Current guidelines recommend the use of direct oral anticoagulants (DOACs) for patients with venous thromboembolism (VTE). However little is known about the use of DOACs in daily practice.
We used ...the RIETE registry to identify predictors of use of DOACs for initial and/or long-term therapy of VTE based on patient-related factors, institution-related factors or over time.
Among 41,678 patients from March 2013 to September 2021, 12,286 (29%) used DOACs: for initial therapy 6,456; for long-term therapy 12,046. On multivariable analysis, independent predictors were: age < 65 years (odds ratio OR: 1.30; 95% CI: 1.23-1.38), body weight <50 kg (OR: 0.54; 95% CI: 0.45-0.65) or >120 kg (OR: 0.64; 95% CI: 0.53-0.77), initial VTE presentation as pulmonary embolism (OR: 1.18; 95% CI: 1.13-1.25), recent bleeding (OR: 0.53; 95% CI: 0.45-0.63), renal insufficiency (OR: 0.44; 95% CI: 0.38-0.51), liver cirrhosis (OR: 0.32; 95% CI: 0.20-0.52), thrombocytopenia (OR: 0.40; 95% CI: 0.34-0.49), atrial fibrillation (OR: 1.58; 95% CI: 1.42-1.75) and prior VTE (OR: 1.14; 95% CI: 1.06-1.22). The DOACs were more likely used in other European countries (OR: 8.97; 95% CI: 8.49-9.49), America (OR: 6.35; 95% CI: 5.67-7.11) or in other countries of the world (OR: 2.99; 95% CI: 2.70-3.31) than in Spain, and progressively increased from 2013-2015 to 2016-2018 (OR: 2.78; 95% CI: 2.62-2.95) and 2019-2021 (OR: 6.36; 95% CI: 5.95-6.80).
In this large multinational VTE registry, variations were observed in the use of DOACs according to patient or country factors, and over time. The safety, costs, and influence of the DOACs on VTE-related outcomes in daily practice warrant further investigation.
Hypospadias is a common male congenital urethral malformation, defined as the displacement of the urethral meatus ventrally from the tip of the glans penis. The importance of androgen receptor in ...male external genitalia development has been well recognized. Recently, the presence of active estrogen receptors (ER) in the developing male external genitalia has also been demonstrated. There are two isoforms of the human estrogen receptor, ESR1 and ESR2, which occur, with distinct tissue and cell patterns of expression. We hypothesized that modifications in these nuclear receptors' genes could lead to hypospadias.
We screened 60 boys with hypospadias for mutations in the coding regions of ESR1 and ESR2 genes, by denaturing high-performance liquid chromatography and automated sequence analysis. We also genotyped the CA repeat polymorphism in ESR2 and the TA repeat polymorphism in ESR1.
The CA repeat polymorphism in ESR2 is prolonged in hypospadias patients compared to controls (p < 0.05). Prolongation of this CA repeat polymorphism has previously been associated with lower levels of testosterone. Six patients presented the genetic variant 2681-4A > G (rs944050) in the heterozygous form in ESR2, which was a significantly higher frequency than in the control population (p < 0.05). One of these patients also presented a 266_267insC in exon 1 of ESR2, which is also a known single nucleotide polymorphism (SNP; rs3832949). In ESR1, no significant gene alteration was found to be associated with hypospadias.
Our results suggest that variations in the ESR2 might influence susceptibility to hypospadias.
To study experimental Neospora caninum infection initiated at the gastrointestinal tract, Toll-like Receptor 4- and functional IL-12Rβ2 chain-deficient C57BL/10 ScCr mice were challenged ...intragastrically with 5 x 10⁶ N. caninum tachyzoites. All parasite-inoculated mice eventually died with disseminated infection. In contrast, immunocompetent BALB/c mice challenged with 1 x 10⁷ N. caninum tachyzoites by the intragastric (i.g.) or the intraperitoneal (i.p.) route remained alive for at least 6 months. Expansion of splenic B- and T-cells, the latter displaying both activated and regulatory phenotypes, and increased levels of IFN-γ and IL-10 mRNA were detected in both groups of infected BALB/c mice compared with non-infected controls, whereas in the Peyer's patches only IFN-γ mRNA levels were found to be increased. Parasite-specific IgG1, IgG2a and IgA antibody levels were elevated in the sera of all infected mice, whereas increased N. caninum-specific IgA levels were detected in intestinal lavage fluids of i.g. challenged mice only. These results show that N. caninum infection can be successfully established in mice by i.g. administration of tachyzoites. They also show that the immune response elicited in i.g. or i.p. infected BALB/c mice, although conferring some degree of protection, was not sufficient for complete parasite clearance.
The prevalence of Toxoplasma gondii in free-ranging chickens is a good indicator of the prevalence of T. gondii oocysts in the soil because chickens feed from the ground. The prevalence of T. gondii ...in 225 free-range chickens (Gallus domesticus) from Portugal was determined. Antibodies to T. gondii were assayed by the modified agglutination test (MAT) and found in 61 chickens with titers of 1:5 in 8, 1:10 in 6, 1:20 in 3, 1:40 in 23, 1:80 in 5, 1:160 in 4, 1:320 in 8, and 1:640 or higher in 4. Hearts, leg muscles, and brains of 15 seropositive (MAT 1:10 or higher) chickens were bioassayed individually in mice. Tissue from 38 chickens with titers of 1:5 or less were pooled and fed to a T. gondii–free cat. Feces of the cat were examined for oocysts, but none was found. Toxoplasma gondii was isolated from 16 of 19 chickens with MAT titers of 1:10 or higher. Genotyping of 12 of these 16 isolates with polymorphisms at the SAG2 locus indicated that 4 were type III, and 8 were type II. None of the isolates was lethal for mice. Phenotypically, T. gondii isolates from chickens from Portugal were different from those of T. gondii isolates from chickens from Brazil.
The Atlantic Forest is one of the most threatened biomes in the world. Despite that, this biome still includes many areas that are poorly known floristically, including several protected areas, such ...as the "Floresta Nacional do Rio Preto" ("Flona do Rio Preto"), located in the Brazilian State of Espírito Santo. This study used a published vascular plant species list for this protected area from the "Catálogo de Plantas das Unidades de Conservação do Brasil" as the basis to synthesise the species richness, endemism, conservation and new species occurrences found in the "Flona do Rio Preto".
The published list of vascular plants was based on field expeditions conducted between 2018 and 2020 and data obtained from herbarium collections available in online databases. Overall, 722 species were documented for the "Flona do Rio Preto", 711 of which are native to Brazil and 349 are endemic to the Atlantic Forest. In addition, 60 species are geographically disjunct between the Atlantic and the Amazon Forests. Most of the documented species are woody and more than 50% of these are trees. Twenty-three species are threatened (CR, EN and VU), while five are Data Deficient (DD). Thirty-two species are new records for the State of Espírito Santo. Our results expand the knowledge of the flora of the Atlantic Forest and provide support for the development of new conservation policies for this protected area.
Novel derivatives of 2‐3‐(trifluoromethyl)‐analinonicotinic acid (niflumic acid) were synthesized. The compounds were compared for their inhibitory effects on 5‐hydroxytryptamine (5‐HT)‐ and ...KCl‐induced contraction of the rat fundus. The aim was to assess structure‐activity relationships regarding the selectivity and potency of these compounds. Niflumic acid (1–100 μM) concentration‐dependently inhibited 5‐HT‐induced tonic contractions with an IC50 value (concentration reducing the control contractile response by 50%, calculated from semilog graphs) of 0.24 × 10−4 M (n = 9). In contrast, it was significantly less potent at inhibiting KCl‐induced responses (IC50 = 1.49 × 10−4 M, n = 9). The methyl ester (NFAme) and amido (NFAm) analogues showed no selectivity between 5‐HT‐ and KCl‐induced contractions with IC50 values of 1.64 × 10−4 M (n = 8) and 1.87 × 10−4 M (n = 9) for 5‐HT responses, and 2.61 × 10−4 M (n = 8) and 2.55 × 10−4 M (n = 7) for KCl‐induced responses, respectively. Our results suggest that alteration of the carboxylic acid moiety of niflumic acid reduces the selectivity and potency of its inhibitory action on 5‐HT‐induced contractile responses of the rat fundus, possibly via a reduced interaction with calcium‐activated chloride channels.
SummaryIn this work, poly(styrenesulfonate) membranes were produced through the sulfonation of wasted polystyrene plastic cups. The produced membranes presented good workability and ion exchange ...capacity of 1.3±0.1 meq/g. The sulfonated membranes showed significantly increase in the water sorption, what is relevant in industry since most of the processes of separation deal with the presence of ions which means of transport is the water. The membrane of sulfonated polystyrene plastic cups (PSSwastecups) was compared with the sulfonated membrane of virgin resin (PSSstandard). The viscosimetric molar weight of PSSstandard was higher than PSSwastecups how indicated by difference between intrinsic viscosity. This fact influences the production of the membrane and consequently the transport property. The PSSwastecups absorbs a higher amount of water than the PSSstandard, what is due to the presence of less macromolecule chain coils, producing low-density regions where clusters may be formed. This diminishes the diffusion coefficient and increases the water sorption in the PSSwastecups membrane.
Sporotrichosis is a chronic subcutaneous mycosis caused by Sporothrix schenckii. This work aimed to evaluate the virulence of two different isolates of S. schenckii from cutaneous (CUT) and systemic ...(SYS) forms of feline sporotrichosis. A standard inoculum with 2 x 10(3) yeast cells/ml was prepared from each of the isolates. The experimental infection was carried out with 0.1 ml of the inoculum from both isolates and then injected in the paw pads of Swiss albino mice of groups CUT and SYS. The clinical evolution of the disease and the diameter of the lesion at the inoculated sites were evaluated during nine weeks. Four necropsies were done to collect material from the lesions (p < 0.01). Group CUT demonstrated a more evident clinical evolution of the disease from week two to week five; large lesions in the paw pad on week four (p < 0.01); and a higher incidence of lesions in other parts of the body (p < 0.01) than group SYS (p < 0.01). S. schenckii was isolated from the inoculated site in groups SYS and CUT until days 30 and 45, respectively. Granulomas with yeast cells usually localized in the central area were observed in histopathology sections on days 15 and 30 post-inoculations. Those yeast cells decreased on day 45 being absent on day 62 when tissue repair initiated. The results showed that distinct clinical isolates of S. schenckii cause significant differences in the clinical evolution of sporotrichosis.
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