Correlated Mixture Between Adiabatic and Isocurvature Fluctuations and Recent CMB Observations

This work presents a reduced chi^2_nu test to search for non-gaussian signals in the CMBR TT power spectrum of recent CMBR data, WMAP, ACBAR and CBI data sets, assuming a mixed density field including adiabatic and isocurvature fluctuations. We assume a skew positive mixed model with adiabatic inflation perturbations plus additional isocurvature perturbations possibly produced by topological defects. The joint probability distribution used in this context is a weighted combination of Gaussian and non-Gaussian random fields. Results from simulations of CMBR temperature for the mixed field show a distinct signature in CMB power spectrum for very small deviations (~ 0.1%) from a pure Gaussian field, and can be used as a direct test for the nature of primordial fluctuations. A reduced chi^2_nu test applied on the most recent CMBR observations reveals that an isocurvature fluctuations field is not ruled out and indeed permits a very good description for a flat geometry Lambda-CDM universe, chi^2_930 ~ 1.5, rather than the simple inflationary standard model with chi^2_930 ~ 2.3. This result may looks is particular discrepant with the reduced chi^2 of 1.07 obtained with the same model in Spergel et al. (2003) for temperature only, however, our work is restricted to a region of the parameter space that does not include the best fit model for TT only of Spergel et al. (2003).Comment: Accepted for publication in Physical Review

Virulence and resistance properties of E. coli isolated from urine samples of hospitalized patients in Rio de Janeiro, Brazil - The role of mobile genetic elements

Extraintestinal pathogenic E. coli (ExPEC) is the most frequent etiological agent of urinary tract infections (UTIs). Particular evolutionary successful lineages are associated with severe UTIs and higher incidences of multidrug resistance. Most of the resistance genes are acquired by horizontal transfer of plasmids and other mobile genetic elements (MGEs), and this process has been associated with the successful dissemination of particular lineages. Here, we identified the presence of MGEs and their role in virulence and resistance profiles of isolates obtained from the urine of hospitalized patients in Brazil. Isolates belonging to the successful evolutionary lineages of sequence type (ST) 131, ST405, and ST648 were found to be multidrug-resistant, while those belonging to ST69 and ST73 were often not. Among the ST131, ST405, and ST648 isolates with a resistant phenotype, a high number of mainly IncFII plasmids was identified. The plasmids contained resistance cassettes, and these were also found within phage-related sequences and the chromosome of the isolates. The resistance cassettes were found to harbor several resistance genes, including blaCTX-M-15. In addition, in ST131 isolates, diverse pathogenicity islands similar to those found in highly virulent ST73 isolates were detected. Also, a new genomic island associated with several virulence genes was identified in ST69 and ST131 isolates. In addition, several other MGEs present in the ST131 reference strain EC958 were identified in our isolates, most of them exclusively in ST131 isolates. In contrast, genomic islands present in this reference strain were only partially present or completely absent in our ST131 isolates. Of all isolates studied, ST73 and ST131 isolates had the most similar virulence profile. Overall, no clear association was found between the presence of specific MGEs and virulence profiles. Furthermore, the interplay between virulence and resistance by acquiring MGEs seemed to be lineage dependent. Although the acquisition of IncF plasmids, specific PAIs, GIs, and other MGEs seemed to be involved in the success of some lineages, it cannot explain the success of different lineages, also indicating other (host) factors are involved in this process. Nevertheless, the detection, identification, and surveillance of lineage-specific MGEs may be useful to monitor (new) emerging clones

Trypanosoma cruzi Adjuvants Potentiate T Cell-Mediated Immunity Induced by a NY-ESO-1 Based Antitumor Vaccine

Immunological adjuvants that induce T cell-mediate immunity (TCMI) with the least side effects are needed for the development of human vaccines. Glycoinositolphospholipids (GIPL) and CpGs oligodeoxynucleotides (CpG ODNs) derived from the protozoa parasite Trypanosoma cruzi induce potent pro-inflammatory reaction through activation of Toll-Like Receptor (TLR)4 and TLR9, respectively. Here, using mouse models, we tested the T. cruzi derived TLR agonists as immunological adjuvants in an antitumor vaccine. For comparison, we used well-established TLR agonists, such as the bacterial derived monophosphoryl lipid A (MPL), lipopeptide (Pam3Cys), and CpG ODN. All tested TLR agonists were comparable to induce antibody responses, whereas significant differences were noticed in their ability to elicit CD4+ T and CD8+ T cell responses. In particular, both GIPLs (GTH, and GY) and CpG ODNs (B344, B297 and B128) derived from T. cruzi elicited interferon-gamma (IFN-γ) production by CD4+ T cells. On the other hand, the parasite derived CpG ODNs, but not GIPLs, elicited a potent IFN-γ response by CD8+ T lymphocytes. The side effects were also evaluated by local pain (hypernociception). The intensity of hypernociception induced by vaccination was alleviated by administration of an analgesic drug without affecting protective immunity. Finally, the level of protective immunity against the NY-ESO-1 expressing melanoma was associated with the magnitude of both CD4+ T and CD8+ T cell responses elicited by a specific immunological adjuvant

Avaliação da capacidade funcional e da qualidade de vida em pacientes renais crônicos submetidos a tratamento hemodialítico

This study aimed at evaluating the functional capacity and health-related quality of life in chronic renal insufficiency (CRI) patients undergoing hemodialysis treatment, also checking possible correlations between these clinical variables and age, body mass index (BMI), and hemodialysis time. Sixteen patients were submitted to functional capacity assessment by means of the six-minute walk test (6WT), measures of maximal inspiratory and expiratory pressures, and by the fatigue severity scale (FSS). Patients also answered the SF-36 questionnaire. Functional capacity proved to be below predicted values at the 6WT and at respiratory, mainly expiratory muscles; mean FSS scores pointed to moderate fatigue. Patients over 60 years old and those with lesser hemodialysis time showed lower functional capacity only as to the distance walked at the 6WT. BMI did not interfere with functional capacity. Mean overall SF-36 scores were low; pain and lesser vitality were pointed as the SF-36 domains that most interfere in quality of life; age, BMI, and hemodialysis time have not shown to be relevant to most SF-36 domains. Results suggest that, with slight interference of age and hemodialysis time, patients with CRI undergoing hemodialysis treatment have poor functional capacity and health-related quality of life.Este estudo visou avaliar a capacidade funcional e a qualidade de vida em pacientes com incapacidade renal crônica (IRC) submetidos a tratamento hemodialítico e verificar possíveis correlações entre essas variáveis clínicas e idade, índice de massa corpórea (IMC) e tempo de hemodiálise. Dezesseis pacientes com IRC foram submetidos à avaliação da capacidade funcional pelo teste de caminhada de seis minutos (TC6'), mensuração das pressões inspiratória e expiratória máxima, e pela aplicação da escala de severidade da fadiga. Também responderam ao questionário SF-36, sobre qualidade de vida relacionada à saúde (QV). A capacidade funcional mostrou-se abaixo dos valores preditos no TC6' e na força dos músculos respiratórios (principalmente expiratórios); e todos apresentaram em média fadiga leve. Pacientes com mais de 60 anos e aqueles com menor tempo de hemodiálise apresentaram baixa capacidade funcional apenas quanto à distância caminhada, sem prejuízo das demais funções. O IMC não interferiu na capacidade funcional. O escore médio no SF-36 foi 72,3; dor e prejuízo na vitalidade foram indicados como os itens que mais interferem em sua QV, tendo os fatores idade, índice de massa corporal e tempo de hemodiálise não se mostrado relevantes na maioria dos domínios avaliados pelo SF-36. Os resultados sugerem que, com pouca interferência da idade e do tempo de hemodiálise, pacientes com IRC submetidos a tratamento hemodialítico apresentam prejuízos na capacidade funcional e na QV

Magnetoliposomes incorporated in peptide-based hydrogels: towards development of magnetolipogels

A major problem with magnetogels is the encapsulation of hydrophobic drugs. Magnetoliposomes not only provide these domains but also improve drug stability and avert the aggregation of the magnetic nanoparticles. In this work, two magnetoliposome architectures, solid and aqueous, were combined with supramolecular peptide-based hydrogels, which are of biomedical interest owing to their biocompatibility, easy tunability, and wide array of applications. This proof-of-concept was carried out through combination of magnetoliposomes (loaded with the model drug curcumin and the lipid probe Nile Red) with the hydrogels prior to pH triggered gelation, and fluorescence spectroscopy was used to assess the dynamics of the encapsulated molecules. These systems allow for the encapsulation of a wider array of drugs. Further, the local environment of the encapsulated molecules after gelation is unaffected by the used magnetoliposome architecture. This system design is promising for future developments on drug delivery as it provides a means to independently modify the components and adapt and optimize the design according to the required conditions.FCT -Fundação para a Ciência e a Tecnologia(UIDB/00686/2020

Accuracy of faecal calprotectin and neutrophil Gelatinase B-associated Lipocalin in evaluating subclinical inflammation in UlceRaTIVE colitis-the ACERTIVE study

Background and Aims: Mucosal healing and histological remission are different targets for patients with ulcerative colitis, but both rely on an invasive endoscopic procedure. This study aimed to assess faecal calprotectin and neutrophil gelatinase B-associated lipocalin as biomarkers for disease activity in asymptomatic ulcerative colitis patients. Methods: This was a multicentric cross-sectional study including 371 patients, who were classified according to their endoscopic and histological scores. These results were evaluated alongside the faecal levels of both biomarkers. Results: Macroscopic lesions [i.e. endoscopic Mayo score >= 1] were present in 28% of the patients, and 9% had active disease according to fht Ulcerative Colitis Endoscopic Index of Severity. Moreover, 21% presented with histological inflammation according to the Geboes index, whereas 15% and 5% presented with focal and diffuse basal plasmacytosis, respectively. The faecal levels of calprotectin and neutrophil gelatinase B-associated lipocalin were statistically higher for patients with endoscopic lesions and histological activity. A receiver operating characteristic-based analysis revealed that both biomarkers were able to indicate mucosal healing and histological remission with an acceptable probability, and cut-off levels of 150-250 mu g/g for faecal calprotectin and 12 mu g/g for neutrophil gelatinase B-associated lipocalin were proposed. Conclusions: Faecal calprotectin and neutrophil gelatinase B-associated lipocalin levels are a valuable addition for assessment of disease activity in asymptomatic ulcerative colitis patients. Biological levels of the analysed biomarkers below the proposed thresholds can rule out the presence of macroscopic and microscopic lesions with a probability of 75-93%. However, caution should be applied whenever interpreting positive results, as these biomarkers present consistently low positive predictive values.Portuguese IBD Group [GEDII - Grupo de Estudo da Doenca Inflamatcria Intestinal]info:eu-repo/semantics/publishedVersio

Co-ingestão Fracionada de bicarbonato de sódio e carboidrato aumenta a performance sem desconforto gastrointestinal

A suplementação aguda de Bicarbonato de Sódio (BS) é sugerida como ergogênica, entretanto pode causar Desconforto Gastrointestinal (DGI). Portanto, o objetivo desse estudo foi observar se a dose fracionada de BS co-ingerida com carboidratos promove efeito ergogênico, sem DGI. Participaram do estudo 5 sujeitos fisicamente ativos e saudáveis (idade: 19 ±4,45 anos; peso: 68,4 ±4,04kg e; altura: 174,5 ±1cm), que consumiram: 5g de BS, em cápsulas, junto a 1,5g·Kg-1 de carboidrato, diluído em 7ml·Kg-1 de água, em quatro momentos, separados por 4 horas (situação BS) ou; uma dose de 3,5g, de suco artificial, diluído em 350ml de água, 30 minutos antes do teste (situação P). Após a suplementação, os sujeitos realizaram um teste experimental de esforço físico até à fadiga volicional. Como resultados, não houve diferença na Frequência Cardíaca-BPM (P: 189,48 ±13; BS 188,10 ±9, p=0,645), e Percepção Subjetiva de Esforço-Borg (P: 17,96 ±3; BS: 17,41 ±4, p=0,506) entre as situações frente ao teste de esforço físico, entretanto, houve diferenças significativas nas concentrações de Lactato-mmol-L (P: 7,20 ±2,82; BS: 9,91 ±4,08, p=0.007) e Tempo Total de Atividade-TTA (P: 376,20’’ ±130,66’’; BS: 461,00 ±218,34’’, p=0,000). Não foi relatado, pelos sujeitos, nenhum tipo de desconforto, em razão dos protocolos de suplementação. Concluímos que em indivíduos fisicamente ativo a suplementação de BA dividida em quatro doses co-ingerida com carboidratos pode ser efetiva para aumentar o desempenho físico sem DGI. ABSTRACTFractionated sodium bicarbonate coingestion with carbohydrate increase performance whitout gastrointestinal discomfortAcute supplementation of Sodium Bicarbonate (SB) is suggested as ergogenic, however may cause Gastrointestinal Discomfort (DGI). Therefore, the aim of this study was to observe whether the fractionated dose of SBingested with carbohydrates promote an ergogenic effect in physically active individuals without DGI. The study included five recreational physically active and healthy subjects (age: 19 ±4.45 years, weight: 68.4 ±4.04 kg and, height: 174.5 ±1 cm) which consumed four times, separated by 4 hours, 5g of SB in capsules together with 1.5gm·Kg-1 of carbohydrate diluted in 7ml·Kg-1 of water (situation BS) or a placebo dose of 3.5g of artificial juice diluted in 350ml of water, 30 minutes before test (situation P). After supplementation, subjects performed an experimental physical stress test-PST to volitional fatigue. As results there was no difference (p<0.05) in Heart Rate-BPM (P: 189.48 ±13; BS: 188.10 ±9 p=0.645) and Perceived Exertion-Borg (P: 17.96 ±3; BS: 17.41 ±4, p= 0.506) between situations (P vs. BS), however, there were significant differences in the concentrations of lactate-mmol-L (P: 17.96 ±3; BS: 17.41 ±4, p=0.506) and total activity time until volitional fatigue (P: 376.20’’ ±130.66’’; BS: 461.00’’ ±218.34’’, p= 0.000). Do not was reported by the subjects any kind of discomfort due to supplementation protocols. We concluded that supplementation of SB divided into four doses ingested with carbohydrate may be effective for increase the performance without GID in healthy recreational physical activity subjects

Stabilization of apoptotic cells: generation of zombie cells

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.Apoptosis is characterized by degradation of cell components but plasma membrane remains intact. Apoptotic microtubule network (AMN) is organized during apoptosis forming a cortical structure beneath plasma membrane that maintains plasma membrane integrity. Apoptotic cells are also characterized by high reactive oxygen species (ROS) production that can be potentially harmful for the cell. The aim of this study was to develop a method that allows stabilizing apoptotic cells for diagnostic and therapeutic applications. By using a cocktail composed of taxol (a microtubule stabilizer), Zn2+ (a caspase inhibitor) and coenzyme Q10 (a lipid antioxidant), we were able to stabilize H460 apoptotic cells in cell cultures for at least 72 h, preventing secondary necrosis. Stabilized apoptotic cells maintain many apoptotic cell characteristics such as the presence of apoptotic microtubules, plasma membrane integrity, low intracellular calcium levels and mitochondrial polarization. Apoptotic cell stabilization may open new avenues in apoptosis detection and therapy.This work was supported by FIS PI10/00543 grant, Ministerio de Sanidad, Spain, and Fondo Europeo de Desarrollo Regional (FEDER-Unión Europea), SAS 111242 grant, Servicio Andaluz de Salud-Junta de Andalucía, Proyecto de Investigación de Excelencia de la Junta de Andalucía CTS-5725, BFU2012-38208 and by AEPMI (Asociación de Enfermos de Patología Mitocondrial).Peer Reviewe

role of female sex hormone receptors

Funding Information: Funding: This study was supported by grant IECT-FAPEMA-05796/18 and FAPEMA IECT 30/2018-IECT Saúde, by the Research Center of the Portuguese Oncology Institute of Porto (project no. PI86-CI-IPOP-66-2017); by European Investment Funds by FEDER/COMPETE/POCI—Operational Competitiveness and Internationalization Program, and national funds by FCT—Portuguese Foundation for Science and Technology under projects UID/AGR/04033/2020, UIDB/CVT/00772/2020 and by Base Funding-UIDB/00511/2020 of the Laboratory for Process Engineering, Environment, Biotechnology, and Energy—LEPABE—funded by national funds through the FCT/MCTES (PID-DAC); Project 2SMART-engineered Smart materials for Smart citizens, with reference NORTE-01-0145-FEDER-000054, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.A growing proportion of oropharyngeal squamous cell carcinomas (OPSCC) are associated with infection by high-risk human papillomavirus (HPV). For reasons that remain largely unknown, HPV+OPSCC is significantly more common in men than in women. This study aims to determine the incidence of OPSCC in male and female HPV16-transgenic mice and to explore the role of female sex hormone receptors in the sexual predisposition for HPV+ OPSCC. The tongues of 30-weeks-old HPV16-transgenic male (n = 80) and female (n = 90) and matched wild-type male (n = 10) and female (n = 10) FVB/n mice were screened histologically for intraepithelial and invasive lesions in 2017 at the Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Por-tugal. Expression of estrogen receptors alpha (ERα) and beta (ERβ), progesterone receptors (PR) and matrix metalloproteinase 2 (MMP2) was studied immunohistochemically. Collagen remodeling was studied using picrosirius red. Female mice showed robust ERα and ERβ expression in intraepithelial and invasive lesions, which was accompanied by strong MMP2 expression and marked collagen remodeling. Male mice showed minimal ERα, ERβ and MMP2 expression and unaltered collagen patterns. These results confirm the association of HPV16 with tongue base cancer in both sexes. The higher cancer incidence in female versus male mice contrasts with data from OPSCC patients and is associated with enhanced ER expression via MMP2 upregulation.publishersversionpublishe