[COVID-19 in Brazil: trends, challenges, and perspectives after 18 months of the pandemicCOVID-19 en Brasil: tendencias, desafíos y perspectivas después de 18 meses de pandemia]. / COVID-19 no Brasil: tendências, desafios e perspectivas após 18 meses de pandemia.

Objective: To analyze the incidence and mortality trends from COVID-19 in Brazil as well as in federation units and their capitals. Method: An ecological study was performed using COVID-19 incidence and mortality data covering the period from 25 February 2020 (first case recorded in Brazil) to 31 July 2021. Data were grouped by month for calculation of crude rates (by 100 000 population) and assessment of time trends in federation units and capitals. Significant changes in time trends were analyzed by joinpoint regression. Results: Two waves of new cases and deaths were identified. The highest incidence rates were recorded in the states of Amapá, Rio Grande do Norte, Rondônia, and Roraima. The states of Amazonas and Rondônia had the highest mortality rates. In general, incidence and mortality rates were worse in the second wave. In the first wave, the mean number of months until the onset of reduction in new cases was higher in capitals, whereas in the second wave the onset of reduction in new cases took longer in the federation units. The decline in mortality began earlier in capital cities in both waves. Conclusion: The regional differences detected underscore the notion that COVID-19 incidence and mortality are associated with political, geographic, cultural, social, and economic factors.

Objetivo: Analizar las tendencias de la incidencia de COVID-19 y la mortalidad por esta enfermedad en Brasil (unidades federativas y capitales). Método: Se realizó un estudio ecológico con datos sobre incidencia de COVID-19 y la mortalidad por esta enfermedad en el período comprendido entre el 25 de febrero del 2020 (fecha del primer caso notificado en Brasil) y el 31 de julio del 2021. Los datos se agruparon por mes para calcular las tasas brutas (por 100 000 habitantes) y evaluar las tendencias temporales observadas en las unidades federativas y sus capitales. Las modificaciones significativas en las tendencias temporales se analizaron con el método de regresión de punto de inflexión (joinpoint). Resultados: Se identificaron dos olas de casos nuevos y muertes. Las unidades federativas con las mayores tasas de incidencia fueron Amapá, Rio Grande do Norte, Rondônia y Roraima; Amazonas y Rondônia tuvieron las mayores tasas de mortalidad. En general, la incidencia y la mortalidad fueron peores en la segunda ola. En la primera ola, el promedio de meses transcurridos hasta que empezó a reducirse el número de casos nuevos fue mayor en las capitales, mientras que, en la segunda ola, fue mayor en los estados. En ambas olas, el número de muertes se redujo en menos tiempo en las capitales. Conclusión: La heterogeneidad regional detectada refuerza la idea de que la incidencia de la COVID-19 y la mortalidad por esta enfermedad guardan relación con factores políticos, geográficos, culturales, sociales y económicos.

Adressing Energy Demand and Climate Change through the Second Law of Thermodynamics and LCA towards a Rational Use of Energy in Brazilian Households.

This study focuses on a typical Brazilian household through the lens of sustainable development, regarding energy demand and GHG emissions. The analysis encompasses both the direct and indirect energy, exergy consumption, and GHG emissions (quantified by life cycle assessment) associated with the usual routine of a household. The household is modeled as a thermodynamic system to evaluate inputs (food, electricity, fuels for transportation) and outputs (solid and liquid residues). The hypothesis is that each input and output contains CO2,eq emissions and exergy derived from its physical-chemical characteristics or production chains. Each household appliance is modeled and tested as a function of external parameters. The contribution of several industries was obtained to the total GHG emissions and exergy flows entering and exiting the household (e.g., fuels for transportation, food, gas, electricity, wastewater treatment, solid waste). It was verified that urban transportation was the flow with the highest GHG and exergy intensity, ranging between 1.49 and 7.53 kgCO2,eq/day and achieving 94.7 MJ/day, almost five times higher than the calculated exergy demand due to electricity. The second largest flow in GHG emissions was food due to the characteristics of the production chains, ranging from 1.6 to 4.75 kgCO2,eq/day, depending on the adopted diet. On the other hand, the electricity presented low GHG emissions due to the main energy sources used to generate electricity, only 0.52 kgCO2,eq/day. Moreover, the chemical exergy of the solid waste was 9.7 MJ/day, and is not irrelevant compared to the other flows, representing an interesting improvement opportunity as it is entirely wasted in the baseline scenario.

Energy, exergy and exergoenvironmental analyses of a sugarcane bagasse power cogeneration system.

One of the strategies to reduce the environmental impacts associated with electricity is to employ renewable resources such as biomass or even waste. However, the evaluation of the sustainability of a power plant depends on the development of several analyses, which should encompass thermodynamic and environmental parameters. Energy, exergy, and exergoenvironmental assessments are carried out for a sugarcane bagasse cogeneration system, along with a Life Cycle Assessment for the Brazilian sugarcane bagasse, employing the Eco-indicator 99 method. The specific environmental impacts of electricity and steam are 6.023 mPt/MJ and 4.038 mPt/MJ, respectively, and the boiler feed pump and radiator presented the highest average environmental impact per exergy of fuel and product, respectively. The component with the highest exergoenvironmental factor was the furnace (60.32%), demonstrating margins for benefits in the formation of pollutants and destruction of exergy. Exergoenvironmental assessments can be utilized to support the adoption of more efficient (although more complex) cogeneration systems, especially in the aftermath of the COVID-19 crisis.

Comparison of self-expanding and balloon-expandable transcatheter aortic valves morphology and association with paravalvular regurgitation: Evaluation using multidetector computed tomography.

OBJECTIVES: Compare final morphology of self-expanding and balloon-expandable prosthesis and association with paravalvular regurgitation (PVR). BACKGROUND: PVR after transcatheter aortic valve replacement (TAVR) remains a frequent complication. A better understanding of the prosthesis geometry may be important to improve selection of the best device for each case and possibly reduce the rates of PVR. METHODS: Retrospective study including patients consecutively submitted to transcatheter aortic valve replacement: August/2007-October/2016. Three months after the procedure a multidetector computed tomography (MDCT) was performed to assess prosthesis geometry: dimensions, eccentricity, and expansion. RESULTS: A total of 147 individuals were included (mean age of 78.8 ± 6.7 and 50.3% males), 57% treated with a self-expanding prosthesis. On the postprocedure MDCT, the self-expanding group had higher eccentricity index (15.0 vs. 7.1%, p < .001) and lower expansion (68.3 vs. 82.8%, p < .001). In that group, the volume of calcium of landing zone had a significant correlation with eccentricity index and under-expansion. Patients with ≥mild PVR presented higher eccentricity (12.6 vs. 7.9%, p < .001) and lower expansion (68 vs. 75%, p = .012). Eccentricity index and landing zone calcium volume were independent predictors of PVR. CONCLUSIONS: Self-expanding prosthesis have greater eccentricity and under-expansion. Calcium burden exerts more influence in the final morphology of that type of valve. Calcification and eccentricity are associated with the development of PVR. These factors should be considered in the selection of the most appropriate type of prosthesis for each scenario.

Epithelial Mesenchymal Transition Induces Aberrant Glycosylation through Hexosamine Biosynthetic Pathway Activation.

Deregulated cellular metabolism is a hallmark of tumors. Cancer cells increase glucose and glutamine flux to provide energy needs and macromolecular synthesis demands. Several studies have been focused on the importance of glycolysis and pentose phosphate pathway. However, a neglected but very important branch of glucose metabolism is the hexosamine biosynthesis pathway (HBP). The HBP is a branch of the glucose metabolic pathway that consumes ∼2-5% of the total glucose, generating UDP-GlcNAc as the end product. UDP-GlcNAc is the donor substrate used in multiple glycosylation reactions. Thus, HBP links the altered metabolism with aberrant glycosylation providing a mechanism for cancer cells to sense and respond to microenvironment changes. Here, we investigate the changes of glucose metabolism during epithelial mesenchymal transition (EMT) and the role of O-GlcNAcylation in this process. We show that A549 cells increase glucose uptake during EMT, but instead of increasing the glycolysis and pentose phosphate pathway, the glucose is shunted through the HBP. The activation of HBP induces an aberrant cell surface glycosylation and O-GlcNAcylation. The cell surface glycans display an increase of sialylation α2-6, poly-LacNAc, and fucosylation, all known epitopes found in different tumor models. In addition, modulation of O-GlcNAc levels was demonstrated to be important during the EMT process. Taken together, our results indicate that EMT is an applicable model to study metabolic and glycophenotype changes during carcinogenesis, suggesting that cell glycosylation senses metabolic changes and modulates cell plasticity.

The scaling of the hydraulic architecture in poplar leaves.

Although much is known about the hydraulics of xylem, the hydraulic interconnectivity and dimensional scaling of phloem with respect to xylem in leaves has not been adequately studied to test alternative hydraulic architectural rules such as da Vinci's rule or Murray's rule, or physiological models such as Münch's Pressure Flow hypothesis. Using confocal and electron microscopy as well as mathematical analyses, we examined the hydraulic architecture of the mature leaves of the model species Populus tremula × alba across all seven hierarchical orders of the vascular branching. We show that: phloem and xylem conductive areas increase from minor to major veins; the sum of the conductive areas for each vein order increases exponentially from major to minor veins; the volume of individual sieve tube and vessel members increases from minor to major veins; and phloem conductive area scales isometrically with respect to xylem area across all vein orders. The application of first principles to our data shows that conductive areas scale according to da Vinci's rule and not according to Murray's rule, and that the phloem network in poplar leaves can generate the pressure gradient envisioned in Münch's hypothesis.

The hydraulic architecture of Ginkgo leaves.

PREMISE OF THE STUDY: The hydraulics of xylem has been widely studied in numerous species and organ types. However, comparatively little is known about how phloem and xylem are hydraulically coupled or about many of the basic structural properties of phloem (such as conducting cell numbers and conductive areas), which nevertheless have direct bearing on understanding phloem loading and unloading. METHODS: Using a combination of light, epifluorescence, confocal, and transmission electron microscopy, we quantified the hydraulic architecture of Ginkgo biloba leaf laminae and examined the scaling relationships between phloem and xylem in five fully mature leaves. KEY RESULTS: The conductive areas and lengths of sieve cells and tracheids increase basipetally toward the petiole in a manner that is consistent with Münch's pressure flow hypothesis for phloem transport. This trend holds true for individual veins, the sum of conductive areas across all veins at any distance from the petiole, and for individual sieve cells and tracheids. Further, the conductive areas of phloem and xylem are isometrically correlated across the entire vasculature of the leaf lamina. The data for conducting cell areas do not conform with the predictions of the hydraulic models of da Vinci and Murray. CONCLUSIONS: The scaling of Ginkgo lamina hydraulics complies with that observed in leaves of other gymnosperms and most angiosperms and is inconsistent with theoretical models that assume that the volume of transported incompressible fluids is conserved.

Ecology and biotechnological potential of bacterial community from three marine sponges of the coast of Rio de Janeiro, Brazil.

Marine sponges has been a large reservoir of microbial diversity, with the presence of many species specific populations as well as producing biologically active compounds, which has attracted great biotechnological interest. In order to verify the influence of the environment in the composition of the bacterial community present in marine sponges and biotechnological potential of bacteria isolated from these organisms, three species of sponges and the waters surrounding them were collected in different beaches of Rio de Janeiro, Brazil. The profile of the bacterial community present in sponges and water was obtained by PCR-DGGE technique and the biotechnological potential of the strains isolated by producing amylase, cellulase, protease and biosurfactants. The results showed that despite the influence of the environment in the composition of the microbial community, studied marine sponges shown to have specific bacterial populations, with some, showing potential in the production of substances of biotechnological applications.

Environmental evaluation of the life cycle of elephant grass fertilization-Cenchrus purpureus (Schumach.) Morrone-using chemical fertilization and biosolids.

Law 12305/10, National Solid Waste Policy of Brazil, banned the disposal in landfills of any solid waste that could be converted to another use. Sludge produced at Industrial Wastewater Treatment Plants, which contains components characteristic of fertilizers, falls into this category. This type of sludge, also known as a biosolid, has great potential to replace commercial chemical fertilization. The use of biosolids in agriculture allows for compliance with new legislation, reducing the burden on landfills and reusing a waste product. The present paper utilizes the life cycle assessment methodology to compare the carbon footprint associated with the use of different quantities of biosolid and selected chemical fertilizers in the production of elephant grass. The IPCC 2013 GWP 100a method, which is based on data published by the Intergovernmental Panel on Climate Change, was selected as the environmental assessment method. The method expresses the emissions of greenhouse gases generated, in kilograms of CO2 equivalent, over a time horizon of 100 years. The biosolid quantities used were based on the Brazilian Environment Council Resolution 375. The chemical fertilizer used contained urea, simple superphosphate, and potassium chloride. The use of biosolids in the amounts calculated according to Brazilian standards resulted in a carbon footprint approximately 17.7% lower than the use of the chemical fertilization mix, with similar productivity in both cases. The transportation of biosolids to the experimental area was responsible for the majority of emissions associated with the use of biosolids. Urea synthesis was the largest contributor to emissions resulting from the use of commercial chemical fertilizer, accounting for 73.6% of total emissions.

Spatiotemporal distribution of essential elements through Populus leaf ontogeny.

We examined the spatiotemporal distribution and accumulation of calcium (Ca), potassium (K), and zinc (Zn) during the growth and maturation of grey poplar (Populus tremula × alba) leaves covering plastochrons 01 through 10. This period spans the sugar sink-to-source transition and requires coordinated changes of multiple core metabolic processes that likely involve alterations in essential and non-essential element distributions as tissues mature and effect a reversal in phloem flow direction. Whole-leaf elemental maps were obtained from dried specimens using micro X-ray fluorescence spectroscopy. Additional cross-sections of fresh leaves were scanned to check for tissue specificity in element accumulation. The anatomical distribution of Zn and K remains relatively consistent throughout leaf development; Ca accumulation varied across leaf developmental stages. The basipetal allocation of Ca to the leaf mesophyll matched spatially and temporally the sequence of phloem maturation, positive carbon balance, and sugar export from leaves. The accumulation of Ca likely reflects the maturation of xylem in minor veins and the enhancement of the transpiration stream. Our results independently confirm that xylem and phloem maturation are spatially and temporally coordinated with the onset of sugar export in leaves.

Exogenous citrate impairs glucose tolerance and promotes visceral adipose tissue inflammation in mice.

Overweight and obesity have become epidemic worldwide and are linked to sedentary lifestyle and the consumption of processed foods and drinks. Citrate is a metabolite that plays central roles in carbohydrate and lipid metabolism. In addition, citrate is the additive most commonly used by the food industry, and therefore is highly consumed. Extracellular citrate can freely enter the cells via the constitutively expressed plasma membrane citrate transporter. Within the cytosol, citrate is readily metabolised by ATP-citrate lyase into acetyl-CoA - the metabolic precursor of endogenously produced lipids and cholesterol. We therefore hypothesised that the citrate ingested from processed foods and drinks could contribute to increased postprandial fat production and weight gain. To test our hypothesis, we administered citrate to mice through their drinking water with or without sucrose and monitored their weight gain and other metabolic parameters. Our results showed that mice receiving citrate or citrate+sucrose did not show increased weight gain or an increase in the weight of the liver, skeletal muscles or adipose tissues (AT). Moreover, the plasma lipid profiles (TAG, total cholesterol, LDL and HDL) were similar across all groups. However, the group receiving citrate+sucrose showed augmented fasting glycaemia, glucose intolerance and the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6 and IL-10) in their AT. Therefore, our results suggest that citrate consumption contributes to increased AT inflammation and altered glucose metabolism, which is indicative of initial insulin resistance. Thus, citrate consumption could be a previously unknown causative agent for the complications associated with obesity.

A Late Cretaceous Piper (Piperaceae) from Colombia and diversification patterns for the genus.

PREMISE OF THE STUDY: Documented fossil floras in the neotropics are sparse, yet their records provide evidence on the spatial and temporal occurrence of taxa, allowing for testing of biogeographical and diversification scenarios on individual lineages. A new fossil Piper from the Late Cretaceous of Colombia is described here, and its importance for assessing diversification patterns in the genus is addressed. METHODS: Leaf architecture of 32 fossil leaf compressions from the Guaduas Formation was compared with that of 294 extant angiosperm species. The phylogenetic position of the fossil named Piper margaritae sp. nov. was established based on leaf traits and a molecular scaffold of Piper. The age of the fossil was independently used as a calibration point for divergence time estimations. KEY RESULTS: Natural affinities of P. margaritae to the Schilleria clade of Piper indicate that the genus occurred in tropical America by the Late Cretaceous. Estimates of age divergence and lineage accumulation reveal that most of the extant diversity of the genus accrued during the last ∼30 Myr. CONCLUSIONS: The recent radiation of Piper is coeval with both the Andean uplift and the emergence of Central America, which have been proposed as important drivers of diversity. This pattern could exemplify a recurrent theme among many neotropical plant lineages.

Toward male individualization with rapidly mutating y-chromosomal short tandem repeats.

Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, >99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RM Y-STRs in identifying and separating unrelated and related males and provides a reference database.

Cenozoic seeds of Vitaceae reveal a deep history of extinction and dispersal in the Neotropics.

The remarkably diverse plant communities of the Neotropics are the result of diversification driven by multiple biotic (for example, speciation, extinction and dispersal) and abiotic (for example, climatic and tectonic) processes. However, in the absence of a well-preserved, thoroughly sampled and critically assessed fossil record, the associated processes of dispersal and extinction are poorly understood. We report an exceptional case study documenting patterns of extinction in the grape family (Vitaceae Juss.) on the basis of fossil seeds discovered in four Neotropical palaeofloras dated between 60 and 19 Ma. These include a new species that provides the earliest evidence of Vitaceae in the Western Hemisphere. Eight additional species reveal the former presence of major clades of the family that are currently absent from the Neotropics and elucidate previously unknown dispersal events. Our results indicate that regional extinction and dispersal have substantially impacted the evolutionary history of Vitaceae in the Neotropics. They also suggest that while the Neotropics have been dynamic centres of diversification through the Cenozoic, extant Neotropical botanical diversity has also been shaped by extensive extinction over the past 66 million years.

First record of Todea (Osmundaceae) in South America, from the early Eocene paleorainforests of Laguna del Hunco (Patagonia, Argentina).

PREMISE OF THE STUDY: The early Eocene Laguna del Hunco caldera-lake paleoflora (ca. 52 Ma) from Chubut Province, Argentina, is notably diverse and includes many conifer and angiosperm lineages that are extinct in South America but extant in Australasian rainforests. No ferns have been previously described from Laguna del Hunco. We describe and interpret a new species of fossil Osmundaceae based on fertile and sterile pinnae. • METHODS: The fossil specimens were compared with other extant and fossil Osmundaceae based on living and herbarium material and published descriptions. A morphological matrix based on 29 characters was constructed for 17 living species in Osmundaceae, four species assigned to the fossil genus Todites, and the new fossil species. Phylogenetic analyses were conducted under parsimony using morphology and total evidence matrices. • KEY RESULTS: Both the new fossil and the Todites species were consistently resolved within the leptopteroid clade of Osmundaceae, and the new species resolved in a clade with the two living Todea species, which are now restricted to Australia, New Guinea, New Zealand, and southern Africa. • CONCLUSIONS: Todea amissa sp. nov. is the first record of Todea, living or fossil, in South America and only the second fossil record worldwide. The distribution of extant Todea on Gondwanan continents other than South America is broadly shared with other taxa from Laguna del Hunco, further indicating that a large component of this flora represents a Gondwanic biome that is no longer found on the South American continent.

Synthesis of trigeneration systems: sensitivity analyses and resilience.

This paper presents sensitivity and resilience analyses for a trigeneration system designed for a hospital. The following information is utilized to formulate an integer linear programming model: (1) energy service demands of the hospital, (2) technical and economical characteristics of the potential technologies for installation, (3) prices of the available utilities interchanged, and (4) financial parameters of the project. The solution of the model, minimizing the annual total cost, provides the optimal configuration of the system (technologies installed and number of pieces of equipment) and the optimal operation mode (operational load of equipment, interchange of utilities with the environment, convenience of wasting cogenerated heat, etc.) at each temporal interval defining the demand. The broad range of technical, economic, and institutional uncertainties throughout the life cycle of energy supply systems for buildings makes it necessary to delve more deeply into the fundamental properties of resilient systems: feasibility, flexibility and robustness. The resilience of the obtained solution is tested by varying, within reasonable limits, selected parameters: energy demand, amortization and maintenance factor, natural gas price, self-consumption of electricity, and time-of-delivery feed-in tariffs.

Visceral Leishmaniasis Associated with HIV Coinfection in Pará, Brazil.

Introduction: Human visceral leishmaniasis (VL) is a zoonosis of great importance to public health due to its epidemiological diversity, with emphasis on the possibility of aggravation by coinfection with the human immunodeficiency virus (HIV). Objective: The aim was to study the epidemiological characteristics of VL cases associated with HIV coinfection in Pará. Methods. Reported cases of VL from January 2006 to December 2016 were investigated. A descriptive epidemiological method related to age, gender, area of residence and coinfection with HIV was used. To calculate variance and test equity, the F-test (Fisher) was performed. To observe the influence of one aspect on another, the chi-square was used to verify if there was dependence or independence between the variables. Results: A total of 1171 cases of VL were reported during the study period. There was an annual mean of LV of 94.9, with a statistical difference (p<0.05) between age groups, with the highest number of cases being observed in children aged 1 to 4 years (27.16%). Males and the urban area had a higher number of cases. There were 57 cases of VL/HIV coinfection, with emphasis on the year 2013 and the municipality of Santarém, which had the highest number of cases. During the ten years studied, there was a correlation between coinfection VL/ HIV, with significant differences between patients with and without HIV who contracted VL (p<0.001). Conclusion: The data reveal the endemic nature of VL in the region, with a high percentage of infection in children living in urban areas. Although the studied region is not identified as a predominant area of HIV cases, this study showed a high annual average (10.3) of cases of VL/HIV coinfection being the first time that cases of VL/HIV coinfection were reported in the Mesoregion of the Lower Amazon and Southwest Pará.

Glucuronoxylomannan from Cryptococcus neoformans down-regulates the enzyme 6-phosphofructo-1-kinase of macrophages.

The encapsulated yeast Cryptococcus neoformans is the causative agent of cryptococosis, an opportunistic life-threatening infection. C. neoformans is coated by a polysaccharide capsule mainly composed of glucuronoxylomannan (GXM). GXM is considered a key virulence factor of this pathogen. The present work aimed at evaluating the effects of GXM on the key glycolytic enzyme, 6-phosphofructo-1-kinase (PFK). GXM inhibited PFK activity in cultured murine macrophages in both dose- and time-dependent manners, which occurred in parallel to cell viability decrease. The polysaccharide also inhibited purified PFK, promoting a decrease on the enzyme affinity for its substrates. In macrophages GXM and PFK partially co-localized, suggesting that internalized polysaccharide directly may interact with this enzyme. The mechanism of PFK inhibition involved dissociation of tetramers into weakly active dimers, as revealed by fluorescence spectroscopy. Allosteric modulators of the enzyme able to stabilize its tetrameric conformation attenuated the inhibition promoted by GXM. Altogether, our results suggest that the mechanism of GXM-induced cell death involves the inhibition of the glycolytic flux.

Decoding the radiomic and proteomic phenotype of epicardial adipose tissue associated with adverse left atrial remodelling and post-operative atrial fibrillation in aortic stenosis.

AIMS: Epicardial adipose tissue (EAT) volume and attenuation on computed tomography (CT) have been associated with atrial fibrillation. Beyond these conventional CT measures, radiomics allows extraction of high-dimensional data and deep quantitative adipose tissue phenotyping, which may capture its underlying biology. We aimed to explore the EAT proteomic and CT-radiomic signatures associated with impaired left atrial (LA) remodelling and post-operative atrial fibrillation (POAF). METHODS AND RESULTS: We prospectively included 132 patients with severe aortic stenosis with no prior atrial fibrillation referred for aortic valve replacement. Pre-operative non-contrast CT images were obtained for extraction of EAT volume and other radiomic features describing EAT texture. The LA function was assessed by 2D-speckle-tracking echocardiography peak atrial longitudinal strain and peak atrial contraction strain. The EAT biopsies were performed during surgery for proteomic analysis by sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS). The POAF incidence was monitored from surgery until discharge. Impaired LA function and incident POAF were associated with EAT up-regulation of inflammatory and thrombotic proteins, and down-regulation of cardioprotective proteins with anti-inflammatory and anti-lipotoxic properties. The EAT volume was independently associated with LA enlargement, impaired function, and POAF risk. On CT images, EAT texture of patients with POAF was heterogeneous and exhibited higher maximum grey-level values than sinus rhythm patients, which correlated with up-regulation of inflammatory and down-regulation of lipid droplet-formation EAT proteins. The CT radiomics of EAT provided an area under the curve of 0.80 (95% confidence interval: 0.68-0.92) for discrimination between patients with POAF and sinus rhythm. CONCLUSION: Pre-operative CT-radiomic profile of EAT detected adverse EAT proteomics and identified patients at risk of developing POAF.

Clinical Impact of the Line Probe Assay and Xpert® MTB/RIF Assay in the Presumptive Diagnosis of Drug-Resistant Tuberculosis in Brazil: A Pragmatic Clinical Trial.

BACKGROUND: Rapid molecular methods such as the line probe assay (LPA) and Xpert® MTB/RIF assay (Xpert) have been recommended by the World Health Organization for drug-resistant tuberculosis (DR-TB) diagnosis. We conducted an interventional trial in DR-TB reference centers in Brazil to evaluate the impact of the use of LPA and Xpert. METHODS: Patients with DR-TB were eligible if their drug susceptibility testing results were available to the treating physician at the time of consultation. The standard reference MGITTM 960 was compared with Xpert (arm 1) and LPA (arm 2). Effectiveness was considered as the start of the appropriate TB regimen that matched drug susceptibility testing (DST) and the proportions of culture conversion and favorable treatment outcomes after 6 months. RESULTS: A higher rate of empirical treatment was observed with MGIT alone than with the Xpert assay (97.0% vs. 45.0%) and LPA (98.2% vs. 67.5%). Patients started appropriate TB treatment more quickly than those in the MGIT group (median 15.0 vs. 40.5 days; p<0.01) in arm 1. Compared to the MGIT group, culture conversion after 6 months was higher for Xpert in arm 1 (90.9% vs. 79.3%, p=0.39) and LPA in arm 2 (80.0% vs. 83.0%, p=0.81). CONCLUSIONS: In the Xpert arm, there was a significant reduction in days to the start of appropriate anti-TB treatment and a trend towards greater culture conversion in the sixth month.