Challenges of Congenital Heart Surgery in Brazil: It is Time to Designate Pediatric Congenital Heart Surgery Subspecialty.

Congenital heart disease (CHD) affects eight to ten out of every 1,000 births, resulting in approximately 23,057 new cases in Brazil in 2022. About one in four children with CHD requires surgery or other procedures in the first year of life, and it is expected that approximately 81% of these children with CHD will survive until at least 35 years of age. Professionals choosing to specialize in CHD surgery face numerous challenges, not only related to mastering surgical techniques and the complexity of the diseases but also to the lack of recognition by medical societies as a separate subspecialty. Furthermore, families face difficulties when access to services capable of providing treatment for these children. To address these challenges, it is essential to have specialized hospitals, qualified professionals, updated technologies, sustainable industry, appropriate financing, quality assessment systems, and knowledge generation. The path to excellence involves specialization across all involved parties. As we reflect on the importance of Pediatric Cardiovascular Surgery and Congenital Heart Diseases establishing themselves as a subspecialty of Cardiovascular Surgery, it is essential to look beyond our borders to countries like the United States of America and United Kingdom, where this evolution is already a reality. This autonomy has led to significant advancements in research, education, and patient care outcomes, establishing a care model. By following this path in Brazil, we not only align our practice with the highest international standards but also demonstrate our maturity and the ability to meet the specific needs of patients with CHD and those with acquired childhood heart disease.

Unlocking the complete blood count as a risk stratification tool for breast cancer using machine learning: a large scale retrospective study.

Optimizing early breast cancer (BC) detection requires effective risk assessment tools. This retrospective study from Brazil showcases the efficacy of machine learning in discerning complex patterns within routine blood tests, presenting a globally accessible and cost-effective approach for risk evaluation. We analyzed complete blood count (CBC) tests from 396,848 women aged 40-70, who underwent breast imaging or biopsies within six months after their CBC test. Of these, 2861 (0.72%) were identified as cases: 1882 with BC confirmed by anatomopathological tests, and 979 with highly suspicious imaging (BI-RADS 5). The remaining 393,987 participants (99.28%), with BI-RADS 1 or 2 results, were classified as controls. The database was divided into modeling (including training and validation) and testing sets based on diagnostic certainty. The testing set comprised cases confirmed by anatomopathology and controls cancer-free for 4.5-6.5 years post-CBC. Our ridge regression model, incorporating neutrophil-lymphocyte ratio, red blood cells, and age, achieved an AUC of 0.64 (95% CI 0.64-0.65). We also demonstrate that these results are slightly better than those from a boosting machine learning model, LightGBM, plus having the benefit of being fully interpretable. Using the probabilistic output from this model, we divided the study population into four risk groups: high, moderate, average, and low risk, which obtained relative ratios of BC of 1.99, 1.32, 1.02, and 0.42, respectively. The aim of this stratification was to streamline prioritization, potentially improving the early detection of breast cancer, particularly in resource-limited environments. As a risk stratification tool, this model offers the potential for personalized breast cancer screening by prioritizing women based on their individual risk, thereby indicating a shift from a broad population strategy.

Native hepatic T1-time as a non-invasive predictor of diastolic dysfunction and a monitoring tool for disease progression and treatment response in patients with pulmonary hypertension.

AIMS: Hepatic T1-time derived from cardiac magnetic resonance imaging (cMRI) reflects venous congestion and may provide a simple alternative to invasive end-diastolic elastance (Eed) for assessment of right ventricular (RV) diastolic function. We investigated the association of native hepatic T1-time with single-beat Eed and the value of hepatic T1-time for longitudinal monitoring in pulmonary hypertension (PH). METHODS AND RESULTS: We retrospectively enrolled 85 patients with suspected PH (59% female; 78 with PH diagnosed; 7 with PH excluded) who underwent standard right heart catheterization and cMRI within 24 h between 2015 and 2020. Hepatic T1-time showed moderate to strong correlations (rho >0.3, P ≤ 0.002) with pulmonary vascular resistance, native myocardial T1-time, Eed, RV size and function, brain natriuretic peptide (BNP) level, and 6-min walk distance, and a significant association with functional class (Kruskal-Wallis P < 0.001). Eed, myocardial T1-time, and BNP were independently linked to hepatic T1-time in multivariable regression. Hepatic T1-time > 598 ms predicted elevated Eed with 72.9% sensitivity and 82.1% specificity. Hepatic T1-time was superior to Eed in predicting clinical worsening. In 16 patients with follow-up assessments, those with decreasing hepatic T1-time (7 patients) showed significant hemodynamic improvements, whereas those with increasing hepatic T1-time (9 patients) did not. In a second retrospective cohort of 27 patients with chronic thromboembolic PH undergoing balloon pulmonary angioplasty, hepatic T1-time decreased significantly and hemodynamics improved after the procedure. CONCLUSIONS: Hepatic T1-time predicts RV diastolic dysfunction and prognosis, and may be useful for monitoring disease progression and treatment response in PH.

Levels and health risk assessment of twenty-one current-use pesticides in urban and riverside waters of the Brazilian Amazon Basin.

In Brazil, the favorable weather conditions and abundant land contribute to the thriving agricultural production. Brazilian crops extensively employ pesticides due to their high efficacy, cost-effectiveness, and permissive regulatory framework. However, pesticide use also endangers water resources, animal organisms, and human health. Due to the lack of data on pesticide use in the Amazonas forest-based Brazil, the present study aimed to assess the levels of twenty-one current-use pesticides (CUPs) from five different classes in river waters collected from urban and riverside areas in this region. Moreover, the non-carcinogenic risks associated with water consumption were also characterized. Thirteen CUPs were detected in concentrations above the limit of detection (LOD) in at least one of the water samples, and most pesticides were detected in riverside areas. In contrast, only 18% of the analyzed samples were considered "clean," with only one compound detected. Fenitrothion showed the highest concentration, with a mean value of 4.86 ng/mL (0.30-14.3 ng/mL). Up to 33% of the samples showed levels of fipronil above the LOD, an issue of environmental and human health concern, mainly because of the adverse effects observed in honeybees. Despite this, the human health risk assessment showed a target hazard quotient below one (HQ < 1) in adults for all substances, suggesting that pesticide exposure through water consumption should not mean risk for the riverside populations. Taking into account the large extension of Brazil, as well as its different agricultural practices throughout the country, it would be of great importance to conduct extensive research in other areas. It would help to gain knowledge in this field and to promote eco-friendly alternatives to mitigate pesticide use and, consequently, to reduce their potential adverse effects on human health and the ecosystems.

Right ventricular pressure-strain relationship-derived myocardial work reflects contractility: Validation with invasive pressure-volume analysis.

Three-dimensional (3D) echocardiography-derived right ventricular (RV) ejection fraction (EF) and global longitudinal strain (GLS) are valuable RV functional markers; nevertheless, they are substantially load-dependent. Global myocardial work index (GMWI) is a novel parameter calculated by the area of the RV pressure-strain loop. By adjusting myocardial deformation to instantaneous pressure, it may reflect contractility. To test this hypothesis, we enrolled 60 patients who underwent RV pressure-conductance catheterization to determine load-independent markers of RV contractility and ventriculo-arterial coupling. Detailed 3D echocardiography was also performed, and we calculated RV EF, RV GLS, and using the RV pressure trace curve, RV GWMI. While neither RV EF nor GLS correlated with Ees, GMWI strongly correlated with Ees. In contrast, RV EF and GLS showed a relationship with Ees/Ea. By dividing the population based on their Reveal Lite 2 risk classification, different characteristics were seen among the subgroups. RV GMWI may emerge as a useful clinical tool for risk stratification and follow-up in patients with RV dysfunction.

Liver stiffness is associated with right heart dysfunction, cardiohepatic syndrome, and prognosis in pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) can lead to congestive hepatopathy, known as cardiohepatic syndrome (CHS). Hepatic congestion is associated with increased liver stiffness, which can be quantified using shear wave elastography. We aimed to investigate whether hepatic shear wave elastography detects patients at risk in the early stages of PH. METHODS: Sixty-three prospectively enrolled patients undergoing right heart catheterization (52 diagnosed with PH and 11 with invasive exclusion of PH) and 52 healthy volunteers underwent assessments including echocardiography and hepatic shear wave elastography. CHS was defined as increased levels of ≥2 of the following: gamma-glutamyl transferase, alkaline phosphatase, and bilirubin. Liver stiffness was defined as normal (≤5.0 kPa) or high (>5.0 kPa). RESULTS: Compared with normal liver stiffness, high liver stiffness was associated with impaired right ventricular (RV) and right atrial (RA) function (median [interquartile range] RV ejection fraction: 54 [49; 57]% vs 45 [34; 51]%, p < 0.001; RA reservoir strain: 49 [41; 54]% vs 33 [22; 41]%, p < 0.001), more severe tricuspid insufficiency (p < 0.001), and higher prevalence of hepatovenous backflow (2% vs 29%, p < 0.001) and CHS (2% vs 10%, p = 0.038). In the patient subgroup with precapillary PH (n = 48), CHS and high liver stiffness were associated with increased European Society of Cardiology/European Respiratory Society 2022 risk scores (p = 0.003). CONCLUSIONS: Shear wave liver elastography yields important information regarding right heart function and may complement risk assessment in patients with (suspected) PH.

Assessment of myocardial strain patterns in patients with left bundle branch block using cardiac magnetic resonance.

Recently, a classification with four types of septal longitudinal strain patterns was described using echocardiography, suggesting a pathophysiological continuum of left bundle branch block (LBBB)-induced left ventricle (LV) remodeling. The aim of this study was to assess the feasibility of classifying these strain patterns using cardiovascular magnetic resonance (CMR), and to evaluate their association with LV remodeling and myocardial scar. Single center registry included LBBB patients with septal flash (SF) referred to CMR to assess the cause of LV systolic dysfunction. Semi-automated feature-tracking cardiac resonance (FT-CMR) was used to quantify myocardial strain and detect the four strain patterns. A total of 115 patients were studied (age 66 ± 11 years, 57% men, 28% with ischemic heart disease). In longitudinal strain analysis, 23 patients (20%) were classified in stage LBBB-1, 37 (32.1%) in LBBB-2, 25 (21.7%) in LBBB-3, and 30 (26%) in LBBB-4. Patients at higher stages had more prominent septal flash, higher LV volumes, lower LV ejection fraction, and lower absolute strain values (p < 0.05 for all). Late gadolinium enhancement (LGE) was found in 55% of the patients (n = 63). No differences were found between the strain patterns regarding the presence, distribution or location of LGE. Among patients with LBBB, there was a good association between strain patterns assessed by FT-CMR analysis and the degree of LV remodeling and LV dysfunction. This association seems to be independent from the presence and distribution of LGE.

Galectin-9 is a target for the treatment of cancer: A patent review.

Galectins, which correspond to a group of proteins capable of recognizing and reversibly binding to ß-galactoside carbohydrates, have been the subject of innovation and development of technological products. Galectins play biological roles, such as cell proliferation and apoptosis, and some studies showed differences in the concentrations of galectins dispersed in serum of patients with cancer. For this reason, different studies have evaluated the biotechnological potential of these proteins as biomarkers for the prognosis and/or diagnosis of physiological disorders. Thus, this review discusses recent technological advancements in targeting galectins for the treatment of cancer and using galectins for cancer prognosis and diagnosis. Data mining was performed using the search descriptors "Galectin 9* and cancer*" and the ESPACENET and Cortellis Drug Discovery Intelligence (CDDI) databases. PRISMA guidelines were followed as a basis for literature review which aimed to conduct a systematic study of galectin-9 patents related to cancer prognosis, diagnosis and treatment. Results showed the importance of galectin-9 protein patents in furthering biomedical advancements in the global fight against cancer.

Hydroxymethylnitrofurazone lymphatic uptake with nanostructured lipid carrier after oral administration in rats.

Background: Leishmaniasis, caused by the protozoan Leishmania sp., infects phagocyte cells present in lymphatic organs. This study demonstrates the influence of nanostructured lipid carrier-loaded hydroxymethylnitrofurazone (NLC-NFOH) on lymphatic uptake using a chylomicron-blocking flow model in rats. Method: Lymphatic uptake of NFOH was assessed 1 h after oral administration of dimethyl sulfoxide with NFOH or NLC-NFOH with and without cycloheximide pretreatment. Result: Dimethyl sulfoxide with NFOH and NLC-NFOH showed NFOH serum concentrations of 0.0316 and 0.0291 µg/ml, respectively. After chylomicron blocking, NFOH was not detected. Conclusion: Despite log P below 5, NFOH was successfully taken up by the lymphatic system. Long-chain fatty acids and particle size might be main factors in these findings. NLC-NFOH is a promising and convenient platform for treating leishmaniasis via oral administration.

Purification, Characterization and Evaluation of the Anticoagulant Effect of an Uncompetitive Trypsin Inhibitor obtained from Bauhinia pulchella (Benth) Seeds.

INTRODUCTION: Trypsin inhibitors (TIs) have the ability to competitively or non-competitively bind to trypsin and inhibit its action. These inhibitors are commonly found in plants and are used in protease inhibition studies involved in biochemical pathways of pharmacological interest. OBJECTIVES: This work aimed to purify a trypsin inhibitor from Bauhinia pulchella seeds (BpuTI), describing its kinetic mechanism and anticoagulant effect. METHODS: Affinity chromatography, protein assay, and SDS-PAGE were used to purify the inhibitor. Mass spectrometry, inhibition assays, and enzyme kinetics were used to characterize the inhibitor. In vitro assays were performed to verify its ability to prolong blood clotting time. RESULTS: Affinity chromatography on a Trypsin-Sepharose 4B column gave a yield of 43.1. BpuTI has an apparent molecular mass of 20 kDa with glycosylation (1.15%). Protein identification was determined by MS/MS, and BpuTI showed similarity to several Kunitz-type trypsin inhibitors. BpuTI inhibited bovine trypsin as an uncompetitive inhibitor with IC50 (3 x 10-6 M) and Ki (1.05 x 10-6 M). Additionally, BpuTI showed high stability to temperature and pH variations, maintaining its activity up to 100ºC and in extreme pH ranges. However, the inhibitor was susceptible to reducing agents, such as DTT, which completely abolished its activity. BpuTI showed an anticoagulant effect in vitro at a concentration of 33 µM, prolonging clotting time by 2.6 times. CONCLUSION: Our results suggest that BpuTI can be a biological tool to be used in blood clotting studies.

The Dark Side of Multimedia Devices: Negative Consequences for Socioemotional Development in Early Childhood.

There is growing concern about the relationship between screen use by young children and negative effects on their development, as children with developmental and socioemotional impairments tend to have difficulties in their relationships and increased academic problems. The aim of our study was to analyse the relationship between the use of multimedia devices and paediatric symptoms in children below 5 years old. Data from 534 Portuguese parents of children aged from 18 to 57 months were collected via a self-report questionnaire. Children's daily exposure to multimedia devices was nearly 2 h per day. Paediatric symptoms were positively associated with watching television and screen time and negatively associated with parents' working hours. Touchscreen use was more frequent among girls and older children. Parents' working hours comprised the most significant predictor of paediatric symptoms. Our findings reinforce past findings on the adverse links between the use of multimedia devices and paediatric symptoms and also highlight the influence of other variables like the child's age and gender, as well as parental factors. The need to both create a more comprehensive framework regarding the long-term effects of multimedia device use and delineate effective strategies for prevention and intervention with parents and children is discussed.

Levels of organic pollutants and metals/metalloids in infant formula marketed in Brazil: Risks to early-life health.

Infant formula intake is recommended to ensure comprehensive nutritional and caloric fulfillment when exclusive breastfeeding is not possible. However, similarly to breast milk, infant formulas may also contain pollutants capable of inducing endocrine-disrupting and neurotoxic effects. Thus, considering the sensitivity of their developing physiological systems and that infants have heightened susceptibility to environmental influences, this study was aimed at assessing the contents of essential elements, and inorganic and organic pollutants in infant formulas marketed in Brazil. Additionally, health risk assessments for selected contaminants were also performed. Measured contents of essential elements (Ca, Fe, Mg, Mn, Cu, Se, and Zn) were congruent with label information. Nevertheless, some toxic elements (Pb, Cd, As, Ni, and Al) were also detected. Notably, in the upper-bound scenario, Pb and Cd surpassed established threshold values when comparing the estimated daily intake (EDI) and tolerable daily intake (TDI - 3.57 and 0.36 µg/kg bw, respectively). Bisphenol P (BPP) and benzyl butyl phthalate (BBP) were frequently detected (84 % detection rate both) with elevated contents (BPP median = 4.28 ng/g and BBP median = 0.24 ng/g). Furthermore, a positive correlation (0.41) was observed between BPP and BBP, implying a potential co-occurrence within packaging materials. Methyl-paraben also correlated positively with BBP (0.57), showing a detection rate of 53 %. The cumulative PBDE contents ranged from 0.33 to 1.62 ng/g, with BDE-154 and BDE-47 the dominant congeners. When comparing EDI values with TDIs, all organic pollutants remained below the thresholds across all exposure scenarios. Moreover, non-carcinogenic risks were below the threshold (HQ > 1) when dividing the EDIs by the respective reference doses for chronic exposure. While the current findings may suggest that infant formula intake poses no immediate risk in terms of the evaluated chemicals, it remains imperative to conduct further research to safeguard the health of infants considering other chemicals, as well as their potential cumulative effects.

Association between urinary concentrations of toxic metals/metalloids and oxidative stress in Brazilians living in areas affected by the Fundão dam failure.

The Fundão Dam failure has been the most significant environmental disaster in Brazil. The catastrophe released large amounts of mining waste into the environment, including toxic metals/metalloids, which are recognized to induce carcinogenic effects. The urinary levels of 8-hydroxy-2'-deoxyguanosine (8OHdG), a widely accepted oxidative stress and carcinogenesis biomarker, provide a potential tool for assessing the disaster's health implications. This study investigated the association between urinary levels of some toxic metals/metalloids and 8OHdG in Brazilian individuals living in areas affected by the Fundão dam failure. Urinary concentrations of arsenic (As), cadmium (Cd), mercury (Hg), nickel (Ni), and lead (Pb) were determined using inductively coupled plasma mass spectrometry, while 8OHdG was analyzed by liquid chromatography-tandem mass spectrometry. Non-parametric bootstrap regression was used to estimate the associations between the urinary levels of toxic elements and 8OHdG. The results showed that except for Hg, urinary concentrations of all metals/metalloids analyzed here exceeded the reference ranges for the Brazilian population. The regression analysis revealed that As (0.337; CI 95%: 0.203; 0.474), Cd (0.268; CI 95%: 0.036; 0.520), and Ni (0.296; CI 950.108; 0.469) were positively associated with creatinine-adjusted urinary 8OHdG levels. Associations were not found for Hg (0.0122; CI 95%: -0.155; 0.183) and Pb (0.201; CI 95%: -0.040; 0.498). The current findings suggest that high exposure to toxic metals/metalloids might increase 8OHdG levels with potential adverse health effects. This study is the first one in which the relationship between toxic metals/metalloids and oxidative stress biomarkers is investigated in populations affected by environmental disasters. Further prospective studies are necessary to monitor exposure levels and explore additional health impacts.

Deep learning for sex determination: Analyzing over 200,000 panoramic radiographs.

The objective of this study is to assess the performance of an innovative AI-powered tool for sex determination using panoramic radiographs (PR) and to explore factors affecting the performance of the convolutional neural network (CNN). The study involved 207,946 panoramic dental X-rays and their corresponding reports from 15 clinical centers in São Paulo, Brazil. The PRs were acquired with four different devices, and 58% of the patients were female. Data preprocessing included anonymizing the exams, extracting pertinent information from the reports, such as sex, age, type of dentition, and number of missing teeth, and organizing the data into a PostgreSQL database. Two neural network architectures, a standard CNN and a ResNet, were utilized for sex classification, with both undergoing hyperparameter tuning and cross-validation to ensure optimal performance. The CNN model achieved 95.02% accuracy in sex estimation, with image resolution being a significant influencing factor. The ResNet model attained over 86% accuracy in subjects older than 6 years and over 96% in those over 16 years. The algorithm performed better on female images, and the area under the curve (AUC) exceeded 96% for most age groups, except the youngest. Accuracy values were also assessed for different dentition types (deciduous, mixed, and permanent) and missing teeth. This study demonstrates the effectiveness of an AI-driven tool for sex determination using PR and emphasizes the role of image resolution, age, and sex in determining the algorithm's performance.

Echocardiographic evaluation of right ventricular diastolic function in pulmonary hypertension.

Background: Right ventricular (RV) diastolic dysfunction may be prognostic in pulmonary hypertension (PH). However, its assessment is complex and relies on conductance catheterisation. We aimed to evaluate echocardiography-based parameters as surrogates of RV diastolic function, provide validation against the gold standard, end-diastolic elastance (Eed), and define the prognostic impact of echocardiography-derived RV diastolic dysfunction. Methods: Patients with suspected PH who underwent right heart catheterisation including conductance catheterisation were prospectively recruited. In this study population, an echocardiography-based RV diastolic function surrogate was derived. Survival analyses were performed in patients with precapillary PH in the Giessen PH Registry, with external validation in patients with pulmonary arterial hypertension at Sapienza University (Rome). Results: In the derivation cohort (n=61), the early/late diastolic tricuspid inflow velocity ratio (E/A) and early tricuspid inflow velocity/early diastolic tricuspid annular velocity ratio (E/e') did not correlate with Eed (p>0.05). Receiver operating characteristic analysis revealed a large area under the curve (AUC) for the peak lateral tricuspid annulus systolic velocity/right atrial area index ratio (S'/RAAi) to detect elevated Eed (AUC 0.913, 95% confidence interval (CI) 0.839-0.986) and elevated end-diastolic pressure (AUC 0.848, 95% CI 0.699-0.998) with an optimal threshold of 0.81 m2·s-1·cm-1. Subgroup analyses demonstrated a large AUC in patients with preserved RV systolic function (AUC 0.963, 95% CI 0.882-1.000). Survival analyses confirmed the prognostic relevance of S'/RAAi in the Giessen PH Registry (n=225) and the external validation cohort (n=106). Conclusions: Our study demonstrates the usefulness of echocardiography-derived S'/RAAi for noninvasive assessment of RV diastolic function and prognosis in PH.

BRACETS: Bimodal repository of auscultation coupled with electrical impedance thoracic signals.

BACKGROUND AND OBJECTIVE: Respiratory diseases are among the most significant causes of morbidity and mortality worldwide, causing substantial strain on society and health systems. Over the last few decades, there has been increasing interest in the automatic analysis of respiratory sounds and electrical impedance tomography (EIT). Nevertheless, no publicly available databases with both respiratory sound and EIT data are available. METHODS: In this work, we have assembled the first open-access bimodal database focusing on the differential diagnosis of respiratory diseases (BRACETS: Bimodal Repository of Auscultation Coupled with Electrical Impedance Thoracic Signals). It includes simultaneous recordings of single and multi-channel respiratory sounds and EIT. Furthermore, we have proposed several machine learning-based baseline systems for automatically classifying respiratory diseases in six distinct evaluation tasks using respiratory sound and EIT (A1, A2, A3, B1, B2, B3). These tasks included classifying respiratory diseases at sample and subject levels. The performance of the classification models was evaluated using a 5-fold cross-validation scheme (with subject isolation between folds). RESULTS: The resulting database consists of 1097 respiratory sounds and 795 EIT recordings acquired from 78 adult subjects in two countries (Portugal and Greece). In the task of automatically classifying respiratory diseases, the baseline classification models have achieved the following average balanced accuracy: Task A1 - 77.9±13.1%; Task A2 - 51.6±9.7%; Task A3 - 38.6±13.1%; Task B1 - 90.0±22.4%; Task B2 - 61.4±11.8%; Task B3 - 50.8±10.6%. CONCLUSION: The creation of this database and its public release will aid the research community in developing automated methodologies to assess and monitor respiratory function, and it might serve as a benchmark in the field of digital medicine for managing respiratory diseases. Moreover, it could pave the way for creating multi-modal robust approaches for that same purpose.

Occurrence of trace elements in print paper products: Non-carcinogenic risk assessment through dermal exposure.

Over time, the risk assessment of dermal exposure to pollutants in print paper products has received considerable attention. Most studies have focused on organic pollutants, especially bisphenol A (BPA). However, little is known about the levels of trace elements in print paper products, despite the knowledge that these elements are components of printing inks and toners. This study was aimed at determining the concentrations of trace elements in 5 types of paper products, namely bulletins, magazines, special events program booklets, handbills, and newspapers. The average daily intake (ADI) of each element was subsequently estimated through dermal exposure to the papers. The detection frequency of the elements of interest was high (nearly 100%) in most paper products, with the exception of chromium, whose detection was low. In contrast, Ag was not detected in any sample. The levels of the elements in the paper products were low and comparable to those found in other personal and consumer products with the potential for skin contact. The range values of estimated ADIs were 1.70-3.90E-08, 2.30-18.2E-10, 2.60-16.4E-09, 3.65-5.75E-08, 1.29-4.38E-08, 6.23-15.6E-10, 1.51-2.80E-10, 1.43-9.16E-09, 0.00-9.47E-09, and 4.68-220E-08 mg/kg bw/day for Mn, Co, Ni, Cu, Zn, As, Cd, Pb, Cr and Fe respectively. These values were well below the dermal standard reference doses (RfD) for each element. The present results indicate that dermal exposure to trace elements from print paper products was low and does not pose significant risks for toxic (non-carcinogenic) effects on humans.

Echocardiographic pressure-strain loop-derived stroke work of the right ventricle: validation against the gold standard.

AIMS: Commercially available integrated software for echocardiographic measurement of stroke work (SW) is increasingly used for the right ventricle, despite a lack of validation. We sought to assess the validity of this method [echo-based myocardial work (MW) module] vs. gold-standard invasive right ventricular (RV) pressure-volume (PV) loops. METHODS AND RESULTS: From the prospectively recruiting EXERTION study (NCT04663217), we included 42 patients [34 patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) and 8 patients with absence of cardiopulmonary disease] with RV echocardiography and invasive PV catheterization. Echocardiographic SW was assessed as RV global work index (RVGWI) generated via the integrated pressure-strain MW software. Invasive SW was calculated as the area bounded by the PV loop. An additional parameter derived from the MW module, RV global wasted work (RVGWW), was correlated with PV loop measures. RVGWI significantly correlated with invasive PV loop-derived RV SW in the overall cohort [rho = 0.546 (P < 0.001)] and the PAH/CTEPH subgroup [rho = 0.568 (P < 0.001)]. Overall, RVGWW correlated with invasive measures of arterial elastance (Ea), the ratio of end-systolic elastance (Ees)/Ea, and end-diastolic elastance (Eed) significantly. CONCLUSIONS: Integrated echo measurement of pressure-strain loop-derived SW correlates with PV loop-based assessment of RV SW. Wasted work correlates with invasive measures of load-independent RV function. Given the methodological and anatomical challenges of RV work assessment, evolution of this approach by incorporating more elaborated echo analysis data and an RV reference curve might improve its reliability to mirror invasively assessed RV SW.