An analytical cross-sectional study with 70 individuals divided into two groups. Group A consisted of 35 volunteers who were being preoperatively prepared for the construction of arteriovenous ...fistula. Group B consisted of 35 non-renal patients selected by convenience. Each participant underwent physical examination, including venous percussion, of the dominant upper limb and then ultrasound. Interobserver agreement was assessed between a trained vascular surgeon performing percussion and fourth-year medical student. Accuracy, sensitivity, specificity, positive predictive value and negative predictive value of percussion were determined in relation to ultrasound. The agreement between the methods, venous percussion and venous duplex ultrasound was also evaluated by the Kappa index.
The overall interobserver agreement for the percussion was 0.74 (95% CI 0.632 to 0.851). It was observed that the results were more favorable in the cephalic vein than in the basilic vein, emphasizing that the cephalic is more used in venous punctures, because of its anatomical location and visibility, and in fistula construction. The 35 percussions of the cephalic forearm vein in Group A resulted in a sensitivity of 1.0 (95% CI 0.63 to 1.00), specificity of 0.96 (95% CI 0.81 to 1.00), a positive predictive value of 0.89(95% CI 0.52 to 1.00) and a negative predictive value of 1.00 (95% CI 0.87 to 1.00), with an accuracy of 0.97 (95% CI 0.85 to 1.00) and Kappa index of 0.92 (95% CI 0.77 to 1.00) in relation to ultrasound. Overall, when all venous segments were analyzed in group A, the Kappa index of agreement between the percussion and the ultrasonography reached 0.56 (95% CI 0.401 to 0.72). All venous segments in Group A had a sensitivity of 0.54 (95% CI 0.37 to 0.70) and a specificity of 0.96 (95% CI 0.90 to 0.99). When all venous segments were analyzed in group B, the Kappa index of agreement between the percussion and the ultrasonography reached 0.48 (95% CI 0.34 to 0.62). All venous segments in Group B had a sensitivity of 0.70 (95% CI 0.59 to 0.79) and a specificity of 0.82 (95% CI 0.69 to 0.91).
Venous percussion of the upper limbs has a high positive predictive value and high specificity, when compared to ultrasound as a way to evaluate the patency and adequacy of the cephalic vein. Although there is not enough evidence to preclude ultrasound, percussion should definitely be included in the traditional physical exam evaluation of upper limbs superficial veins.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gangliosides are glycosphingolipids abundantly expressed in the vertebrate nervous system, and are classified into a‐, b‐, or c‐series according to the number of sialic acid residues. The enzyme GD3 ...synthase converts GM3 (an a‐series ganglioside) into GD3, a b‐series ganglioside highly expressed in the developing and adult retina. The present study evaluated the visual system of GD3 synthase knockout mice (GD3s–/–), morphologically and functionally. The absence of b‐ series gangliosides in the retinas of knockout animals was confirmed by mass spectrometry imaging, which also indicated an accumulation of a‐series gangliosides, such as GM3. Retinal ganglion cell (RGC) density was significantly reduced in GD3s–/– mice, with a similar reduction in the number of axons in the optic nerve. Knockout animals also showed a 15% reduction in the number of photoreceptor nuclei, but no difference in the bipolar cells. The area occupied by GFAP‐positive glial cells was smaller in GD3s–/– retinas, but the number of microglial cells/macrophages did not change. In addition to the morphological alterations, a 30% reduction in light responsiveness was detected through quantification of pS6‐expressing RGC, an indicator of neural activity. Furthermore, electroretinography (ERG) indicated a significant reduction in RGC and photoreceptor electrical activity in GD3s–/– mice, as indicated by scotopic ERG and pattern ERG (PERG) amplitudes. Finally, evaluation of the optomotor response demonstrated that GD3s–/– mice have reduced visual acuity and contrast sensitivity. These results suggest that b‐series gangliosides play a critical role in regulating the structure and function of the mouse visual system.
Gangliosides are lipid molecules important in the developing and adult nervous system. GD3 synthase enzyme is necessary to synthesize several gangliosides, denominated b‐ and c‐series. Here, we evaluated the impact of GD3 synthase deletion on the structure and function of the visual system in adult mice. GD3 knockout mice had reductions in two retinal populations, retinal ganglion cells and photoreceptors, and also showed functional visual deficits. These results suggest that b‐series gangliosides play a critical role in mouse visual system, and GD3 knockout mice are a model to investigate ganglioside functions in the nervous system during development and adulthood.
The Müller-Lyer Illusion (MLI) has been suggested as a potential marker for the perceptual impairments observed in schizophrenia patients. Along with some positive symptoms, these deficits are not ...easily modeled in rodent experiments, and novel animal models are warranted. Previously, MK-801 was shown to reduce susceptibility to MLI in monkeys, raising the prospects of an effective perception-based model. Here, we evaluate the translational feasibility of the MLI task under NMDA receptor blockage as a primate model for schizophrenia. In Experiment 1, eight capuchin monkeys (
Sapajus
spp.) were trained on a touchscreen MLI task. Upon reaching the learning criteria, the monkeys were given ketamine (0.3 mg/kg; i.m.) or saline on four consecutive days and then retested on the MLI task. In Experiment 2, eight chronic schizophrenia patients (and eight matching controls) were tested on the Brentano version of the MLI. Under saline treatment, monkeys were susceptible to MLI, similarly to healthy human participants. Repeated ketamine administrations, however, failed to improve their performance as previous results with MK-801 had shown. Schizophrenic patients, on the other hand, showed a higher susceptibility to MLI when compared to healthy controls. In light of the present and previous studies, the MLI task shows consistent results across monkeys and humans. In spite of potentially being an interesting translational model of schizophrenia, the MLI task warrants further refinement in non-human primates and a broader sample of schizophrenia subtypes.
ObjectivesTo estimate the national prevalence of rheumatic and musculoskeletal diseases (RMDs) in the adult Portuguese population and to determine their impact on health-related quality of life ...(HRQoL), physical function, anxiety and depression.MethodsEpiReumaPt is a national health survey with a three-stage approach. First, 10 661 adult participants were randomly selected. Trained interviewers undertook structured face-to-face questionnaires that included screening for RMDs and assessments of health-related quality of life, physical function, anxiety and depression. Second, positive screenings for ≥1 RMD plus 20% negative screenings were invited to be evaluated by a rheumatologist. Finally, three rheumatologists revised all the information and confirmed the diagnoses according to validated criteria. Estimates were computed as weighted proportions, taking the sampling design into account.ResultsThe disease-specific prevalence rates (and 95% CIs) of RMDs in the adult Portuguese population were: low back pain, 26.4% (23.3% to 29.5%); periarticular disease, 15.8% (13.5% to 18.0%); knee osteoarthritis (OA), 12.4% (11.0% to 13.8%); osteoporosis, 10.2% (9.0% to 11.3%); hand OA, 8.7% (7.5% to 9.9%); hip OA, 2.9% (2.3% to 3.6%); fibromyalgia, 1.7% (1.1% to 2.1%); spondyloarthritis, 1.6% (1.2% to 2.1%); gout, 1.3% (1.0% to 1.6%); rheumatoid arthritis, 0.7% (0.5% to 0.9%); systemic lupus erythaematosus, 0.1% (0.1% to 0.2%) and polymyalgia rheumatica, 0.1% (0.0% to 0.2%). After multivariable adjustment, participants with RMDs had significantly lower EQ5D scores (β=−0.09; p<0.001) and higher HAQ scores (β=0.13; p<0.001) than participants without RMDs. RMDs were also significantly associated with the presence of anxiety symptoms (OR=3.5; p=0.006).ConclusionsRMDs are highly prevalent in Portugal and are associated not only with significant physical function and mental health impairment but also with poor HRQoL, leading to more health resource consumption. The EpiReumaPt study emphasises the burden of RMDs in Portugal and the need to increase RMD awareness, being a strong argument to encourage policymakers to increase the amount of resources allocated to the treatment of rheumatic patients.
Prostate cancer is the most common cancer in men, accounting for 15% of all diagnosed cancers and is the sixth leading cause of cancerrelated deaths amongst men worldwide. Abiraterone and ...enzalutamide were the first two novel hormonal agents approved for the treatment of metastatic prostate cancer but there is a lack of quality evidence regarding which is associated with better outcomes and who would benefit the most with one or another of these drugs.
To evaluate the clinical outcomes of real-world patients submitted to treatment with novel hormonal agents, enzalutamide and abiraterone, for castration resistant metastatic prostate cancer in an academic center.
We retrospectively reviewed patients treated for castration-resistant prostate cancer with either abiraterone or enzulatamide between January 1, 2016 and December 31, 2019. The primary endpoints were biochemical response, biochemical progression, radiological progression, clinical deterioration (attributed to disease progression) and death.
Enzalutamide had a higher biochemical response rate than abiraterone in patients with mCRPC (77.1% vs 58.1%, p = 0.016). Achieving a biochemical response was associated with a lower risk of biochemical progression (OR: 0.248, p = 0.017) and death (OR: 0.302, p = 0.038).
Enzalutamide conferred higher biochemical response rate than abiraterone in patients with mCRPC. Despite the trend to better performance of other endpoints in the enzalutamide group, it did not achieve statistical significance. Well-designed prospective studies are needed to elucidate the comparative efficacies of these agents.
Harmful environmental stimuli during critical stages of development can profoundly affect behavior and susceptibility to diseases. Alzheimer disease (AD) is the most frequent neurodegenerative ...disease, and evidence suggest that inflammatory conditions act cumulatively, contributing to disease onset. Here we investigated whether infection early in life can contribute to synapse damage and cognitive impairment induced by amyloid-β oligomers (AβOs), neurotoxins found in AD brains. To this end, wild-type mice were subjected to neonatal (post-natal day 4) infection by Escherichia coli (1 × 10
CFU/g), the main cause of infection in low-birth-weight premature infants in the US. E. coli infection caused a transient inflammatory response in the mouse brain starting shortly after infection. Although infected mice performed normally in behavioral tasks in adulthood, they showed increased susceptibility to synapse damage and memory impairment induced by low doses of AβOs (1 pmol; intracerebroventricular) in the novel object recognition paradigm. Using in vitro and in vivo approaches, we show that microglial cells from E. coli-infected mice undergo exacerbated activation when exposed to low doses of AβOs. In addition, treatment of infected pups with minocycline, an antibiotic that inhibits microglial pro-inflammatory polarization, normalized microglial response to AβOs and restored normal susceptibility of mice to oligomer-induced cognitive impairment. Interestingly, mice infected with by E. coli (1 × 10
CFU/g) during adolescence (post-natal day 21) or adulthood (post-natal day 60) showed normal cognitive performance even in the presence of AβOs (1 pmol), suggesting that only infections at critical stages of development may lead to increased susceptibility to amyloid-β-induced toxicity. Altogether, our findings suggest that neonatal infections can modulate microglial response to AβOs into adulthood, thus contributing to amyloid-β-induced synapse damage and cognitive impairment.
The filtered radiative transfer equation has been solved without subgrid-scale model and compared to a-priori estimations from direct numerical simulation of statistically stationary homogeneous ...isotropic turbulence. The importance of the large eddy simulation non-resolved scales on the thermal radiation is analysed in this academic case. The influence of the mean and variance of temperature of the system on the subgrid-scale correlations is studied. It is shown that the turbulence–radiation interaction (TRI) is greater for low-temperature flows, where the radiative transfer is lower. Moreover, the strongest subgrid-scale correlations, which are the temperature self-correlation and the absorption coefficient-temperature correlation, have opposite effects, which suggests that it is better to neglect both correlations, instead of modelling only one. Therefore, the assumption of neglecting the TRI in LES leads to good predictions. Three-dimensional filtering effects, as well as the grid influence on non-local quantities, such as the radiation intensity, are also analysed. These effects have a local influence, but are negligible in the tested cases.
In large eddy simulations (LES) of radiative heat transfer, the subgrid-scale (SGS) radiative emission and the SGS radiative absorption are two unclosed terms that arise after applying the filtering ...operation to the radiative transfer equation and which represent the effect of the SGS motions on the evolution of the resolved radiative heat flux. In the present work,
a-priori tests based on direct numerical simulation of homogeneous isotropic turbulence have been carried out. It was found that the effect of the SGS radiative absorption may be neglected in LES, whereas the SGS radiative emission has to be modelled, particularly for engineering applications where the grids are generally coarse, and in flows with high turbulence intensities. Future works should be devoted to the development of SGS models for radiative transfer.
Rheumatic and musculoskeletal diseases (RMD) are prevalent and leading causes of disability and consumption of healthcare and social resources. EpiReumaPt is a national population-based survey ...developed by the Portuguese Society of Rheumatology that aimed to estimate the prevalence of RMDs and determine their impact on function, quality of life, mental health and use of healthcare resources. This article describes in detail the design, methodology and planned analyses of EpiReumaPt. Recruitment started in September 2011 and finished in December 2013. This study involved a three-stage approach. The first step was a face-to-face survey performed by trained interviewers at the household of 10,661 subjects who where randomly selected by a stratified multistage sampling. A highly sensitive screening questionnaire for RMDs was used. Secondly, participants who screened positive (64%) for at least one RMD as well as 20% of individuals with a negative screening were invited for assessment by a rheumatologist. In total, 3,877 subjects participated in this second phase, where they were also invited to donate a blood sample to be stored at the Biobanco-IMM. History and physical examination, followed by appropriate laboratory and imaging tests were performed. At the end of the visit, the rheumatologist established a diagnosis. Finally, a team of three experienced rheumatologists reviewed all the clinical data and defined the diagnoses according to previously validated criteria. The EpiReumaPt dataset, containing data from several questionnaires, various clinical measurements and information from laboratory and imaging tests, comprises an invaluable asset for research. The large amount of information collected from each participant and the large number of participants, with a wide age range covering and being representative of the adults from the entire country, makes EpiReumaPt the largest study of RMDs performed in Portugal.
Mycobacterium bovis is the causative agent of bovine tuberculosis (BTB), the pathogen responsible for serious economic impact on the livestock sector. In order to obtain data on isolated M. bovis ...strains and assist in the control and eradication program for BTB, a cross sectional descriptive molecular epidemiology study in the Brazilian Midwest was conducted. Through spoligotyping and 24-loci MIRU-VNTR methods, 37 clinical isolates of M. bovis circulating in the region were analyzed, 10 isolated from the state of Mato Grosso, 12 from the state of Mato Grosso do Sul and 15 from the state of Goiás. The spoligotyping analysis identified 10 distinct M. bovis profiles (SB0121 n = 14, SB0295 n = 6, SB0140 n = 6, SB0881 n = 3, SB1144 n = 2, SB1145 n = 2, SB0134 n = 1, SB1050 n = 1, SB1055 n = 1, SB1136 n = 1) grouped in six clusters and four orphan patterns. The MIRU-VNTR 24-loci grouped the same isolates in six clusters and 22 unique orphan patterns, showing higher discriminatory power than spoligotyping. When associating the results of both techniques, the isolates were grouped in five clusters and 24 unique M. bovis profiles. Among the 24-loci MIRU-VNTR evaluated, two, ETR-A and QUB 11b loci, showed high discriminatory ability (h = ≥ 0.50), while MIRU 16, MIRU 27, ETR-B, ETR-C, Mtub21 and QUB 26 loci showed moderate ability (h = 0.33 or h = 0.49) and were the most effective in evaluating the genotypic similarities among the clinical M. bovis isolate samples. Herein, the 29 patterns found amongst the 37 isolates of M. bovis circulating in the Brazilian Midwest can be due to the animal movement between regions, municipalities and farms, thus causing the spread of various M. bovis strains in herds from Midwest Brazil.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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