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Este trabalho apresenta as condições do atendimento psicológico realizado na modalidade teleremota (ou modalidade de telepsicologia) para pacientes idosos que testaram positivo para COVID-19 no município de Alto Alegre/RR, usando o Aconselhamento Psicológico para atender aos anseios desse público, considerando sua condição de saúde e nível de escolaridade formal. A verificação através de pesquisas realizadas por muitos autores confirma a necessidade de uma atenção mais especializada a esta parcela da população, apontando principalmente o papel social do idoso, a importância da família na terceira idade bem como a atuação do profissional de psicologia que pode acontecer através de atendimentos clínicos, terapias grupais, entre outras que se pode realizar com o intuito de melhorar a qualidade de vida deste indivíduo, resgatar sua história de vida dentro do contexto em que se encontra e delimitar ou projetar metas para seu futuro. É importante conhecer o grupo da terceira idade a fim de melhorar os tratamentos já dispensados à essa população que vem crescendo gradualmente tanto em quantidade quanto em tempo de vida e que neste momento pandêmico está sendo assolado de diversas formas apresentando assim comprometimento maior em sua saúde física e emocional e também em sua qualidade de vida. Os resultados da pesquisa apresentam indícios de que o atendimento remoto ofertado foi satisfatório com a amostra de idosos analfabetos participantes, pois os aproximou do profissional capaz de ajustar as expectativas geradoras de angústia e a buscar soluções em conformidade com a sua realidade

Established in vitro assays for regulatory testing of skin sensitisation partly suffer from only moderate sensitivity, specificity, and predictivity when testing specific groups of chemicals. This may be due to limited biomarker response in vitro in cell types that interact as crucial players of in vivo skin sensitisation pathogenesis. Here, we propose a molecular approach to overcome this limitation. In our model, we apply genome editing and blocking of immunoregulatory molecules to increase the range of biomarker modulation by sensitising chemicals. To this end, aryl hydrocarbon receptor (AhR) knockout was done by CRISPR/Cas9 technology in THP-1 cells and combined with Programmed Cell Death-Ligand (PD-L)1 blockade. AhR-knockout THP-1 in coculture with HaCaT keratinocytes showed increased CD54 expression compared to wild type cells after stimulation with 10 µmol/L dinitrochlorobenzene (DNCB) that was further enhanced by anti-PD-L1. After stimulation of AhR-knockout THP-1 with 200 µmol/L mercaptobenzothiazol or 10 µmol/L DNCB, cocultivated Jurkat T cells significantly increased expression of T cell receptor-associated CD3. No such increase was detected after prior treatment of THP-1 with 150 µmol/L of irritant sodium lauryl sulphate. Additionally, higher levels of inflammatory cytokines MIP-3α, MIP-1β, TNF-α, and IL-8 were found in supernatants of enhanced loose-fit co-culture based sensitisation assay (eLCSA) after substance treatment. Hence, eLCSA allowed to discriminate between sensitisers and non-sensitisers. Thus, inhibition of immunoinhibitory pathway signalling by combining AhR knockout and PD-L1 antibody blockage into an assay involving main acting cell types in skin sensitisation may increase sensitivity and specificity of such assays and allow potency derivation.

Background: Glomerular hyperfiltration (GH) is an important mechanism in the development of albuminuria in hypertension. Upregulation of COX2 (cyclooxygenase 2) and prostaglandin E 2 (PGE 2 ) was linked to podocyte damage in GH. We explored the potential renoprotective effects of either separate or combined pharmacological blockade of EP2 (PGE 2 receptor type 2) and EP4 (PGE 2 receptor type 4) in GH. Methods: We conducted in vivo studies in a transgenic zebrafish model ( Tg[fabp10a:gc-EGFP] ) suitable for analysis of glomerular filtration barrier function and a genetic rat model with GH, albuminuria, and upregulation of PGE 2 . Similar pharmacological interventions and primary outcome analysis on albuminuria phenotype development were conducted in both model systems. Results: Stimulation of zebrafish embryos with PGE 2 induced an albuminuria-like phenotype, thus mimicking the suggested PGE 2 effects on glomerular filtration barrier dysfunction. Both separate and combined blockade of EP2 and EP4 reduced albuminuria phenotypes in zebrafish and rat models. A significant correlation between albuminuria and podocyte damage in electron microscopy imaging was identified in the rat model. Dual blockade of both receptors showed a pronounced synergistic suppression of albuminuria. Importantly, this occurred without changes in arterial blood pressure, glomerular filtration rate, or tissue oxygenation in magnetic resonance imaging, while RNA sequencing analysis implicated a potential role of circadian clock genes. Conclusions: Our findings confirm a role of PGE 2 in the development of albuminuria in GH and support the renoprotective potential of combined pharmacological blockade of EP2 and EP4 receptors. These data support further translational research to explore this therapeutic option and a possible role of circadian clock genes.

Lettuce (Lactuca sativa L.) is the most common leafy vegetable produced hydroponically in the United States. Although hydroponic systems are advantageous due to lower pest and disease pressure, and reduced water and nutrient requirements, the increasing prices of fertilizers, including phosphorus (P), still influences the profitability of hydroponic production of lettuce. Characterizing lettuce germplasm capable of producing high yield using less P inputs may help reduce fertilizer use, production costs, and P loads in wastewater. In this study, 12 lettuce accessions were grown in four experiments in a nutrient film technique system. In the first two experiments, the treatments consisted of two P concentrations (3.1 and 31 mg·L−1). Lettuce cultivated with 3.1 mg·L−1 of P had variable shoot and root biomass, root–shoot ratio, P uptake efficiency, and P utilization efficiency, indicating the existence of genetic variation. Five accessions (‘Little Gem’, 60183, ‘Valmaine’, BG19-0539, and ‘Green Lightning’) were considered efficient to P because produced similar shoot biomass with the low and high P treatments. In the third and fourth experiments, the treatments consisted of two P sources (monosodium phosphate (NaH2PO4) and tricalcium phosphate [TCP; Ca3(PO4)2]. Initially, extra 5 mM of calcium (Ca) was added to the TCP solution to reduce the TCP solubility and, hence, P bioavailability to plants. All accessions produced similar shoot and root weight with both treatments, indicating that the TCP treatment did not cause low-P stress to the plants. After, the extra Ca concentration added to TCP was increased to 10 mM, resulting in low-P stress and a significant reduction in shoot weight of all accessions. Despite the severe P stress, ‘Little Gem’ and 60183 were among the accessions with the least shoot weight reduction in the TCP treatment. Variability was observed in root biomass root–shoot ratio among accessions under the TCP treatment, suggesting that lettuce accessions responded differently to P stress conditions. The genetic variation for P use efficiency (PUE) and PUE-related traits in lettuce grown hydroponically suggests the feasibility of breeding new lettuce cultivars from elite lettuce germplasm adapted to low P availability in hydroponics.

The use of crop modeling can be useful to understand the interactions between the soil-plant-atmosphere system. The objective of this study was to evaluate sensitivity analysis of the AquaCrop model parameters for wheat crop in the Campos Gerais Region. The varietie tested was TBIO Sinuelo in Castro, Ponta Grossa and Itaberá cities. The analyzed parameters refer to crop phenology, transpiration, biomass production, yield formation, stresses and soil management. The sensitivity analysis was realized varying individually each input parameter in the AquaCrop for the calculation of the Relative Sensitivity Index (SI). The most sensitive parameters of the AquaCrop were: reference harvest index (HIo); water productivity normalized for evapotranspiration and CO2 concentration (WP*); crop coefficient when canopy expansion is complete (KcTR,x); fertility levels; and maximum canopy cover (CCx). The higher sensitivity of HIo and WP* is because they are directly related to two main equations of AquaCrop, linked to the estimates of dry above-ground biomass and yield formation, respectively. The AquaCrop counts WP* reflecting directly on dry above-ground biomass production and on final grain yield. The canopy decline coefficient (CDC) presented considerable sensitivity only in Castro due to the longer duration of the phenological cycle. Fertility levels and saturated hydraulic conductivity (Ksat) in Castro was the least sensitive parameters in the analysis.

This study aimed to evaluate the frequency of IgG antibodies against A. marginale, the occurrence of this bacterium by qPCR, and the effect of bovine anaplasmosis as a risk factor for clinical cases of retained placenta, mastitis, and abomasal displacement in dairy cattle. For that 179 Holstein cows out of three dairy herds, in the municipality of Sertão, Rio Grande do Sul, Brazil. These cows were on farms that were vulnerable to risk factors that are crucial to susceptibility among these animals to this intracellular hemoparasite. The mean seropositivity for A. marginale from the periods evaluated was 54% on farm A, 69.4% on farm B, and 27.3% on farm C. Molecular diagnosis was performed with qPCR and the mean positivity for A. marginale among the cows on farms A, B, and C in December 2017 was 34.6% (67/179). Infected animals showed clinical cases of retained placenta (6.1%), mastitis (6.1%), and abomasal displacement (0.5%). The association between positivity for anaplasmosis and these clinical cases was assessed through the odds ratio. Our results show that females with a positive qPCR assay for A. marginale had 52.48 times increased probability (OR) to develop clinical cases of retained placenta and mastitis (P 0.001). These clinical cases negatively impact the productivity of positive females. Thus, implementing preventive and prophylactic control measures to ensure the sanitary quality of the herds is needed to avoid losses due to morbidity and mortality and diminish the economic losses suffered by farmers.

Immune checkpoint inhibitors and adoptive T cell therapies have been valuable additions to the toolbox in the fight against cancer. These treatments have profoundly increased the number of patients with a realistic perspective toward a return to a cancer-free life. Yet, in a number of patients and tumor entities, cancer immunotherapies have been ineffective so far. In solid tumors, immune exclusion and the immunosuppressive tumor microenvironment represent substantial roadblocks to successful therapeutic outcomes. A major contributing factor to the depressed anti-tumor activity of immune cells in tumors is the harsh metabolic environment. Hypoxia, nutrient competition with tumor and stromal cells, and accumulating noxious waste products, including lactic acid, pose massive constraints to anti-tumor immune cells. Numerous strategies are being developed to exploit the metabolic vulnerabilities of tumor cells in the hope that these would also alleviate metabolism-inflicted immune suppression. While promising in principle, especially in combination with immunotherapies, these strategies need to be scrutinized for their effect on tumor-fighting immune cells, which share some of their key metabolic properties with tumor cells. Here, we provide an overview of strategies that seek to tackle lactate metabolism in tumor or immune cells to unleash anti-tumor immune responses, thereby opening therapeutic options for patients whose tumors are currently not treatable.

Pericarditis is a challenging diagnosis with nonspecific manifestations, significant clinical implications, and possible mortality. The advancement of imaging, such as echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI), has improved the sensitivity of diagnosis, although limitations remain. In this study, we investigated the prevalence of pericarditis identified at autopsy and correlated these findings with antemortem imaging studies and clinical information. Thirty-four decedents were identified in our archival autopsy records (prevalence, 1.23%) from 2010 to 2021 with a postmortem diagnosis of pericarditis. Thirty-five antemortem imaging studies were performed on 32 decedents, of which CT was the most common (18/35, 51.4%). The sensitivity of antemortem imaging was poor, with CT showing the highest sensitivity at 16.7% (3/18), while echocardiography studies, transthoracic (TTE) and transesophageal (TEE), each had a sensitivity of 0.0%. Pericarditis was determined as the immediate cause of death by autopsy in 13 decedents, of which 3 were diagnosed antemortem. It was considered contributory to the death in 6 decedents, none of which were diagnosed antemortem. In summary, antemortem imaging has limited utility in the diagnosis of pericarditis. It is imperative to examine the pericardium during autopsy to identify a possible cause of death or contributing factor.

To investigate the effect of methacrylate polyhedral oligomeric silsesquioxanes (POSS-8) on various material properties and mineral precipitation potential of a resin infiltrant.A TEGDMA-based resin infiltrant was mixed with 0.5, 1, 3, 5 or 10 wt% POSS-8 or left unchanged (control). Degree of conversion (DC), water sorption (WS), viscosity, elastic modulus (E-modulus), flexural strength (FS), Knoop microhardness (KHN) and softening ratio (SR) were assessed. Growth of calcium phosphate (Ca/P) precipitates infiltrant-treated bovine enamel and dentin specimens immersed in artificial saliva or artificial dentinal fluid, respectively, for 28 days was analyzed by scanning electron microscopy and energy-dispersive X-ray spectroscopy. For viscosity assessment, pure TEGDMA filled with 0-10 wt% POSS-8 was used. Statistical analyses were performed using ANOVA and Tukey's post-hoc tests (p 0.05).POSS-8 did not change the flexural strength, water sorption and softening ratio. The apparent degree of conversion was increased at lower concentrations only while E-modulus remained constant in almost all groups. The particles led to a slight decrease of KHN at concentrations below 3%. The effect on viscosity is comparable to the reinforcement effect. Ca/P precipitates formed on dentin specimens treated with POSS-8-filled infiltrant after 4 weeks of immersion, but were not detected on the control infiltrant. The mineral precipitation on enamel was not improved by POSS-8.POSS-8 particles did not worsen the material properties of the resin infiltrant, while the Ca/P precipitation on dentin was stimulated.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was first identified in December 2019 and emerged into an ongoing global pandemic. Both the pandemic itself and the associated public restrictive measures of social mobility established with different intensity over different periods in various countries have significantly affected the everyday activities and lifestyles of people all over the world. The impact of lockdown and quarantine measures on hypertension incidence and blood pressure (BP) control is an important topic that requires further investigation. The aim of this review is: a) to present the current evidence regarding the actual effects of public restrictive measures on BP levels and control, originating primarily from studies investigating the impact of public restrictive measures on BP control with the use of various BP phenotypes; b) to summarize the possible pandemic-related effects of factors known to affect BP levels, including both traditional (e.g. dietary habits including alcohol and sodium intake, body weight, smoking and physical activity) and non-traditional (e.g. sleep patterns, air pollution, environmental noise, delayed diagnosis and medication adherence) ones.

In an article published in the Journal of the American Philosophical Association, Nick Zangwill (2021) argues that “eating meat is morally good” (p. 295). It is “our duty” to eat animals, he says, “when it is part of a practice that has benefited animals” (Zangwill, 2021, p. 295). Since certain animals can be said to exist in some sense only because of meat-eating practices, and those practices benefit animals if they have good lives, argues Zangwill, that's why we owe it to the animals to eat them—it is our moral duty. I carefully dissect this crude argument into its components and debunk its conclusion.

Does political realism have anything to contribute to the debates about migration in normative political theory? Anything well-established ‘moralist’ theories do not already acknowledge, that is? Addressing Jaggar’s (Aristotelian Soc Suppl Vol. XCIV, pp. 87–113, 2020) and Finlayson’s (Aristotelian Soc Suppl Vol. XCIV, pp. 115–139, 2020) critical intercessions into contemporary discourse about migration I argue that a political realist approach to the theory of migration faces what I call the ‘surplus challenge’: realists supposedly have no normative surplus over (liberal) cosmopolitan and nationalist moralist approaches. This nothing-more-to-add narrative is a common argument against the possibility and integrity of political realism (as seen in, inter alia, Leader-Maynard and Worsnip in Ethics 128(4), pp. 756–787, 2018). I show how it misconstrues the realist agenda. Finlayson, on the other hand, paints the realist intervention as primarily about paying closer attention to colonialism’s long legacy. A properly radical intrusion, however, addresses the unchecked and unwarranted, overbearing normative power of moral principles. I will conclude that for the realist, shaking up the discipline will not come as easy as pointing at some overly historicised facts. However, and despite this, the realist intervention rightly problematises contemporary philosophy of migration for its moral normativism. A radical realist approach to issues of migration, which unmasks the unjustified ‘microphysics’ political power hiding behind normative veneers, is a properly cataclysmic intrusion and the right way forward.

The 2017 American College of Cardiology/American Heart Association and 2018 European Society of Cardiology/European Society of Hypertension clinical practice guidelines for management of high blood pressure/hypertension are influential documents. Both guidelines are comprehensive, were developed using rigorous processes, and underwent extensive peer review. The most notable difference between the 2 guidelines is the blood pressure cut points recommended for the diagnosis of hypertension. There are also differences in the timing and intensity of treatment, with the American College of Cardiology/American Heart Association guideline recommending a somewhat more intensive approach. Overall, there is substantial concordance in the recommendations provided by the 2 guideline-writing committees, with greater congruity between them than their predecessors. Additional harmonization of future guidelines would help to underscore the commonality of their core recommendations and could serve to catalyze changes in practice that would lead to improved prevention, awareness, treatment, and control of hypertension, worldwide.

Previous work suggests that musical training can enhance acculturation processes. This study examined this assumption among third-graders with migrant backgrounds within a longitudinal framework. A total of 54 children (31 females; 23 males; mean age: 8.85 years) were assigned to one of three groups in a quasi-randomized procedure: (a) music training (singing or instrumental), (b) game-based mathematical training (board and card games), and (c) controls (do-nothing). We assumed that the music children showed increases in host culture orientation, perceived school integration, and in their individual self-concept in comparison to their peers with alternative or without additional training. Music children received weekly 45 min sessions over a period of 10 months. Data were collected at baseline, after one school year, and at a follow-up about six months after intervention. Results showed no advantages for music children across dependent measures. Increases of perceived school integration and self-concept were significant across groups. In sum, our results failed to replicate the main findings from previous studies. They suggest that weekly musical training over a period of 10 months might not be sufficient to improve the acculturation process or to enhance the self-concept of primary school children with a migration background.

O presente trabalho avaliou em termos ambientais, as nascentes, poços escavados e os poços tubulares profundos utilizados como fonte de acesso a água potável na bacia hidrográfica do Rio São Matheus, no município de Terra Boa – PR. Foram realizadas análises laboratoriais para os parâmetros microbiológicos (Escherichia coli e coliformes totais) e físico-químicos (Ferro, Zinco, Manganês e de turbidez) das amostras coletadas. Após processamento laboratorial e exame estatístico dos dados, chegou-se aos seguintes resultados: 1) A maior parte das amostras coletadas em nascente apresentou níveis elevados de contaminação por E. Coli (75%) e coliformes totais (75%); 2) poços escavados rasos apresentaram contaminação em 80% dos casos analisados; 3) Foram observados valores de Fe acima do indicado pela portaria 05/2017 do Ministério da Saúde, especialmente nas amostras coletadas em poços tubulares profundos; 4) Os valores das análises de Fe e Zn permitiram observar uma clara distinção entre os diferentes tipos de mananciais.

Atomic mutagenesis is the key to advance our understanding of RNA recognition and RNA catalysis. To this end, deazanucleosides are utilized to evaluate the participation of specific atoms in these processes. One of the remaining challenges is access to RNA-containing 1-deazaguanosine (c

Atherosclerotic renovascular disease (ARVD) is the most common type of renal artery stenosis. It represents a common health clinical problem with clinical presentations relevant to many medical specialties and carries high risk for future cardiovascular and renal events, as well as overall mortality. The available evidence regarding the management of ARVD is conflicting. Randomized controlled trials failed to demonstrate superiority of percutaneous transluminal renal artery angioplasty (PTRA) with or without stenting in addition to standard medical therapy compared with medical therapy alone in lowering blood pressure levels or preventing adverse renal and cardiovascular outcomes in patients with ARVD, but they carried several limitations and met important criticism. Observational studies showed that PTRA is associated with future cardiorenal benefits in patients presenting with high-risk ARVD phenotypes (i.e. flash pulmonary oedema, resistant hypertension, or rapid loss of kidney function). This clinical practice document prepared by experts from the European Renal Best Practice (ERBP) board of the European Renal Association (ERA) and from the Working Group on Hypertension and the Kidney of the European Society of Hypertension (ESH) summarizes current knowledge in epidemiology, pathophysiology and diagnostic assessment of ARVD and presents, following a systematic literature review, key evidence relevant to treatment, with an aim to support clinicians in decision-making and everyday management of patients with this condition.

Investigating North Pacific climate variability during warm intervals prior to the Common Era can improve our understanding of the behavior of ocean-atmosphere teleconnections between low latitudes and the Arctic under future warming scenarios. However, most of the existing ice core records from the Alaska/Yukon region only allow access to climate information covering the last few centuries. Here we present a surface-to-bedrock age scale for a 210-meter long ice core recovered in 2013 from the summit plateau of Begguya (Mt. Hunter; Denali National Park, Central Alaska). Combining dating by annual layer counting with absolute dates from micro-radiocarbon dating, a continuous chronology for the entire ice core archive was established using an ice flow model. Calibrated 14C ages from the deepest section (209.1 m, 7.7 to 9.0 ka cal BP) indicate that basal ice on Begguya is at least of early Holocene origin. A series of samples from a shallower depth interval (199.8 to 206.6 m) were dated with near uniform 14C ages (3 to 5 ka cal BP). Our results suggest this may be related to an increase in annual net snow accumulation rates over this period following the Northern Hemisphere Holocene Climate Optimum (around 8 to 5 ka BP). With absolute dates constraining the timescale for the last > 8 ka, this paleo archive will allow future investigations of Holocene climate and the regional evolution of spatial and temporal changes in atmospheric circulation and hydroclimate in the North Pacific.

O último Plano Nacional de Educação (PNE 2014-2024) reitera ser estratégica a curricularização da extensão, em no mínimo 10% da carga horária dos cursos de graduação, como forma de colaborar na ampliação de matrículas no Ensino Superior. Contudo, em dois importantes fóruns de discussões sobre a educação em Computação da Sociedade Brasileira de Computação (SBC), ainda são poucos os relatos da inserção da extensão na matriz curricular de cursos de graduação de Computação no país. Este artigo apresenta experiências de curricularização da extensão em cursos de Computação da Universidade Federal do Pampa (Unipampa). Ao fazê-lo, analisa essas experiências a partir das diretrizes enunciadas na Política Nacional de Extensão. Propõem-se, assim, reflexões sobre o processo de curricularização da extensão em cursos de Computação.

Hypertension (HTN) involves genetic variability in the renin-angiotensin system and characterizing this variability will help advance precision antihypertensive treatments. We previously reported that angiotensinogen (AGT) mRNA is endogenously bound by mir-122-5p and that rs699 A>G significantly decreases reporter mRNA in the functional mirSNP assay PASSPORT-seq. TheAGTpromoter variant rs5051 C>T is in linkage disequilibrium (LD) with rs699 A>G and increasesAGTtranscription. We hypothesized that the increasedAGTby rs5051 C>T counterbalancesAGTdecrease by rs699 A>G, and when these variants occur independently, would translate to HTN-related phenotypes. The independent effect of each of these variants is understudied due to their LD, therefore, we usedin silico, in vitro, in vivo, and retrospective clinical and biobank analyses to assess HTN andAGTexpression phenotypes where rs699 A>G occurs independently from rs5051 C>T.In silico, rs699 A>G is predicted to increase mir-122-5p binding strength by 3%. Mir-eCLIP assay results show that rs699 is 40-45 nucleotides from the strongest microRNA binding site in theAGTmRNA. Unexpectedly, rs699 A>G increasesAGTmRNA in a plasmid cDNA HepG2 expression model. GTEx and UK Biobank analyses demonstrate that liverAGTexpression and HTN phenotypes were not different when rs699 A>G occurs independently from rs5051 C>T, allowing us to reject the original hypothesis. However, both GTEx and ourin vitroexperiments suggest rs699 A>G confers cell-type specific effects onAGTmRNA abundance. We found that rs5051 C>T and rs699 A>G significantly associate with systolic blood pressure in Black participants in the UK Biobank, demonstrating a 4-fold larger effect than in White participants. Further studies are warranted to determine if the altered antihypertensive response in Black individuals might be due to rs5051 C>T or rs699 A>G. Studies like this will help clinicians move beyond the use of race as a surrogate for genotype.

RNA performs a wide range of functions regulated by its structure, dynamics, and often post-transcriptional modifications. While NMR is the leading method for understanding RNA structure and dynamics, it is currently limited by the inability to reduce spectral crowding by efficient segmental labeling. Furthermore, because of the challenging nature of RNA chemistry, the tools being developed to introduce site- specific modifications are increasingly complex and laborious. Here we use a previously designed Tgo DNA polymerase mutant to present SegModTeX — a versatile, one-pot, copy-and-paste approach to address these challenges. By precise, stepwise construction of a diverse set of RNA molecules, we demonstrate the technique to be superior to RNA polymerase driven and ligation methods owing to its substantially high yield, fidelity, and selectivity. We also show the technique to be useful for incorporating fluorescent- and a wide range of other probes, which significantly extends the toolbox of RNA biology in general.

Supplementary Data from Up-Regulation of Krüppel-Like Factor 5 in Pancreatic Cancer Is Promoted by Interleukin-1β Signaling and Hypoxia-Inducible Factor-1α

Likelihood ratios are frequently utilized as basis for statistical tests, for model selection criteria and for assessing parameter and prediction uncertainties, e.g. using the profile likelihood. However, translating these likelihood ratios into p-values or confidence intervals requires the exact form of the test statistic's distribution. The lack of knowledge about this distribution for nonlinear ordinary differential equation (ODE) models requires an approximation which assumes the so-called asymptotic setting, i.e. a sufficiently large amount of data. Since the amount of data from quantitative molecular biology is typically limited in applications, this finite-sample case regularly occurs for mechanistic models of dynamical systems, e.g. biochemical reaction networks or infectious disease models. Thus, it is unclear whether the standard approach of using statistical thresholds derived for the asymptotic large-sample setting in realistic applications results in valid conclusions. In this study, empirical likelihood ratios for parameters from 19 published nonlinear ODE benchmark models are investigated using a resampling approach for the original data designs. Their distributions are compared to the asymptotic approximation and statistical thresholds are checked for conservativeness. It turns out, that corrections of the likelihood ratios in such finite-sample applications are required in order to avoid anti-conservative results., This the a light-weight version of https://doi.org/10.5281/zenodo.7738793 (51.2 GB)

Lawsonia intracellularis is the etiologic agent of porcine proliferative enteropathy (PPE), an inflammatory bowel disease with a major economic impact on the pig industry. The serological diagnosis of PPE can be performed using Blocking or Indirect ELISA, Immunoperoxidase Monolayer Assay (IPMA) and Indirect Fluorescence Antibody Test (IFAT). Here, we designed a most sophisticated immunological method for the detection of porcine anti-L. intracellularis IgGs, named Flow Cytometry Antibody Test - FCAT. This assay uses whole, live-attenuated L. intracellularis bacteria derived from a commercial vaccine. For the assay, we set up the optimal antigen concentration (106 bacterium/assay), primary antibody dilution (1:100), time of incubation (20 min), antigen stability (15 days), precision (coefficient of variation - CV < 10%), reproducibility (CV ≤ 13%) and Receiver Operating Characteristic (ROC). When using a cut-off of >15.15% for FCAT, we determined that it showed a sensitivity of 98.8% and specificity of 100%. The rate of agreement with IPMA was 84.09% with a kappa index of 0.66. FCAT was used to screen 1,000 sera from non-vaccinated pigs housed in 22 different farms and we found that 730 pigs (73%) from 16 farms (72.7%) had L. intracellularis IgG. This high prevalence confirms that L. intracellularis is endemic on Brazilian pig farms. Finally, we determined that FCAT is an easy to perform diagnostic assay and we would highly recommend it for: i) seroepidemiological studies; ii) evaluation of infection dynamics; and iii) characterization of the humoral response profile induced by vaccines.

Introduction: Epidemiological studies in children suggested that in utero exposure to chlorpyrifos (CPF), an organophosphate insecticide, may cause developmental neurotoxicity (DNT). We applied quantitative in vitro–in vivo extrapolation (QIVIVE) based on in vitro concentration and non-choline esterase-dependent effects data combined with Benchmark dose (BMD) modelling to predict oral maternal CPF exposure during pregnancy leading to fetal brain effect concentration. By comparing the results with data from epidemiological studies, we evaluated the contribution of the in vitro endpoints to the mode of action (MoA) for CPF-induced DNT.Methods: A maternal-fetal PBK model built in PK-Sim® was used to perform QIVIVE predicting CPF concentrations in a pregnant women population at 15 weeks of gestation from cell lysate concentrations obtained in human induced pluripotent stem cell-derived neural stem cells undergoing differentiation towards neurons and glia exposed to CPF for 14 days. The in vitro concentration and effect data were used to perform BMD modelling.Results: The upper BMD was converted into maternal doses which ranged from 3.21 to 271 mg/kg bw/day. Maternal CPF blood levels from epidemiological studies reporting DNT findings in their children were used to estimate oral CPF exposure during pregnancy using the PBK model. It ranged from 0.11 to 140 μg/kg bw/day.Discussion: The effective daily intake doses predicted from the in vitro model were several orders of magnitude higher than exposures estimated from epidemiological studies to induce developmental non-cholinergic neurotoxic responses, which were captured by the analyzed in vitro test battery. These were also higher than the in vivo LOEC for cholinergic effects. Therefore, the quantitative predictive value of the investigated non-choline esterase-dependent effects, although possibly relevant for other chemicals, may not adequately represent potential key events in the MoA for CPF-associated DNT.

In this paper, we consider the new family of recurrence sequences of (q,k)-generalized Fibonacci numbers. These sequences naturally extend the well-known sequences of k-generalized Fibonacci numbers and generalized k-order Pell numbers. We shall obtain a Binet-style formula and study the asymptotic behavior of dominant root of characteristic equation. Moreover, we shall prove some auxiliary results about these sequences. In particular, we characterize the first (q,k)-generalized Fibonacci numbers in terms of binary sequences.

Baseando-se na Política Nacional de Recursos Hídricos (PNRH), faz-se um paralelo com as etapas de diagnóstico, definição e planejamento de ações, inerentes ao processo de elaboração dos Planos de Recursos Hídricos, da Bacia Hidrográfica do Rio Tramandaí. E também foram realizadas análises de documentos e informações do CBHRT. Objetivando-se os instrumentos da PNRH que fazem parte do processo de planejamento desenvolvido pela Agência Nacional de Águas e Saneamento Básico (ANA) e pelos órgãos gestores de recursos hídricos junto aos comitês de bacia tendo em vista os requisitos legais. Pode-se ressaltar a necessidade de avançar ainda mais em todos os campos e temáticas que cercam e nos impulsionam em defesa da água e compreender a importância da legislação acerca dos corpos d’água na sua biodiversidade. A partir de todo esse levantamento, estudos e pesquisa sobre a Bacia Hidrográfica (BH) do Rio Tramandaí, consegue-se compreender a importância da legislação acerca dos corpos d’água e todas as suas diversidades de origem, permanência, qualidade, uso e preservação. Compreende-se que as instituições de pesquisa, monitoramento, órgãos de fiscalização, e espaços democráticos de representação e organização são de extrema necessidade para que se possam avançar ainda mais em todos os campos e temáticas que cercam e nos impulsionam em defesa da água enquanto elemento essencial pra vida humana, vegetal e animal, para o solo, para o ciclo da água, para o desempenho do equilíbrio climático, para o planeta.

A randomised clinical trial was conducted on 20 healthy, low-habitual fibre consumers to assess the short-term effects of water intake (2 l/day) on fibre supplementation with wheat bran, pectin, and green banana flour. During the 14-days trial, fibre intake doubled in both fibre (