Hypoxia-induced immortalization of primary cells depends on Tfcp2L1 expression.

Cellular senescence is a stress response mechanism that induces proliferative arrest. Hypoxia can bypass senescence and extend the lifespan of primary cells, mainly by decreasing oxidative damage. However, how hypoxia promotes these effects prior to malignant transformation is unknown. Here we observed that the lifespan of mouse embryonic fibroblasts (MEFs) is increased when they are cultured in hypoxia by reducing the expression of p16INK4a, p15INK4b and p21Cip1. We found that proliferating MEFs in hypoxia overexpress Tfcp2l1, which is a main regulator of pluripotency and self-renewal in embryonic stem cells, as well as stemness genes including Oct3/4, Sox2 and Nanog. Tfcp2l1 expression is lost during culture in normoxia, and its expression in hypoxia is regulated by Hif1α. Consistently, its overexpression in hypoxic levels increases the lifespan of MEFs and promotes the overexpression of stemness genes. ATAC-seq and Chip-seq experiments showed that Tfcp2l1 regulates genes that control proliferation and stemness such as Sox2, Sox9, Jarid2 and Ezh2. Additionally, Tfcp2l1 can replicate the hypoxic effect of increasing cellular reprogramming. Altogether, our data suggest that the activation of Tfcp2l1 by hypoxia contributes to immortalization prior to malignant transformation, facilitating tumorigenesis and dedifferentiation by regulating Sox2, Sox9, and Jarid2.

Early detection of interstitial lung disease in rheumatic diseases: A joint statement from the Portuguese Pulmonology Society, the Portuguese Rheumatology Society, and the Portuguese Radiology and Nuclear Medicine Society.

INTRODUCTION: Interstitial lung disease (ILD) contributes significantly to morbidity and mortality in connective tissue disease (CTD). Early detection and accurate diagnosis are essential for informing treatment decisions and prognosis in this setting. Clear guidance on CTD-ILD screening, however, is lacking. OBJECTIVE: To establish recommendations for CTD-ILD screening based on the current evidence. METHOD: Following an extensive literature research and evaluation of articles selected for their recency and relevance to the characterization, screening, and management of CTD-ILD, an expert panel formed by six pulmonologists from the Portuguese Society of Pulmonology, six rheumatologists from the Portuguese Society of Rheumatology, and six radiologists from the Portuguese Society of Radiology and Nuclear Medicine participated in a multidisciplinary discussion to produce a joint statement on screening recommendations for ILD in CTD. RESULTS: The expert panel achieved consensus on when and how to screen for ILD in patients with systemic sclerosis, rheumatoid arthritis, mixed connective tissue disease, Sjögren syndrome, idiopathic inflammatory myopathies and systemic lupus erythematous. CONCLUSIONS: Despite the lack of data on screening for CTD-ILD, an expert panel of pulmonologists, rheumatologists and radiologists agreed on a series of screening recommendations to support decision-making and enable early diagnosis of ILD to ultimately improve outcomes and prognosis in patients with CTD.

A method to produce a flexible and customized fuel models dataset.

Simulation of vegetation fires very often resorts to fire-behavior models that need fuel models as input. The lack of fuel models is a common problem for researchers and fire managers because its quality depends on the quality/availability of data. In this study we present a method that combines expert- and research-based knowledge with several sources of data (e.g. satellite and fieldwork) to produce customized fuel models maps. Fuel model classes are assigned to land cover types to produce a basemap, which is then updated using empirical and user-defined rules. This method produces a map of surface fuel models as detailed as possible. It is reproducible, and its flexibility relies on juxtaposing independent spatial datasets, depending on their quality or availability. This method is developed in a ModelBuilder/ArcGis toolbox named FUMOD that integrates ten sub-models. FUMOD has been used to map the Portuguese annual fuel models grids since 2019, supporting regional fire risk assessments and suppression decisions. Datasets, models and supplementary files are available in a repository (https://github.com/anasa30/PT_FuelModels). •FUMOD is a flexible toolbox with ten sub-models included that maps updated Portuguese fuel models.

Approaching the airway in prehospital emergency is a common and potentially life-saving practice.

Management by the environment is complex, which means a much higher percentage of difficult airways than in a regulated environment such as the operating room. Failure or prolonged attempt to tracheal intubation is associated with unfavorable outcomes and serious complications. Acute epiglottitis is a life-threatening disorder, classified as a medical emergency within the diseases of the upper respiratory airway and characterized by its sudden and deadly evolution if rapid intubation is not achieved to allow oxygenation of the patient. We describe a 36-year-old male patient with stridor, dyspnea e hypoxemia due to total obstruction of airway, caused by an acute epiglottitis. We aim to highlight this unusual injury and its management from the prehospital until discharge illustrating the severity of the clinical presentation, current treatment and outcome.

Predicting lung nodules malignancy.

BACKGROUND: It is critical to developing an accurate method for differentiating between malignant and benign solitary pulmonary nodules. This study aimed was to establish a predicting model of lung nodules malignancy in a real-world setting. METHODS: The authors retrospectively analysed the clinical and computed tomography (CT) data of 121 patients with lung nodules, submitted to percutaneous CT-guided transthoracic biopsy, between 2014 and 2015. Multiple logistic regression was used to screen independent predictors for malignancy and to establish a clinical prediction model to evaluate the probability of malignancy. RESULTS: From a total of 121 patients, 75 (62%) were men and with a mean age of 64.7 years old. Multivariate logistic regression analysis identified six independent predictors of malignancy: age, gender, smoking status, current extra-pulmonary cancer, air bronchogram and nodule size (p<0.05). The area under the curve (AUC) was 0.8573. CONCLUSIONS: The prediction model established in this study can be used to assess the probability of malignancy in the Portuguese population, thereby providing help for the diagnosis of lung nodules and the selection of follow-up interventions.

Modulation of persistent current in graphene quantum rings.

We investigate the effect of long-range impurity potentials on the persistent current of graphene quantum rings in the presence of an uniform perpendicular magnetic field. The impurity potentials are modeled as finite regions of the ring with a definite length. We show that, due to the relativistic and massless character of the charge carriers in graphene, the effect of such non-uniform potentials on the energy spectrum and on the persistent current of the rings can be reliably modeled by assuming a non-perturbed ring and including an additional phase due to the interaction of the charge carriers with the potential. In addition, the results show the presence of localized states in the impurity regions. Moreover, we show that for the case of a potential created by a p-n-p junction, the persistent current can be modulated by controlling the voltage at the junction.

Approaching the airway in prehospital emergency is a common and potentially life-saving practice. / Entorno prehospitalario y manejo en UCI de epiglotitis en un adulto.

Management by the environment is complex, which means a much higher percentage of difficult airways than in a regulated environment such as the operating room. Failure or prolonged attempt to tracheal intubation is associated with unfavorable outcomes and serious complications. Acute epiglottitis is a life-threatening disorder, classified as a medical emergency within the diseases of the upper respiratory airway and characterized by its sudden and deadly evolution if rapid intubation is not achieved to allow oxygenation of the patient. We describe a 36-year-old male patient with stridor, dyspnea e hypoxemia due to total obstruction of airway, caused by an acute epiglottitis. We aim to highlight this unusual injury and its management from the prehospital until discharge illustrating the severity of the clinical presentation, current treatment and outcome.

Gate potential-controlled current switching in graphene Y-junctions.

In this work we investigate the ballistic transport of electrons through three-terminal graphene-based devices. The system consists of a Y-shaped junction formed by three armchair-edged graphene nanoribbons with a rectangular gate potential applied to one of the output branches, whereby current control can be established by the controlling of the refractive index in graphene p-n junctions. Transport properties are obtained by using the Landauer-Büttiker formalism and the tight-binding model within the nearest-neighbor approximation, which allows the calculation of the conductance as function of the Fermi energy, the applied potential, and the system size, as well as the current density. The results demonstrate that the applied electric field can tune the current transmission between the input and two output leads and, consequently, the proposed system acts as a current switch.

Burnout among Portuguese radiographers during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has had a global impact, including in health services, placing health professionals under enormous tension, pressure, and stress. Professionals involved in the care, diagnosis, and treatment of COVID-19-infected patients have been subject to emotional and physical distress that can potentially enhance the development of occupational diseases. The aim of this study was to assess the impact of the COVID-19 pandemic on the incidence of burnout among Portuguese radiographers. METHODS: This was a cross-sectional, quantitative study. Burnout levels were estimated using the Maslach Burnout Inventory-Human Services Survey, composed of 22 questions. Specific questions were developed to characterize the socio-demographic situation and the impact of the pandemic on the radiographers. Data were descriptively analyzed and Mann-Whitney and Kruskal-Wallis tests were used for correlation analysis. RESULTS: The study sample comprised 386 radiographers, 68.7% of whom where female and 31.3% male. The mean sample age was 36.3 (±9.1) years. A total of 43.5% and 45.5% of subjects had a high level of emotional exhaustion and depersonalization, respectively, and 59.8% experienced low personal accomplishment. Altogether, 23.3% of study participants were at high risk of burnout in the three dimensions assessed and 77.2% in at least one. CONCLUSION: Study results showed that radiographers were at high risk of developing burnout in the COVID-19 pandemic setting. Health institutions should actively monitor these professional's mental health and develop restorative strategies that enable their emotional wellbeing, preventing absenteeism and increasing patients' quality of care. IMPLICATIONS FOR PRACTICE: Burnout of health professionals has a strong impact on health services organization, resulting in increased absenteeism and error probability, frequent work delays, low productivity and job satisfaction, inter- and intra-professional conflicts, high job turnover, high job quit, and decreased quality of care perceived by users.

Twenty-first century droughts have not increasingly exacerbated fire season severity in the Brazilian Amazon.

Biomass burning in the Brazilian Amazon is modulated by climate factors, such as droughts, and by human factors, such as deforestation, and land management activities. The increase in forest fires during drought years has led to the hypothesis that fire activity decoupled from deforestation during the twenty-first century. However, assessment of the hypothesis relied on an incorrect active fire dataset, which led to an underestimation of the decreasing trend in fire activity and to an inflated rank for year 2015 in terms of active fire counts. The recent correction of that database warrants a reassessment of the relationships between deforestation and fire. Contrasting with earlier findings, we show that the exacerbating effect of drought on fire season severity did not increase from 2003 to 2015 and that the record-breaking dry conditions of 2015 had the least impact on fire season of all twenty-first century severe droughts. Overall, our results for the same period used in the study that originated the fire-deforestation decoupling hypothesis (2003-2015) show that decoupling was clearly weaker than initially proposed. Extension of the study period up to 2019, and novel analysis of trends in fire types and fire intensity strengthened this conclusion. Therefore, the role of deforestation as a driver of fire activity in the region should not be underestimated and must be taken into account when implementing measures to protect the Amazon forest.

Metabolizable amino acids and energy requirements of Nellore and crossbred Angus × Nellore bulls fed rations of different crude protein concentrations.

Growth rate of cattle depends on their genetic makeup and nutrient intake. Moreover, increased growth rate may lead to increased amino acid (AA) requirements. Therefore, we evaluated the AA content of the empty body and estimated the net AA and energy requirements of purebred and crossbred beef bulls fed rations of different dietary CP concentrations. We performed a comparative slaughter experiment with 24 Nellore and 24 Angus × Nellore (A × N) bulls (8 months; initial shrunk BW: Nellore = 208.0 ±â€¯12.78 kg; A × N = 221.9 ±â€¯14.16 kg). Eight bulls (four Nellore and four A × N) were designated as the reference group, eight bulls (four Nellore and four A × N) were fed to maintenance level and 32 bulls (16 Nellore and 16 A × N) were fed ad libitum. The 32 bulls fed ad libitum were distributed using a completely randomized design in a 2 × 3 factorial scheme with two genetic groups (Nellore or A × N) and three dietary CP contents (100, 120 or 140 g CP/kg DM), being four groups with five bulls and two groups with six bulls. The experimental period lasted for 224 days. There were no interactions (P ≥ 0.056) between the dietary CP contents and genetic groups for any of the response variables. The dietary CP contents did not affect (P ≥ 0.062) the AA content in the empty body (g/kg empty BW [EBW]), with exception for Tryptophan (P = 0.027, linear effect). The dietary CP contents did not affect (P ≥ 0.051) AA content in the empty body (g/100 g of CP), with exception for Alanine (P = 0.013) that responded quadratically to dietary CP increase. The equations to estimate the net Lysine (Lys) and Methionine (Met) requirements (g/100 g of CP) were: Lys = 5.1 × EBW0.0594 and Met = 1.7 × EBW0.0255. Metabolizable Lys and Met to metabolizable energy (ME) ratios decreased as bulls EBW increased. Also, the metabolizable protein to ME ratio decreased as bulls EBW increased. In conclusion, the present study provides useful information regarding net and metabolizable requirements of AA of purebred and crossbred beef bulls. In the future, after the validation of the equations, these results can be used to calculate the AA requirements for growth of purebred and crossbred beef bulls. Nevertheless, it is important to highlight that the small sample size was one limitation of this present experiment.

Chest CT imaging features of COVID-19 pneumonia: First radiological insights from Porto, Portugal.

INTRODUCTION: The outbreak of a highly infectious respiratory disease - COVID-19 - has spread globally and a novel type of coronavirus (SARS-CoV-2) was identified as its cause. Chest CT findings have been described as an aid for COVID-19 diagnosis and management. We aimed to describe the CT imaging characteristics in a group of COVID-19 patients while we also intended to assess if any of these radiological features were associated with short-term prognosis. MATERIALS AND METHODS: CT examinations from 164 consecutive patients with at least one positive RT-PCR nucleic acid assay for SARS-CoV-2 were retrospectively analyzed. Numerous CT imaging features were recorded independently by two radiologists. Patients were grouped according to their status 14 days after the initial CT scan in either discharged/hospitalized in a non-ICU ward (favorable prognosis group) versus deceased/admitted to an intensive care unit (unfavorable prognosis group). RESULTS: Ground-glass opacities (89.0 %) and consolidations (73.2 %) with multilobar involvement were the predominant imaging findings, while a nodular pattern (3.7 %) and cavitation (1.2 %) were uncommon. Mean age was higher in the mortality/ICU group. Ground-glass opacities and consolidations were dominant in both groups, but distribution pattern of abnormalities was different, being more often diffuse in the mortality/ICU group. Linear opacities and opacities that were rounded in shape were more frequently observed in the favorable prognosis group. CT severity index was significantly higher in the mortality/ICU group. For assessing unfavorable prognosis, the best cut-off for CT severity index was 24 (sensitivity 78 %; specificity 59 %). Interobserver agreement for all CT findings was excellent. CONCLUSION: COVID-19 pneumonia in Porto, Portugal, manifests as multilobar ground-glass opacities and consolidations. Older age, diffuse distribution and increasing CT severity index are associated with worse short-term prognosis while linear opacities resembling organizing pneumonia and rounded opacities herald a more favorable prognosis.

Current modulation in graphene p-n junctions with external fields.

In this work we describe a proposal for a graphene-based nanostructure that modulates electric current even in the absence of a gap in the band structure. The device consists of a graphene p-n junction that acts as a Veselago lens that focuses ballistic electrons on the output lead. Applying external (electric and magnetic) fields changes the position of the output focus, reducing the transmission. Such device can be applied to low power field effect transistors, which can benefit from graphene's high electronic mobility.

Anthromes displaying evidence of weekly cycles in active fire data cover 70% of the global land surface.

Across the globe, human activities have been gaining importance relatively to climate and ecology as the main controls on fire regimes and consequently human activity became an important driver of the frequency, extent and intensity of vegetation burning worldwide. Our objective in the present study is to look for weekly cycles in vegetation fire activity at global scale as evidence of human agency, relying on the original MODIS active fire detections at 1 km spatial resolution (MCD14ML) and using novel statistical methodologies to detect significant periodicities in time series data. We tested the hypotheses that global fire activity displays weekly cycles and that the weekday with the fewest fires is Sunday. We also assessed the effect of land use and land cover on weekly fire cycle significance by testing those hypotheses separately for the Villages, Settlements, Croplands, Rangelands, Seminatural, and Wildlands anthromes. Based on a preliminary data analysis of the daily global active fire counts periodogram, we developed an harmonic regression model for the mean function of daily fire activity and assumed a linear model for the de-seasonalized time series. For inference purposes, we used a Bayesian methodology and constructed a simultaneous 95% credible band for the mean function. The hypothesis of a Sunday weekly minimum was directly investigated by computing the probabilities that the mean functions of every weekday (Monday to Saturday) are inside the credible band corresponding to mean Sunday fire activity. Since these probabilities are small, there is statistical evidence of significantly fewer fires on Sunday than on the other days of the week. Cropland, rangeland, and seminatural anthromes, which cover 70% of the global land area and account for 94% of the active fires analysed, display weekly cycles in fire activity. Due to lower land management intensity and less strict control over fire size and duration, weekly cycles in Rangelands and Seminatural anthromes, which jointly account for 53.46% of all fires, although statistically significant are weaker than those detected in Croplands.

Heterozygous TERT gene mutation associated with familial idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown cause that occurs sporadically, but it can also occur in families and so named as Familial Pulmonary Fibrosis (FPF). Some forms of FPF overlaps IPF features, namely the radiological and histological pattern of usual interstitial pneumonia (UIP). Genetic and environmental factors commonly play an important role in the pathogenesis of FPF and the most commonly identified mutations involve the telomerase complex. Here, we report a rare case of FPF in a male at the age of 44, in whom genetic testing showed heterozygous variants for the telomerase reverse transcriptase gene (TERT). Our report highlights the importance of compiling a thorough family history in younger patients identified with UIP serving as a resource for identifying the current and future genetic links to disease. Families with UIP hold a great promise in defining UIP pathogenesis, potentially suggesting targets for the development of future therapies.

Melissa officinalis L. ethanolic extract inhibits the growth of a lung cancer cell line by interfering with the cell cycle and inducing apoptosis.

Melissa officinalis is a plant from the family Lamiaceae, native in Europe particularly in the Mediterranean region. Given our interest in identifying extracts and compounds capable of inhibiting tumor cell growth, and given the antioxidant content and the high consumption of Melissa officinalis in Portugal, this study aimed to test the tumor cell growth inhibitory activity of five different extracts of this plant (aqueous, methanolic, ethanolic, hydromethanolic and hydroethanolic) in three human tumor cell lines: MCF-7, AGS and NCI-H460. All extracts decreased cell growth in all cell lines in a concentration-dependent manner. The ethanolic extract was the most potent one, presenting a GI50 concentration of approximately 100.9 µg mL-1 in the NCI-H460 lung cancer cells. This extract was characterized by LC-DAD-ESI/MS regarding its phenolic composition, revealing rosmarinic acid as the most abundant compound. The GI75 concentration of this extract affected the cell cycle profile of these cells. In addition, both the GI50 and the GI75 concentrations of the extract induced cellular apoptosis. Moreover, treatment of NCI-H460 cells with this extract caused a decrease in pro-caspase 3 and an increase in p53 levels. This study emphasizes the relevance of the study of natural products as inhibitors of tumor cell growth.

Monitoring Walker Assistive Devices: A Novel Approach Based on Load Cells and Optical Distance Measurements.

This paper presents a measurement system intended to monitor the usage of walker assistive devices. The goal is to guide the user in the correct use of the device in order to prevent risky situations and maximize comfort. Two risk indicators are defined: one related to force unbalance and the other related to motor incoordination. Force unbalance is measured by load cells attached to the walker legs, while motor incoordination is estimated by synchronizing force measurements with distance data provided by an optical sensor. The measurement system is equipped with a Bluetooth link that enables local supervision on a computer or tablet. Calibration and experimental results are included in the paper.

Dietary protein reduction on microbial protein, amino acid digestibility, and body retention in beef cattle: 2. Amino acid intestinal absorption and their efficiency for whole-body deposition.

The objective of this study was to determine the apparent and true intestinal digestibility of total and individual AA, and to estimate the efficiency of whole-body AA retention from individual and total absorbed AA. Four Nellore animals (241.3 kg initial BW) and four crossbred Angus × Nellore (263.4 kg initial BW) cannulated in rumen and ileum were randomly allocated in two 4 × 4 Latin squares. The experiment lasted four 17 d periods, with 10 d for adaptation to diets and another 7 d for data collection. The diets consisted of increasing CP levels: 100, 120, or 140 g/kg of DM offered ad libitum, and restricted intake diet with 120 g CP/kg DM (experiment 1). In experiment 2, forty-four bulls (22 Nellore and 22 crossbred F1 Angus × Nellore) with 8 months and initial shrunk BW 215.0 ± 15.0 kg (Nellore = 208.0 ± 12.78 kg; Angus × Nellore = 221.9 ± 14.16 kg) were used. Eight of those animals were slaughtered at the beginning of the experiment. The remaining 36 bulls were allocated in a completely randomized design with six replicates, in a 2 (genetic groups) × 3 (CP contents) factorial scheme. The amount of essential AA (EAA) and nonessential AA (NEAA) reaching the small intestine increased linearly (P < 0.05) in response to CP content. The apparent digestibility of EAA was not affected (P > 0.05) by CP content, with exception for histidine (P = 0.07, linear effect), leucine (P = 0.01, linear effect), and methionine (P = 0.05, linear effect). Differences existed among AA when compared the apparent digestibility of NEAA. The apparent digestibility of alanine (P = 0.05), aspartic acid (P = 0.07), glutamic acid (P = 0.02), glycine (P = 0.05), proline (P = 0.02), and serine (P = 0.04) responded quadratically to CP content increase. However, the apparent digestibility of cystine and tyrosine was not affected (P > 0.05) by increasing dietary CP. The true intestinal digestibilities of total, essential, nonessential AA, lysine, and methionine were 75.0%, 77.0%, 74.0%, 77.0%, and 86%, respectively. The true intestinal digestibility of total microbial AA was 80%. The efficiency of utilization of total AA for whole-body protein deposition was 40%. The efficiency of utilization of lysine and methionine was 37% and 58%, respectively. It was concluded that the AA flow to the omasum increases in response to dietary CP content. In addition, there are differences among AA in the efficiency that they are used by beef cattle.

Impact of antibiotic therapy in severe community-acquired pneumonia: Data from the Infauci study.

Antibiotic therapy (AT) is the cornerstone of the management of severe community-acquired pneumonia (CAP). However, the best treatment strategy is far from being established. To evaluate the impact of different aspects of AT on the outcome of critically ill patients with CAP, we performed a post hoc analysis of all CAP patients enrolled in a prospective, observational, multicentre study. Of the 502 patients included, 76% received combination therapy, mainly a ß-lactam with a macrolide (80%). AT was inappropriate in 16% of all microbiologically documented CAP (n=177). Hospital and 6months mortality were 34% and 35%. In adjusted multivariate logistic regression analysis, combination AT with a macrolide was independently associated with a reduction in hospital (OR 0.17, 95%CI 0.06-0.51) and 6months (OR 0.21, 95%CI 0.07-0.57) mortality. Prolonged AT (>7days) was associated with a longer ICU (14 vs. 7days; p<0.001) and hospital length of stay (LOS) (25 vs. 17days; p<0.001). Combination AT with a macrolide may be the most suitable AT strategy to improve both short and long term outcome of severe CAP patients. AT >7days had no survival benefit and was associated with a longer LOS.