A User-Centered Chatbot (Wakamola) to Collect Linked Data in Population Networks to Support Studies of Overweight and Obesity Causes: Design and Pilot Study

[EN] Background: Obesity and overweight are a serious health problem worldwide with multiple and connected causes. Simultaneously, chatbots are becoming increasingly popular as a way to interact with users in mobile health apps. Objective: This study reports the user-centered design and feasibility study of a chatbot to collect linked data to support the study of individual and social overweight and obesity causes in populations. Methods: We first studied the users' needs and gathered users' graphical preferences through an open survey on 52 wireframes designed by 150 design students; it also included questions about sociodemographics, diet and activity habits, the need for overweight and obesity apps, and desired functionality. We also interviewed an expert panel. We then designed and developed a chatbot. Finally, we conducted a pilot study to test feasibility. Results: We collected 452 answers to the survey and interviewed 4 specialists. Based on this research, we developed a Telegram chatbot named Wakamola structured in six sections: personal, diet, physical activity, social network, user's status score, and project information. We defined a user's status score as a normalized sum (0-100) of scores about diet (frequency of eating 50 foods), physical activity, BMI, and social network. We performed a pilot to evaluate the chatbot implementation among 85 healthy volunteers. Of 74 participants who completed all sections, we found 8 underweight people (11%), 5 overweight people (7%), and no obesity cases. The mean BMI was 21.4 kg/m(2) (normal weight). The most consumed foods were olive oil, milk and derivatives, cereals, vegetables, and fruits. People walked 10 minutes on 5.8 days per week, slept 7.02 hours per day, and were sitting 30.57 hours per week. Moreover, we were able to create a social network with 74 users, 178 relations, and 12 communities. Conclusions: The Telegram chatbot Wakamola is a feasible tool to collect data from a population about sociodemographics, diet patterns, physical activity, BMI, and specific diseases. Besides, the chatbot allows the connection of users in a social network to study overweight and obesity causes from both individual and social perspectives.Moreover, the authors acknowledge the funding support for this study provided by the CrowdHealth Project (Collective Wisdom Driving Public Health Policies, 727560).Asensio-Cuesta, S.; Blanes-Selva, V.; Conejero, JA.; Frigola, A.; Portolés, MG.; Merino-Torres, JF.; Rubio Almanza, M.... (2021). A User-Centered Chatbot (Wakamola) to Collect Linked Data in Population Networks to Support Studies of Overweight and Obesity Causes: Design and Pilot Study. JMIR Medical Informatics. 9(4):1-14. https://doi.org/10.2196/17503S1149

Differences in MEF2 and NFAT Transcriptional Pathways According to Human Heart Failure Aetiology

BACKGROUND:Ca(2+) handling machinery modulates the activation of cardiac transcription pathways involved in heart failure (HF). The present study investigated the effect of HF aetiology on Ca(+2) handling proteins and NFAT1, MEF2C and GATA4 (transcription factors) in the same cardiac tissue. METHODOLOGY AND PRINCIPAL FINDINGS:A total of 83 hearts from ischemic (ICM, n = 43) and dilated (DCM, n = 31) patients undergoing heart transplantation and controls (CNT, n = 9) were analyzed by western blotting. Subcellular distribution was analyzed by fluorescence and electron microscopy. When we compared Ca(+2) handling proteins according to HF aetiology, ICM showed higher levels of calmodulin (24%, p<0.01), calcineurin (26%, p<0.01) and Ca(2+)/Calmodulin-dependent kinase II (CaMKIIδ(b) nuclear isoform 62%, p<0.001) than the CNT group. However, these proteins in DCM did not significantly increase. Furthermore, ICM showed a significant elevation in MEF2C (33%, p<0.01), and GATA4 (49%, p<0.05); also NFAT1 (66%, p<0.001) was increased, producing the resultant translocation of this transcriptional factor into the nuclei. These results were supported by fluorescence and electron microscopy analysis. Whereas, DCM only had a significant increase in GATA4 (52%, p<0.05). Correlations between NFAT1 and MEF2C in both groups (ICM r = 0.38 and DCM r = 0.59, p<0.05 and p<0.01, respectively) were found; only ICM showed a correlation between GATA4 and NFAT1 (r = 0.37, p<0.05). CONCLUSIONS/SIGNIFICANCE:This study shows an increase of Ca(2+) handling machinery synthesis and their cardiac transcription pathways in HF, being more markedly increased in ICM. Furthermore, there is a significant association between MEF2, NFAT1 and GATA4. These proteins could be therapeutic targets to improve myocardial function

Increased Expression of Fatty-Acid and Calcium Metabolism Genes in Failing Human Heart

Heart failure (HF) involves alterations in metabolism, but little is known about cardiomyopathy-(CM)-specific or diabetes-independent alterations in gene expression of proteins involved in fatty-acid (FA) uptake and oxidation or in calcium-(Ca(2+))-handling in the human heart.RT-qPCR was used to quantify mRNA expression and immunoblotting to confirm protein expression in left-ventricular myocardium from patients with HF (n = 36) without diabetes mellitus of ischaemic (ICM, n = 16) or dilated (DCM, n = 20) cardiomyopathy aetiology, and non-diseased donors (CTL, n = 6).Significant increases in mRNA of genes regulating FA uptake (CD36) and intracellular transport (Heart-FA-Binding Protein (HFABP)) were observed in HF patients vs CTL. Significance was maintained in DCM and confirmed at protein level, but not in ICM. mRNA was higher in DCM than ICM for peroxisome-proliferator-activated-receptor-alpha (PPARA), PPAR-gamma coactivator-1-alpha (PGC1A) and CD36, and confirmed at the protein level for PPARA and CD36. Transcript and protein expression of Ca(2+)-handling genes (Two-Pore-Channel 1 (TPCN1), Two-Pore-Channel 2 (TPCN2), and Inositol 1,4,5-triphosphate Receptor type-1 (IP3R1)) increased in HF patients relative to CTL. Increases remained significant for TPCN2 in all groups but for TPCN1 only in DCM. There were correlations between FA metabolism and Ca(2+)-handling genes expression. In ICM there were six correlations, all distinct from those found in CTL. In DCM there were also six (all also different from those found in CTL): three were common to and three distinct from ICM.DCM-specific increases were found in expression of several genes that regulate FA metabolism, which might help in the design of aetiology-specific metabolic therapies in HF. Ca(2+)-handling genes TPCN1 and TPCN2 also showed increased expression in HF, while HF- and CM-specific positive correlations were found among several FA and Ca(2+)-handling genes

Variability of NT-proBNP and Its Relationship with Inflammatory Status in Patients with Stable Essential Hypertension: A 2-Year Follow-Up Study

The variability of NT-proBNP levels has been studied in heart failure, yet no data exist on these changes over time in hypertensive patients. Furthermore, studies on the relationship between natriuretic peptides and inflammatory status are limited.220 clinically and functionally asymptomatic stable patients (age 59 ± 13, 120 male) out of 252 patients with essential hypertension were followed up, and NT-proBNP was measured at baseline, 12 and 24 months. No differences in NT-proBNP were found with respect to the basal stage in the hypertrophic group, but significant changes were found in non-hypertrophic subjects. The reproducibility of NT-proBNP measurements was better in patients with hypertrophy than in the non-hypertrophic group for the three intervals (stage I-basal; stage II-stage I; stage II-basal) with a reference change value of 34%, 35% and 41%, respectively, in the hypertrophic group. A more elevated coefficient of correlation was obtained in the hypertrophic group than in patients without hypertrophy: basal versus stage I (r = 0.79, p < 0.0001 and r = 0.59, p < 0.0001) and stage I versus stage II (r = 0.86, p < 0.0001 and r = 0.56, p < 0.0001). Finally, levels of NT-proBNP significantly correlated with sTNF-R1 (p < 0.0001) and IL-6 (p < 0.01) during follow-up. A multivariate linear regression analysis showed that sTNF-R1 is an independent factor of NT-proBNP.This work shows that there is good stability in NT-proBNP levels in a follow-up study of asymptomatic patients with stable hypertension and left ventricular hypertrophy. As a consequence, assessment of NT-proBNP concentrations may be a useful tool for monitoring the follow-up of hypertensive patients with hypertrophy. Measured variations in peptide levels, exceeding 35% in a 12-month follow-up and 41% in a 24-month follow-up, may indicate an increase in cardiovascular risk, and therefore implies adjustment in the medical treatment. In addition, this study shows a link between neurohormonal and inflammatory activation in these patients

Heart Mitochondrial Proteome Study Elucidates Changes in Cardiac Energy Metabolism and Antioxidant PRDX3 in Human Dilated Cardiomyopathy

<div><p>Background</p><p>Dilated cardiomyopathy (DCM) is a public health problem with no available curative treatment, and mitochondrial dysfunction plays a critical role in its development. The present study is the first to analyze the mitochondrial proteome in cardiac tissue of patients with DCM to identify potential molecular targets for its therapeutic intervention.</p><p>Methods and Results</p><p>16 left ventricular (LV) samples obtained from explanted human hearts with DCM (n = 8) and control donors (n = 8) were extracted to perform a proteomic approach to investigate the variations in mitochondrial protein expression. The proteome of the samples was analyzed by quantitative differential electrophoresis and Mass Spectrometry. These changes were validated by classical techniques and by novel and precise selected reaction monitoring analysis and RNA sequencing approach increasing the total heart samples up to 25. We found significant alterations in energy metabolism, especially in molecules involved in substrate utilization (ODPA, ETFD, DLDH), energy production (ATPA), other metabolic pathways (AL4A1) and protein synthesis (EFTU), obtaining considerable and specific relationships between the alterations detected in these processes. Importantly, we observed that the antioxidant PRDX3 overexpression is associated with impaired ventricular function. PRDX3 is significantly related to LV end systolic and diastolic diameter (r = 0.73, <i>p</i> value<0.01; r = 0.71, <i>p</i> value<0.01), fractional shortening, and ejection fraction (r = −0.61, <i>p</i> value<0.05; and r = −0.62, <i>p</i> value<0.05, respectively).</p><p>Conclusion</p><p>This work could be a pivotal study to gain more knowledge on the cellular mechanisms related to the pathophysiology of this disease and may lead to the development of etiology-specific heart failure therapies. We suggest new molecular targets for therapeutic interventions, something that up to now has been lacking.</p></div

Levels of mRNA expression determined by RNAseq.

<p>(a) mRNA levels of the ODPA gene (<i>PDHA1</i>), ETFD gene (<i>ETFDH</i>), AL4A1 gene (<i>ALDH4A1</i>), ATPA gene (<i>ATP5A1</i>), and EFTU gene (<i>TUFM</i>) were increased in the dilated group compared to the control group. The data are expressed as mean ± SEM in mRNA relative expression. (b) The scatter plots show the relationship between the mRNA expression of molecules altered involved in substrate utilization (<i>PDHA1</i> and <i>ETFDH</i>) and also with other altered protein implicated in metabolic processes (<i>ALDH4A1</i>) and protein synthesis (<i>TUFM</i>). These genes showed a relevant correlation with <i>ATP5A1</i>, which is involved in energy production. CNT, control; DCM, dilated cardiomyopathy; ODPA, pyruvate dehydrogenase E1 component subunit α, somatic form; ETFD, electron transfer flavoprotein-ubiquinone oxidoreductase; AL4A1, delta-1-pyrroline-5-carboxylate dehydrogenase; ATPA, ATP synthase subunit α; EFTU, elongation factor Tu. *<i>p</i> value<0.05, **<i>p</i> value<0.01.</p

Mitochondrial proteins differentially regulated in dilated cardiomyopathy <i>vs.</i> controls.

<p>Mitochondrial proteins differentially regulated in dilated cardiomyopathy <i>vs.</i> controls.</p

Mitochondrial protein overexpression in dilated human hearts according to immunofluorescence techniques.

<p>Influence of dilated cardiomyopathy on the amount of each representative protein involved in cardiac energy metabolism (ODPA, ETFD, DLDH, AL4A1, and ATPA), protein biosynthesis (EFTU), and the stress response (PRDX3). Immunofluorescence of (a) ODPA, (b) ETFD, (c) DLDH, (d) AL4A1, (e) ATPA, (f) EFTU, and (g) PRDX3 were significantly increased in patients with dilated cardiomyopathy compared with the control group. Here we show the nucleus co-stained with DAPI (blue). All of the micrographs are representative of the results obtained in four independent experiments for each group and protein studied, DCM (n = 4) and CNT (n = 4). The bar represents 100 µm. The bar graph shows the relative fluorescence intensity in dilated compared to control hearts. The data are expressed as mean ± SEM. CNT, control; DCM, dilated cardiomyopathy; ODPA, pyruvate dehydrogenase E1 component subunit α, somatic form; ETFD, electron transfer flavoprotein-ubiquinone oxidoreductase; DLDH, dihydrolipoyl dehydrogenase; AL4A1, delta-1-pyrroline-5-carboxylate dehydrogenase; ATPA, ATP synthase subunit α; EFTU, elongation factor Tu; PRDX3, thioredoxin-dependent peroxide reductase. *<i>p</i> value<0.05, **<i>p</i> value<0.01.</p

Clinical and echocardiographic characteristics of heart failure patients.

<p>Duration of disease from diagnosis of heart failure until heart transplant. BMI, body mass index; DCM, dilated cardiomyopathy; NYHA, New York Heart Association.</p><p>Clinical and echocardiographic characteristics of heart failure patients.</p

Mitochondrial protein localization and overexpression in dilated human hearts analyzed using transmission electron microscopy.

<p>Influence of dilated cardiomyopathy on the amount and localization of the representative proteins involved in cardiac energy metabolism (ODPA, ETFD, DLDH, AL4A1, and ATPA), protein biosynthesis (EFTU), and stress response (PRDX3). We observed an increase in immunogold labeling in all proteins studied in DCM hearts. We also confirmed the location of all proteins analyzed and observed a similar distribution of each protein upon comparing pathological with control samples. The bar represents 100 nm. CNT, control; DCM, dilated cardiomyopathy; ODPA, pyruvate dehydrogenase E1 component subunit α, somatic form; ETFD, electron transfer flavoprotein-ubiquinone oxidoreductase; DLDH, dihydrolipoyl dehydrogenase; AL4A1, delta-1-pyrroline-5-carboxylate dehydrogenase; ATPA, ATP synthase subunit α; EFTU, elongation factor Tu; PRDX3, thioredoxin-dependent peroxide reductase.</p