. This is particularly challenging for single-charge particles due to the low number of photons they produce in their Cherenkov rings, which makes the reconstruction easily disrupted by noise. Hence, identifying the sources and cleaning the sample from the background is essential for ensuring the quality of the rings. In this paper, we propose a novel approach to track the events whose mass is misidentified due to interactions inside the AMS-02 detector. Based on the actual location of these interactions, we propose a novel strategy to mitigate the background effectively and with high efficiency, which includes using cut-based selection criteria and a multivariate estimator based on the signals detected by the RICH.
The measurement of the isotopic composition of cosmic rays (CRs) provides essential insights into the understanding of the origin and propagation of these particles, namely the CR source spectra, the ...propagation processes and the galactic halo size. The Alpha Magnetic Spectrometer (AMS-02), a CR experiment operating aboard the International Space Station since May 2011, has the capability of performing these measurements due to its precise determination of the velocity provided by its Time of Flight (TOF) and Ring Imaging Cherenkov (RICH) detectors. The correct interpretation of the data requires the measurements to be deconvoluted from the instrumental effects. The unique design of AMS-02, with more than one detector being used to measure the same particle flux, requires a novel approach to unfold the measured fluxes. In this work, we apply for the first time the so-called iterative-bayesian approach in the context of the direct measurement of the cosmic-ray fluxes. Moreover, we introduce a non-parametric regularization method for the detector response functions and a single, smooth flux prior covering the range of measurements from both detectors, TOF and RICH. The accuracy of the method is assessed using a simulated flux based on previous AMS-02 measurements and taking into account the full detector response. In addition, the estimation of the errors and a discussion about the performance of the method are also shown, demonstrating that the method is fast and reliable, allowing for the recovery of the true particle fluxes in the whole energy range.
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