Endothelial cells give a boost to senescence surveillance.

Senescence is a specialized form of cell cycle arrest induced in response to damage and stress. In certain settings, senescent cells can promote their own removal by recruitment of the immune system, a process that is thought to decline in efficiency with age. In this issue of Genes & Development, Yin et al. (pp. 533-549) discover a surprising cross-talk where senescent cells instruct endothelial cells to help organize the clearance of the senescent population. This uncovers yet another layer of complexity in senescent cell biology, with implications for cancer treatment and aging.

The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice.

Young mammals possess a limited regenerative capacity in some tissues, which is lost upon maturation. We investigated whether cellular senescence might play a role in such loss during liver regeneration. We found that following partial hepatectomy, the senescence-associated genes p21, p16Ink4a, and p19Arf become dynamically expressed in different cell types when regenerative capacity decreases, but without a full senescent response. However, we show that treatment with a senescence-inhibiting drug improves regeneration, by disrupting aberrantly prolonged p21 expression. This work suggests that senescence may initially develop from heterogeneous cellular responses, and that senotherapeutic drugs might be useful in promoting organ regeneration.

Production and characterization of the lipopeptide with anti-adhesion for oral biofilm on the surface of titanium for dental implants.

Titanium implants are subject to bacterial adhesion and peri-implantitis induction, and biosurfactants bring a new alternative to the fight against infections. This work aimed to produce and characterize the biosurfactant from Bacillus subtilis ATCC 19,659, its anti-adhesion and antimicrobial activity, and cell viability. Anti-adhesion studies were carried out against Streptococcus sanguinis, Staphylococcus aureus, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Proteus mirabilis as the minimum inhibitory concentration and the minimum bactericidal concentration. Cell viability was measured against osteoblast and fibroblast cells. The biosurfactant was classified as lipopeptide, with critical micelle concentration at 40 µg mL- 1, and made the titanium surface less hydrophobic. The anti-adhesion effect was observed for Staphylococcus aureus and Streptococcus sanguinis with 54% growth inhibition and presented a minimum inhibitory concentration of 15.7 µg mL- 1 for Streptococcus sanguinis and Aggregatibacter actinomycetemcomitans. The lipopeptide had no cytotoxic effect and demonstrated high potential application against bacterial biofilms.

Assessment of Cardiorespiratory and Metabolic Contributions in an Extreme Intensity CrossFit® Benchmark Workout.

Our purpose was to characterize the oxygen uptake kinetics (VO2), energy systems contributions and total energy expenditure during a CrossFit® benchmark workout performed in the extreme intensity domain. Fourteen highly trained male CrossFitters, aged 28.3 ± 5.4 years, with height 177.8 ± 9.4 cm, body mass 87.9 ± 10.5 kg and 5.6 ± 1.8 years of training experience, performed the Isabel workout at maximal exertion. Cardiorespiratory variables were measured at baseline, during exercise and the recovery period, with blood lactate and glucose concentrations, including the ratings of perceived exertion, measured pre- and post-workout. The Isabel workout was 117 ± 10 s in duration and the VO2 peak was 47.2 ± 4.7 mL·kg-1·min-1, the primary component amplitude was 42.0 ± 6.0 mL·kg-1·min-1, the time delay was 4.3 ± 2.2 s and the time constant was 14.2 ± 6.0 s. The accumulated VO2 (0.6 ± 0.1 vs. 4.8 ± 1.0 L·min-1) value post-workout increased substantially when compared to baseline. Oxidative phosphorylation (40%), glycolytic (45%) and phosphagen (15%) pathways contributed to the 245 ± 25 kJ total energy expenditure. Despite the short ~2 min duration of the Isabel workout, the oxygen-dependent and oxygen-independent metabolism energy contributions to the total metabolic energy release were similar. The CrossFit® Isabel requires maximal effort and the pattern of physiological demands identifies this as a highly intensive and effective workout for developing fitness and conditioning for sports.

Restoring Skeletal Muscle Health through Exercise in Breast Cancer Patients and after Receiving Chemotherapy.

Breast cancer (BC) stands out as the most commonly type of cancer diagnosed in women worldwide, and chemotherapy, a key component of treatment, exacerbates cancer-induced skeletal muscle wasting, contributing to adverse health outcomes. Notably, the impact of chemotherapy on skeletal muscle seems to surpass that of the cancer itself, with inflammation identified as a common trigger for muscle wasting in both contexts. In skeletal muscle, pro-inflammatory cytokines modulate pathways crucial for the delicate balance between protein synthesis and breakdown, as well as satellite cell activation and myonuclear accretion. Physical exercise consistently emerges as a crucial therapeutic strategy to counteract cancer and chemotherapy-induced muscle wasting, ultimately enhancing patients' quality of life. However, a "one size fits all" approach does not apply to the prescription of exercise for BC patients, with factors such as age, menopause and comorbidities influencing the response to exercise. Hence, tailored exercise regimens, considering factors such as duration, frequency, intensity, and type, are essential to maximize efficacy in mitigating muscle wasting and improving disease outcomes. Despite the well-established anti-inflammatory role of aerobic exercise, resistance exercise proves equally or more beneficial in terms of mass and strength gain, as well as enhancing quality of life. This review comprehensively explores the molecular pathways affected by distinct exercise regimens in the skeletal muscle of cancer patients during chemotherapy, providing critical insights for precise exercise implementation to prevent skeletal muscle wasting.

Unravelling the genetic variability of host resilience to endo- and ectoparasites in Nellore commercial herds.

BACKGROUND: Host resilience (HR) to parasites can affect the performance of animals. Therefore, the aim of this study was to present a detailed investigation of the genetic mechanisms of HR to ticks (TICK), gastrointestinal nematodes (GIN), and Eimeria spp. (EIM) in Nellore cattle that were raised under natural infestation and a prophylactic parasite control strategy. In our study, HR was defined as the slope coefficient of body weight (BW) when TICK, GIN, and EIM burdens were used as environmental gradients in random regression models. In total, 1712 animals were evaluated at five measurement events (ME) at an average age of 331, 385, 443, 498, and 555 days, which generated 7307 body weight (BW) records. Of the 1712 animals, 1075 genotyped animals were used in genome-wide association studies to identify genomic regions associated with HR. RESULTS: Posterior means of the heritability estimates for BW ranged from 0.09 to 0.54 across parasites and ME. The single nucleotide polymorphism (SNP)-derived heritability for BW at each ME ranged from a low (0.09 at ME.331) to a moderate value (0.23 at ME.555). Those estimates show that genetic progress can be achieved for BW through selection. Both genetic and genomic associations between BW and HR to TICK, GIN, and EIM confirmed that parasite infestation impacted the performance of animals. Selection for BW under an environment with a controlled parasite burden is an alternative to improve both, BW and HR. There was no impact of age of measurement on the estimates of genetic variance for HR. Five quantitative trait loci (QTL) were associated with HR to EIM but none with HR to TICK and to GIN. These QTL contain genes that were previously shown to be associated with the production of antibody modulators and chemokines that are released in the intestinal epithelium. CONCLUSIONS: Selection for BW under natural infestation and controlled parasite burden, via prophylactic parasite control, contributes to the identification of animals that are resilient to nematodes and Eimeria ssp. Although we verified that sufficient genetic variation existed for HR, we did not find any genes associated with mechanisms that could justify the expression of HR to TICK and GIN.

TiO2/MWCNT/Nafion-Modified Glassy Carbon Electrode as a Sensitive Voltammetric Sensor for the Determination of Hydrogen Peroxide.

In this work we describe a straightforward approach for creating a nanocomposite comprising multiwalled carbon nanotubes (MWCNTs) and titanium dioxide (TiO2) using the hydrothermal technique, which is then characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectrometer (EDS), X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FTIR), and thermal gravimetric analysis (TGA) to assess its properties. Nafion is employed as a reticular agent for the nanocomposite on the glassy carbon electrode (GCE), creating the MWCNT/TiO2/Nafion/GCE system. The electrochemical behavior of the system was evaluated using cyclic voltammetry, revealing its remarkable electrocatalytic activity for detecting hydrogen peroxide in water. The developed sensor showcased a broad linear response range of 14.00 to 120.00 µM, with a low detection limit of 4.00 µM. This electrochemical sensor provides a simple and highly sensitive method for detecting hydrogen peroxide in aqueous solutions and shows promising potential for various real-world applications, particularly in H2O2 monitoring.

Sugarcane yeast with urea in replace of soybean meal in the diet of Murrah buffaloes does not cause metabolic, endocrine, and mineral disorders.

The aim of this study was to evaluate the effect of the replacement of soybean meal by increasing levels of sugarcane yeast and urea on the energy, enzymatic, protein, mineral, and hormonal profiles of buffalo heifers. Twenty Murrah heifers with an average body weight of 168 ± 2.0 kg and 1 year old were used in a completely randomized design. The treatments consisted of the replacement of soybean meal by increasing levels of sugarcane yeast and urea (0, 33, 67, and 100% dry matter). The animals were weighed at the beginning and end of the experimental period, and blood was collected on the final day. The replacement of soybean meal with sugarcane yeast influenced the performance and metabolic dynamics, with total weight gain (P = 0.005) and average daily gain (P = 0.015), presenting, for both variables, a quadratic effect. Considering the biochemical profile, there was an influence on the serum concentration of triglycerides (P = 0.055), the serum activities of aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase (P < 0.05), in addition to the serum concentration of phosphorus (P = 0.007) and potassium (P = 0.053), which showed positive linear effects. The hormonal profile was not influenced by diets (P > 0.05). The elements copper, iron, and zinc were able to be quantified at all levels of sugarcane yeast and urea in the diets offered. The use of sugarcane yeast with urea promotes adequate metabolic response of buffalo heifers and can replace up to 100% of soybean meal in the concentrate.

Unveiling the role of exercise training in targeting the inflammatory paradigm of heart failure with preserved ejection fraction: a narrative review.

Heart failure with preserved ejection fraction (HFpEF) is currently lacking an effective pharmacological treatment with impact on major outcomes such as hospitalization and mortality. Exercise training (EXT) is recognized as an important nonpharmacological tool, capable of improving exercise capacity and quality of life, and has even been associated with a reduction in hospitalization and cardiovascular mortality risk. However, this positive impact largely lacks a physiological explanation. The aim of this narrative review was to provide an overview of the available data supporting the hypothesis that the beneficial role of EXT in HFpEF might be due to its effects on targeting the inflammatory paradigm described for this disease. A comprehensive literature search was conducted using the PubMed-NCBI database. We reviewed the effects of EXT throughout each step of the pathophysiological pathway leading to HFpEF and found clinical and/or preclinical evidence supporting the reduction of systemic inflammation, endothelial dysfunction, microvascular rarefaction, and myocardial stiffness. We also highlighted some gaps in the knowledge or topics that deserve further clarification in future studies. In conclusion, despite the scarcity of clinical studies in this population, there is compelling evidence suggesting that EXT modulates crucial aspects of the inflammatory pathway described for HFpEF and future investigation on cellular and molecular mechanisms are encouraged.

Physical activity and exercise training in heart failure with preserved ejection fraction: gathering evidence from clinical and pre-clinical studies.

Conventional treatments for heart failure have failed to improve survival in heart failure with preserved ejection fraction (HFpEF). The current therapy recommendations highlight the importance of symptom management and improvement of patient's well-being or other health-related outcomes. Physical activity/exercise training might be an adjuvant treatment option, since several studies in HFpEF patients reported beneficial effects on exercise intolerance, which is the main symptom associated with this disease. In addition, exercise training was shown to improve quality of life and, in some studies, to improve cardiac function. However, the mechanisms behind these effects are not completely known. The objective of this narrative review is to summarize the main clinical findings regarding the role of physical activity/exercise training in several outcomes, such as hospitalization and mortality, exercise capacity, quality of life, and cardiac function and remodeling. In addition, we will briefly discuss the findings provided by pre-clinical studies. In conclusion, while the impact of physical activity/exercise training on exercise intolerance and quality of life is already well known, its effect on mortality and hospitalization is not well documented, and whether it benefits diastolic function needs further investigation. Some clinical studies showed that exercise training can improve diastolic function, and evidences from pre-clinical studies suggest that this effect is mediated through reduced myocardial stiffness.

Exercise training counteracts the cardiac metabolic remodelling induced by experimental pulmonary arterial hypertension.

Exercise training provides several cardiovascular benefits in both physiological and pathological conditions; however, its use as a therapeutic tool for pulmonary arterial hypertension (PAH) has been poorly explored. This study aimed to extend the comprehension of the cardioprotective effects of exercise training in the set of PAH focusing on the metabolic changes promoted by exercise in the right ventricle (RV). The monocrotaline animal model of PAH was used and male Wistar rats were submitted to two weeks of treadmill exercise training (5 days/week, 60 min/day, 25 m/min) following disease establishment. Trained rats showed an improved diastolic function (lower end-diastolic pressure and tau) despite the presence of cardiac overload (increased peak systolic pressure, end-diastolic pressure and arterial elastance). This enhanced hemodynamic response was paralleled by an increased uptake of glucose to cardiomyocytes through glucose transporter type 4 (GLUT4) followed by increased lactate dehydrogenase (LDH) activity. Exercise did not reverse the decrease of fatty acid oxidation related to PAH but increased the content of the transcription factors peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Two weeks of exercise did not modulate the changes in amino acid metabolism secondary to PAH. Our work suggests that continuous aerobic exercise of moderate intensity, despite its short-term duration and application in a late stage of the disease, supports the RV response to PAH by promoting a shift in the cardiac metabolic phenotype.

Congenital heart defects associated with pathogenic variants in WAC gene: Expanding the phenotypic and genotypic spectrum of DeSanto-Shinawi syndrome.

WAC-related intellectual disability, also known as DeSanto-Shinawi syndrome, is a rare autosomal dominant genetic disorder caused by pathogenic variants in WAC gene. This syndrome is characterized by developmental delay, intellectual disability, behavioral abnormalities, and dysmorphic facial features, including deep-set eyes, flat nasal bridge, bulbous nasal tip, and synophrys. Chromosomal deletions at 10p12p11 encompassing WAC gene have been described in patients with a similar phenotype, presenting with developmental delay, intellectual disability, visual impairments, abnormal behavior, and dysmorphic features. An important clinical difference between the two groups of patients, is that those with large deletions frequently present with congenital cardiac defects, which were rarely reported in patients with pathogenic variants in WAC. The genes underlying heart defects in patients with the deletion have not yet been fully clarified. Here, we describe two unrelated Portuguese patients with de novo pathogenic variants in WAC gene, previously unreported in the literature. Both patients present with microcephaly, developmental delay, intellectual disability, behavioral problems, and facial dysmorphisms. Interestingly, the youngest patient has a severe congenital cardiac malformation, showing that intragenic pathogenic WAC variants can also be associated with heart defects. Therefore, this report expands the phenotypic and genotypic spectrum of this rare syndrome and provides deeper insights by comparing the clinical features of our patients with previously reported cases.

Cancer- and cardiac-induced cachexia: same fate through different inflammatory mediators?

BACKGROUND: Inflammation is widely recognized as the driving force of cachexia induced by chronic diseases; however, therapies targeting inflammation do not always reverse cachexia. Thus, whether inflammation per se plays an important role in the clinical course of cachectic patients is still a matter of debate. AIMS: To give new insights into cachexia's pathogenesis and diagnosis, we performed a comprehensive literature search on the contribution of inflammatory markers to this syndrome, focusing on the noncommunicable diseases cancer and cardiovascular diseases. METHODS: A systematic review was performed in PubMed using the keywords ("cancer" OR "cardiac" cachexia AND "human" OR "patient" AND "plasma" or "serum"). A total of 744 studies were retrieved and, from these, 206 were selected for full-text screening. In the end, 98 papers focusing on circulating biomarkers of cachexia were identified, which resulted in a list of 113 different mediators. RESULTS: Data collected from the literature highlight the contribution of interleukin-6 (IL-6) and C-reactive protein (CRP) to cachexia, independently of the underlying condition. Despite not being specific, once the diagnosis of cachexia is established, CRP might help to monitor the effectiveness of anti-cachexia therapies. In cardiac diseases, B-type natriuretic peptide (BNP), renin, and obestatin might be putative markers of body wasting, whereas in cancer, growth differentiation factor (GDF) 15, transforming growth factor (TGF)-ß1 and vascular endothelial growth factor (VEGF) C seem to be better markers of this syndrome. Independently of the circulating mediators, NF-κB and JAK/STAT signaling pathways play a key role in bridging inflammation with muscle wasting; however, therapies targeting these pathways were not proven effective for all cachectic patients. CONCLUSION: The critical and integrative analysis performed herein will certainly feed future research focused on the better comprehension of cachexia pathogenesis toward the improvement of its diagnosis and the development of personalized therapies targeting specific cachexia phenotypes.

Serum concentrations of folic acid and cobalamin and energy metabolism of ewes as a function of the energy density of the diet, peripartum period, and pregnancy toxemia.

The aim of this study was to determine the serum levels of folic acid, cobalamin, and indicators of energy metabolism during the peripartum period of ewes submitted to different diets and with or without pregnancy toxemia. Forty Santa Inês ewes were divided into three groups, a group of 20 animals fed only roughage-diet with low energy density (G1), a group of 10 ewes submitted to diet containing roughage and concentrate-diet with high energy density (G2), and a group of 10 ewes with diagnosis of pregnancy toxemia (PT) (G3). In the ewes of groups G1 and G2, blood samples were collected -30, -15, -7 days pre-partum, on the day of partum, and 7, 15, and 30 days postpartum; blood samples from G3 animals were collected during the veterinary clinic care. Significant variations were observed in the plasma concentration of glucose and serum folic acid, cobalamin, fructosamine, NEFA, and ß-hydroxybutyrate in the groups fed diets with different energy levels, with and without PT (P < 0.05). A positive correlation of folic acid and cobalamin was observed with plasma glucose and serum NEFA concentrations, in addition to negative correlation of glucose with NEFA and ß-hydroxybutyrate and positive correlation between the latter biomarkers of energy metabolism. The ewes diagnosed with PT showed higher levels of folic acid, NEFA, and ß-hydroxybutyrate (P < 0.05). Ewes fed diet containing roughage and concentrate present higher serum levels of folic acid, cobalamin, and glucose, in the pre-partum period and in the lactation period. The results obtained contribute to better understanding of the application of blood concentration tests for folic acid and cobalamin in the energy metabolism and in PT in ewes.

A high CD8 to FOXP3 ratio in the tumor stroma and expression of PTEN in tumor cells are associated with improved survival in non-metastatic triple-negative breast carcinoma.

BACKGROUND: Triple-negative mammary carcinoma (TNBC) is an aggressive breast cancer subtype associated with dismal prognosis. The interaction between the immune system and the cancer cells plays a crucial role in tumor development and progression. However, it is still unclear how each diverse cell of the immune system contributes to the prognosis of patients with breast cancer. In this study, we investigated how the cell composition of the immune cell infiltrated modifies the survival of patients with resected TNBC. METHODS: Retrospectively, we collected data from 76 patients diagnosed with non-metastatic TNBC with available tissue blocks for tissue micro-array (TMA) construction. The TMA was constructed using two cores from each tumor block. The expression of CD4, CD8, FOXP3, CD20, CD68, CD163, PD-1, PD-L1, PTEN and phospho-STAT1 was determined by immunohistochemistry. RESULTS: We observed that the inflammatory infiltrate in TNBC is enriched for M2 macrophages and T lymphocytes (CD4+, CD8+). PD-L1 expression in the stroma was associated with the percentage of TILs (p = 0.018) as, PD-L1 expression in the tumor was associated with the percentage of TILs (p = 0.049). We found a correlation between TILs and PD-L1 expression in stroma cells (p = 0.020) and in tumor cells (p = 0.027). In our cohort, we observed a trend for improved survival associated with higher CD8+ (p = 0.054) and CD4 + (p = 0.082) cell counts, but the results were not statistically significant. Conversely, the expression of PTEN in tumor cells and a low number of FOXP3+ cells in tumor stroma were both associated with improved OS. The CD8 to FOXP3 ratio and the CD4 to FOXP3 ratio were associated with better OS as well, however, only the CD8 to FOXP3 ratio had its prognostic impact confirmed in the METABRIC TNBC cohort. There was no association between PD-L1 expression and OS. CONCLUSION: TNBC tumor microenvironment is enriched for lymphocytes and macrophages. FOXP3 expression and the CD8 to FOXP3 ratio in the tumor stroma as well as the loss of PTEN expression in tumor cells are prognostic factors in non-metastatic TNBC.

Histological and haemodynamic characterization of right ventricle in sedentary and trained rats with heart failure with preserved ejection fraction.

NEW FINDINGS: What is the central question of this study? Right ventricle (RV) dysfunction is highly prevalent in heart failure with preserved ejection fraction (HFpEF), nearly doubling the risk of death: what are the RV functional and structural changes in HFpEF and how does aerobic exercise impact them? What is the main finding and its importance? The HFpEF ZSF1 rat model presents RV structural and functional changes mimicking the human condition. Aerobic exercise prevented the decline in V̇O2max , lowered surrogate markers of RV overload (e.g., higher mean and maximum systolic pressure) and improved diastolic dysfunction (e.g., end-diastolic pressure and relaxation time constant). This emphasizes the importance of using exercise to manage HFpEF. ABSTRACT: Right ventricle (RV) dysfunction is highly prevalent in heart failure with preserved ejection fraction (HFpEF) and is a marker of poor prognosis. We assessed the obese ZSF1 rat model of HFpEF to ascertain if these animals also develop RV dysfunction and evaluated whether aerobic exercise could prevent this. Obese ZSF1 rats were randomly allocated to an aerobic exercise training group (n = 7; treadmill running, 5 days/week, 60 min/day, 15 m/min for 5 weeks) or to a sedentary group (n = 7). We used lean ZSF1 rats (n = 7) as the control group. After 5 weeks, rats were submitted to an exercise tolerance test and invasive haemodynamic evaluation, killed and samples from the RV collected for histological analysis. Obese sedentary ZSF1 rats showed lower V̇O2max , RV pressure overload (e.g., higher mean and maximum systolic pressure) and diastolic dysfunction (e.g., higher minimum and end-diastolic pressure and relaxation time constant), paralleled by RV cardiomyocyte hypertrophy. Except for cardiomyocyte hypertrophy, aerobic exercise prevented these functional changes. Our data support that this model of HFpEF shows functional and structural changes in the RV that resemble the human HFpEF phenotype, reinforcing its utility to understand this pathophysiology and to adress novel therapeutic targets to manage HFpEF. In addition, we showed that aerobic exercise is cardioprotective for the RV. A deeper knowledge of the mechanisms underlying the benefits of aerobic exercise could also lead to the identification of therapeutic targets to be further explored.

Effects of chronic moderate alcohol consumption on right ventricle and pulmonary remodelling.

NEW FINDINGS: What is the central question of this study? Does the consumption of a moderate amount of alcohol differentially impact the heart ventricles and pulmonary vasculature. What is the main finding and its importance? Moderate alcohol consumption for a short period of time impaired pulmonary vascular cellular renewal through an apoptosis resistance pattern that ultimately affected the right ventricular function and structure. These findings support the need for a deeper understanding of effects of moderate alcohol consumption on the overall cardiovascular and pulmonary systems. ABSTRACT: Over the past decades, observational studies have supported an association between moderate alcohol consumption and a lower risk of cardiovascular disease and mortality. However, recent and more robust meta-analyses have raised concerns around the robustness of the evidence for the cardioprotective effects of alcohol. Also, studies of the functional, structural and molecular changes promoted by alcohol have focused primarily on the left ventricle, ignoring the fact that the right ventricle could adapt differently. The aim of this study was to evaluate the bi-ventricular impact of daily moderate alcohol intake, during a 4-week period, in a rodent model. Male Wistar rats were allowed to drink water (Control) or a 5.2% ethanol mixture (ETOH) for 4 weeks. At the end of the protocol bi-ventricular haemodynamic recordings were performed and samples collected for further histological and molecular analysis. ETOH ingestion did not impact cardiac function. However, it caused right ventricle hypertrophy, paralleled by an activation of molecular pathways responsible for cell growth (ERK1/2, AKT), proteolysis (MURF-1) and oxidative stress (NOX4, SOD2). Furthermore, ETOH animals also presented remodelling of the pulmonary vasculature with an increase in pulmonary arteries' medial thickness, which was characterized by increased expression of apoptosis-related proteins expression (BCL-XL, BAX and caspases). Moderate alcohol consumption for a short period of time impaired the lungs and the right ventricle early, before any change could be detected on the left ventricle. Right ventricular changes might be secondary to alcohol-induced pulmonary vasculature remodelling.

Evaluation of different approaches to applying the standard additions calibration method.

The extrapolation approach, traditionally used with standard additions (SA), is compared with the alternative strategies of interpolation, reversed-axis, and normalization. The interpolation approach is based on employing twice the analytical signal recorded for the sample (ysam) to determine an unknown analyte concentration. In the reversed-axis strategy, x- and y-axes are swapped when building the SA calibration plot to facilitate uncertainty estimation. A new strategy, based on signal normalization using ysam, is also described and compared to the other approaches. Results from 3 instrumental methods, 396 sample replicates, 16 analytes, and 2 certified reference materials are included in this study. For most applications, all four SA approaches provide statistically similar trueness and precision. However, extrapolation and reversed-axis provide more consistent values (within narrower ranges) than the other strategies when employing inductively coupled plasma optical emission spectrometry (ICP OES). On the other hand, normalization provides better trueness for the less robust method of microwave-induced plasma OES (MIP OES), as it is capable of minimizing systematic errors associated with different points of the calibration curve. Normalization is particularly useful for quickly processing data, without the need for inspecting each individual calibration plot to identify outlying points. Reversed-axis and normalization are the most adequate approaches for SA applications involving MIP OES and ICP-based methods. In addition to providing similar accuracies to the traditional extrapolation approach, these strategies present the advantage of a simple uncertainty estimation, which can be easily calculated using commonly available software such as Microsoft Excel and R.

On the predictability of postoperative complications for cancer patients: a Portuguese cohort study.

Postoperative complications are still hard to predict despite the efforts towards the creation of clinical risk scores. The published scores contribute for the creation of specialized tools, but with limited predictive performance and reusability for implementation in the oncological context. This work aims to predict postoperative complications risk for cancer patients, offering two major contributions. First, to develop and evaluate a machine learning-based risk score, specific for the Portuguese population using a retrospective cohort of 847 cancer patients undergoing surgery between 2016 and 2018, for 4 outcomes of interest: (1) existence of postoperative complications, (2) severity level of complications, (3) number of days in the Intermediate Care Unit (ICU), and (4) postoperative mortality within 1 year. An additional cohort of 137 cancer patients from the same center was used for validation. Second, to improve the interpretability of the predictive models. In order to achieve these objectives, we propose an approach for the learning of risk predictors, offering new perspectives and insights into the clinical decision process. For postoperative complications the Receiver Operating Characteristic Curve (AUC) was 0.69, for complications' severity AUC was 0.65, for the days in the ICU the mean absolute error was 1.07 days, and for 1-year postoperative mortality the AUC was 0.74, calculated on the development cohort. In this study, predictive models which could help to guide physicians at organizational and clinical decision making were developed. Additionally, a web-based decision support tool is further provided to this end.

Comparison of questionnaire and accelerometer-based assessments of physical activity in patients with heart failure with preserved ejection fraction: clinical and prognostic implications.

Objective. (i) To compare daily physical activity (PA) levels evaluated by the International Physical Activity Questionnaire (IPAQ) and by triaxial accelerometry in heart failure with preserved ejection fraction (HFpEF) patients; (ii) to describe daily PA patterns based in objective measurements; and (iii) to observe the association between prognostic indicators and PA measurements. Design. This is a cross-sectional study with 24 stable HFpEF patients. PA was assessed through the IPAQ short version and triaxial accelerometer. Time spent in moderate-to-vigorous PA (MVPA) from IPAQ was computed as self-reported walking and MVPA. Prognostic indicators were: distance on the 6-minute-walking test (6MWT), oxygen consumption (VO2) during the test, quality of life (QoL), BNP plasma level, and E/e' ratio. Results. Compared to accelerometry, IPAQ underestimated sedentary time (253 ± 156 vs. 392 ± 104 min/day, p = .001) and overestimated MVPA (44 ± 56 vs. 19.3 ± 26 min/day, p < .001). Accelerometer-derived data showed that HFpEF patients spent 50% of their waking time in sedentary behaviours and 2.5% in MVPA. Of measured surrogate prognostic markers, functional capacity (6MWT, r = 0.652, p = .04; VO2, r = 0.512, p = .02) and QoL (r=-0.490, p = .04) were correlated with MVPA. Conclusions. The IPAQ underestimated sedentary time and over-estimated MVPA in HFpEF patients. Using accelerometer-derived data, HFpEF patients spent only a minority of their time involved in MVPA, which was the only PA pattern positively associated with prognostic indicators.