Our results also indicate that sadism is a robust predictor of violence, however weaker than parental burnout and borderline personality. These results emphasize the importance of preventing parental burnout and supporting parents with borderline personality.Parental burnout is a severe disorder resulting from the exposure to chronic stress in the parental role, that can translate into neglectful and violent parental behaviors towards the offspring. This study (N = 1003 parents) aims to examine the relative weight of parental burnout, job burnout, depression, generalized anxiety disorder, borderline personality, sadism, psychopathy, Machiavellianism, narcissism, and child abuse potential, in predicting violence and neglect towards the offspring. Social desirability was controlled. When all predictors are entered together in the model, violence  Parental burnout research recently boomed and unveiled the strong repercussion parental burnout has on parental behaviors towards the offspring. Parental burnout drastically increases neglectful and violent behaviors, and this has been observed in correlational2, cross-lagged3 and experimental4 designs.Parental burnout is a severe disorder resulting from the exposure to chronic stress in the parental role6. As regards mood disorders, this is particularly the case for depression7 and stress/anxiety disorders8. As regards personality traits, the most documented risk factors are borderline personality9, sadism10, psychopathy11, Machiavellianism12 and narcissism13. Other child abuse risk factors  have been gathered in the Child Abuse Potential14 which is logically also a strong predictor of child maltreatment.However, violence and neglect  are not only a consequence of parental burnout. Mood disorders and several personality traits also enhance the risk of child maltreatmentWhile many psychological disorders or traits increase the risk of child maltreatment, no study has ever compared their relative weight in a single model. Whether parental burnout deserves specific attention is therefore unknown. Controlling for the effect of other predictors is all the more important as they are not independent from each other. The aim of this study is to examine the relative weight of parental burnout, job burnout, depression, generalized anxiety disorder, borderline personality, sadism, psychopathy, Machiavellianism, narcissism, and child abuse potential, in predicting violence and neglect towards the offspring. We expected that parental burnout, job burnout, depression, generalized anxiety disorder, borderline personality, sadism, psychopathy, Machiavellianism, narcissism, and child abuse potential, would be positively correlated with violence and neglect towards the offspring. As regards to relative weight of each of the aforementioned variables when entered together in the same model, we did not have specific hypotheses, although some variables  were more expected to stand out because their bivariate correlations with child maltreatment in previous studies were of large magnitude. Considering that violence towards the offspring is a taboo subject in current society, it is subject to social desirability. Thus, we included it as a variable in both regression models, allowing to interpret results whilst controlling for social desirability.15.The study was designed and carried out in accordance with relevant guidelines and regulations, such as the Declaration of Helsinki, and it received approval from the ethical committee of Cliniques Universitaires Saint-Luc (Belgium). Participants had to be parents and had to have at least one child still living at home. The study was created on Qualtrics, and it was posted on various online groups, websites, social media networks. Participants gave their free and informed consent prior to participating in the study. As an additional motivation, after participating parents could sign up to take part to a raffle by leaving their e-mail address , with the possibility of winning 250 euros. Statistical analyses were conducted using SPSS, version 28t(998) = −2.9, p = 0.003), slightly less well educated (t(998) = 2.28, p = 0.005), mostly not working (t(998) = −23.4, p < 0.001), slightly poorer (t(998) = 5.28, p < 0.001), and with a higher level of parental burnout (t(998) = −25.1, p < 0.001). The authors would also like to point out that missingness was proportionate with the length of the study . However, although we observed a consistent decrease in responses for most of the study, there was a sudden drop of participation when the participants were faced with the sadism measure, showing how uncomfortable it can be when answering that questionnaire. For ethical reasons, we did not force the respondents to answer all the questions, thus leaving us with 680 participants. In the current sample, the average age was 38.6 years. Most parents had completed higher education, such as bachelor’s degree (41.8%%) and master’s degree (29.3%), followed by higher secondary education (17.4%), third cycle education (5.9%), lower secondary education (4.7%), and primary education (1%). Almost half of the sample (41.0%) had a monthly income of 2500–4000 Euros, followed by 4000–5500 Euros (27.4%), 1000–2500 Euros (17.5%), 5500–7000 Euros (10.9%), higher than 7000 Euros (2.6%), and 0–1000 Euros (0.6%). Most parents were either married (47.6%) or legally cohabitating (35.9%), and 16.5% were in single-parenting situations. The majority of parents lived in Belgium (82.1%) or France (16.2%). About 89.3% of the sample had between 1 and 3 children, and for more than half of the parents (53.1%) the first child was between 1 and 12 years of age . Thus, compared to the population of Belgium and France, the current sample was over-representative of mothers and not fathers, slightly over-educated, just-representative in terms of income, representative in terms of married and legal-cohabitating parents, slightly over-representative of single-parenting situations, and representative of the populations in terms of number of children.In total, 1494 parents participated to the study. Given our aim to compare predictors’ relative weights, only participants who completed the entire survey were kept . Survey participants were recruited through social media, websites, youth movement groups and word of mouth. Analyses were carried out to determine whether values were missing due to random reasons, or due to specific reasons. T-tests revealed that the values where not missing at random, in fact missing participants tended to be more women (16), which encompasses 23 items  rated on a 7-point frequency scale: Never (0), a few times a year (1), once a month or less (2), a few times a month (3), once a week (4), a few times a week (5), every day (6). Total score was computed by summing item responses together, and for all measures hereafters, except if stated otherwise. Job burnout was assessed using the Maslach Burnout Inventory General Survey17, which encompasses 16 items rated  on the same 7-point Likert frequency scale as above (α = 0.88). Depression was measured with the Patient Health Questionnaire18, including 9 items  representing each DSM symptom of depression. Participants indicated how often they have experienced specific symptoms during the last two weeks on a frequency scale: Not at all (0), Several Days (1), More than Half the Days (2), Nearly Every Day (3) (α = 0.89). Generalized Anxiety was assessed with the GAD-719, a 7-item questionnaire  measuring the presence of anxiety symptoms during the last 14 days on a 4-point frequency scale: Not at all (0), Several days (1), More than half the days (2), and nearly every day (3) (α = 0.92). Borderline Personality was assessed with the Borderline Evaluation of Severity over Time , which is a 15-item  questionnaire (α = 0.86). For the first 12 items, the Likert scale goes from “None/Slight” (1) to “Extreme” (5), whereas for items 13–15, the scores go from “Almost Never” (1) to “Almost Always” (5). Sadism was measured using the Assessment of Sadistic Personality , which is a 9-item questionnaire  rated on a 5-point Likert scale from 1 (strongly disagree) to 5 (strongly agree) (α = 0.82). Psychopathy, Machiavellianism, and narcissism were measured using the Short Dark Triad Scale22, a 27-item questionnaire  in which each aforementioned variable is measured with 9 items rated on a 5-point Likert scale from “Disagree strongly” (1) to “Agree strongly” (5) . Total score for the three subscales were created by averaging the items. Child Abuse Potential was assessed using the Brief Child Abuse Potential , a questionnaire encompassing 21 items  rated on a binary scale: agree (0) or disagree (1) (α = 0.86). Total score was computed by averaging the items. Violence and neglect were measured using the Neglect and Violence Scales2. The former encompasses 17 items  , the latter 15 items , all rated on a 8-point frequency scale: never (0), less than once a month (1), about once a month (2), a few times a month (3), once a week (4), several times a week (5), every day (6), several times a day (7) . Total scores were created by averaging the items. Social desirability was measured using the short form of the Marlowe-Crowne Social Desirability scale25, which is a 12-item  questionnaire rated on a binary scale: true (1) or false (0) (α = 0.60).Parental burnout was measured using the Parental Burnout Assessment  and secondly the remaining variables. Hierarchical regression models were tested with and without a bootstrapping of 1000 samples to ensure that presented results are robust.Correlation estimates and their significance level can be seen in Table F = 41.01, p < 0.001; R2 = 0.40). In this model, only four predictors remained significant: Parental burnout (t(668) = 9.15, p < 0.001) and borderline personality (t(668) = 9, p < 0.001) stood out as strong predictors of violence; sadism also stood out but to a lesser extent (t(668) = 2.1, p = 0.04). Job burnout (t(668) = −2.06, p = 0.04) was also significant, but it negatively predicted violence . The model remained the same even after bootstrapping of 1000 samples.Hierarchical regression analyses  = 24.38, p < 0.001; R2 = 0.29). Among all the predictors, only borderline personality  = 7.9, p < 0.001) and parental burnout  = 5.9, p < 0.001) stood out as positive predictors of neglect. Child abuse potential also stood out but it was negatively related to neglect  = −2.9, p = 0.004) . The model remained the same even after bootstrapping of 1000 samples.Concerning neglect, the global model was significant , as their bivariate correlations were positive.The aim of the current study was to examine the relative weight of various predictors of child maltreatment. Our findings suggest that violence 27 and knowing that it is especially when parents are emotionally distant from their children that neglect and violence kick in28, identifying parents at the exhaustion stage  is crucial in order to treat the parents and, by doing so, preventing neglect or violence to occur. Also, the current study identified borderline personality as another factor of tremendous importance in predicting violence and neglect towards the children. Knowing this, prevention should be reinforced. Until 2015, few programs to support parenting in parents with borderline personality existed but things are starting to change30; the current findings suggests that these endeavors should be supported.The implications of these findings are consequential, both for research and clinical practice. To begin, the importance of parental burnout prevention is key, as it is a robust and consistent predictor of violence and neglect towards the offspring. Knowing that parental burnout develops in stages and that it begins with emotional exhaustionAs advised by reviewers, additional analyses were performed. First, the previous regression models were re-analyzed by adding socio-demographic variables. In predicting neglect, results show that parental burnout, narcissism, abuse potential, being a man, and having younger children increases the risk of neglect. In predicting violence, parental burnout, borderline personality, and lower levels of education increase the risk of violence (results can be viewed in Supplementary Tables 4. Also, the authors did not account for the fact that some parents in the sample could be from the same family, this precluding the independence of observations. However, considering that the vast majority of participants were mothers, it is not very likely that this bias had an effect on the statistical analyses. Future research should be conducted to assess whether borderline personality is a precursor of parental burnout, whether/how borderline personality interacts with parental burnout, and whether the interaction has an additive effect on the violent and neglectful behavioral outbursts.Despite its strengths, this study also has limitations. The main one is that the study is correlational, precluding causal interpretations. However, the causal effect of parental burnout on violence and neglect towards the offspring has already been demonstratedSupplementary Tables.


Six distinct minerals were identified and quantified in beetroot soups, namely Na, K, Mg, Mn, Zn and P. Beetroot soup microencapsulated in starch or maltodextrin complied with microbiological quality guidelines for consumption, with good acceptance and purchase intention throughout 90 days of storage. Microencapsulated beetroot soup may, thus, comprise a novel attractive strategy to offer high contents of bioaccessible dietary nitrate and antioxidant compounds that may aid in the improvement of vascular-protective effects.Beetroot is a tuber rich in antioxidant compounds, i.e., betanin and saponins, and is one of the main sources of dietary nitrate. The aim of the present study was to microencapsulate a ready-to-eat beetroot soup by lyophilization using different encapsulating agents, which supply the required amount of bioactive nutrients. Particle size distributions ranged from 7.94 ± 1.74 to 245.66 ± 2.31 µm for beetroot soup in starch and from 30.56 ± 1.66 to 636.34 ± 2.04 µm in maltodextrin. Microparticle yields of powdered beetroot soup in starch varied from 77.68% to 88.91%, and in maltodextrin from 75.01% to 80.25%. The NO Vegetabegularly ,3,4.Beta vulgaris L., a tuberous plant belonging to the Chenopodiaceae family, is a source of NO3−, phenolic compounds and betalains, as well as dietary fiber and minerals  [3−, improves vascular function by converting NO3− to NO [3−. Dietary NO3− increases rapidly in plasma, and about 60% of the absorbed NO3− is excreted in the urine, while 25% is extracted by the salivary glands, concentrated in the saliva through the entero-salivary cycle. In the oral cavity, NO3− is reduced to nitrite (NO2−) through the action of the nitrate-reductase enzyme, expressed by oral commensal bacteria that use this anion as a terminal electron acceptor to generate ATP or to incorporate it into their biomass [2− is protonated, forming nitrous acid (HNO2), which spontaneously decomposes  to NO and other bioactive nitrogen oxides, such as nitrogen dioxide (NO2), dinitrogen trioxide (N2O3) and nitrosonium ion (NO+) [3− can be used as a precursor for endogenous NO synthesis, new physiological, therapeutic and nutritional approaches concerning this anion have been developed. The accumulation of NO3− and NO2− from dietary sources takes place from these anions synthesized endogenously through the L-arginine/NO pathway [3− is lost by renal clearance and a small part is extracted by the salivary glands, concentrating in the saliva to continue the entero-salivary cycle [3− and NO2− may be reduced by the enzyme xanthine oxidoreductase (XOR), similar to saliva nitrate-reductase. Xanthine oxidoreductase does not depend on O2 to catalyze NO formation from remaining NO3− and NO2−, so NO can be formed under hypoxia and ischemia conditions, where XOR expression and activity are increased. NO2− can be reduced to NO by deoxyhemoglobin (deoxyHb) and deoxymyoglobin (deoxyMb), especially under low O2 levels [2− to its bioactive form, NO [Red beetroot, nd zinc) ,6,7,8. Bnd zinc) . Red beend zinc) . Further3− to NO ,14,15,16 biomass ,17. Subson (NO+) ,15. As d pathway . Most NOry cycle . Additio2 levels . Other eThe food industry has developed versatile, practical or ready-to-be-consumed fruit and vegetable products in recent years with adequate sensorial attributes and, above all, providing health benefits . HoweverFood-grade microparticles can be obtained by lyophilization, a viable and economical process that results in the crystallization of food suspensions at low temperatures . Lyophil3−, betacyanins, saponins and minerals. Microparticle production yields and their characteristics, i.e., size, morphology, water activity, solubility, hygroscopicity, thermogravimetric features, infra-red absorption spectroscopy and bioactive compound composition originally found in the beetroot matrix, were determined. The sensory attributes of the powdered beetroot soups and purchase intention were evaluated, as well as shelf life and microbiological safety during 90 days of storage.Herein, in natura beetroot was used to formulate a powdered and microencapsulated lyophilized soup preserving functional compounds found in the beetroot matrix, such as dietary NO®-BD150 and Milk Powder 1549 were used to assess method accuracy . Ultra-pure water (resistivity > 18.2 MΩ cm) obtained from a Milli-Q® INTEGRAL 10 system  was used to prepare all reagents.Standard solutions and reagents were purchased from Sigma-Aldrich Chemical Co. . All solvents, including methanol (MeOH), ethanol and acetonitrile with HPLC grade were purchased from Tedia Company Inc. . Agar yeast, extract glucose, chloramphenicol (YGC) and agar glucose and yeast extract were purchased from Hexis Científica . Agar Man, Rogosa and Sharpe (MRS) was purchased from Acumedia ; 3M PetrifilmTM Salmonella Express Sy and 3M PetrifilmTM E. coli Count Plate were purchased from 3M Health Care . All reagents were analytical grade. Nitric acid  was purified by sub-boiling followed by distillation in a quartz still . The multi-element standard solution Merck IV  comprising 29 elements in nitric acid was employed to prepare standard analytical curves. Two reference materials, certified Skimmed Milk Powder ERMBeta vulgaris L.) purchased from local stories in the municipality of Rio de Janeiro, RJ, Brazil, without any signs of deterioration, such as cracks, spots or wet areas, were sanitized as recommended by the Brazilian Health Regulatory Agency ANVISA , cut into cubes, baked for 60 min at 160 °C, ground in a food processor , cooked for 20 min at 160 °C and seasoned with leek, salt and chives  at 13,500 rpm. Each encapsulating agent was mixed with the beetroot soup at different ratios  by stirring and homogenization employing a GOstirrer-MS-H-Pro  at 600 rpm for 30 min followed by lyophilization  where sublimation of the aqueous samples was performed for 4 to 5 days until a powdery appearance was achieved. The microencapsulated beetroot soups were then ground using a mortar and pestle and the microparticles were placed in a sealed plastic container and maintained at room temperature in a cool, dry and dark place, considering the necessary headspace in order to avoid product overflow during the sealing process.Microparticles were prepared as described by Mazuco et al.  using twMicroparticle morphology was evaluated by scanning electron microscopy (SEM), according to Maia et al. . SamplesThe size distribution of the microparticles was determined by laser diffraction employing a Mastersizer MicroPlus MAF 2000 particle size analyzer  from 0.02 to 2000.000 μm. Samples were dispersed in water reaching an obscuration index of 10% according to three consecutive readings and the results were expressed as d (0.1), d (0.5) and d (0.9), corresponding to the maximum size, in µm, of 10%, 50% and 90% of the analyzed particles, in addition to the “span” scattering index determination .−1 resolution. Each sample was homogenized with KBr to form pellets employed in the spectra acquisition, according to [Infrared absorption spectra were acquired on an Excalibur 3100 Varian FT-IR spectrophotometer  set in the infrared region, in the transmittance mode, accumulating 20 scans and 2 cmrding to .w/v) and analyses were recorded at mV, in triplicate.Microparticle zeta potentials (ZP) were determined using a Zetasizer LAB  at 25 °C. Samples were diluted in deionized water :The moisture of the lyophilized beetroot soups was determined by loss of moisture and volatile substances at 105 °C according to the Association of Official Analytical Chemists .g for 5 min. A 25 mL aliquot of each supernatant was then dried in an oven at 105 °C for 5 h and the solubility (%) of each sample, corresponding to the difference in weight before and after this procedure, was calculated [The solubility of beetroot microparticles was determined by adding 1 g of each sample to 100 mL of Milli-Q water, followed by homogenization for 5 min at 15.000 rpm and centrifuging at 3000× lculated .wa) of beetroot microparticles was measured directly at 25 °C using a Novasina LabMaster-aw analyzer  according to Favilla et al. [The water activity , using an apparatus comprising an automatic injector and RF-10AXL fluorescence detector , as described by Baião et al. [The NOo et al. .®, São Paulo, SP, BRA). The total elemental concentrations determined in the CRMs  were compared to certified values and the recovery values were adequate for all determined elements, ranging from 83 to 106%  were determined according to Almeida et al. ,34 by in to 106% . The res to 106% .Total saponin content was determined by the vanillin-sulfuric acid assay, as described by Baião et al. , where aSoup ash, protein, lipid and total dietary fiber contents were determined according to the Association of Official Analytical Chemists . Total c−1 scans under an N2 atmosphere (30 mL·min−1) [The hygroscopicity of the beetroot soups was determined by maintaining 500 mg of powdered beetroot soup in a desiccator containing a saturated NaCl solution (UR = 75%) at room temperature for 7 days. After this period, the microparticles were weighed and hygroscopicity expressed as the percentage of absorbed mass water . ThermogL·min−1) .®, Chiyoda, TKO, JPN) and a refractive index detector RID-10A  coupled to a signal integrator CBM-20A The fructose, glucose, sucrose and maltose contents of the beetroot microparticles were evaluated as described by Baião et al.  employing for 30 min at 4 °C. The supernatants were then collected and an extraction step repeated three times was combined prior to betalain quantification. Sample absorbances were recorded using a UV 2800 Shimadzu UV/Vis spectrophotometer  at 538 nm and 480 nm for betacyanins and betaxanthins, respectively.Beetroot soup betalains were determined by a modification of the method described by Kusznierewicz et al. . BrieflyMw = 550 g·mol−1, e = 60,000 L·mol−1 cm−1 for betacyanin and Mw = 308 g·mol−1, e = 48,000 L·mol−1 cm−1 for betaxanthin.A comprises absorptions at 538 nm and 480 nm for betacyanins and betaxanthins, respectively, DF is the dilution factor and L the cuvette path length.Betalain contents were determined by applying Equation (2) proposed by Stintzing et al. . The empEE) in starch and maltodextrin were determined individually for each pigment  as described by McNamee et al. [BLT comprises total betalains and BLS supernatant betalains. To calculate the EE%, a 1 mL aliquot of the beetroot soup extract was diluted in 10 mL of water and total betalain quantification (betacyanins + betaxanthins mg·g−1) was carried out. The betalain contents of the microencapsulated beetroot soups were determined by spectrophotometry at wavelengths 538 nm and 480 nm, according to Equation (2). Encapsulation efficiency was determined by the ratio between supernatant betalain content and the content retained in the core.The efficiencies of betalain microencapsulation  assays, respectively. Total and fecal coliforms were evaluated by the most probable number per gram (MNP·g−1) standard methodology. Bacillus cereus were determined in selective MYP medium , according to APHA [Yeast and mold counts were performed according to the American Public Health Association (APHA) . Salmone to APHA .Non-trained judges were recruited through invitation signals posted at the Federal University of Rio de Janeiro (UFRJ) and invitations to individuals of both genders aged 18–60 years old. Before the beginning of the sensory test, each panelist signed a Free and Informed Consent Form .All participants received instructions for carrying out the tasting and questionnaire answering, accompanied by a researcher who remained throughout the entire procedure to clarify any doubts. The participants evaluated the features of the powdered beetroot soup within 90 days of manufacturing by considering characteristic beetroot color, texture and aroma maintenance and regular powder appearance. Each volunteer evaluated the three types of powdered beetroot soup differentiated by acronyms just after manufacturing (time 0) and after 30, 60 and 90 days of storage. Sensory evaluations were carried out in a closed cabin with white lighting and the samples were randomly served accompanied by an evaluation form. Beetroot soup formulations were evaluated individually for acceptability by assessing powder attributes  and overall impression through a 9-point structured hedonic scale. To encourage non-trained judges to perform a more conscientious purchase intention analysis, purchase intention was scored using a 5-point hedonic scale, ranging from “I would certainly buy it” (score 5) or “I would certainly not buy it” (score 1) .® .A one-way analysis of variance (ANOVA) with repeated measures was performed to identify lyophilized combination differences employed for characterization and stability analyses. When the F value was significant, an additional post hoc test was performed by applying a Bonferroni correction analysis. Data were expressed as means ± standard deviations (SD). All statistical analyses were performed using Graphpad Prism software v. 5 for Windowsw/w) and 1:3 (w/w) ratios resulted in smaller-sized microparticles and a discrete span, while a 1:1 (w/w) ratio between microencapsulated beetroot soup in starch or maltodextrin favored microparticle size heterogeneity.The particle size distribution and the span scattering index results indicated particle diameters ranging from 7.94 ± 1.74 to 245.66 ± 2.31 µm for beetroot soup microencapsulated in starch, and from 30.56 ± 1.66 to 636.34 ± 2.04 µm in maltodextrin . The beew/w) wall/core ratios. The obtained SEM images demonstrated that microparticles in starch presented spherical and irregular geometric conformations, without invaginations or roughness . Furthermore, the characteristic bands present at 1333 cm−1 and 995 cm−1 were attributed to the angular deformation of C-H bonds and the stretching of C-O bonds, respectively  ratio in maltodextrin, which reached <0.69  and -20.28 ± 1.04 at the 1:2 (w/w) ratio. Furthermore, the zeta potential increased with increasing starch-to-beetroot ratios. On the other hand, encapsulation in maltodextrin promoted an increased surface charge of the soup at a magnitude greater than in starch at the 1:2 (w/w)  ratio (Pure beetroot soup exhibited a low surface charge (−8.36 ± 0.01 mV), while starch microencapsulation increased the zeta potential, reaching −21.29 ± 0.14 at 1:3 (n) ratio .w/w) beetroot soup/encapsulating agent ratios and that of pure beetroot soup are presented in The color of the beetroot soup microparticles in starch or maltodextrin at 1:1, 1:2 and 1:3 (3− contents of beetroot soup microencapsulated in starch at 1:1 and 1:2 (w/w) ratios, of 16.67 ± 0.19 and 10.46 ± 0.22 mmol·100 g−1 fresh weight basis, respectively, were higher than values observed for beetroot soup microencapsulated in maltodextrin (15.98 ± 0.33 and 8.43 ± 0.09 mmol·100 g−1 fresh weight basis). No changes in NO2− contents were observed when comparing beetroot soup microencapsulated in starch or maltodextrin  ratios. However, pure beetroot soup  contained the highest NO3−, NO2− and saponin contents compared to beetroot soup microencapsulated in either starch or maltodextrin . No changes were observed in saponin content when comparing beetroot soup microencapsulated in starch or maltodextrin considering the 1:1, 1:2 and 1:3  ratio comprised a solid, granular and heterogeneous powder. Beetroot soup lyophilization with no encapsulating agent was dark red, while beetroot soup microencapsulated with starch at the 1:2 (w/w) ratio was clear red and beetroot soup microencapsulated with maltodextrin at the 1:2 (w/w) ratio was bright red. Powdered beetroot soups in the presence of encapsulating agents exhibit a sweeter and slightly earthy odor and aroma when compared to the product prepared without any encapsulating agent. The texture of the powdered soups encapsulated with starch and maltodextrin is solid, regular and slightly rough, whereas the texture of powdered soups with no encapsulating agent is solid, irregular and very rough  ratio are depicted in −1), betaxanthin (142.2 ± 2.63 mg·g−1) and total betalain (400.2 ± 2.17 mg·g−1) contents compared to beetroot soup microencapsulated in starch and maltodextrin (1:2). The encapsulation efficiencies were higher than 50% for betacyanins, betaxanthins and total betalains considering beetroot soup encapsulated in both starch and maltodextrin. Furthermore, no significant differences were observed in betacyanin, betaxanthin and total betalain contents and, consequently, in the encapsulation efficiency of these compounds among the microencapsulated beetroot soups.The total betalain, betacyanin and betaxanthin encapsulation efficiencies of beetroot soup encapsulated at the 1:2 (w/w) ratio were evaluated by microbial quality testing for 90 days , were more homogeneous, with a narrower size distribution and less size variability. These results are similar to those reported by Murali et al. [Beetroot soup encapsulated in maltodextrin formed larger and more heterogenous microparticles compared to beetroot soups encapsulated in starch, as maltodextrin favors the rapid formation of a glassy surface, which allows for air expansion inside the microparticles, resulting in increased average sizes. Similar results were reported by Rezende et al.  concernii et al. , where mw/w) ratios, leading to smaller microparticles with smaller spans. The 1:1 (w/w) ratio between microencapsulated beetroot soup in starch or maltodextrin, however, favored span increase.It is important to note that microparticle size influences several product features, such as solubility, dispersibility and the release of matrix-entrapped compounds . HomogenMicroparticle microstructure, size, polydispersity and morphology during lyophilization can undergo changes depending on the encapsulating matrix composition and properties, the core:wall material ratio and drying and storage conditions . No morp−1, characteristic of the betanin imine bond (C=N), and the band detected at 3300 cm−1, indicating O-H bond stretching, also present in betanin, indicate that the betanin structure was preserved in beetroot soup microparticles [−1, referring to O-H bond stretching, and a band at 2929 cm−1, referring to the vibrational stretching of the C-H bond of saturated carbon (C sp3). In addition, a 1333 cm−1 band was also noted, which can be attributed to the angular deformation of C-H bonds. In the typical polysaccharide region, bands at 1147 cm−1 and 1076 cm−1 can be attributed to vibrational C-O bond stretching, while a band at 995 cm−1 is attributed to the absorption of the C-O-C bond [The infrared spectra of powdered beetroot soups microencapsulated at three different starch ratios mostly displayed similar bands regardless of starch ratio and bands referring to beetroot soup, indicating that chemical component structures were preserved during the microencapsulation/lyophilization process. The band at 1640 cmarticles ,51. The O-C bond ,53.−1 referring to O-H bond stretching, while a band at 2925 cm−1 refers to the vibrational stretching of the C-H bond of an alkyl group. Furthermore, the characteristic bands at 1639 cm−1 and 1358 cm−1 can be attributed to the angular straining of OH bonds (referring to absorbed water) and angular straining of C-H bonds, respectively. Bands at 1147 cm−1, 1076 cm−1 and 927 cm−1 were observed in the characteristic carbohydrate absorption region, referring to C-O-C and C-O deformations [w/w) ratio, a band at 1744 cm−1, characteristic of pure beetroot soup, is still observed  ratio for beetroot soup and polysaccharides. However, starch microencapsulation yields were higher than maltodextrin, maybe due to the molecular structure of starch, which allows for fast sample drying. Indeed, lower final product drying times may be considered an advantage concerning the beetroot soup lyophilized process [Microencapsulation yields increased with higher encapsulating agent concentrations, as well as higher solid contents, indicating a successful drying process. These results are satisfactory for technological improvements, particularly at the 1:2  for maltodextrin microencapsulation should be avoided. Microencapsulated beetroot soup displayed better performance than pure beetroot soup and should, therefore, be considered a safer and more stable food product.The a et al.  evaluateFurthermore, the high moisture in powdered food favors deterioration by altering sensory attributes, also affecting overall product acceptability . The micThe solubility of lyophilized products is an important marketing parameter and must be considered when choosing the encapsulating agent, with carbohydrates recommended to obtain high solubilization-capacity microparticles when reconstituted in water ,60,61. ICaryocar brasiliense) oil-maltodextrin microparticles in other studies [The magnitude of the zeta potential measures colloidal system stability, as electrostatic repulsions decrease Van der Waals forces of attraction, favoring dispersion stability . Colloid studies ,65,66. TIn the present study, a color analysis was applied to assess any undesirable beetroot soup characteristics. Color affects the attractiveness of food products, interfering with sensory evaluations and purchase decisions , particuThe first property that consumers observe in every food product is appearance. Color can be altered during food processing due to pigment degradation, darkening reactions and/or compound oxidation. Some synthetic dyes, although largely applied in the food industry, can be harmful if consumed in high concentrations, while natural dyes have been proven to display anticancer and antioxidant properties . BetalaiAll these pigments seem to be preserved following beetroot soup microencapsulation and storage for at least 90 days, as the encapsulating agents act as physical obstacles that can reduce the effects of oxygen, light, heat and humidity on the encapsulated material, certainly contributing to consumer acceptance and purchase intention, as well as towards microencapsulated beetroot soup shelf life, as demonstrated previously .3− was considered a toxic compound derived from unfavorable diets, as it was erroneously associated with the development of certain malignancies such as gastric cancer [3−·kg−1 of body weight daily intake, the same content adopted by the European Food Safety Authority [3−·day−1. The adoption of vegetarian diets, in general, however, increases NO3− consumption by over 400 mg NO3−·day−1 for 80 kg adults, well above the acceptable daily intake values [3− and NO2− intake and cancer development in humans [3− to NO2− and subsequently to NO, comprising an alternative route to the L-arginine/NO pathway [Strict standards regarding the levels of these anions have been regulated in food and drinking water in the past. Until a decade ago, NOc cancer ,14,15. Tn humans , making 3− is absorbed in the proximal portion of the small intestine, where it accumulates endogenously as NO3−. About 30% of the NO3− absorbed is extracted by the salivary glands, concentrated in saliva and reduced to NO2− through nitrate-reductase [2− is protonated, forming nitrous acid (HNO2), which spontaneously decomposes to NO and other bioactive nitrogen oxides. In addition, a small part of plasmatic NO3− and NO2− may be reduced to NO by xanthine oxidoreductase (XOR), deoxyhemoglobin (deoxyHb) and deoxymyoglobin (deoxyMb), aldehyde oxidase (AO), aldehyde dehydrogenase (ALDH) and carbonic anhydrase (CA) [2+ cytosol concentrations. The low intracellular Ca2+ concentrations decrease complexation to calmodulin, promoting vascular smooth muscle cell relaxation, decreasing arterial stiffness and improving endothelial functional adaptation [When ingested, dietary NOeductase ,11. Uponase (CA) . The proaptation .3− intake comes from vegetables belonging to several botanica families [3−·kg−1 and are commonly used in dietary interventions to improve cardiovascular performance through decreased central blood pressure and arterial stiffness reduction, improving overall vascular function [3− supplementation should be long term (over 20 days) and greater than 370 mg (6.0 mmol) per day [3− concentrations in the human body may be a limiting factor in ensuring adherence to long-term nutritional interventions [w/w) ratios, beet powder:encapsulating polysaccharide, contain NO3− concentrations over 10 mmol·100 g−1. Thus, the novel microencapsulated beetroot soup technology was able to overcome the challenge, developing a high-acceptance beetroot soup containing pharmacological NO3− concentrations in an adequate serving portion, presenting a long shelf life, easily reconstituted and consumed as a meal, favoring continuous intake and better adherence to a non-drug long-term-strategy therapy.In the Western diet, about 85% of NOfamilies . Red beefunction ,13,16,69erm over 0 days an per day ,16,69,70ventions ,71. The Beta vulgaris L., saponin concentrations can vary from 7.66 to 12.2 mg∙g−1 dry weight, but this vegetable may be enriched according to the final product processing [−1, respectively [−1, pure and microencapsulated beetroot soup  contained three-fold higher saponin contents or more when compared to beetroot juice and beetroot gel.Saponins, triterpene glycosides in which the aglycone is covalently linked to one or two sugar chains through a glycosidic ester (C-28) or ether (C-3) bond , are widocessing . Saponin−1), Mg (23 mg∙100 g−1), Mn (0.329 mg∙100 g−1), Na (78 mg∙100 g−1), P (40 mg∙100 g−1) and Zn (0.35 mg∙100 g−1) [−1). Fresh beetroot contains 87.6 mg∙100 g−1 of water and nutrients and minerals are diluted in the aqueous medium in the vegetable matrix. Removing water by sublimation leads to an increased matrix density [Red beetroot is a tuber rich in several minerals, such as K (325 mg∙100 g100 g−1) ,75,76. Hw/w) ratios presented mineral concentrations greater than or equal to raw beetroot. Mineral content variations seem to be associated to the type of microencapsulating agent and its behavior during lyophilization, as the capacity to hold in the core of the microparticles depends on the polysaccharide interaction with micronutrients [The microencapsulated beetroot soups contain significantly lower mineral content when compared to pure beetroot soup formulations, as the food matrix was mixed at different ratios of the encapsulating polysaccharides in the microencapsulated beetroot soup formulations, resulting in lower mineral content. However, the beetroot soup microencapsulated in starch at the 1:1 and 1:2 (utrients . Starch w/w) ratio chosen to provide dietary NO3− included the polysaccharides as the encapsulating agents, which increased total dietary fiber and carbohydrate contents and, consequently, the energy value of the final product. The total dietary fibers in beetroot soup microencapsulated in starch and maltodextrin at a 1:2 (w/w) ratio were 3.57 ± 0.37 and 3.40 ± 0.36 g∙100 g−1, respectively, classifying microencapsulated beetroot soups as dietary fiber food sources, as they contain above 3 g∙100 g−1 of dietary fibers [As the aim of novel technological beetroot product development is to perform nutritional interventions in individuals at cardiovascular risk for CVD, overall product characteristics were carefully considered. The formulation of microencapsulated beetroot soups with starch and maltodextrin at a 1:2  by spray drying.Betalains are easily degraded if exposed to light or oxygen, high water activity and physicochemical conditions or enzymes found in the gastrointestinal tract, reducing their absorption following oral administration and also leading to low bioavailability ,81,82,83Although partial betalain microencapsulation was observed in pure beetroot soup in the present study, betalain content in the microcapsules was higher than doses considered as effective following pre-clinical and clinical assays ,89,90,91During the manufacturing and storage of the powdered beetroot soups, all procedures and analyses were performed according to the IN 60/2019, in addition to the RDC 331/2019 norm that establishes the microbiological analyses for ready-to-eat foods by the current Brazilian legislation ,92. The The development of new products must be followed by acceptability assessments. Sensory analyses are an important tool in this process, comprising an interdisciplinary science that uses the complex interaction of the sense organs and the food’s chemical and physical characteristics to evoke, measure, evaluate and interpret sensorial characteristics and acceptability and/or preference for food products and many other materials. Sensory methods are based on responses to stimuli, which produce intensity, extension, duration, quality and pleasure or displeasure sensations . In the Studies on the psychological or nutritional factors that encourage consumers to accept or not a certain product are common, and some initially perceived attributes directly contribute to individual initial choices. In this regard, food appearance is the first attribute appreciated by humans, followed by odor, consistency, texture and flavor. Vision allows for assessments on color, shape, brightness and a multitude of attributes, leading to final positive or negative judgments. Consumers expect certain colors, as they commonly associate color to other characteristics, such as flavor and sweetness for example, so reaching acceptable food colors is paramount . The sta3− concentrations, dietary fiber contents and overall acceptability.The acceptability index of the beetroot soups reached 70%, allowing the products to be launched on the market . All att3− and dietary fiber contents. The adherence to long-term supplementation with microencapsulated beetroot soups should, therefore, be successful following sensory valuation. Thus, the chronic consumption of microencapsulated beetroot soups may be achieved and applied to improve endothelial function with consequent blood pressure reduction in normal and hypertensive individuals, particularly those at high risk for cardiovascular diseases, also improving cerebrovascular hemodynamics.Encapsulation can improve the overall finished product, extending product stability and, consequently, shelf life, while still maintaining similar nutritional values and aromas between manufacturing and consumption times. Although encapsulation can be used as a means of masking the aroma or color of certain ingredients, which is of paramount importance in foods where flavor, aroma and visual appearance are usually key components affecting purchase decisions, the beetroot soups microencapsulated in starch or maltodextrin displayed overall acceptability, indicating a well-designed food product considering nutritional characteristics such as NO3−, betacyanins and other antioxidant compounds present at effective concentrations in a powdered food product with extended shelf life are adequate for adherence to long-term supplementation for specific health purposes. The best microparticle performance considering morphology, size distribution, physicochemical and rheological features, shelf-life stability and sensory analyses was obtained by using starch as the encapsulating agent at a 1:2 (w/w) ratio. Therefore, the beetroot soup microencapsulated in starch can be employed as an adjuvant with vascular-protective effects in healthy, physically active individuals and in individuals who exhibit at least one CVD-related risk or those with established CVD. The findings reported herein encourage future studies concerning dietary NO3− interventions with microencapsulated beetroot soup, including careful endothelial function and hemodynamic parameter evaluations in randomized controlled crossover trials.Microencapsulation in starch or maltodextrin was successfully achieved for the development of a technological, ready-to-eat and tasty beetroot soup in order to formulate a food product especially designed to fulfill therapeutic purposes. Dietary NO


The purpose of this study was to establish an estimating equation to predict the 5-level EQ-5D version (EQ-5D-5L) utility score in patients taking iron preparations for heavy menstrual bleeding (HMB) or anemia and to evaluate whether the presence of nausea or vomiting was a significant predictor of EQ-5D-5L-based quality of life.A cross-sectional survey was conducted to collect EQ-5D-5L utility scores and other patient reported outcomes from 385 patients taking iron preparations for HMB or anemia who were selected from the disease patient panel. Using the utility scores as objective variables, explanatory variable candidates were selected considering correlations, multicollinearity, and clinical validity. Predicting models were constructed using regression-based models , Tobit model). Stepwise regression method was applied for selecting statistically significant (p < 0.05) predictors. Goodness-of-fit of models were assessed by mean absolute error and mean squared error (MSE).The EQ-5D-5L utility scores (mean ± standard deviation) of 96 patients with nausea/vomiting and 289 patients without nausea/vomiting were 0.67 ± 0.16 and 0.84 ± 0.14, respectively (p < 0.001). The presence of nausea/vomiting was shown to be the most significant factor reducing the utility score in the statistical models using the explanatory variable candidates selected in the study. As the results of the goodness-of-fit test, GLM with the smallest MSE was selected to establish the estimating equation.The estimating equation to predict the EQ-5D-5L utility scores in patients taking iron preparations for HMB or anemia was established. The presence of nausea/vomiting was found to be a factor significantly reducing utility scores, with a decrement of the value estimated to be -0.117.http://www.umin.ac.jp/ctr/). Registered on October 11, 2021.UMIN000045700 (The online version contains supplementary material available at 10.1186/s12905-023-02652-1. The World Health Organization (WHO) reported that global anemia prevalence in women aged 15 to 49 years was 29.9% in 2019 and failure to reduce anemia prevalence may impair health and quality of life (QOL) of those women . HMB, irIn patients with HMB or anemia, treatment with iron preparations is performed in addition to the treatment of a primary disease for HMB and lifestyle modification. However, gastrointestinal symptoms, including nausea and vomiting, often appear as adverse events/reactions to iron preparations. It was reported that there was a significant correlation between these gastrointestinal symptoms, as adverse reactions, and a reduction in patients’ drug adherence . In a meCost-effectiveness evaluation (CEE) is applied for policies in countries around the world to prioritize various medical services for adequate allocation in a limited budget. Public organizations responsible for these assessments, including the National Institute for Health and Care Excellence (NICE) in England, exist in many countries. In Japan, a public evaluation organization, the Center for Outcomes Research and Economic Evaluation for Health (C2H), was also established, and CEE was officially institutionalized from 2019. In the analysis guideline for CEE in Japan [Therefore, to conduct a CEE in accordance with the analysis guideline for assessing the value of treatment for patients with nausea/vomiting due to taking iron preparations for HMB or anemia, it is essential to determine how much this nausea/vomiting impact on the patient’s QOL value, i.e., to generate the disutility value due to nausea/vomiting as measured by EQ-5D-5L.Several studies evaluated the relationship between IDA or nausea/vomiting and QOL. Ando et al. followed up 92 females with IDA  for 3 months after the start of oral iron preparation  administration, and evaluated the QOL using the 36-item short-form health survey (SF-36). They reported that there were significant increases in all domains but role-emotional  . These sIn this study, we evaluated the QOL using the EQ-5D-5L utility score in patients taking iron preparations for HMB or anemia, and collected information on the presence of nausea/vomiting, other patient reported outcomes (PROs) and characteristics to establish an estimating equation for predicting the EQ-5D-5L utility score based on the hypothesis that the presence of nausea/vomiting related to the administration of iron preparations may reduce the QOL. Next, we assessed whether the presence of nausea/vomiting related to the administration of iron preparations is a significant predictive factor that influences EQ-5D-5L utility scores in the patients taking iron preparations for HMB or anemia from the estimating equation.This study was a cross-sectional web-based survey questionnaires on a personal computer, a cell phone or a tablet, and the data were collected from patients taking iron preparations for HMB or anemia who were selected from the disease patient panel produced by INTAGE Healthcare Inc., . INTAGE annually investigates “current status of symptoms”, “therapeutic diseases”, and “drugs in use” with about 500,000 healthcare consumers/patients nationwide . Based oThe survey items included a questionnaire of EQ-5D items , sex, age, and the following items: primary disease , HMB, others), medication use , estrogen preparation, others), whether during menstruation period, presence of current symptoms . The timing of nausea or vomiting was the day patients answered the questionnaire, the frequency of nausea or vomiting was assessed by an open-ended question of “From how many days ago?”, the frequency of vomiting within 24 hours was assessed by an open-ended question of “How many times in a day?” and the severity of nausea was assessed by the question of “How terrible is your symptom (0 − 10)?”, respectively. These outcome measures may influence the QOL of the patients in this study from a clinical perspective and were determined after consultation with a physician specialized in obstetrics and gynecology.The primary diseases were defined based on the options and the basis of self-report that the patients responded to as “diseases currently being treated by a gynecologist.” Medication use was defined as having medication if responding that a patient had taken drugs at least within the past 3 months. If at least one of the responses of “nausea” or “vomiting” was selected as a current symptom, it was defined “with nausea/vomiting”. The patients were defined as “currently having menstrual symptoms” if one of the responses of “during menstrual period” or “currently having symptoms of PMS” was selected. If at least one of the following responses was selected as a current symptom: “lightheadedness”, “shortness of breath”, “dizziness”, “lethargy”, or “tiredness”, the patient was defined as “currently having anemia”. HMB was defined as having HMB if the primary disease was HMB or at least one of the following responses was selected as the menstrual situation: “the amount of menstrual blood is so large that a regular sanitary napkin does not last for an hour,” “there are large blood clots like liver mixed with the menstrual blood,” or “the amount of menstrual blood is so large that it interferes with daily life such as frequently soiling bedding and clothes and making work impossible.”The EQ-5D-5L is a generic preference-based health state utility scale which includes a health descriptive system based on 5 dimensions. The dimensions cover mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, and are characterized by 5 levels . The responses of the EQ-5D-5L were converted to Japanese EQ-5D-5L utility scores using the coefficient and intercept estimated by time-trade-off (TTO) data reported by Shiroiwa et al. .This study was approved by the ethics review committee, “Non-Profit Organization MINS Institutional Review Board” on September 16, 2021, and clinical trial registration was made on October 11, 2021 (UMIN000045700). Before this study was conducted, electronic informed consent was obtained from all the subjects.The following procedure was used to confirm variables overlapped or correlated with the EQ-5D-5L utility scores.EQ-5D-5L utility scores were used as objective variables, and a univariate regression analysis was performed on each of the explanatory variables to confirm the relationships between the objective variable and each explanatory variable. However, to avoid missing important variables due to confounding effects, variable selection based on the results of the univariate regression analysis was not performed, but only confirmation of the relationships was conducted.The correlation coefficient (r) and Variance Inflation Factor (VIF) between all the explanatory variables were calculated. Among variables for which r was greater than 0.7 or VIF was greater than 5 and considered to be multicollinear between variables, one explanatory variable candidate was selected based on the results of the univariate regression analysis in Step 1, its clinical importance, and versatility in the estimation of the EQ-5D-5L utility scores.The explanatory variable candidates were narrowed down in terms of the clinical validity.Predicting models were constructed using three regression-based types of statistical algorithms. The linear model is applied widely in order to estimate unknown parameters in a linear regression model by minimizing the sum of squared errors from the data. The generalized linear model (GLM) method can be applicable for the non-normal distribution of dependent variables and predict the disutility value (1-(EQ-5D-5L utility score)). The GLM estimated using a Gaussian distribution with a link function of log form was shown to be appropriate for this study. Since the dependent variable showed a ceiling effect, the Tobit model was also used in this study for addressing the censored nature of EQ-5D-5L data. For selecting the final statistically significant (p < 0.05) predictors, the stepwise regression method was applied.As no external data were available for this study, the hold-out method was used for validating the alternative models. That is, all samples were randomly divided into two groups: 70% of the data (estimation dataset) were selected to create the predicting models. The remaining 30%  were set aside to verify the goodness-of-fit of the model. The goodness-of-fit of the fitting model was tested with two commonly used indicators: mean absolute error (MAE) and mean squared error (MSE). Moreover, the Spearman rank correlation coefficient was also examined to determine the strength of correlations between the predicted values and observed values.The assessment process of the goodness-of-fit are explained briefly. (i) Data partitioning: the samples were divided into two groups at a ratio of 7:3, with each group as an estimation dataset and a validation dataset, (ii) Estimation and prediction: the parameters of the model were estimated using the estimation dataset, and the predicted values were calculated by inputting the validation dataset into the model, (iii) Calculation of indicators: the MAE and MSE were calculated to assess the goodness-of-fit of the models. The model with the smallest MSE was selected, and the equation of the EQ-5D-5L utility scores was reconstructed using the entire dataset.All statistical analyses were conducted in SAS version 9.4  or Stata version 15.0 . P-values represent the p-values resulting from the Pearson’s chi-square test for discrete variables and the t-test for continuous variables, and p-values of < 0.05 were considered significant.A total of 385 patients were enrolled in the web-based survey. Of the 385 patients, 96 were patients had nausea/vomiting, of which 94 had nausea and 27 had vomiting. All the patients were female with a mean age of 41.6 ± 7.7 years (mean ± standard deviation (SD)). Descriptive statistics for the questionnaire responses are summarized in Additional file 1.The EQ-5D-5L utility score (mean ± SD) of 385 patients was 0.79 ± 0.16. The EQ-5D-5L utility scores (Mean ± SD) of 96 patients with nausea/vomiting and 289 patients without nausea/vomiting were 0.67 ± 0.16 and 0.84 ± 0.14, respectively , “age group (40 and over)” (p = 0.001), “drug_low dose oral contraceptives” (p = 0.019), “drug_iron preparation (IV)” (p = 0.037), “drug_estrogen preparation” (p = 0.012), “during menstrual period” (p < 0.001), “symptom_PMS” (p = 0.002), “symptom_menstrual pain” (p < 0.001), “symptom_menstrual symptoms” (p < 0.001), “symptom_anemia” (p < 0.001), “symptom_nausea” (p < 0.001), “symptom_vomiting” (p < 0.001), “symptom_nausea/vomiting” (p < 0.001), “nausea_severity” (p < 0.001), and “vomiting_frequency” (p < 0.001).In the evaluation of correlation between the explanatory variables, for two variables with an absolute value of r greater than or equal to 0.7, one of them was selected from the viewpoint of clinical and versatility . The variables with VIF greater than 5 were “symptom_nausea/vomiting”, “symptom_nausea”, “primary disease_dysmenorrhea/PMS”, “primary disease_all”, and “primary disease_dysmenorrhea”. However, for the three variables other than “symptom_nausea/vomiting” and “symptom_nausea”, no new variable selection was made because it was already conducted in the variable selection by correlation coefficients considering possibility of multicollinearity. The nested questions including “symptom_nausea/vomiting” and “symptom_nausea” were excluded from the evaluation in Step 2 because r between other variables cannot be calculated. These were re-evaluated in Step 3 to determine whether they could be explanatory variable candidates.The three variables, “drug_low dose oral contraceptives”, “drug_estrogen preparation”, and “drug_others”, were excluded from the explanatory variable candidates because they were intervention factors and might be dependent on the variable related to the primary disease. “Symptom_menstrual pain” is a nested question for patients who responded that they were during the menstrual period. However, it was added to the explanatory variable candidates because menstrual pain was determined to obviously affect the QOL of the patients from a clinical perspective. For “symptom_nausea” and “symptom_nausea/vomiting,” for which multicollinearity was observed in Step 2, “symptom_nausea/vomiting” was selected as an explanatory variable candidate because 94 cases were found to overlap between patients with “symptom_nausea” (n = 94) and those with “symptom_nausea/vomiting” (n = 96).The variables that were candidates for explanatory variables as a result of evaluation in Step 1 through Step 3 are shown in Additional file 3.Table The results of the goodness-of-fit using the estimation dataset and validation dataset are summarized in Table 𝑄𝑂𝐿=exp.Estimation with the GLM model indicated that the decrement of the EQ-5D-5L utility score (disutility) related to nausea/vomiting was − 0.117 in the patients taking iron preparations for HMB or anemia Table b).In this study, we conducted a cross-sectional web-based survey involving 385 patients taking iron preparations for HMB or anemia . We established an estimating equation for predicting the EQ-5D-5L utility score by evaluating the QOL using the EQ-5D-5L questionnaire and collecting information on the presence of nausea/vomiting or other outcome measures. In addition, we assessed whether the presence of nausea/vomiting is a significant predictive factor for the EQ-5D-5L utility score in patients taking iron preparations for HMB or anemia. When establishing an estimating equation for predicting the EQ-5D-5L utility score, we examined the accuracy of the three statistical models. It was shown that estimation with GLM was the most appropriate. However, there were no marked differences in the degree of goodness-of-fit among the three statistical models. The explanatory variables selected as statistically significant variables were also almost always consistent.The EQ-5D-5L utility score (mean ± SD) of 385 participants in this study was 0.79 ± 0.16. The score was lower than the reported EQ-5D-5L utility score (mean ± SD) in the age group of 40 to 49 years Japanese women’s values of 0.945 ± 0.090 . As prevBased on the estimating equation for predicting the EQ-5D-5L utility score, significant variables for the EQ-5D-5L utility score in patients taking iron preparations for HMB or anemia included “symptom_nausea/vomiting”, “symptom_anemia”, “symptom_menstrual pain”, “symptom_PMS”, and “primary disease_PMS”. These were evaluated as variables that significantly decrease the EQ-5D-5L utility score. In particular, “symptom_nausea/vomiting” was the most important factor that reduces the EQ-5D-5L utility score (coefficient: -0.165). Estimation with the GLM model indicated that the decrement of the EQ-5D-5L utility score (disutility) related to nausea/vomiting was − 0.117 in the patients taking iron preparations for HMB or anemia. To our knowledge, this is the first report to statistically evaluate that the presence of nausea/vomiting in patients taking iron preparations for HMB or anemia significantly reduces the EQ-5D-5L utility score, that is, QOL. Fujii et al. conducted a single-center retrospective descriptive study and evaluated the EQ-5D-5L utility values for patients receiving outpatient cancer chemotherapy in Japan [The presence of menstrual pain was also shown to be an important factor that reduces the EQ-5D-5L utility score (coefficient: -0.10562). A study involving Japanese females evaluated the relationship between the EQ-5D-5L utility score and menstrual symptoms , and indWhen establishing an estimating equation for predicting the EQ-5D-5L utility score, PMS remained as a significant explanatory variable that reduces the EQ-5D-5L utility score among the primary diseases  for the explanatory variables input to the stepwise method shown in Table It was indicated that the EQ-5D-5L utility score further decreased when symptoms of PMS were present (coefficient: -0.06672). However, the influence of differences in the severity of PMS on the EQ-5D-5L utility score could not be evaluated because this study was a questionnaire survey involving patients, and no data on severity have been collected. The relationship between the severity of PMS symptoms and EQ-5D-5L utility score should be further evaluated.Several limitations in this study need to be considered. First, generalization of the patients in this study. As this was a web-based survey involving patients registered on the disease patient panel, the patient group’s representativeness may not have been sufficiently secured. However, the peak age of onset for IDA in females is 40 to 49 years ; therefoIn this study, we collected information on the presence of nausea/vomiting, other patient reported outcomes and characteristics from 385 patients taking iron preparations for HMB or anemia, and established an estimating equation for predicting the EQ-5D-5L utility score. It was shown that the presence of nausea/vomiting significantly reduced the EQ-5D-5L utility score in patients taking iron preparations for HMB or anemia. The decrement of the value was estimated to be -0.117. Reproductive-aged women worldwide are frequently suffered by HMB or anemia. Not only does this in itself affect the QOL, but nausea and vomiting caused by taking iron preparations were also found to negatively impact QOL. Our society needs to recognize and address this problem.Below is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2Supplementary Material 3


Individuals with diabetes experience a wide variety of psychosocial responses to their illness due, in part, to the nature of type 1 and type 2 diabetes. Variation in patient weight may play a central role in these differences, yet its influence on psychosocial variation is largely unknown. The current study investigates the relationship between patients’ perceived weight status and aspects of psychosocial well-being among individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D).Individuals who were diagnosed with type 1 or type 2 diabetes were assessed via an online survey from the Diabetes, Identity, Attributions, and Health Study. Participants were categorized into a lower v. higher weight status group based on their self-reported perceived weight. Analyses of covariance were conducted to assess differences in measures of disease onset blame, diabetes stigma, and identity concerns among diabetes type and perceived weight status. Covariates included in our models were gender, age, education, and time since diagnosis. Bonferroni correction was used for post-hoc tests to assess any significant interactions found in our models.Findings indicated that weight moderates multiple psychosocial outcomes pertinent to illness experience. Those with T2D and lower weight blamed themselves less for their disease onset, while those with higher weight felt blamed more for their disease onset by others, regardless of diabetes type. Individuals with T1D and higher weight were more frequently and more concerned about being mistaken for having the other disease type  compared to those with lower weight.Weight is a key influence on the psychosocial outcomes for people with diabetes, but it operates differently in type 1 versus type 2 diabetes. By further examining the unique interaction between disease type and weight status we may be able to improve psychological well-being among affected individuals of all sizes. Individuals with diabetes experience varying psychosocial responses to their illness due, in part, to the nature of type 1 diabetes (T1D) and type 2 diabetes (T2D) and due to other individual differences apart from disease type. One central factor in this regard is patient weight. Common stereotypes suggest that individuals affected by T1D are likely to be lean whereas those with T2D tend to be heavy; however, weight status is not homogeneous within either type [Although approximately 70% of adults with T1D meet criteria for overweight, , 3 reseaAs such, individuals with T2D are frequent targets of weight stigma and blame, and in turn experience feelings of depression, worry, anger, and overall distress , 9. WhilIn general, it is unknown whether differences in one’s own perceived weight influences one’s illness experience, and how this may differ by diabetes type. We focus on perceived as opposed to objective weight status  because past research has shown perceived weight to be more relevant for psychological outcomes associated with weight and weight stigma . BMI is Perceived blame refers to the extent to which individuals affected with diabetes perceive that they are judged by others for factors related to their disease; we focus here on disease onset. In T2D, perceived blame for disease onset is a salient aspect of the illness experience and is highly related to stigma and self-blame , 20. SucSelf-blame can develop from internalizing judgment from others as well as individuals’ understanding of their own disease trajectory. Individuals with T2D frequently report blaming themselves for multiple aspects of their disease, including onset and suboptimal management , 11, 20.Investigation of self-blame among individuals with T1D is sparse, but the literature does support its occurrence. A study in one young adult population with T1D found that self-blame about disease management was one of the most important predictors of psychological maladjustment . Weight Diabetes stigma is frequently cited as a root cause of a variety of negative psychological outcomes among affected individuals  . AttitudT1D-specific stigma also involves similar components of judgment and discrimination. Again, blame and judgment can arise from perceived irresponsibility in diabetes management. A salient component of T1D stigma is misplaced judgment, or “stigma by association” with T2D . Like thDiabetes mis-categorization, or being mistaken for having the incorrect diabetes type, has been recognized as a salient factor of T1D illness experience , 28. QuaThere is no literature to date on the existence or psychological impact of diabetes mis-categorization for those with T2D. Mis-categorization may be more likely if an individual with T2D does not fit into the stereotype of being “heavy.” Preferred self-categorization by affected individuals suggests that T1D is perceived as the “higher status subgroup.” . Some daThe current study investigates perceived blame and self-blame for disease onset, diabetes stigma, and negative affect in response to diabetes mis-categorization in relation to perceived weight status in a sample of adults affected by T1D or T2D  will more frequently be mis-categorized compared to those who are congruent with their stereotype.We hypothesized the following:Data came from the Diabetes, Identity, Attributions, and Health Study (DINAH), a cross-sectional study conducted in 2017 which investigates causal attributions for diabetes in relation to affected and unaffected individuals’ perceptions, management, and attitudes surrounding diabetes . EligiblParticipants reported their perceived weight status with a single item . This was measured on a 4-point scale .Participants reported on perceived blame with a single item . This was measured on a 4-point scale . This measure was created a priori as a face-valid assessment.Participants reported on self-blame with a single item . This was measured on a 4-point scale . This measure was created a priori as a face-valid assessment.Participants with T1D reported on stigma with the Diabetes Stigma Assessment Scale (DSAS-1), a 19-item scale developed to assess perceived and experienced stigma specific to adults with T1D.  This scaParticipants with T2D reported on stigma with the Diabetes Stigma Assessment Scale (DSAS-2), a 19-item scale developed to assess perceived and experienced stigma specific to adults with T2D . This scParticipants reported on diabetes mis-categorization with a single item to assess the extent to which they are mis-categorized by other people as having the incorrect diabetes type /T1D (T2D survey version)). This was measured on a 5-point scale .Participants reported on diabetes mis-categorization with a single item to assess the extent to which they would feel upset if mis-categorized as having the wrong diabetes type by another person /T1D (T2D survey version)). This was measured on a 7-point scale .Participants completed this online survey anonymously via SurveyMonkey. After consenting to the study through an online consent form, individuals responded to a variety of items including self-blame for disease onset, perceived blame for disease onset, diabetes stigma, items related to diabetes mis-categorization, demographics , and perceived weight status. Measures were administered to all participants except for the Diabetes Stigma Assessment Scales, which were specific to diabetes type.Perceived weight status was coded as a binary variable due to the categorical nature of this item and its non-normal distribution. Participants who responded “underweight” or “about right” for this item were combined into a group labeled “lower perceived weight status” (n = 114), and respondents who responded “overweight” or “very overweight” for this item were combined into a group labeled “higher perceived weight status” (n = 258). A binary categorization was chosen to ensure large enough group sizes for analysis.Analyses of covariance (ANCOVA) were conducted using a univariate general linear model to assess differences in measures by diabetes type and perceived weight status. Covariates included in our models were gender, age, education, and time since diagnosis, where there was difference between demographic groups and theoretical reason to believe a given variable may be a confounder. Bonferroni correction was applied to post-hoc tests assessing significant interactions.Sample characteristics and descriptive statistics for the sample can be found in Table p = 0.016, ηp2 = 0.04. There was no main effect for diabetes type and no significant interaction observed .See Table p < 0.001, ηp2 = 0.14. There was also a main effect of perceived weight status, such that there were significantly higher levels of self-blame among those with a higher weight status compared to those with a lower weight status, F = 57.73, p = 0.015, ηp2 = 0.02. Main effects were qualified by a significant interaction between diabetes type and perceived weight status, F = 4.67, p = 0.031, ηp2 = 0.01  = 57.73, 65 = 57.7p = 0.035, ηp2 = 0.03  = 4.50, p2 = 0.00, 0.02, and 0.01, respectively)  = 38.99, p < 0.001, ηp2 = 0.09  = 12.07, p = 0.001, ηp2 = 0.03. Specifically, among those with T1D, those with a higher weight status reported diabetes mis-categorization more frequently than those with a lower weight status. Among those with T2D, this relationship was in the opposite direction, such that those with a lower weight status reported diabetes mis-categorization more frequently than those with a higher weight status.There was a main effect of diabetes type, such that there were significantly higher levels of diabetes mis-categorization among those with T1D compared to those with T2D, see Fig. . A signiF = 34.48, p < 0.001, ηp2 = 0.09  = 8.86, p = 0.003, ηp2 = 0.02. Specifically, among those with T1D, participants with a lower weight status reported significantly lower levels of feeling upset over diabetes mis-categorization than those with a higher weight status. Among those with T2D, this pattern trends in the opposite direction, although the relationship did not reach statistical significance  . Among oIn accordance with our hypotheses, individuals who were weight-incongruent with their illness stereotype  perceived that they were more frequently mis-categorized as the other diabetes type compared to those who were weight-congruent. Additionally, individuals with T1D were more upset about being mis-categorized than were individuals with T2D, particularly when those with T1D had higher weight. This is consistent with studies indicating that diabetes mis-categorization is a common concern among those with T1D , 28. Howwho is doing the miscategorizing. For example, healthcare professionals who do not fully understand the difference between T1D and T2D or incorrectly assume a patient’s diabetes type can impede the development of a proper care plan or place strain on the patient-provider relationship.Negative affect about mis-categorization likely stems from similar mechanisms seen in the blame-related constructs. Individuals with T1D who have higher weight may experience blame and stigma typically reserved for individuals with T2D, in that it is associated with perceptions of causal responsibility. In turn, these individuals may feel that negative perceptions and treatment are unfair or unwarranted. Individuals with T2D were less upset about mis-categorization and this was unrelated to perceived weight. Indeed, individuals with T2D perceive those with T1D as being judged less harshly for their condition, , 20, 29 and T1D illness experiences and to directly compare the two. Overall, weight status was found to be linked to experiences of self-blame, perceived blame, and responses to diabetes mis-categorization, while stigma as measured by the Diabetes Stigma Assessment Scales seems to function independently of weight status. Results suggest that, among those with T2D, lower weight acts as a protective factor against several negative psychosocial outcomes. Additionally, results for those with T1D suggest that public perceptions related to T2D and weight may have consequences for the psychosocial well-being of this community. These effects may be particularly prevalent given high rates of overweight and obesity among Americans with T1D.This report is the first to directly examine weight as a moderator of T2D Research on weight-related blame and stigma has been typically confined to understanding the experiences of those with T2D; however, the present study highlights the importance of investigating weight in the context of T1D as well. This report also sheds light on an important yet under-researched problem among the diabetes community: negative perceptions of the other diabetes type may fuel feelings of blame and concern over diabetes mis-categorization. The current results indicate that public misconceptions about weight and its relation to diabetes type can lead to a variety of psychosocial consequences that impact both the T1D and T2D communities.Limitations include but are not restricted to the following. Recruitment via an online research registry and diabetes support groups likely biased the sample towards individuals who perceive diabetes as more central to their identity and may not be representative across individuals with diabetes. Participants were majority white and women, and we were unable to examine the impact of race and ethnicity in this analysis. Given racial health disparities in diabetes and that diabetes and weight-related perceptions and outcomes vary by race and ethnicity, –33 futurThese psychosocial themes of blame, stigma, and identity concern are known to influence diabetes self-management and risks of illness complications , 25. The


Recent studies proved that academic procrastination is a very common pervasive problem that has a negative impact on general well-being, causing distress, anxiety, remorse and unhappiness. It could also result in poor academic performance and negatively affect students’ satisfaction with themselves and their academic life.The aim of this study was to explore the influence of self-esteem and self-efficacy on academic procrastination among Tunisian medical students.We conducted a cross-sectional, descriptive and analytical study among medical students from Tunisia. Data were collected through an anonymous online questionnaire, exploring sociodemographic characteristics, the “Tuckman Procrastination Scale” (TPS), the “Rosenberg’s self-esteem scale” (RSES) and the “General Self-Efficacy Short Scale” (GSESS).A total of 133 participants completed the questionnaire. Their mean age was 26 ± 3,8 years, with a sex-ratio (F/M) of 4,5. Among them 87.2% were engaged in academic procrastination, 57,1% showed low self-esteem and 55,6% perceived themselves as non-effective.GSESS score were higher among males (p=0.019)TPS score was negatively correlated with RSES score . RSES score was positively correlated with GSESS score .No relationship was proved between TPS and GSESS.Even though procrastination is most of the time considered as a maladaptive and detrimental behavior with a psychological cost, some authors consider it acting in a beneficial way, as it reflects self-reliance, autonomy and self-confidence knowing that they are able to finish their task in time. As a result, procrastination is linked to feelings of superiority and it should be recoined as “purposeful delay”.None Declared


Bangladesh has made substantial progress in improving socioeconomic and health indicators over the past 50 years, but data on national disease burden are scarce. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to estimate the burden of diseases and risk factors in Bangladesh from 1990 to 2019.For this systematic analysis, we analysed data from vital registration systems, surveys, and censuses using multistage modelling processes to estimate life expectancy at birth, mortality rate, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs). Additionally, we compared the health status of Bangladesh with that of the other countries in the GBD south Asia region—Bhutan, India, Nepal, and Pakistan.Life expectancy at birth in Bangladesh increased from 58·2 years  in 1990 to 74·6 years (72·4–76·7) in 2019. Between 1990 and 2019, the age-standardised mortality rate decreased from 1509·3 (1428·6–1592·1) to 714·4 (604·9–838·2) deaths per 100 000 population. In 2019, non-communicable diseases represented 14 of the top 20 causes of death; the leading three causes were stroke, ischaemic heart disease, and chronic obstructive pulmonary disease. High blood pressure, high fasting plasma glucose, and smoking were the top three risk factors. From 1990 to 2019, the rate of all-cause DALYs decreased by 54·9% (48·8–60·4). In 2019, the leading causes of DALYs and YLLs were neonatal disorders, stroke, and ischaemic heart disease, whereas musculoskeletal disorders, depressive disorders, and low back pain were the leading causes of YLDs. Bangladesh has the lowest age-standardised rates of mortality, YLDs, and YLLs and the highest life expectancy at birth in south Asia.Over the past 30 years, mortality rates have reduced by more than half in Bangladesh. Bangladesh must now address the double burden of communicable and non-communicable diseases. Cost-effective, multisectoral efforts are needed to prevent and control non-communicable diseases, promote healthy lifestyles, and prevent premature mortality and disabilities.Bill & Melinda Gates Foundation.For the Bangla translation of the abstract see Supplementary Materials section. This six-part Series presented case studies on Bangladesh's exceptional health advances at low cost. Additionally, several national and subnational studies have reported the burden of different diseases and risk factors in Bangladesh at different points during the past three decades. However, to our knowledge, there are no studies on the burden and trends of diseases in Bangladesh that enable global comparisons. Bangladesh has experienced demographic and epidemiological transitions over the past three decades. Although the country already has a high prevalence of communicable diseases, the increasing pattern of sedentary lifestyles and energy-dense but poorly nutritious diets among the young and middle-aged population of Bangladesh is contributing to the pervasive burden of non-communicable diseases. Such epidemiological transformations might further weaken the already fragile health service delivery system. To prepare the health system, understanding the prevalence and trends of the burden of diseases and their risk factors is necessary.We searched PubMed, Google Scholar, and governmental websites for estimates of the burden of diseases in Bangladesh using the search terms “burden”, “cause of death”, “death”, “prevalence”, “epidemiology”, “morbidity”, “mortality”, “trends”, “disability”, “DALY”, “Bangladesh”, “chronic diseases”, “NCD”, “noncommunicable diseases”, “communicable diseases”, “cardiovascular diseases”, “chronic obstructive pulmonary disease”, and “cancer”, from database inception to July 4, 2023 and without language or other publication restrictions. The 2013 Series Added value of this studyTo our knowledge, this study is the first to systematically analyse the trends in the burden of diseases and risk factors from 1990 to 2019 in Bangladesh. We used standardised and globally comparable metrics, adjusting for variability in data sources and removing potential biases, to generate results comparable with those of other countries. We analysed 286 causes of death, 369 diseases and injuries, and 87 behavioural, metabolic, and environmental and occupational risks among the Bangladeshi population with a comprehensive analysis of changes in population health from 1990 to 2000, 2000 to 2010, and 2010 to 2019. Our results provide important information for assessing health progress and for attaining the goals and targets set by the Health, Population, and Nutrition Sector Development Program of the Bangladesh Government and the UN's Sustainable Development Goals. Additionally, we compared the performance of Bangladesh's health system with that of health systems in other countries of the Global Burden of Diseases, Injuries, and Risk Factors Study south Asia region to identify crucial areas of improvement and challenges faced by Bangladesh's health sector.Implications of all the available evidenceAlthough the all-cause mortality rate has reduced over the past three decades in Bangladesh, the top-ranked causes of death now include stroke, ischaemic heart disease, cancer, and diabetes. Road-traffic injuries, musculoskeletal disorders, depressive disorders, low back pain, headache disorders, age-related hearing loss, dietary iron deficiency, blindness and vision loss, and gynaecological disorders are emerging issues on which public health interventions, policies, and programmes should have a strong focus. Both communicable and non-communicable disease risk factors contribute to mortality and morbidity in the Bangladeshi population. Therefore, a multisectoral, coordinated approach targeting prevention, care, and rehabilitation is needed to ensure the sustainability of the country's health-care system.Bangladesh has made substantial health advances over the past 30 years despite spending less on health care than other countries in south Asia.We accessed country-specific burden of disease estimates for Bangladesh from GBD 2019 using the Global Health Data Exchange, the GBD Results tool, and the GBD Compare tool. In this study, data were obtained from a total of 688 data sources: scientific literature (n=380), survey data (n=132), epidemiological surveillance data (n=45), reports (n=42), administrative data (n=33), estimate data (n=14), vital registration systems (n=10), environmental monitoring data (n=10), event data (n=7), census data (n=6), demographic surveillance data (n=5), registries (n=3), and intervention studies (n=1). All data sources are described in The data sources listed in the previous subsection were used to examine total fertility rate, age-standardised and all-cause mortality, and cause-specific mortality using GBD methods described previously.The Cause of Death Ensemble model (CODEm) was used to estimate cause-specific mortality for each combination of sex, age, location, and year. We used a Bayesian meta-regression method We compared estimates for Bangladesh with estimates for the four other countries in the GBD south Asia region , which have similar socioeconomic profiles to that of Bangladesh. We compared age-standardised rates of all-cause mortality, YLLs, and YLDs, as well as life expectancy at birth and HALE, and ranked the five countries on the basis of these metrics between 1990 and 2019. Unless otherwise specified, we report age-standardised rates per 100 000 population, with each point estimate presented with 95% UIs generated using a Monte Carlo approach.The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.The total fertility rate among women of reproductive age in Bangladesh was 4·4 (95% UI 4·3–4·5) in 1990 and decreased consistently over the subsequent years to 1·8 (1·6–2·0) in 2019. In 1990, the life expectancy at birth was 58·2 years (57·1–59·2), which by 2019 had increased to 74·6 years (72·4–76·7). Bangladesh also achieved a substantial improvement in HALE between 1990 (50·7 years [48·3–52·8]) and 2019  per 100 000 population in 2019—a 52·7% (44·2–60·4) reduction in mortality rate relative to 1990  in Bangladesh was 132·9 deaths (95% UI 124·8–142·0) per 1000 livebirths. This rate decreased over subsequent years to 29·1 deaths (24·9–34·2) per 1000 livebirths in 2019 . NeonataAge-standardised DALYs  in Bangladesh decreased by 54·9% (48·8–60·4) from 67 634·8 DALYs per 100 000 population (95% UI 63 291·5–72 763·3) in 1990 to 30 475·3 DALYs per 100 000 population (26 366·7–35 154·8) in 2019 . CMNN diThe rate of age-standardised YLDs per 100 000 population  was 11 667·2 (95% UI 8684·2–15 122·6) in 1990 and 10 865·3 (8169·9–14 008·8) in 2019—a decrease of 6·9% (4·5–9·1) between these years , table 3The rate of age-standardised YLLs per 100 000 population  decreased by 65·0% (95% UI 58·2–70·9) between 1990 and 2019. Age-standardised YLLs for all causes were 55 967·6 (52 916·4–59 448·6) in 1990 and 19 610·0 (16 543·8–23 230·0) in 2019 , table 3In 2019, of the top ten risk factors for all-cause mortality, five were metabolic, three were behavioural, and two were environmental and occupational . High syEstimates for Bangladesh were compared with those for the other countries within the GBD south Asia region—Bhutan, India, Nepal, and Pakistan. Of these countries, Bangladesh had the lowest rate of age-standardised mortality, YLLs, and YLDs in 2019  within the compared countries in terms of life expectancy at birth; however, in 2019, Bangladesh had the highest life expectancy at birth and ranked first for HALE in south Asia .In 1990, Bangladesh had the second-highest under-5 mortality rate of the compared countries in south Asia, with Nepal ranking first. However, over the years, this rate has decreased substantially in both countries. In 2019, Bangladesh had the second-lowest under-5 mortality rate  in the region . In 2019This study is the first, to our knowledge, to provide a comprehensive and systematic analysis of disease burden and trends in Bangladesh. Our analysis shows that Bangladesh has made remarkable achievements in reducing mortality rates and health loss by more than half from 1990 to 2019. However, the prevalence of non-communicable diseases—including stroke, ischaemic heart disease, COPD, diabetes, and chronic kidney disease—has increased steadily since 1990. Although downward trends were observed in deaths due to CMNN diseases, including malaria and measles, four infectious diseases remained in the top ten causes of mortality in 2019. Musculoskeletal disorders, low back pain, diabetes, and neonatal disorders were the leading causes of non-fatal burden from 1990 to 2019. Our results highlight an increase in premature mortality from Alzheimer's disease between 1990 and 2019, whereas premature mortality due to stroke, ischaemic heart disease, COPD, and diabetes declined during this time period. Substantial downward trends in premature mortality were observed for diarrhoeal diseases, tetanus, measles, and malaria, demonstrating success in Bangladesh's communicable diseases programmes. Additionally, life expectancy at birth and HALE increased in Bangladesh from 1990 to 2019. These findings reflect improved health-promotion activities and the increase in health-care service provision nationwide. However, Bangladesh still faces a double burden of communicable and non-communicable diseases. If the current trend continues, management of the increased burden of non-communicable diseases will be a considerable challenge for the country's health system.·4% had diabetes.Over the past three decades, the total number of deaths due to non-communicable diseases in Bangladesh has decreased, which is consistent with previous reports.Health loss attributed to the leading causes, as measured by DALYs, decreased between 1990 and 2019, with steep declines for protein-energy malnutrition, tetanus, measles, malaria, diarrhoeal diseases, and drowning. This achievement might reflect successful public health policies and practices focused in those areas . Although drowning rates have decreased since 1990, Bangladesh still has the highest rate of child drowning in south Asia, with nearly 46 children aged 0–17 years drowning each day in 2016.During the past three decades, the Government of Bangladesh has worked to improve sanitation; provide safe drinking water, oral rehydration solution, and healthy diets and nutrients for children; promote high coverage of vaccines and use of insecticide-treated bednets; and improve maternal health services and pregnancy care. This success can be attributed to Bangladesh's pluralistic health-care system, involving participation from numerous national and international non-governmental organisations.Compared with the other countries in the south Asia region, Bangladesh had the highest life expectancy at birth, highest HALE, lowest mortality rate, lowest rates of premature mortality, and lowest non-fatal burden in 2019. Maternal health remains a considerable public health issue in Bangladesh and other south Asian countries: almost half of all maternal deaths worldwide occur in these countries.Our study is subject to the limitations of the GBD methodology, which have been described previously.In Bangladesh, life expectancy at birth has increased by more than 16 years since 1990, therefore increasing the ageing population. Bangladesh is now experiencing an epidemiological transition from CMNN diseases towards non-communicable diseases and disabilities. Multisectoral policies and practices prioritising the prevention and management of and rehabilitation from non-communicable diseases are mandatory to control the increase in mortality and morbidity. A focus on cardiovascular health, maternal health, musculoskeletal disorders, neurological diseases, and cancer care is necessary. Our findings can be used to prioritise health-care needs, identify gaps in health-care systems, and guide future research and investments to improve health outcomes in Bangladesh.http://ghdx.healthdata.org/gbd-2019.To download the data used in these analyses, please visit the Global Health Data Exchange at S M S Islam reports support for this manuscript from an Emerging Leadership Fellowship from the National Health and Medical Research Council of Australia (APP1195406) and Vanguard grants from the National Heart Foundation of Australia. S M S Islam has unpaid roles, outside the submitted work, with the IT Committee of the Cardiac Society of Australia and New Zealand, as a volunteer on the Cardiac Devices Committee of the ESC Heart Failure Association, and as a volunteer topic group leader for the WHO-ITU Global Initiative on AI for Health. K M Livingstone reports support for this manuscript from a National Health and Medical Research Council of Australia grant (APP1173803).