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Consent for publication
Not applicable.
PMC10712103
Competing interests
The authors declare no competing interests.
PMC10712103
References
PMC10712103
1. Introduction
obesity, postprandial blood glucose, macrovascular complications, blood glucose excursions, weight gain, T2DM, Postprandial blood glucose, diabetes
OBESITY, TYPE 2 DIABETES, PATHOGENESIS, DIABETES
People with fast eating habits have been reported to have an increased risk of diabetes and obesity. To explore whether the speed of eating a test meal (tomato, broccoli, fried fish, and boiled white rice) influences postprandial blood glucose, insulin, triglyceride, and free fatty acid levels, 18 young, healthy women consumed a 671 kcal breakfast at fast speed (10 min) and slow speed (20 min) with vegetables first and slow speed (20 min) with carbohydrate first on three separate days. This study was conducted using a within-participants cross-over design in which all participants consumed identical meals of three different eating speeds and food orders. Significant ameliorations of both fast and slow eating with vegetables first regimen on postprandial blood glucose and insulin levels at 30 and 60 min were observed compared with those of slow eating with carbohydrates first. In addition, the standard deviation, large amplitude of excursion, and incremental area under the curve for blood glucose and insulin in both fast and slow eating with vegetables first were all significantly lower than those of slow eating with carbohydrate first. Interestingly, there was no significant difference between fast and slow eating on postprandial blood glucose and insulin levels as long as vegetables were consumed first, although postprandial blood glucose at 30 min was significantly lower in slow eating with vegetables first than that of fast eating with the same food order. These results suggest that food order with vegetables first and carbohydrate last ameliorates postprandial blood glucose and insulin concentrations even if the meal was consumed at fast speed.The number of people with diabetes is currently estimated to be as many as 537 million, and it is predicted to increase up to 783 million by 2045, with more than 90% of them estimated to be type 2 diabetes (T2DM) [Postprandial blood glucose elevation and mean amplitude of glycemic excursions (MAGE) are associated with the pathogenesis of micro- and macrovascular complications in individuals with diabetes and the incidence of T2DM [Recent studies including our research indicate that the food order of preloading vegetables, protein, or fat with slow eating can ameliorate postprandial blood glucose excursions and decrease insulin secretion in both individuals with and without T2DM [On the other hand, epidemiological and cohort studies demonstrated that fast eating speed resulted in weight gain [We previously reported that eating fast (10 min) with a mixed eating of vegetables, protein, and carbohydrate demonstrated significant higher glycemic excursions compared with eating slow (20 min) with vegetables first in young healthy women [
PMC10005673
2. Methods
PMC10005673
2.1. Study Design
eating disorders
METABOLIC DISEASES
Participants were enrolled from volunteers from the Kyoto Women’s University, Kyoto, Japan. All volunteers were informed of the purpose, protocol, and risks of the research before the study began. Twenty-one participants were registered in the study. Written informed consents were obtained from all participants. The study was conducted between April 2022 and July 2022. None of the participants were pregnant or smokers. The participants were also free from eating disorders, metabolic diseases, other diets, and any medications and supplements identified to affect their blood glucose, insulin, and lipid levels.This study was conducted using an unblind randomized within-participants cross-over design in which all participants consumed identical meals on three separate days. The study protocol relating to human subjects was approved by the Ethics Committee of Kyoto Women’s University (2021-21) according to the guidelines of the Declaration of Helsinki. The study protocol was registered in the UMIN Clinical Trials Registry (UMIN000050266). Each participant consumed identical test meals on three separate days, and each study day was 1 week apart with three different eating patterns of fast speed and slow speed with vegetables first and slow speed with carbohydrate first, as shown in Carbohydrate first with slow eating speed: carbohydrate (boiled white rice) first for 6 min, and then protein (fried fish) for 7 min, and then vegetables (tomato and broccoli with sesame oil) for 7 min, for a total eating time of 20 min.Vegetables first with slow eating speed: vegetables (tomato and broccoli with sesame oil) first for 7 min, and then protein (fried fish) for 7 min, and then carbohydrate (boiled white rice) for 6 min, for a total eating time of 20 min.Vegetables first with fast eating speed: vegetables (tomato and broccoli with sesame oil) first for 4 min, and then protein (fried fish) for 3 min, and then carbohydrate (boiled white rice) for 3 min, for a total eating time of 10 min.The study flow is shown in On the study day, the participants arrived at 8:30 at the Kyoto Women’s University after a 12 h overnight fast, and each meal was consumed at 9:00 under the experimental conditions that were randomly assigned to the participants (
PMC10005673
2.2. Meals for the Study
The macronutrient amounts of the test meal (63% from carbohydrate, 15% from protein, 22% from fat) are shown in
PMC10005673
2.3. Primary and Secondary Measurements and Statistical Analysis
TG
On the first day of the study, anthropometric measurements of height and body weight, and the hemoglobin A1c (HbA1c) of the participants were measured at Kyoto Women’s University in the morning after an overnight fast. All blood samples were examined by Nihon Rinsho, Inc, Kyoto, Japan. Plasma glucose concentration was measured by HK-G6PDH methods (KANTO CHEMICAL CO., INC. Tokyo, Japan). HbA1c levels were determined by NGSP method (Kyowa Medix CO., INC, Tokyo, Japan). Serum insulin levels were determined by CLEIA method (FUJIREBIO. CO., INC. Tokyo, Japan). Serum TG concentrations were determined by GK-GPO method (SEKISUI MEDICAL CO., LTD. Tokyo, Japan). Serum FFA concentrations were determined by ACS-ACOD method (FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan).In the present study, a total of fourteen participants was calculated as the sample size to provide 95% power to detect 5% difference in postprandial blood glucose levels (G*Power 3.1, Heinrich-Heine-Universität Düsseldorf, Germany), matched to our study of consuming test meals of different food order in young, healthy women [
PMC10005673
3. Results
Among the 21 participants, 3 participants could not complete the study defined by the study protocol, so the results were analyzed based on 18 young, healthy women [age 21.3 ± 0.4 years, BMI 19.6 ± 1.6 kg/mBlood glucose and insulin parameters of different speeds with different food orders were shown in
PMC10005673
4. Discussion
obesity, diabetic complications, metabolic syndrome, T2DM, diabetes
OBESITY, CARDIOVASCULAR DISEASES, DIABETES, INSULIN RESISTANCE, DIABETIC COMPLICATIONS, METABOLIC SYNDROME, DYSLIPIDEMIA
This is the first interventional study to demonstrate that fast eating with vegetables first ameliorates postprandial blood glucose elevation and insulin secretion in young, healthy women. Our present study indicates that as long as vegetables are consumed first, eating speed, whether slow (20 min) or fast (10 min), does not affect postprandial blood glucose and insulin levels, except slow eating with vegetables first showed lower postprandial blood glucose concentration at 30 min than that of fast eating with the same food order. It is important to “eat vegetables first and carbohydrate last” to ameliorate postprandial blood glucose and insulin even in fast eating, as supported by our previous study showing that eating fast with a mixed eating with vegetable, protein, and carbohydrate elevated postprandial blood glucose compared with slow eating with vegetables first [As the test meals were provided in the morning after 12 h fasting, postprandial blood FFA concentrations decreased after consumption of the meal in all three days, while postprandial blood glucose and insulin secretion increased after consuming the meal. This seems reasonable because the postprandial blood FFA concentrations were inversely correlated to the blood glucose concentration. Thus, the postprandial blood FFA concentrations in slow eating with carbohydrate first were lower than those of slow and fast eating with vegetables first. The reason of higher postprandial blood TG concentrations shown in slow and fast eating with vegetables first compared with those in slow eating with carbohydrate first might be explained by the sesame oil consumed first with vegetables. Although postprandial parameters of blood TG and FFA in fast and slow eating with vegetables first showed statistically higher than the values in slow eating with carbohydrate first, all of the values were within the normal range of a healthy population without dyslipidemia, suggesting these variations were normal, rather than any pathological phenomena.Shukla et al. reported that a food order with vegetables for 10 min, followed by a 10 min interval, and then eating protein and carbohydrate for 10 min was effective to suppress postprandial blood glucose elevation and insulin secretion [The food order and eating speed in the present study, i.e., “eating vegetables first, then the main dish (protein), and then carbohydrate last for 10 min”, is easier to maintain in real life than other methods of medical nutrition therapy for T2DM. For instance, we have reported previously that the dietitian-led medical nutrition therapy of food order with vegetables first has been reported to be effective in the long term, up to 5 years, on glycemic control and the prevention of diabetic complications in individuals with T2DM [One of the possible reasons for the amelioration of postprandial blood glucose and insulin concentration observed in fast eating with vegetables first may be explained by the preloading of dietary fiber contained in vegetables (7.1 g of dietary fiber in the test meal). The dietary fiber in the test meal was digested slowly to ameliorate postprandial blood glucose elevation and reduce insulin secretion [Various cohort and epidemiological studies revealed that a faster eating speed showed a positive correlation with body weight, blood glucose concentration, insulin resistance, and the risk of metabolic syndrome and T2DM [On the other hand, some research has reported that eating speed does not affect postprandial blood glucose, insulin, and incretin hormone levels in individuals with and without T2DM [Various evidence-based studies suggest that a diet rich in vegetables and low GI grains is the substantial dietary pattern predicting low risk in T2DM, obesity, and cardiovascular diseases [Furthermore, cost–benefit analysis suggests that dietary education would produce a significant potential cost-saving effect in national healthcare budgets [Our results indicate that in addition to the amount of energy, carbohydrate, fat, protein, dietary fiber, and other nutrient contents, food order, rather than eating speed, is the most important factor for postprandial blood glucose and insulin responses. It is essential to avoid only eating carbohydrates, such as boiled rice, noodles, and bread, for preventing postprandial blood glucose elevation. Obviously, medical nutrition therapy with food order should require counselling patients to support the individual’s dietary habit, socio-economic situation, and lifestyle, as well as their medical condition.The current study has limitations to be mentioned. First, the present experiment was designed to examine the acute effects of eating speed with different food order in a single meal, requiring additional investigations to clarify the long-term effect on glycemic control and the improvement of diabetic complications in T2DM management, and the chronic effect of diabetes prevention in individuals without T2DM. Second, the study participants were Japanese young women without T2DM and dyslipidemia; therefore, it is uncertain whether the present results could be applied to individuals with T2DM and dyslipidemia, and of other gender, age groups, or racial groups. Third, incretin hormones may be involved in the mechanisms for amelioration of blood glucose, insulin, and the gastric emptying rate, because enhanced GLP-1 secretion is reported to delay gastric emptying in both individuals with and without T2DM [
PMC10005673
Author Contributions
T.M.
Conceptualization, S.I. and S.K. (Shizuo Kajiyama); methodology, S.I., S.K. (Shizuo Kajiyama), and K.K.; data collection and formal analysis, S.I. and K.K.; original draft preparation, S.I. and K.K.; review and editing, S.I., S.K. (Shizuo Kajiyama), K.K., T.M., S.M., N.O., S.K. (Shintaro Kajiyama), Y.H. and M.F. All authors have read and agreed to the published version of the manuscript.
PMC10005673
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of Kyoto Women’s University (2021-21) and the study protocol was registered in the UMIN Clinical Trials Registry (UMIN000050266).
PMC10005673
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the subjects to publish this paper.
PMC10005673
Data Availability Statement
The data are not publicly available due to privacy reasons. Data supporting the reported results are available upon reasonable request and in accordance with the ethical principles.
PMC10005673
Conflicts of Interest
Johnson & Johnson k.k
Potential conflicts of interest were follows: Y.H. reports grants from Asahi Kasei Pharma and personal fees from Mitsubishi Tanabe Pharma Corp., Novo Nordisk Pharma Ltd., Sanofi K.K., and Daiichi Sankyo Co. Ltd. outside the submitted work. M.F. received grants from Takeda Pharma Co. Ltd., Sanofi K.K., Kissei Phama Co. Ltd., Mitsubishi Tanabe Pharma Corp, Astellas Pharma Inc., Nippon Boehringer Ingelheim Co. Ltd., Daiichi Sankyo Co. Ltd., MSD K.K., Sanwa Kagagu Kenkyusho CO., LtD., Kowa Pharma Co. Ltd., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharma Co. Ltd., Eli Lilly Japan K.K., Taisho Pharma Co., Ltd., Tejin Pharma LtD., Nippon Chemiphar Co., Ltd., Johnson & Johnson k.k. Medical Co., Abbott japan Co. Ltd., and Terumo Corp., and personal fees from Teijin Pharma Ltd., Arkray Inc., Kissei Pharma Co., Ltd., Novo Nordisk Pharma Ltd., Mitsubishi Tanabe Pharma Corp., Sanofi K.K., Takeda Pharma Co. Ltd., Astellas Pharma Inc., MSD K.K., Kyowa Kirin Co. Ltd., Sumitomo Dainippon Pharma Co. Ltd., Daiichi Sankyo Co. Ltd., Kowa Pharma Co. Ltd., Ono Pharma Co. Ltd., Sanwa Kagaku Kenkyusho Co. Ltd., Nippon Boehringer Ingelheim Co., Ltd., Taisho Pharma Co., Ltd., Bayer Yakuhin, Ltd., AstraZeneca K.K., Mochida Pharma Co. Ltd., Abbott japan Co. Ltd., Eli Lilly Japan K.K., Medtronic Japan Co. Ltd., and Nipro Corp. outside the submitted work. The sponsors were not involved in the study design; in the collection, analysis, interpretation of data; in the writing of this manuscript; or in the decision to submit the article for publication. The authors, their immediate families, and any research foundations with which they are affiliated have not received any financial payments or other benefits from any commercial entity related to the subject of this article. The authors declare that although they are affiliated with a department that is supported financially by a pharmaceutical company, the authors received no current funding for this study and this does not alter their adherence to all the journal policies on sharing data and materials. The other authors have nothing to disclose.
PMC10005673
References
TG, Postprandial blood glucose
BLOOD
Study protocol. All participants consumed identical test meals in 3 different eating patterns: eating slow (20 min) with carbohydrate first, eating slow (20 min) with vegetables first, and eating fast (10 min) with vegetables first. Each meal was consumed at 9:00 under the following experimental conditions that were assigned in the unblind randomized cross-over trial: 1. Carbohydrate first with slow eating speed: carbohydrate (boiled white rice) first for 6 min, and then protein (fried fish) for 7 min, and then vegetables (tomato and broccoli with sesame oil) for 7 min, for a total eating time of 20 min. 2. Vegetables first with slow eating speed: vegetables (tomato and broccoli with sesame oil) first for 7 min, and then protein (fried fish) for 7 min, and then carbohydrate (boiled white rice) for 6 min, for a total eating time of 20 min. 3. Vegetables first with fast eating speed: vegetable (tomato and broccoli with sesame oil) first for 4 min, and then protein (fried fish) for 3 min, and then carbohydrate (boiled white rice) for 3 min, for a total eating time of 10 min. Blood samples were collected at 0, 30, 60, and 120 min after consuming the test meals. Postprandial blood glucose, insulin, triglyceride (TG) and free fatty acid (FFA) concentrations were examined. Veg.; vegetables, Carb.; carbohydrate.Study flow. Registered participants were divided into 3 groups with 7 participants each. All participants consumed the identical test meals for three days according to the study protocol shown in The postprandial blood glucose (Macronutrient contents of the test meal.Blood glucose and insulin parameters of different speeds with different food orders in young, healthy women.Data are mean ± SEM. MBG; mean blood glucose, BG; blood glucose, SD; standard deviation, LAGE; large amplitude of glucose excursion, IAUC; incremental area under the curve. Slow eating with carb. first vs. Fast eating with veg. first;
PMC10005673
Background
peripheral arterial disease
PERIPHERAL ARTERIAL DISEASE
Communicated by Massimo Pagani.Walking is the preferred therapy for peripheral arterial disease in early stage. An effect of walking exercise is the increase of blood flow and fluid shear stress, leading, triggered by arteriogenesis, to the formation of collateral blood vessels. Circulating micro-RNA may act as an important information transmitter in this process. We investigated the acute effects of a single bout of 1) aerobic walking with moderate intensity; and 2) anaerobic walking with vigorous intensity on miRNA parameters related to vascular collateral formation.
PMC9684818
Methods
peripheral arterial disease, claudication
PERIPHERAL ARTERIAL DISEASE
Ten (10) patients with peripheral arterial disease with claudication (age 72 ± 7 years) participated in this two-armed, randomized-balanced cross-over study. The intervention arms were single bouts of supervised walking training at (1) vigorous intensity on a treadmill up to volitional exhaustion and (2) moderate intensity with individual selected speed for a duration of 20 min. One week of washout was maintained between the arms. During each intervention, heart rate was continuously monitored. Acute effects on circulating miRNAs and lactate concentration were determined using pre- and post-intervention measurement comparisons.
PMC9684818
Results
Vigorous-intensity walking resulted in a higher heart rate (125 ± 21 bpm) than the moderate-intensity intervention (88 ± 9 bpm) (
PMC9684818
Conclusion
PERIPHERAL ARTERIAL DISEASE
Moderate-intensity walking seems to be more feasible than vigorous exercises to induce changes of blood flow and endurance training-related miRNAs in patients with peripheral arterial disease. Our data thus indicates that effect mechanisms might follow an optimal rather than a maximal dose response relation. Steady state walking without the necessity to reach exhaustion seems to be better suited as stimulus.
PMC9684818
Supplementary Information
The online version contains supplementary material available at 10.1007/s00421-022-05091-2.
PMC9684818
Keywords
Open Access funding enabled and organized by Projekt DEAL.
PMC9684818
Introduction
death, Tan, stenosis, PAD
PERIPHERAL ARTERIAL DISEASE, CARDIOVASCULAR DISEASE, PAD, PERIPHERAL ARTERIAL DISEASE, STENOSIS
Cardiovascular diseases are some the most common causes of death (Heil et al. Peripheral arterial disease, inter alia, impairs lower limb performance (Dopheide et al. Supervised exercise therapies aim to improve quality of life as well as lower limb symptoms and performance. Therapy options in non-clinical settings include home-based walking and resistance exercises (Guidon and McGee The exact cellular and molecular mechanisms leading to these performance improvements have not yet been unravelled (Düppers et al. Long-term effects on increased blood flow may be mostly attributed to arteriogenesis, in particular the formation of collateral blood vessels to bypass a stenosis or occlusion (Tan et al. The sketched mechanistic is mainly seen in healthy people. In these individuals’, cardiovascular adaptions improve with higher exercise intensity. However, it is currently unclear whether these adaptions occur in patients with PAD. Although initially seen as by-product of anaerobic metabolism or fuel for specific muscle cells, lactate is currently discussed as transmitter or signaling molecule for processes including angiogenesis (Porporato et al. The background of, inter alia, the relevance of investigating is the role of miRNA in the therapy of peripheral arterial disease. Based on recent evidence, miRNAs could be developed as potential circulating biomarkers for the diagnosis and prognosis of PAD (Bresler et al. The aim of the present study was to investigate the influence of walking exercise itself and different exercise intensities on cardiometabolic outcomes and the expression of miRNAs which are related to short term vascular response and arteriogenesis in patients with peripheral arterial disease. We hypothesise that vigorous-intensity training leads to a higher metabolic and to a different profile of circulating miRNAs compared to moderate-intensity training.
PMC9684818
Materials and methods
PMC9684818
Ethical standard and study design
The study adopts a randomized-balanced crossover design. Ethical approval was obtained from the local independent institutional review board (protocol-number 2019–04, 05.03.2019, Ethics Committee Department 5 Psychology and Sports Sciences Goethe-University Frankfurt). The trial was conducted in accordance with the ethical standards set down by the declaration of Helsinki (World medical Association Declaration of Helsinki–Ethical Principles for Medical Research Involving Human Subjects) with its recent modification of 2013 (Fortaleza). All participants gave written informed consent prior to study enrolment.
PMC9684818
Sample
peripheral arterial disease, muscle soreness, claudication, pain
CRITICAL LIMB ISCHEMIA, PERIPHERAL ARTERIAL DISEASE, ACUTE INFECTION
Adults (> 17 years of age) of any sex/gender were included. Participants had to have diagnostically confirmed peripheral arterial disease of any grade and claudication. Exclusion criteria included (1) critical limb ischemia, (2) acute infection or severe illnesses that have an impact on quality of life or physical performance, (3) use of perception-altering substances, (4) muscle soreness or severe pain in the lower extremities, (5) existing pregnancy or breastfeeding period.
PMC9684818
Experimental design
The cross-sectional study consisted two visits (on two different days with a washout period of at least seven days), in a randomized, balanced sequence. Visit A was the vigorous-intensity intervention and included a treadmill walking intervention with gradual increase in the angle of ascent until volitional exhaustion. Visit B, the moderate-intensity intervention involved guided walking training at individual walking speed. During each training intervention, loading-associated outcomes were monitored. The acute effects were determined using pre- and post-intervention measurements.
PMC9684818
Intervention
claudication pain, pain
In the vigorous-intensity intervention, participants executed a step incremental walking exercise until volitional exhaustion on a treadmill. The intervention was based on to the incremental Gardner-Skinner protocol (Gardner et al. The moderate-intensity intervention was conducted as an interval-training with standardized duration and individualized intensity. This exercise therefore aimed at mimicking real-life situations during habitual behaviours (such as health enhancing physical activity or activities of daily living). Participants were instructed to walk a standardized track multiple times within 20 min. The subjects selected their maximum gait speed, which they were able to maintain constantly over 20 min. In case of pain in the legs, the participants were allowed to take a short break at any time. The claudication pain usually subsides quickly at rest, so a short break is characteristically during walking exercises. On each test day, a standardized control condition (“do-nothing” phase) was performed for 20 min prior to the beginning of the testing condition.
PMC9684818
Outcomes
PMC9684818
Blood lactate concentration
Before and directly after each intervention, capillary blood was taken by pricking the earlobe with a safety lancet. The sample was applied directly (maximal 30 s after intervention) to a test strip to determine lactate concentration (mmol/l) by means of a portable, hand-held unit (Lactate Scout, SensLab GmbH, Leipzig, Germany). The unit proves to be a reliable lactate measurement system with an inter-rater reliability with a correlation coefficient of
PMC9684818
Heart rate
During the intervention, a chest belt (Polar H7) and heart rate receiver (Polar M 430) continuously measured heart rate (beats/min). The maximum heart rate was selected for further analyses.
PMC9684818
miRNA profiling
PMC9684818
Blood sampling and plasma preparation for miRNA quantification
haemolysis
BLOOD
To minimize pre-analytical variables that might influence the miRNA expression profile, collection of blood and the preparation of plasma was conducted with a minimal risk of blood cell contamination and haemolysis. Before and after each intervention, fingertip capillary blood samples (≥ 200 μL) were collected in microvettes (system for capillary blood collection) containing Ethylenediaminetetraacetic acid (EDTA). Blood samples were centrifuged for 10 min at 3000 rpm and 4 °C. After the first centrifugation step, the upper plasma phase was transferred to a new tube without disturbing the intermediate buffy coat layer. The plasma samples were centrifuged a second time for 10 min at 15,000 rpm and 4 °C. The cleared supernatant was carefully transferred to a new tube and frozen at − 80 °C.
PMC9684818
miRNA isolation
Sample amounts were standardized by volume: The same volume of plasma was used for each RNA isolation, and the same volume of purified RNA was used for all further analyses. The miRNAs were isolated from 50 µL of plasma using a column-based protocol (miRNeasy Serum/Plasma Advanced Kit, (Qiagen, Hilden, Germany) according to the manufacturer’s protocol. cel-miR-39 from
PMC9684818
Reverse transcription and quantitative real-time-PCR
APPENDIX
For reverse transcription, the miRCURY LNA RT Kit (Qiagen, Hilden, Germany) was used and quantitative real-time PCR was performed using miRCURY LNA miRNA PCR assays (Appendix A) in a 10 µl reaction containing 3 µL of cDNA (1:30) and a CFX real-time PCR detection system (BioRad, Munich, Germany). Assays were performed in duplicate. The amount of the respective miRNA was normalized to miR-425-3p (previously determined as being stably expressed pre and post training intervention) and cel-miR-39 (spike-in control). A Ct cut-off of 35 was set as the lower limit of detection and the fold change was calculated as (2 − ΔΔ
PMC9684818
Data analyses and statistics
After the range-data-plausibility control, outcomes were analysed using pre and post exercise values and absolute pre- to post-differences. Variables continuously monitored during the exercise bouts were processed in their absolute values. All analyses were performed using parametric or non-parametric testing based on the underlying assumptions (data structure, distribution of the variances and variance homogeneity). Between-group differences and pre- to post-changes were determined using omnibus and, in case of a significant omnibus main effect, follow-up post hoc testing. For the statistical calculations, SPSS 23 (SPSS Inc., Chicago, IL, USA) was used. For all statistical analyses, an alpha-error level of 5% was considered a relevant cut-off value for significance testing,
PMC9684818
Results
PMC9684818
Sample
celiac disease, PAD
CELIAC DISEASE, PAD, SECONDARY, CORONARY ARTERY DISEASE
The sample consisted of Participant CONSORT flow diagramThe amount of physical activity time averaged 12.5 h per week (standard deviation 7.22 h). The date of diagnosis varied among the patients from January 2012 to December 2018, with secondary diagnosis including coronary artery disease (2 participants), arterial hypertension (6 participants) and celiac disease (1 participant). No participant was smoker during study participation. The ankle–brachial index ranged from 0.6 to 0.85. Based on the ankle–brachial index, 5 patients had a low-grade of PAD and 5 patients a moderate-grade PAD.
PMC9684818
Training outcomes
PMC9684818
Walking distance and total training time
During the moderate-intensity walking training, a higher total walking distance was covered compared to the vigorous intensive training on the treadmill (
PMC9684818
Lactate concentration
Lactate concentration was increased after vigorous-intensity training (The interventions resulted in two different lactate progressions in the post-exercise phase (Fig. Differences in lactate progression pre-and post-exercise until 10 min post-intervention. Data are displayed as mean and 95% confidence interval.
PMC9684818
Heart rate
The heart rate was increased during both training interventions (
PMC9684818
miRNAs
Concentrations of eight different training-associated ci-miRNAs were analyzed in each patient before and after moderate or vigorous-intensity intervention. During the moderate-intensity intervention, two of the eight miRNAs were up-regulated: miRNA142-5p (Differences in miRNA expression pre- and post-training. Data are displayed as mean and 95% confidence intervals.
PMC9684818
Discussion
peripheral arterial disease, arteriogenesis, PAD, diabetes mellitus, heart failure, atherosclerosis
CELIAC DISEASE, PERIPHERAL ARTERIAL DISEASE, DIABETES MELLITUS, HYPOXIC, NEOVASCULARISATION, PAD, HEART FAILURE, PERIPHERAL ARTERIAL DISEASE, ATHEROSCLEROSIS, CORONARY ARTERY DISEASE
We investigated the concentration of eight circulating miRNAs in patients with peripheral arterial disease in the lower extremities before and after a vigorous- and a moderate-intensity bout of walking exercise. In the vigorous-intensity intervention, a higher anaerobic metabolic response but no significant intervention effect on miRNA expression occurred. Although lactate response was lower, the moderate-intensity intervention led to an upregulation of two miRNA concentrations. Exercise intensity and consecutive metabolic response, indicated by lactate, showed no significant association to miRNA expression. Hypothesis 1, that vigorous-intensity training leads to a higher metabolic response than moderate-intensity training, is thus only partially verified. Hypothesis 2, that moderate-intensity training leads to a different profile of circulating miRNAs compared to high intensity training, is verified.The moderate-intensity walking training led to lower lactate and maximal heart rate values compared to the vigorous-intensity walking training. The vigorous-intensity intervention was terminated after reaching subjective exertion one time and the distances covered on the treadmill ranged from 671 to 1213 m and thus was shorter than the distance covered in the moderate-intensity walking intervention. The variance in the covered distance until exhaustion underlines the different manifestations of peripheral arterial disease-related impairments, that may result in different metabolic responses during exercise. When comparing the heart rate during interventions to the calculated maximal heart rate, the participants averagely reached 56% of their individual maximal heart rate after the moderate walking training, with a spread of the difference from 48 to 64%. In contrast, after the vigorous-intensity training, the participants had a significantly higher percentage heart rate with a mean value of 78% of HRmax (min: 63%, max: 95%). According to the relative intensity table (Bjarnason-Wehrens et al. In conservative therapy, the effect of exercise on arteriogenesis is considered as an important mechanism. Physical training is thought to have the potential to stimulate neovascularisation in hypoxic and ischaemic tissues, such as the myocardium or peripheral limbs (Guerreiro et al. The regulation of miRNAs appears to be complex and is certainly not fully understood (Gulyaeva and Kushlinskiy The individual miRNAs are associated with different metabolic reactions, different parts of the human organism and different signalling pathways. MiRNA-142-5p is, among others, associated, with the pathways of VEGF and mTOR signalling, especially in cardiac muscles. This miRNA could be a factor for improvements of the vascular system and arteriogenesis. Moreover, the upregulation of miR‑142‑5p expression is related with the apoptosis in human macrophages by targeting TGF‑β2, this effect could play an important role in the progression of atherosclerosis (Xu et al. MiRNA-424-5p is associated with the expression of selected endothelial angiogenetic mediators in response to these growth factors (VEGF and bFGF) and is, therefore, considered as a “hypoximiR” (Chamorro-Jorganes et al. A study limitation is the small number of subjects as a result to the corona pandemic. Individuals with PAD tend to have many comorbidities that may be related to the observed outcomes. Some comorbidities affect similar cardiovascular and metabolic mechanisms as PAD. Examples include diabetes mellitus, coronary artery disease, heart failure, arterial hypertension and celiac disease.Our results are consistent with the proposed epigenetic potential of activity interventions that may alter miRNA expression. Since each miRNA is predicted to have many targets, we did not identify any direct association with other measures. Therefore, we postulate that further studies are necessary to adjust the intensity and extent of training to gain more information about the relationship between individual miRNAs, Peripheral arterial disease and human metabolism. This could be an added value (1) in training control and (2) in diagnostic screening of miRNAs to stratify responders and non-responders for individualization of treatment in PAD patients.
PMC9684818
Conclusion
peripheral arterial occlusive disease
PERIPHERAL ARTERIAL DISEASE, PERIPHERAL ARTERIAL OCCLUSIVE DISEASE, DISEASE PROGRESSION
In conclusion, walking training induces changes in circulating miRNA expression in patients with peripheral arterial disease. These changes only occur during moderate walking training for at least 20 min. Future studies are needed to find out whether (1) longer intensive training sessions, e.g. as interval training, and (2) several training sessions over a longer training period induce changes in miRNAs-expression and whether (3) these changes in miRNAs play a physiological role by which walking training positively influences whole-body metabolism in patients with peripheral arterial occlusive disease and favours disease progression of recovery.
PMC9684818
Supplementary Information
Below is the link to the electronic supplementary material.Supplementary file1 (DOCX 13 KB)
PMC9684818
Acknowledgements
The authors thank Monika Rieschel for excellent technical assistance.
PMC9684818
Author contributions
JS, KT, TE and LV designed the experiments. JS, KT, TE and DN interpreted the findings. JS and KT wrote the first draft of the manuscript. JS, KT, CT and DN analyzed and performed the experiments. DN performed statistical analyses. CT, TSR and WB discussed the results and revised the manuscript. All authors edited and approved the manuscript.
PMC9684818
Funding
Open Access funding enabled and organized by Projekt DEAL.
PMC9684818
Declarations
PMC9684818
Conflict of interest
The authors declare no conflict of interests.
PMC9684818
References
PMC9684818
Background
pneumonia, dyspnea, AECOPD, congestive heart failure, COPD
PNEUMONIA, CLINICAL SYNDROME, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, COPD, CONGESTIVE HEART FAILURE
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a clinical syndrome with various causes. It is not uncommon that COPD patients presenting with dyspnea have multiple causes for their symptoms including AECOPD, pneumonia, or congestive heart failure occurring concurrently.
PMC10426055
Methods
AECOPD, COPD, dyspnea
COPD, DISEASE
To identify clinical, radiographic, and laboratory characteristics that might help distinguish AECOPD from another dominant disease in patients with a history of COPD, we conducted a retrospective cohort study of hospitalized patients with admitting diagnosis of AECOPD who were screened for a prospective randomized controlled trial from Sep 2016 to Mar 2018. Clinical characteristics, course in hospital, and final diagnosis at discharge were reviewed and adjudicated by two authors. The final diagnosis of each patient was determined based on the synthesis of all presenting signs and symptoms, imaging, and laboratory results. We adhered to AECOPD diagnosis definitions based on the GOLD guidelines. Univariate and multivariate analyses were performed to identify any associated features of AECOPD with and without other acute processes contributing to dyspnea.
PMC10426055
Results
pleural effusion, dyspnea, AECOPD, pulmonary edema, cough, purulence, COPD
COPD, PULMONARY EDEMA, LOBAR PNEUMONIA, PLEURAL EFFUSION
Three hundred fifteen hospitalized patients with admitting diagnosis of AECOPD were included. Mean age was 72.5 (SD 10.6) years. Two thirds (65.4%) had spirometry defined COPD. The most common presenting symptom was dyspnea (96.5%), followed by cough (67.9%), and increased sputum (57.5%). One hundred and eighty (57.1%) had a final diagnosis of AECOPD alone whereas 87 (27.6%) had AECOPD with other conditions and 48 (15.2%) did not have AECOPD after adjudication. Increased sputum purulence (OR 3.35, 95%CI 1.68–6.69) and elevated venous pCO2 (OR 1.04, 95%CI 1.01 – 1.07) were associated with a diagnosis of AECOPD but these were not associated with AECOPD alone without concomitant conditions. Radiographic evidence of pleural effusion (OR 0.26, 95%CI 0.12 – 0.58) was negatively associated with AECOPD with or without other conditions while radiographic evidence of pulmonary edema (OR 0.31; 95%CI 0.11 – 0.91) and lobar pneumonia (OR 0.13, 95%CI 0.07 – 0.25) suggested against the diagnosis of AECOPD alone.
PMC10426055
Conclusion
AECOPD
The study highlighted the complexity and difficulty of AECOPD diagnosis. A more specific clinical tool to diagnose AECOPD is needed.
PMC10426055
Supplementary Information
The online version contains supplementary material available at 10.1186/s12890-023-02587-1.
PMC10426055
Keywords
PMC10426055
Introduction
AECOPD, COPD
CHRONIC OBSTRUCTIVE PULMONARY DISEASE, COPD, SECONDARY, DISEASE
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with increased morbidity, mortality, and healthcare cost [We aimed to identify clinical, radiographic, and laboratory characteristics that might help distinguish AECOPD from symptoms secondary to another dominant disease in patients with a history of COPD.
PMC10426055
Methods
PMC10426055
Study population/setting
AECOPD
We conducted a retrospective cohort study of patients identified from a prospective pilot randomized controlled trial (IPRAC) that aimed to determine feasibility of monthly intravenous immunoglobulin infusions for one year to prevent recurrent AECOPD in hospitalized patients with AECOPD from Sep 2016 to Mar 2018 [
PMC10426055
Data collection
AECOPD
The electronic medical records of patients included in our retrospective cohort were divided equally to be reviewed and extracted in a systematic manner by AJP, AP, and SA. AP and JC independently reviewed the extracted data and determined the final diagnosis based on discharge diagnosis and documentation which included a synthesis of all presenting signs and symptoms, imaging, and laboratory results available over the admission. Discrepancy of the final diagnosis was then discussed between AP and JC to agree on a final diagnosis. We categorized final diagnosis into AECOPD alone or AECOPD with other conditions, or no AECOPD. Our terminology is an elaboration of that published in the
PMC10426055
Data analysis
AECOPD
REGRESSION, PLEURAL EFFUSION, LOBAR PNEUMONIA, PULMONARY EDEMA
We described the distribution of baseline demographic and clinical characteristics of patients using numbers (proportions) and means [standard deviation (SD)], as appropriate. Univariable and multivariable logistic regression models were fit to investigate relationship between i) AECOPD with and without other conditions as the dependent variable, and potential risk factors as independent variables, ii) AECOPD alone as the dependent variable, and potential risk factors as independent variables. Five independent variables (subjective increase in sputum purulence, venous pCO2, radiographic evidence of pleural effusion, pulmonary edema, and lobar pneumonia) in multivariable analysis were selected based on univariate analysis results and clinical importance agreed among study investigators. All statistical analyses were conducted using SAS for windows version 9.4(SAS Institute, Cary, NC).
PMC10426055
Results
PMC10426055
Clinical characteristics associated with AECOPD alone, vs patients with AECOPD and other conditions
pleural effusion, blood eosinophilia, AECOPD, pulmonary edema, COPD
COPD, PULMONARY EDEMA, LOBAR PNEUMONIA, PLEURAL EFFUSION
Univariate analysis of all extracted variables revealed that female sex (OR 1.81; 95%CI 1.08 – 3.04) and spirometrically defined COPD (OR 1.92; 95%CI 1.13 – 3.29) were positively associated with having the diagnosis of AECOPD alone, while blood eosinophilia (OR 0.91; 95%CI 0.85 – 0.97), radiographic evidence of pleural effusion (OR 0.43; 95%CI 0.21 – 0.87), and lobar pneumonia on CXR (OR 0.13; 95%CI 0.07 – 0.25) were negatively associated with this outcome. In the multivariable analysis, radiographic evidence of pulmonary edema (OR 0.31; 95%CI 0.11 – 0.91) and lobar (OR 0.15; 95%CI 0.08 – 0.29) was negatively associated with the diagnosis of AECOPD alone (Table Association between clinical features and AECOPD alone
PMC10426055
Discussion
pleural effusion, pneumonia, AECOPD, pulmonary edema, purulence, COPD
PLEURAL EFFUSION, PNEUMONIA, PULMONARY EDEMA, COPD
Our study highlights the challenge of diagnosing AECOPD. The data indicates a limited utility of clinical and/or laboratory findings to distinguish classical AECOPD from AECOPD associated with other acute processes/illnesses. Among the 3 symptoms listed in the clinical criteria of AECOPD diagnosis, all were associated with AECOPD in univariate analysis. However, none of the clinical symptoms analyzed could differentiate AECOPD alone from AECOPD with other acute process. Not surprisingly, our study found that elevated venous pCO2 was associated with a diagnosis of AECOPD while radiographic findings of pleural effusion suggested against AECOPD, and radiographic evidence of pulmonary edema or pneumonia suggest against AECOPD only diagnosis. This is consistent with existing literature [Interestingly, approximately 12% of patients in our study did not have AECOPD by our adjudication criteria but were labeled as such on admission. Unfortunately, there is limited literature available on the incidence of misdiagnosis of exacerbation, but this does highlight the challenge of making a diagnosis of AECOPD. One reason the diagnosis of AECOPD can be so challenging may be related to frequency of misdiagnosis of COPD in the general population. In Ontario, only one third of patients in the general population labeled with COPD have received spirometry to confirm the diagnosis [Our determination of whether a patient’s presentation of AECOPD was accompanied by another condition was potentially limited by subjectivity since a reference standard is lacking in the field. The manifestations of AECOPD are protean, non-specific, and could represent a variety of non-AECOPD conditions. The GOLD report recommends that differential diagnoses are excluded before making a diagnosis of AECOPD [Increased sputum purulence was shown to be associated with the presence of bacteria in the lower respiratory tract [The study’s major limitation was the small sample size which limited our ability to fit many variables in the multivariate analysis. Other limitations include the subjective adjudication of definition based on clinical presentation and retrospective nature of the study which did not allow for assessment of detailed time course of clinical symptoms and laboratory parameters. Additionally, some laboratory parameters such as C-reactive protein, procalcitonin, BNP, or D-dimer which could help discern AECOPD from AECOPD with other acute processes/illnesses were not included because these tests were not consistently measured in all study patients.This study highlighted the difficulty of AECOPD diagnosis. We identified increased sputum purulence and venous pCO2 to be predictors for AECOPD, but pleural effusion on chest radiographs suggested against AECOPD. A more accurate and specific clinical tool to diagnose AECOPD with different phenotypes is needed.
PMC10426055
Acknowledgements
We thank Dr. Sara Abdallah for assisting with the data extraction.
PMC10426055
Authors’ contributions
JC conceptualized and designed the study, coordinated and supervised data analysis, interpreted study results, reviewed and revised the manuscript. AJP collected, analyzed data, and drafted the initial manuscript. AP collected, analyzed data, interpreted study results, reviewed and revised the manuscript. SM, SDA, and VL interpreted study results, reviewed, and revised the manuscript. THZ, XB, and MK analyzed data, reviewed, and revised the manuscript. All authors read and approved the final manuscript.
PMC10426055
Funding
The authors received no specific funding for this work.
PMC10426055
Availability of data and materials
The dataset supporting the conclusions of this article is available within the paper and Supplementary File
PMC10426055
Declarations
PMC10426055
Ethics approval and consent to participate
AECOPD
The study was conducted in accordance with the Declaration of Helsinki. Included patients in this study were identified from a prospective pilot randomized controlled trial (IPRAC) that aimed to determine feasibility of monthly intravenous immunoglobulin infusions for one year to prevent recurrent AECOPD in hospitalized patients with AECOPD from Sep 2016 to Mar 2018 [
PMC10426055
Consent for publication
Not applicable.
PMC10426055
Competing interests
JC received honoraria from GSK, Merck, Sanofi Genzyme, Takeda, CSL Behring, Biogen unrelated to this work. MK is a consultant for VIDA Diagnostics Inc. (Coralville, IA, USA). AJP, AP, TZ, VL, XB, SM, SDA do not have competing interests.
PMC10426055
References
PMC10426055
Background
depression, anxiety, Stress, perinatal mood
DISORDERS
Stress is a risk factor for poor physical and mental health, affecting new mothers’ ability, especially those with perinatal mood and anxiety disorders, to maintain their everyday lives. Over the past 50 years, global incidences of depression and anxiety disorders have increased, reaching pandemic levels. These incidences represent major public health issues that are challenging to detect and treat. Mindfulness programs are viable for reducing stress, anxiety, and depression. The present study evaluates mindfulness intervention effects on stress, anxiety, depression, and mother–infant bonding.
PMC10388457
Methods
depression, anxiety
We collected data on 102 women participating in a prenatal mindfulness program between July 2021 and March 2022; they were parallel and randomly assigned to experimental or control groups. The intervention group received an 8-week course in a prenatal mindfulness program, and the control group received usual standard prenatal care. The self-reported stress, pregnancy-related anxiety, and depression were assessed before and after the intervention and at 36 weeks of gestation. At 2 and 4 months postpartum, all participants provided self-reported their levels of stress, depression, and quality of mother-infant bonding.
PMC10388457
Results
depression, anxiety
PRENATAL STRESS
Compared to the control group, the experimental group that received the prenatal mindfulness intervention experienced reduced prenatal stress, anxiety, and depression and reduced postnatal stress and depression. Despite this, there was no significant difference between the groups in terms of the quality of mother-infant bonding.
PMC10388457
Conclusions
depression, anxiety
DISORDERS
Mindfulness prenatal programs are convenient and effective methods of decreasing stress, anxiety, and depression during the perinatal period. Based on our findings, prenatal mindfulness may play a role in mitigating mood and anxiety disorders and should be considered in future approaches to preventing psychological distress.
PMC10388457
Trial registration number
This trial has been prospectively registered at ClinicalTrials.gov (NCT04693130) and the first registration date was 12/24/2020.
PMC10388457
Keywords
PMC10388457
Background
depression, anxiety
EVENTS, DISORDERS
The perinatal period is a time of high risk for developing mental illnesses, such as anxiety and depression disorders, which can occur during the antenatal period and up to one year after childbirth [Mother-infant relationships refers to the primary emotional relationship between mother and infant. Particularly during the first year after childbirth, the quality of the relationship has been shown to directly affect the child’s physical, psychological, and developmental health [Women with PMAD face many challenges when adapting to life changes, and the importance of facilitating adaptation should be emphasized when developing interventions. Sawyer, Kaim [Mindfulness is defined as a state of deep awareness, which is consciousness characterized by clarity of focus, flexibility of attention, and a non-preconceived awareness of accepting events in the present moment [As pregnancy is a major transition in a woman’s life, stress increases and mood disorders are common during pregnancy [Mindfulness refers to focusing one’s attention on the present moment, including physical sensations and sensory impressions (e.g., breathing, smelling, and hearing) experienced at that time. This practice helps individuals experience the moment rather than dwelling on negative emotions. Individuals can use cognitive reappraisal to reduce stress, decreasing psychological distress [
PMC10388457
Objectives
reduced perinatal mood distress
SECONDARY
The aim of this study was to evaluate the effects of prenatal mindfulness intervention that can help women with PMAD overcome stress and psychological distress to promote a positive relationship with their infants in the postnatal period. The primary outcome is reduced perinatal mood distress. The secondary outcome is successful mother–infant bonding, which is also seen as the program’s long-term effect. Tertiary outcomes are obstetric data, especially on different types of postpartum confinement care, i.e., family care, yuesao care, and postpartum care centers.
PMC10388457
Methods
PMC10388457
Design and setting
This study adopted a two-arm, randomized longitudinal pre– and post-intervention design. Data were collected between July 2021 and March 2022. The study was approved by the Institutional Review Board of the study hospital and registered with ClinicalTrials.gov (NCT04693130).
PMC10388457
Participants
Depression, psychiatric
DISORDERS, RECRUITMENT, COMPLICATIONS
Women were recruited from an antenatal clinic at a teaching hospital in Taipei, Taiwan, using a convenience sampling method. Women who met the following criteria were included in the study: (1) age ≥ 20 years; (2) EPDS score ≥ 10; (3) singleton pregnancy at 13–28 weeks of gestation; and (4) willingness to participate in the mindfulness educational program. Women with high-risk maternal or fetal complications and psychiatric disorders were excluded.Prior to recruitment, we asked potential participants using the Edinburgh Postnatal Depression Scale (EPDS) to indicate possible PMAD [
PMC10388457
Intervention
painUsing, depression, anxiety, pain
The intervention course was designed specifically for pregnant women with potential depression or anxiety symptoms. The intervention was adapted from Nancy Bardacke’s traditional mindfulness-based childbirth and parenting (MBCP) program, which was designed to prepare parents for childbirth and parenting [ Overview of the 8-week perinatal mindfulness program interventionUnderstand your inner workings during pregnancyAutomated guidanceEating a raisin with mindfulness meditationBreathing meditation with babyBody scanMindfulness principlesAwareness of breathing and bodyNormal delivery process and childbirthMindfulness of sounds and thoughtsMindfulness yoga during pregnancyIce cube exerciseMindful stretching and walkingMindfulness practices for coping with pain and touch practiceSitting meditation focusing on a difficult or stressful situationCoping with difficultyBe the best teammate in childbirthMindfulness practices for coping with advanced painUsing the 3-min breathing space in stressful/painful situationsHow can I best take care ofmyself and my baby?My baby is the best mindfulness teacherIdentifying postpartum depression triggers in the confinement periodsUsing what has been learnedto deal with future moodsCourse reviewKeep a long-term meditation practice for postnatal lifeThe prenatal mindfulness program was delivered by two staff members who had previously taught MBCP together for five years. To reduce the potential drop-out rate during the research period, the experimental group was invited to join the mindfulness team communication tool and the freeware app LINE. Participation in LINE was only encouraged, but not required. The LINE provided weekly information regarding mindfulness pregnancy and parenting and allowed group members to interact with each other. The women in the intervention group and control group received standard antenatal care at the study hospital. This included regular antenatal examination, antenatal care counseling, delivery care, and postpartum nursing management.
PMC10388457
Measurements
depression
Demographic variables, including age, education, marital status, and employment status et al. were collected. A repeated assessment design, including baseline before randomization (T0), post-intervention (T1), 36 weeks of gestation (T2), 2 months after childbirth (T3), and 4 months after childbirth (T4) was used to evaluate the effectiveness of the intervention on depression and stress symptoms. The testing time points were selected because they are typical PMAD screening time points [
PMC10388457
Edinburgh postnatal depression scale
depressive, depressive symptoms
The EPDS is designed to measure the intensity of depressive symptoms over the past week, using 10 items scored using a 4-point Likert scale. Each item is scored from 0 to 3, and the total score ranges from 0 to 40. Higher scores indicated more depressive symptoms, which resulted in good reliability (Cronbach’s α = 0.77) [
PMC10388457
Pregnancy-related thoughts questionnaire
Anxiety, anxiety
Anxiety symptoms were assessed using the Pregnancy-Related Thoughts Questionnaire (PRT), which employs a 10-item scale to measure the frequency with which a person has worried or paid attention to baby health, labor, delivery, and caring for babies over the past 7 days. Each item uses a 4-point Likert scale, and the total score ranges from 10 to 40, with higher scores indicating more anxiety [
PMC10388457
Perceived stress scale-10
Perceived stress was assessed using the Perceived Stress Scale-10 (PSS-10). The PSS-10 assesses perceived stressful experiences or stress responses that occurred during the past month, using a 5-point Likert scale (0 = never and 4 = very often). Total scores range from 0 to 40, with higher scores indicating greater perceived stress. Scores of 0–13 indicate ”low stress”, scores of 14–26 indicate “moderate stress”, and scores of 27–40 indicate “high stress” [
PMC10388457
Postpartum bonding questionnaire
anger, ’s feelings or attitudes toward her baby, anxiety
The mother’s feelings or attitudes toward her baby were assessed using the Postpartum Bonding Questionnaire (PBQ), which is a 25-item scale designed to measure quality of mother-infant bonding. Each item is rated on a 6-point Likert scale (0 = always and 5 = never), and the PBQ includes four subscales: reflect impaired bonding (12 items), rejection and anger (7 items), anxiety about care (4 items), and risk of abuse (2 items) [
PMC10388457
Sample size
For a repeated-measures analysis of variance (ANOVA) with between-factors analysis, the following parameters were utilized: f = 0.25, alpha = 0.05, power = 0.80, number of groups = 2, number of measures = 5, and correlation among repeated measures = 0.5. Based on a previous mindfulness study, an attrition rate of 30% was expected [
PMC10388457
Randomization
Our study participants were randomly assigned in a 1:1 ratio to each group and divided into blocks 6, 8 and 12. A trained research assistant collected data using a computer-generated random number sequence previously prepared by the researcher, which was stored in an opaque sealed envelope. Each participant received an explanation of the study from a research assistant and was enrolled after providing written informed consent. They were asked to complete the study questionnaire, each taking approximately 20 min to complete. Participants received remuneration equivalent to 4–5 USD after each completed questionnaire to reduce attrition. Participants were blinded to their groups, and medical care providers, and the team of data monitoring and analysis were blinded to group assignments.
PMC10388457
Data analysis
Data obtained in the present study were analyzed using SPSS 26.0 (SPSS Inc. Chicago, IL, USA). Descriptive statistics (percentage, mean, standard deviation) were applied, and skewness and kurtosis values were calculated to assess whether numerical variables fit a normal distribution. Each dependent variable was z-standardized before the generalized estimating equation (GEE) and independent analyses to facilitate interpreting the effect. The dependent t-test was used to compare the mean PBQ scores between the two study groups, and GEE [
PMC10388457
Depression in women with PMAD
depression, Depression
The baseline scores were 12.88 ± 2.99 in the intervention group and 13.70 ± 3.78 in the control group, indicating near “depression”. After participation in this program, the mean EPDS scores decreased with time, with a mean score of 9.12, 9.18, 7.18, and 9.43 in that order. This indicates “no depression” at all time points in the experimental group (Fig.  Changes in outcome measures over timeT0 = Before the intervention; T1 = After the intervention; T2 = 36 weeks of gestation. T3 = 2 months postpartum; T3 = 4 months postpartum; EPDS = Edinburgh Postnatal Depression Scale; PSS = Perceived Stress Scale; PRT = Pregnancy-Related Thoughts Questionnaire; PBQ = Postpartum Bonding Questionnaire. Assessing the effects of the intervention on outcome measures using the GEE model or T-test (The experimental and control groups each consisted of 33 participants; GEE = Generalized Estimating Equation;
PMC10388457
Stress in women with PMAD
The baseline score for stress was 18.45 ± 4.91 for the intervention group and 18.97 ± 3.78 for the control group, indicating “moderate stress.” After participation in this program, the mean PSS-10 scores decreased with time; the mean score was 14.18, 14.85, 13.88, and 14.40 in that order, which indicated “mild stress” at all time points in the experimental group (Fig. 
PMC10388457
Anxiety in women with PMAD
Over the course of the program was completed, the mean scores for the PRT level decreased. There was a mean score of 24.21 for the intervention group and 22.69 for the control group before this program began. In the intervention group, mean scores decreased to 17.53 and 18.05 points post-intervention (Fig. 
PMC10388457
Mother–infant bonding in women with PMAD
After participating in the program, the average PBQ level score showed a downward trend. The average scores at T3 were 17.69 and 19.02 and at T4 were 13.39 and 16.50 for the intervention group and the control group, respectively (Fig. 
PMC10388457
Discussion
depression, depressive, anxiety
DISORDERS
The objective of this study was to explore the effects of a mindfulness program on psychological distress and mother–infant bonding in perinatal women. The study findings support the feasibility, acceptability, and efficacy of the intervention among women with PMAD. Compared with the control group (standard antenatal care), the intervention group experienced significant reductions in self-reported depression, stress, and anxiety that persisted up to four months postpartum. Furthermore, after the intervention, the anxiety effect was large, except at 36 weeks of gestation (before delivery). Stress and depression effect sizes were moderate and significantly smaller after four months postpartum.In our study, about 66% of the participants had moderate to high perceived stress. However, the mindfulness intervention resulted in not only a decrease in perceived stress but also an improvement in mental health indicators, such as symptoms of anxiety and depression. Individuals with increased mindfulness have been shown to have a more benign approach to cognitive assessments of stressful situations and use more adaptive coping strategies [It is important to note that our findings of improvement in psychological distress are consistent with those of several meta-analyses and review studies conducted in pregnancy and postpartum periods on women with or without pre-existing stress, depressive or anxiety disorders [Bögels et al. [There are several limitations to this study. In spite of the fact that the initial sample size was sufficient for the purposes of this study, there was a high attrition rate (35.29%). The effect size may be overestimated, but there was no significant difference in attrition between the intervention and control groups. To capture the ongoing effects of the course more accurately, future studies should focus on strategies to improve questionnaire retention. The study also had the limitation that participants in this study were women with a predisposition for depression, using an EPDS screening score of 10 or higher; therefore, these results cannot be generalized to all women with PMAD. Thirdly, self-reported outcome measures were utilized to assess depression, stress, anxiety, quality of mother-infant bonding, and mindfulness practice time. The fourth limitation of this study is that the participants were Taiwanese and the study was conducted during the COVID-19 pandemic, which might limit their generalizability to other cultures and periods. Future studies should seek to replicate these results with a more diverse sample and a typical time context.
PMC10388457