Exploring the bioaccessibility and intestinal absorption of major classes of pure phenolic compounds using in vitro simulated gastrointestinal digestion.

The bioaccessibility and bioavailability of phenolic compounds (PC) influence directly their role in disease prevention/control. Studies have evaluated this ability through complex plant and food matrices, which may reflect more a synergistic effect of the matrix than the ability of the PCs, hindering their individual exploitation in nutraceutical or pharmaceutical applications. In the present study ten pure PCs representing major classes were evaluated for their bioaccessibility and intestinal absorption in an in vitro simulated gastrointestinal digestion (SGD). This is the first study concerning the bioaccessibility evaluation of pure phloretin, phloroglucinol, naringin, naringenin and daidzein, while no in vitro SGD has been performed before for the other compounds considered here. PCs were analyzed through ultra-high-performance liquid chromatography coupled with diode-array detection and tandem mass spectrometry (UHPLC-DAD-MSn). Most of the compounds remained present along the gastrointestinal tract, and the bioaccessibility was in general higher than 50%, except for quercetin, epigallocatechin gallate, and ellagic acid. All compounds were highly absorbed in the intestine, with phloretin showing the lowest percentage at about 82%. The study findings provide new knowledge on the bioaccessibility and intestinal absorption of different PCs classes.

Children's satisfaction with nursing care during hospitalization: A cross-sectional study.

PURPOSE: To assess hospitalized children's satisfaction with nursing care. DESIGN AND METHODS: Cross-sectional study using the "Children Care Quality at Hospital" questionnaire. 61 children admitted to the Pediatrics Department of a hospital in the Northern Region of Portugal were enrolled. RESULTS: The ranged age of the participants was 6 to 15 (10,61 ± 2,66 years), and most were male (52.46%; n = 32). The mean score in the three domains was 128 (77.11%), reflecting children's high satisfaction with the nursing care provided during hospitalization. The domain most valued was Nurse Characteristics, while the least valued was Nursing Environment. CONCLUSION: Results provide essential input for the dimensions to be considered when planning nursing care for children, managing care, and the physical environment in the wards. IMPLICATIONS FOR PRACTICE: These results highlight the need to hear children's voices. This must encourage nurses to reflect on how children evaluate nursing care and, by doing so, to increase the quality of nursing care provided in Pediatrics settings.

Enhanced Antimalarial Activity of Extracts of Artemisia annua L. Achieved with Aqueous Solutions of Salicylate Salts and Ionic Liquids.

Artemisinin, a drug used to treat malaria, can be chemically synthesized or extracted from Artemisia annua L. However, the extraction method for artemisinin from biomass needs to be more sustainable while maintaining or enhancing its bioactivity. This work investigates the use of aqueous solutions of salts and ionic liquids with hydrotropic properties as alternative solvents for artemisinin extraction from Artemisia annua L. Among the investigated solvents, aqueous solutions of cholinium salicylate and sodium salicylate were found to be the most promising. To optimize the extraction process, a response surface method was further applied, in which the extraction time, hydrotrope concentration, and temperature were optimized. The optimized conditions resulted in extraction yields of up to 6.50 and 6.44 mg·g-1, obtained with aqueous solutions of sodium salicylate and cholinium salicylate, respectively. The extracts obtained were tested for their antimalarial activity, showing a higher efficacy against the Plasmodium falciparum strain compared with pure (synthetic) artemisinin or extracts obtained with conventional organic solvents. Characterization of the extracts revealed the presence of artemisinin together with other compounds, such as artemitin, chrysosplenol D, arteannuin B, and arteannuin J. These compounds act synergistically with artemisinin and enhance the antimalarial activity of the obtained extracts. Given the growing concern about artemisinin resistance, the results here obtained pave the way for the development of sustainable and biobased antimalarial drugs.

Lifecycle of Dryocosmus kuriphilus Yasumatsu and Diversity and Importance of the Native Parasitoid Community Recruited in the Northern Region of Portugal.

In this work, the objective was to learn the life cycle of D. kuriphilus and the diversity of native parasitoids in the northern region of Portugal between 2017 and 2019. The places studied belonged to the regions of Entre-Douro-e-Minho, Beira Interior, and Trás-os-Montes. To achieve the proposed objectives, buds were collected for egg and larva observation, galls were collected for larva, pupa, and adult observation and monitoring, and emergency boxes were used to identify the fauna present in the galls. In this study, 92% of D. kuriphilus adults emerged between June and July, with emergences occurring until September. We also obtained adults in winter, so it is important to study, in future works, the hypothesis of this pest performing diapause. Regarding the study of native parasitoids, compared to other countries, the same families emerged, with good rates of natural parasitism, although with fluctuations over the years. In the three municipalities under study, 11 species were identified (Eupelmus azureus Ratzeburg, Eupelmus urozonus Dalman, Eurytoma brunniventris Ratzeburg, Megastigmus dorsalis (Fabricius), Ormyrus pomaceus (Geoffroy), Sycophila iracemae Nieves Aldrey, Sycophila variegata (Curtis), Sycophila biguttata (Swederus), Torymus flavipes (Walker), Torymus auratus (Mueller), and Torymus notatus (Walker)). The average parasitism rates varied between 1.92% and 10.68%.

Streptococcus pyogenes Meningitis in a Pediatric Patient: Case Report.

Streptococcus pyogenes causes a wide spectrum of diseases in children. However, meningitis due to this pathogen is highly uncommon. Although rare, it is associated with a high case fatality rate and can result in severe neurological sequelae. We report a case of Streptococcus pyogenes meningitis in a previously healthy 3-year-old boy. The purpose of this case report is to emphasize that this agent should be considered a cause of meningitis in previously healthy infants because of its frequent association with complications, sequelae, and high mortality rates.

Unravelling a novel role for cannabidivarin in the modulation of subventricular zone postnatal neurogenesis.

Postnatal neurogenesis has been shown to rely on the endocannabinoid system. Here we aimed at unravelling the role of Cannabidivarin (CBDV), a non-psychoactive cannabinoid, with high affinity for the non-classical cannabinoid receptor TRPV1, on subventricular zone (SVZ) postnatal neurogenesis. Using the neurosphere assay, SVZ-derived neural stem/progenitor cells (NSPCs) were incubated with CBDV and/or 5'-Iodoresinferotoxin (TRPV1 antagonist), and their role on cell viability, proliferation, and differentiation were dissected. CBDV was able to promote, through a TRPV1-dependent mechanism, cell survival, cell proliferation and neuronal differentiation. Furthermore, pulse-chase experiments revealed that CBDV-induced neuronal differentiation was a result of cell cycle exit of NSPCs. Regarding oligodendrocyte differentiation, CBDV inhibited oligodendrocyte differentiation and maturation. Since our data suggested that the CBDV-induced modulation of NSPCs acted via TRPV1, a sodium-calcium channel, and that intracellular calcium levels are known regulators of NSPCs fate and neuronal maturation, single cell calcium imaging was performed to evaluate the functional response of SVZ-derived cells. We observed that CBDV-responsive cells displayed a two-phase calcium influx profile, being the initial phase dependent on TRPV1 activation. Taken together, this work unveiled a novel and untapped neurogenic potential of CBDV via TRPV1 modulation. These findings pave the way to future neural stem cell biological studies and repair strategies by repurposing this non-psychoactive cannabinoid as a valuable therapeutic target.

Effectiveness of educational video on deaf people's knowledge and skills for cardiopulmonary resuscitation: a randomized controlled trial.

OBJECTIVE: To analyze the effectiveness of an educational video on deaf people's knowledge and skills about cardiopulmonary resuscitation. METHOD: A randomized trial, carried out at three schools with 113 deaf people (control group = 57 and intervention group = 56). After the pre-test, the control group was exposed to the lecture, while the intervention group was exposed to the video. The post-test occurred immediately after the intervention and was repeated after 15 days. A validated instrument was used, with 11 questions, presented in video/Libras (to enable understanding by deaf people) and in written/printed form (to record the answers). RESULTS: In the analysis of knowledge, the median of correct answers in the pre-test was similar between the groups (p = 0.635), while the intervention group had a higher accuracy in the immediate post-test (p = 0.035) and after 15 days (p = 0.026). In the skill analysis, the median of correct answers in the pre-test was higher in the control group (p = 0.031). There was no difference in the immediate post-test (p = 0.770), and there was a higher accuracy in the intervention group in the post-test after 15 days (p = 0.014). CONCLUSION: The video proved to be effective in increasing deaf people's knowledge and skills about cardiopulmonary resuscitation. Brazilian Registry of Clinical Trials: RBR-5npmgj.

Substrate Conformation Regulates Aromatic C-H Vs C-F Bond Activation in Heme-Dependent Tyrosine Hydroxylase.

A recently discovered heme-dependent enzyme tyrosine hydroxylase (TyrH) offers a green approach for functionalizing the high-strength C-H and C-F bonds in aromatic compounds. However, there is ambiguity regarding the nature of the oxidant (compound 0 or compound I) involved in activating these bonds. Herein, using comprehensive molecular dynamics (MD) simulations and hybrid quantum mechanical/molecular mechanical calculations, we reveal that it is compound I (Cpd I) that acts as the primary oxidant involved in the functionalization of both C-F and C-H bonds. The energy barrier for C-H and C-F activation using compound 0 (Cpd 0) as an oxidant was very high, indicating that Cpd 0 cannot be an oxidant. Consistent with the previous experimental finding, our simulation shows two different conformations of the substrate, where one orientation favors the C-H activation, while the other conformation prefers the C-F activation. As such, our mechanistic study shows that nature utilizes just one oxidant, that is, Cpd I, but it is the active site conformation that decides whether it selects C-F or C-H functionalization which may resemble involvement of two different oxidants.

Exploiting the Integrated Valorization of Eucalyptus globulus Leaves: Chemical Composition and Biological Potential of the Lipophilic Fraction before and after Hydrodistillation.

E. globulus leaves have been mainly exploited for essential oil recovery or for energy generation in industrial pulp mills, neglecting the abundance of valuable families of extractives, namely, triterpenic acids, that might open new ways for the integrated valorization of this biomass. Therefore, this study highlights the lipophilic characterization of E. globulus leaves before and after hydrodistillation, aiming at the integrated valorization of both essential oils and triterpenic acids. The lipophilic composition of E. globulus leaves after hydrodistillation is reported for the first time. Extracts were obtained by dichloromethane Soxhlet extraction and analyzed by gas chromatography-mass spectrometry. In addition, their cytotoxicity on different cell lines representative of the innate immune system, skin, liver, and intestine were evaluated. Triterpenic acids, such as betulonic, oleanolic, betulinic and ursolic acids, were found to be the main components of these lipophilic extracts, ranging from 30.63-37.14 g kg-1 of dry weight (dw), and representing 87.7-89.0% w/w of the total content of the identified compounds. In particular, ursolic acid was the major constituent of all extracts, representing 46.8-50.7% w/w of the total content of the identified compounds. Other constituents, such as fatty acids, long-chain aliphatic alcohols and ß-sitosterol were also found in smaller amounts in the studied extracts. This study also demonstrates that the hydrodistillation process does not affect the recovery of compounds of greatest interest, namely, triterpenic acids. Therefore, the results establish that this biomass residue can be considered as a promising source of value-added bioactive compounds, opening new strategies for upgrading pulp industry residues within an integrated biorefinery context.

Same but different: The influence of context framing on subjective disgust, eye movements and pupillary responses.

The adaptive value of disgust has been associated with situations of threat to our survival. This study explored this topic using eye-tracking, which provides an objective measurement of attention, while solving previous methodological issues (e.g., not considering discrete emotions and comparing across perceptually-different stimuli). We used the same stimuli and manipulated the emotional state via contextual framing. Participants' eye movements and pupillary responses were recorded while they explored pictures of objects held by clean or dirty hands; the latter were framed in a disease or a non-disease context. Pictures were then rated for arousal, disgust, and valence. Framing stimuli in a disease (vs non-disease) context induced a more adverse subjective emotional experience. Importantly, our objective measures revealed that such manipulation also led to a higher information-seeking behavior and greater pupil constriction. Overall, our data suggest that the same stimuli can effectively be used to induce different emotional states by manipulating their framing.

Impact of the T296S mutation in P450 GcoA for aryl-O-demethylation: a QM/MM study.

Lignin, a complex plant cell wall component, holds promise as a renewable aromatic carbon feedstock. p-Vanillin is a key product of lignin depolymerization and a precursor of protocatechuic acid (PCA) that has tremendous potential for biofuel production. While the GcoAB enzyme, native to Amycolatopsis sp., naturally catalyzes aryl-O-demethylation toward guaiacol, recent research introduced a single mutation, T296S, into the GcoAP450 enzyme, enabling it to catalyze aryl-O-demethylation of p-vanillin. This structural modification increases the efficiency of GcoAP450 for the natural substrate while being active for p-vanillin. This study reveals the increased flexibility of p-vanillin and its ability to adapt a favorable conformation by aligning the methoxy group in close proximity to Fe(IV) = O of Cpd I in the active site of the T296S variant. The QM/MM calculations in accordance with the experimental data validated that the rate-limiting step for the oxidation of p-vanillin is hydrogen atom abstraction and provided a detailed geometric structure of stationary and saddle points for the oxidation of p-vanillin.

Effectiveness of educational video on deaf people's knowledge and skills for cardiopulmonary resuscitation: a randomized controlled trial / Efectividad de video educativo sobre conocimiento y habilidad de personas sordas para reanimación cardiopulmonar: ensayo controlado aleatorizado / Efetividade de vídeo educativo no conhecimento e habilidade de surdos para ressuscitação cardiopulmonar: ensaio randomizado controlado

ABSTRACT Objective: To analyze the effectiveness of an educational video on deaf people's knowledge and skills about cardiopulmonary resuscitation. Method: A randomized trial, carried out at three schools with 113 deaf people (control group = 57 and intervention group = 56). After the pre-test, the control group was exposed to the lecture, while the intervention group was exposed to the video. The post-test occurred immediately after the intervention and was repeated after 15 days. A validated instrument was used, with 11 questions, presented in video/Libras (to enable understanding by deaf people) and in written/printed form (to record the answers). Results: In the analysis of knowledge, the median of correct answers in the pre-test was similar between the groups (p = 0.635), while the intervention group had a higher accuracy in the immediate post-test (p = 0.035) and after 15 days (p = 0.026). In the skill analysis, the median of correct answers in the pre-test was higher in the control group (p = 0.031). There was no difference in the immediate post-test (p = 0.770), and there was a higher accuracy in the intervention group in the post-test after 15 days (p = 0.014). Conclusion: The video proved to be effective in increasing deaf people's knowledge and skills about cardiopulmonary resuscitation. Brazilian Registry of Clinical Trials: RBR-5npmgj.

RESUMEN Objetivo: Analizar la efectividad de un video educativo sobre el conocimiento y la habilidad de las personas sordas acerca de la reanimación cardiopulmonar. Método: Ensayo aleatorizado, realizado en tres escuelas con 113 personas sordas (grupo control = 57 y grupo intervención = 56). Después de la prueba previa, el grupo de control fue expuesto a la conferencia, mientras que el grupo de intervención fue expuesto al video. La posprueba se realizó inmediatamente después de la intervención, y se repitió a los 15 días. Se utilizó un instrumento validado, con 11 preguntas presentadas en video/Libras (para que los sordos comprendan) y en forma escrita/impresa (para registrar las respuestas). Resultados: En el análisis de conocimientos, la mediana de aciertos en la preprueba fue similar entre los grupos (p = 0,635), mientras que el grupo intervención tuvo mayor acierto en la posprueba inmediato (p = 0,035) y después 15 días (p = 0,026). En el análisis de habilidades, la mediana de aciertos en la preprueba fue mayor en el grupo control (p = 0,031). No hubo diferencia en la posprueba inmediato (p = 0,770), y el grupo intervención tuvo más éxito en la posprueba a los 15 días (p = 0,014). Conclusión: El video demostró ser efectivo para aumentar el conocimiento y las habilidades de las personas sordas sobre la reanimación cardiopulmonar. Registro Brasileño de Ensayos Clínicos: RBR-5npmgj.

RESUMO Objetivo: Analisar a efetividade de vídeo educativo no conhecimento e habilidade de surdos acerca da ressuscitação cardiopulmonar. Método: Ensaio randomizado, realizado em três escolas com 113 surdos (grupo controle = 57 e grupo intervenção = 56). Após o pré-teste, o grupo controle foi exposto à aula expositiva, enquanto o grupo intervenção foi exposto ao vídeo. O pós-teste ocorreu imediatamente depois da intervenção, e foi repetido após 15 dias. Foi utilizado instrumento validado, com 11 questões apresentadas em vídeo/libras (para viabilizar compreensão dos surdos) e de forma escrita/impressa (para registro das respostas). Resultados: Na análise do conhecimento, a mediana dos acertos do pré-teste foi semelhante entre os grupos (p = 0,635), enquanto houve maior acerto do grupo intervenção no pós-teste imediato (p = 0,035) e após 15 dias (p = 0,026). Na análise da habilidade, a mediana dos acertos do pré-teste foi maior no grupo controle (p = 0,031). Não houve diferença no pós-teste imediato (p = 0,770), e houve maior acerto do grupo intervenção no pós-teste após 15 dias (p = 0,014). Conclusão: O vídeo mostrou-se efetivo no aumento do conhecimento e habilidade de surdos acerca da ressuscitação cardiopulmonar. Registro Brasileiro de Ensaios Clínicos: RBR-5npmgj.

Lipophilic Compounds and Antibacterial Activity of Opuntia ficus-indica Root Extracts from Algeria.

The chemical composition, investigated by gas chromatography-mass spectrometry, and antibacterial activity of lipophilic extractives of three varieties of Opuntia ficus-indica roots from Algeria are reported in this paper for the first time. The results obtained revealed a total of 55 compounds, including fatty acids, sterols, monoglycerides and long chain aliphatic alcohols that were identified and quantified. ß-Sitosterol was found as the major compound of the roots of the three varieties. Furthermore, considerable amounts of essential fatty acids (ω3, ω6, and ω9) such as oleic, linoleic, and linolenic acids were also identified. The green variety was the richest among the three studied varieties. The antibacterial activity, evaluated with disc diffusion method, revealed that lipophilic extracts were effective mainly against Gram-positive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) (19~23 mm). Gram-negative strains mainly Pseudomonas aeruginosa gave an inhibition zone of 18 mm, which is considered high antibacterial activity. The minimal inhibitory concentrations of the tested bacteria revealed interesting values against the majority of bacteria tested: 75-100 µg mL-1 for Bacillus sp., 250-350 µg/mL for the two Staphylococcus strains, 550-600 µg mL-1 for E. coli, and 750-950 µg mL-1 obtained with Pseudomonas sp. This study allows us to conclude that the lipophilic fractions of cactus roots possess interesting phytochemicals such as steroids, some fatty acids and long chain alcohols that acted as antibiotic-like compounds countering pathogenic strains.

Major anthocyanins in elderberry effectively trap methylglyoxal and reduce cytotoxicity of methylglyoxal in HepG2 cell line.

The accumulation of advanced glycation end-products (AGEs) in the body is implicated in numerous diseases, being methylglyoxal (MGO) one of the main precursors. One of the strategies to reduce AGEs accumulation might be acting in an early stage of glycation by trapping MGO. Thus, this work aimed to evaluate, for the first time, the potential of elderberries polyphenols to trap MGO, access the formation of MGO adducts, and evaluate the cytoprotection effect in HepG2 and Caco-2 cells. The results demonstrated that monoglycosylated anthocyanins (cyanidin-3-glucoside and cyanidin-3-sambubioside) are very efficient in trapping MGO, forming mono- and di-adducts. Quercetin-3-glucoside and quercetin-3-rutinoside reacted slowly, while diglycosylated anthocyanins did not react. The trapping of MGO by elderberry monoglycosylated anthocyanins significantly decreased the MGO cytotoxicity in HepG2 cells (∼70 % of cell viability), while the effect in Caco-2 cells was lower (∼50 %). Thus, elderberry phenolics present antiglycation potential by trapping MGO.

Synchronization and cyclicality of social spending in economic crises.

This paper expands the analysis of the cyclical characteristics of social spending by providing information on its joint behaviour across OECD countries. With this aim we propose the use of dynamic factor analysis and recursive models to estimate synchronization and cyclicality of social policies within a broad perspective. By considering the synchronization of social spending it is possible to assess the short-run characteristics of the joint response to changes in the economic cycle. We find that synchronization of social spending was only possible for advanced economies, achieving the highest countercyclical stabilization effect during the Global Financial Crisis. Emerging market economies are not able to join the synchronized response, maintaining independent and, in most cases, procyclical stances in the behaviour of their social policies. Supplementary Information: The online version contains supplementary material available at 10.1007/s10663-022-09545-w.

Single-Site Mutation Induces Water-Mediated Promiscuity in Lignin Breaking Cytochrome P450GcoA.

Cytochrome P450GcoA is an enzyme that catalyzes the guaiacol unit of lignin during the lignin breakdown via an aryl-O-demethylation reaction. This reaction is intriguing and is of commercial importance for its potential applications in the production of biofuel and plastic from biomass feedstock. Recently, the F169A mutation in P450GcoA elicits a promiscuous activity for syringol while maintaining the native activity for guaiacol. Using comprehensive MD simulations and hybrid QM/MM calculations, we address, herein, the origin of promiscuity in P450GcoA and its relevance to the specific activity toward lignin-derived substrates. Our study shows a crucial role of an aromatic dyad of F169 and F395 by regulating the water access to the catalytic center. The F169A mutation opens a water aqueduct and hence increases the native activity for G-lignin. We show that syringol binds very tightly to the WT enzyme, which blocks the conformational rearrangement needed for the second step of O-demethylation. The F169A creates an extra room favoring the conformational rearrangement in the 3-methoxycatechol (3MC) and second dose of the dioxygen insertion. Therefore, using MD simulations and complemented by thorough QM/MM calculations, our study shows how a single-site mutation rearchitects active site engineering for promiscuous syringol activity.

Chemical Profile of Lipophilic Fractions of Different Parts of Zizyphus lotus L. by GC-MS and Evaluation of Their Antiproliferative and Antibacterial Activities.

Zizyphus lotus L. is a perennial shrub particularly used in Algerian folk medicine, but little is known concerning the lipophilic compounds in the most frequently used parts, namely, root bark, pulp, leaves and seeds, which are associated with health benefits. In this vein, the lipophilic fractions of these morphological parts of Z. lotus from Morocco were studied by gas chromatography-mass spectrometry (GC-MS), and their antiproliferative and antimicrobial activities were evaluated. GC-MS analysis allowed the identification and quantification of 99 lipophilic compounds, including fatty acids, long-chain aliphatic alcohols, pentacyclic triterpenic compounds, sterols, monoglycerides, aromatic compounds and other minor components. Lipophilic extracts of pulp, leaves and seeds were revealed to be mainly composed of fatty acids, representing 54.3-88.6% of the total compounds detected. The leaves and seeds were particularly rich in unsaturated fatty acids, namely, (9Z,12Z)-octadeca-9,12-dienoic acid (2431 mg kg-1 of dry weight) and (9Z)-octadec-9-enoic acid (6255 mg kg-1 of dry weight). In contrast, root bark contained a high content of pentacyclic triterpenic compounds, particularly betulinic acid, accounting for 9838 mg kg-1 of dry weight. Root bark extract showed promising antiproliferative activity against a triple-negative breast cancer cell line, MDA-MB-231, with a half-maximal inhibitory concentration (IC50) = 4.23 ± 0.18 µg mL-1 of extract. Leaf extract displayed interesting antimicrobial activity against Escherichia coli, methicillin-sensitive Staphylococcus aureus and Staphylococcus epidermis, presenting minimum inhibitory concentration (MIC) values from 1024 to 2048 µg mL-1 of extract. Our results demonstrate that Zizyphus lotus L. is a source of promising bioactive components, which can be exploited as natural ingredients in pharmaceutical formulations.

Heart failure quantified by underlying cause and multiple cause of death in Brazil between 2006 and 2016.

BACKGROUND: The Global Burden of Disease (GBD) does not produce estimates of heart failure (HF) since this condition is considered the common end to several diseases (i.e., garbage code). This study aims to analyze the interactions between underlying and multiple causes of death related to HF in Brazil and its geographic regions, by sex, from 2006 to 2016. METHODS: Descriptive study of a historical series of death certificates (DCs) related to deaths that occurred in Brazil between 2006 and 2016, including both sexes and all age groups. To identify HF as the underlying cause of death or as a multiple cause of death, we considered the International Classification of Diseases (ICD) code I50 followed by any digit. We evaluated the deaths and constructed graphs by geographic region to compare with national data. RESULTS: We included 1,074,038 DCs issued between 2006 and 2016 that included code I50 in Parts I or II of the certificate. The frequency of HF as the multiple cause of death in both sexes was nearly three times higher than the frequency of HF as an underlying cause of death; this observation remained consistent over the years. The Southeast region had the highest number of deaths in all years (about 40,000 records) and approximately double the number in the Northeast region and more than four times the number in the North region. Codes of diseases clinically unrelated to HF, such as diabetes mellitus, chronic obstructive pulmonary disease, and stroke, were mentioned in 3.11, 2.62, and 1.49% of the DCs, respectively. CONCLUSIONS: When we consider HF as the underlying cause of death, we observed an important underestimation of its impact on mortality, since when analyzed as a multiple cause of death, HF is present in almost three times more deaths recorded in Brazil from 2006 to 2016. The mentioning of conditions with little association with HF at the time of the death highlights the importance of HF as a complex syndrome with multiple components that must be considered in the analysis of mortality trends for implementation of public health management programs.