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This Study
EMA
To evaluate these changes, we implemented 2 randomized controlled trials (RCTs) within the ongoing Health@NUS study. The practical nature of these nested RCTs (ie, to act to improve overall EMA survey response rate in an ongoing study) meant that publishing a protocol before starting the study was not feasible. The out...
PMC10623229
Participants
word of mouth
RECRUITMENT, RECRUITMENT, EMA
Participants were recruited to Health@NUS via email, campus posters, and word of mouth. To be eligible, participants had to (1) be a full-time student at the NUS, (2) be aged 18 to 26 years, (3) be a citizen or permanent resident of Singapore, and (4) own a smartphone compatible with the study app (ie, minimum iOS 10 o...
PMC10623229
EMA Details
PMC10623229
Burst 1 of EMA Surveys
GROUP B, EMA
Before burst 1 (baseline), the participants received an email to notify them of the upcoming EMA burst. A second reminder email and one push notification reminder were sent midway through the EMA burst (see the left-hand side of During burst 1, all participants received 42 EMA surveys over 10 days within a 14-day perio...
PMC10623229
Burst 3 of EMA Surveys
EMA
The original 14-day schedule was condensed into 7 days, and the overall number of EMA surveys was reduced to 30 (see the right-hand side of Before the start of burst 3, participants received an SMS text message (instead of an email) notifying them of the upcoming EMA burst plus they received an SMS text message every 3...
PMC10623229
Measures
EMA
At baseline, participants self-reported their age (date of birth); sex (male or female); ethnicity (Chinese, Indian, Malay, or Other); marital status (single or never married, currently married, separated but not divorced, divorced, widowed, or refuse to answer); monthly household income (<SG $2000 [US $1466], SG $2000...
PMC10623229
Primary Outcome
EMA
The primary outcome measure was the response rate (ie, percentage of completed EMA surveys from all sent EMA surveys) for each burst of EMA surveys.
PMC10623229
Statistical Methods
EMA
Baseline characteristics were analyzed descriptively. Separate 1-way ANOVAs were used to estimate the effect of changing the reward structure (aim 1, reward RCT) or the schedule length (aim 2, schedule length RCT) on the response rate at burst 2 and burst 3, respectively. A sensitivity analysis was conducted using anal...
PMC10623229
Ethical Considerations
EMA
Ethics approval was obtained from the National Healthcare Group in Singapore (reference 2019/00285). All participants provided written informed consent before commencing the study and consented for their deidentified data to be used for research purposes. For this study, the maximum compensation available to participan...
PMC10623229
Results
PMC10623229
Participant Flow
EMA
Between October 2020 and March 2021, 384 participants were recruited and enrolled into this study, and data collection was complete by October 2021.Following burst 1 and before burst 2, the participants were randomized to group A (n=96), group B (n=95), group C (n=96), or group D (n=97). Following burst 2 and before bu...
PMC10623229
Discussion
PMC10623229
Principal Findings
SECONDARY, EMA
This study experimentally evaluated the effect of rewards and schedule length on EMA response rates within the context of an ongoing study implementing repeated bursts of EMA surveys. Reducing the number of days of EMA surveys led to a significantly lower response rate. However, changing the available rewards did not s...
PMC10623229
Findings in Context
EMA
The finding that neither offering greater reward amounts nor reducing the schedule length led to an increase in the response rate is broadly consistent with systematic reviews of factors associated with EMA compliance [Rewards were selected as the first intervention target as the rewards available in burst 1 were low c...
PMC10623229
Strengths and Limitations
HOLIDAYS, SECONDARY, BLIND, EMA
The strengths and limitations of this study should be considered. Our RCTs were embedded within an ongoing cohort study that required participants to fulfill several mandatory requirements (eg, minimum Fitbit wear time and food diary logging/mo), whereas completing the EMA surveys was optional but highly encouraged, an...
PMC10623229
Conclusions
EMA
This study is one of the first to experimentally evaluate the effect of incentives and schedule length on EMA response rates. It is also the first study to consider factors related to response in the context of an ongoing prospective cohort study administering repeated bursts of EMA over a 2-year period. By embedding R...
PMC10623229
Abbreviations
Consolidated Standards of Reporting Trialsecological momentary assessmentHealth PointsNational University of Singaporerandomized controlled trial
PMC10623229
Data Availability
Deidentified data that support the findings of this study may be available from the corresponding author (SME) upon reasonable request.
PMC10623229
Key Points
PMC9926359
Question
Does a dosage of 1000 IU per day compared with 400 IU per day of supplemental vitamin D in infants born with serum 25-hydroxyvitamin D concentrations less than 50 nmol/L (ie, 20 ng/mL) present advantages to bone outcomes throughout infancy?
PMC9926359
Findings
SECONDARY
In this prespecified secondary analysis of a double-blinded randomized clinical trial including 139 healthy term infants, whole-body bone mineral content, lumbar spine bone mineral content and density, and bone biomarkers were not different among dosage groups from age 1 to 12 months.
PMC9926359
Meaning
SECONDARY
This study supports a standard daily supplemental dose of 400 IU of vitamin D in breastfed infants in Montreal, even if born with serum 25-hydroxyvitamin D concentrations less than 50 nmol/L.This prespecified secondary analysis of a randomized clinical trial evaluates whether a higher dose of supplemental vitamin D (10...
PMC9926359
Importance
The dose of supplemental vitamin D needed in infants born with serum 25-hydroxyvitamin D (25[OH]D) concentrations less than 50 nmol/L (ie, 20 ng/mL) is unclear.
PMC9926359
Objective
To determine whether a higher dose (1000 IU vs 400 IU per day) is required in infants born with 25(OH)D concentrations less than 50 nmol/L for bone mineral accretion across infancy.
PMC9926359
Design, Setting, and Participants
SECONDARY
In this prespecified secondary analysis of a double-blinded randomized clinical trial, conducted from March 2016 to March 2019 in a single center in Greater Montreal, Quebec, Canada, a consecutive sample of 139 healthy term singletons were recruited from 866 infants screened for vitamin D status at birth. Data were ana...
PMC9926359
Interventions
Capillary blood was collected 24 to 36 hours after birth to measure serum total 25(OH)D concentrations. Infants with 25(OH)D concentrations less than 50 nmol/L were randomized to receive either 1000 IU or 400 IU per day of oral vitamin D
PMC9926359
Main Outcomes and Measures
Measures at age 1, 3, 6, and 12 months were preplanned and included whole-body bone mineral content, lumbar spine bone mineral content, and bone mineral density using dual-energy x-ray absorptiometry, and serum 25(OH)D
PMC9926359
Results
Of 139 included infants, 81 (58.3%) were male, and the median (IQR) gestational age at birth was 39.6 (38.9-40.6) weeks. A total of 49 infants were included in the 1000 IU per day group, 49 infants in the 400 IU per day group, and 41 in the reference group. Mean (SD) whole-body bone mineral content was not different be...
PMC9926359
Conclusions and Relevance
In this study, a higher dose of vitamin D supplementation in infants born with 25(OH)D concentrations less than 50 nmol/L did not present advantages to bone mass in infancy. This study supports a standard dose of 400 IU per day of vitamin D supplementation for breastfed infants in Montreal.
PMC9926359
Trial Registration
ClinicalTrials.gov Identifier:
PMC9926359
Introduction
Vitamin D status at birth reflects maternal-fetal transfer of 25-hydroxyvitamin D (25[OH]D).A dose-response relation exists between vitamin D intake and 25(OH)D concentration in infants, and the lower the initial concentration, the greater the rise in vitamin D status.The objective of this study was to compare the effe...
PMC9926359
Methods
PMC9926359
Study Design
SECONDARY
This was a prespecified secondary analysis of a double-blinded, parallel group randomized clinical parallel group trial conducted in Montreal, Quebec, Canada, from March 2016 to March 2019 and followed the Consolidated Standards of Reporting Trials (
PMC9926359
Participant Flow Diagram
LGA
RECRUITMENT
Participant flow diagram showing number of mother-infant dyads assessed for eligibility 24 to 36 hours after delivery, enrolled to newborn screening, screened, enrolled to the postnatal study, and allocated to either the trial group (serum 25-hydroxyvitamin D (25[OH]D) concentrations less than 50 nmol/L [ie, 20 ng/mL])...
PMC9926359
Bone Outcomes
Whole-body (WB) and lumbar spine (LS) vertebrae L1 to L4 BMC and BMD were measured using dual-energy x-ray absorptiometry methodology, as described elsewhere.
PMC9926359
Biochemistry
BLOOD
Blood samples from the infants and their mothers were collected, as previously reported.In infants at birth, serum total 25(OH)D concentrations were measured using an automated chemiluminescent immunoassay (LIAISON analyzer; DiaSorin), as previously reported,During the trial, infant serum (200 μL) was used to measure 2...
PMC9926359
Dietary and Lifestyle Data
At baseline, maternal nutritional intake (energy, protein, carbohydrates, fat, vitamin D, calcium, magnesium, and phosphorus) during pregnancy from food and supplements was assessed using a validated semiquantitative food frequency questionnaire,
PMC9926359
Statistical Analysis
REGRESSION, SKIN, SECONDARY
This analysis is the secondary objective of the trial. The primary objective was focused on lean mass outcomes, with the aim of recruiting a minimum of 46 infants per trial group and up to 74 to account for dropouts.Differences between the trial groups over time in bone outcomes (dual-energy x-ray absorptiometry and bi...
PMC9926359
Results
Characteristics of infants and their mothers are provided in the
PMC9926359
Characteristics at Birth and at Baseline
weight gain
REGRESSION
Abbreviations: BMI, body mass index; ITA, individual typology angle; 24,25(OH)Seasons are based on equinox and solstice dates for each year.Serum 25(OH)D concentrations measured using chemiluminescent immunoassay and standardized using Deming regression (standardized concentration [in nmol/L] calculated as 0.9634 [meas...
PMC9926359
Whole-Body Bone Mineral Content (BMC), Lumbar Spine BMC, and Lumbar Spine Bone Mineral Density (BMD) of Infant Groups Over Time
REGRESSION
Data are reported as means with SDs and were analyzed using a linear mixed-effects regression model for group-by-time interaction and time; the model included participant-level random intercepts and slopes for time. Post hoc testing showed no significant differences between trial groups over time adjusted for multiple ...
PMC9926359
Biomarkers of Calcium and Bone Metabolism of Infant Groups Over Time
REGRESSION
Data are reported as means with SDs and were analyzed using a linear mixed-effects regression model for group-by-time interaction and time; the model included participant-level random intercepts and slopes for time. Post hoc testing showed no differences between trial groups over time. The 1000 IU per day group and 400...
PMC9926359
Discussion
SECONDARY
In the absence of robust trials investigating the effect of a dose of vitamin D supplementation higher than the standard of care (400 IU per day) on bone mineral accretion and density in infants born with 25(OH)D concentrations less than 50 nmol/L, this prespecified secondary analysis of a randomized clinical trial pro...
PMC9926359
Strengths and Limitations
Strengths of this study are its design that implemented targeted entrance criteria on the basis of serum 25(OH)D concentrations less than 50 nmol/L at birth and that it provides valuable data on bone mass, calcium homeostasis, and multiple vitamin D metabolites in infancy. This study also has limitations. Outcomes were...
PMC9926359
Conclusions
In conclusion, in infants with 25(OH)D concentrations less than 50 nmol/L at birth, both 400 and 1000 IU per day of vitamin D supplementation normalized and maintained 25(OH)D concentrations that align with skeletal health. The 1000 IU per day dosage of vitamin D supplementation did not lead to measurable improvements ...
PMC9926359
1. Introduction
obesity, obese, overweight, weight loss
OBESITY, OVERWEIGHT AND OBESITY, OBESE
Studies investigating the effect of multispecies synbiotic supplementation in obesity management are limited. The current study was performed to evaluate the effects of multispecies probiotics mixed with fructooligosaccharides on body composition, antioxidant status, and gut microbiome composition in overweight and obe...
PMC10141052
2. Materials and Methods
PMC10141052
2.1. Participants
The study recruited participants from Chulalongkorn University in Bangkok, Thailand, through social media advertisements. Inclusion criteria for participants were: (1) being between the ages of 18 and 45, and (2) having a body mass index (BMI) between 23 and 30 kg/m
PMC10141052
2.2. Study Design
overweight
OBESE
A double-blind, placebo-controlled, randomized, parallel design was conducted on overweight and obese individuals between March 2021 and January 2022 at Chulalongkorn University in Bangkok, Thailand. The total sample size required for this study was calculated to be In the current study, a total of 80 individuals were ...
PMC10141052
2.3. Body Composition Assessment
Body weight, body mass index (BMI), and body fat percentage were assessed using bioelectrical impedance analysis (BIA) (TANITA BC-402, Tokyo, Japan) while participants were dressed in light clothing and no shoes [
PMC10141052
2.4. Biochemical Assessment
BLOOD, OXIDATIVE STRESS
We collected venous blood samples using sodium fluoride and EDTA blood collection tubes for plasma samples and no anticoagulant tubes for serum samples. Blood samples were centrifuged at 3000 rpm for 15 min at 4 °C, and the plasma and serum were aliquoted and stored at −20 °C for further analysis. Plasma glucose, serum...
PMC10141052
2.5. Gut Microbiome Analysis
Stool samples were obtained from all participants, who were instructed to self-collect the specimens at home. Stools (100 g) from each participant were collected and stored at −80 °C in tubes containing DNA/RNA Shield™ solution (Zymo Research, Irvine, CA, USA). Participants were also provided with a poster describing t...
PMC10141052
2.6. Dietary Assessment
At baseline and at weeks 6 and 12 of the study, participants were asked to complete a three-day dietary record (two weekdays and one weekend day) to estimate calorie intake. Additionally, all participants were asked to complete a 24 h dietary recall to ensure they maintained their intake and to reduce any bias from the...
PMC10141052
2.7. Statistical Analysis
Data are represented as mean ± standard deviation (SD). The Kolmogorov–Smirnov test was applied to ensure a normal distribution of body composition, biochemical blood profiles, and gut microbiota composition. A paired sample
PMC10141052
3. Results
PMC10141052
3.1. Participant Characteristics
Eighty participants were recruited for the study (
PMC10141052
3.2. Body Composition Measurement
The consumption of synbiotics for 12 weeks resulted in a significant decrease in waist circumference (
PMC10141052
3.4. Dietary Measurement
The results of the dietary assessment, conducted after subjects consumed synbiotics, are presented in
PMC10141052
4. Discussion
obesity, obese, Obesity-related metabolic disturbances, overweight, weight loss
OBESITY, OXIDATIVE STRESS, OBESE
Recent research has indicated that synbiotic interventions may be a promising approach for overweight and obesity management [The study highlights the potential benefits of a multispecies synbiotic intervention, combining probiotic bacteria (Changes in calorie intake can potentially impact alterations in waist circumfe...
PMC10141052
5. Conclusions
The synbiotic treatment showed notable improvement in body composition (waist circumference and body fat percentage), antioxidant status, and gut microbiota (
PMC10141052
Supplementary Materials
The following supporting information can be downloaded at: Click here for additional data file.
PMC10141052
Author Contributions
Conceptualization, P.O., S.N., T.S. and S.A.; Data curation, P.O., P.C. and V.S.; Investigation, P.O., P.C. and V.S.; Methodology, P.O., T.S., S.P. and S.A.; Formal analysis, P.O., P.C., S.P., C.C. and V.S.; Supervisor, S.A. and T.S.; Writing—original draft preparation and writing—review and editing, P.O., T.S., C.C., ...
PMC10141052
Institutional Review Board Statement
COA No.
The study was approved by the office of the Ethics Review Committee for Research Involving Human Research Subjects, Human Science Group, Chulalongkorn University (COA No. 276/2563).
PMC10141052
Informed Consent Statement
All participants provided written informed consent in this study.
PMC10141052
Data Availability Statement
The data presented in the manuscript are available on request from corresponding author.
PMC10141052
Conflicts of Interest
The authors declare no conflict of interest.
PMC10141052
References
overweight
OBESE
The CONSORT flow diagram of the study.Effect of 12-week synbiotic intervention on gut microbiota composition in overweight and obese subjects. (Percent relative abundance of dominant phylum across second treatment groups. (Principal coordinate analysis (PCoA) using Bray–Curtis distances demonstrates the beta diversity ...
PMC10141052
Abstract
PMC10291993
Objective
anal fistula
LYMPHOMA
In this study, we investigated the impact of Zibai ointment on wound healing by analyzing the expression levels of two key apoptosis‐related factors—B‐cell lymphoma 2 (Bcl‐2) and Bcl‐2‐associated X protein (Bax), in patients following surgery for anal fistula.
PMC10291993
Methods
We included 90 patients with anal fistulas who were treated in the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine. Patients were randomly assigned to receive treatment with Zibai ointment (
PMC10291993
Results
The results of ELISA showed that on Day 21 after the surgery, the levels of Bcl‐2 and Bax in the Zibai ointment group were significantly different compared to the petroleum jelly group, with values of (60.11 ± 1.31) ng/mL and (7.05 ± 0.01) versus (83.79 ± 1.74) ng/mL and (6.00 ± 0.05) ng/mL, respectively (
PMC10291993
Conclusion
fistula
We found that Zibai ointment effectively promoted wound healing in patients following anal fistula surgery, possibly by regulating Bcl‐2 and Bax apoptosis‐related factors.In this study, we found that Zibai ointment effectively promoted wound healing in patients after anal fistula surgery, possibly by regulating Bcl‐2 a...
PMC10291993
INTRODUCTION
anal fistula, fistula
DISEASES
Common anorectal diseases like anal fistula can only be treated surgically. However, postoperative wound healing can be challenging and unpleasant due to the anatomical features of the lesion site and the surrounding area. Patients experience a great deal of discomfort due to the lengthy postoperative recovery period. ...
PMC10291993
MATERIALS AND METHODS
PMC10291993
Clinical materials
PMC10291993
Diagnostic criteria
anal fistula
The diagnostic criteria for anal fistula used in this study are based on the
PMC10291993
Inclusion criteria
anal fistula, fistula, abnormal anal morphology and function
LOCAL INFILTRATION
(1) Patients who met the above diagnostic criteria for anal fistula; (2) Patient aged > 18 years and <60 years; (3) The surgical method used was conventional anal fistula resection; (4) All surgeries were performed under either local infiltration anesthesia or lumbar anesthesia; (5) Patients without previous history of...
PMC10291993
Exclusion criteria
allergic, perianal eczema, anal papilloma, malignant tumors, psychiatric
PERIANAL ABSCESS, GASTROINTESTINAL INFECTIONS, RECTAL POLYPS, ANAL FISSURE, MALIGNANT TUMORS, DISEASES, CHRONIC DIARRHEA
(1) Patients with other anal diseases, such as anal fissure, perianal abscess, perianal eczema, rectal polyps, anal papilloma; (2) Patients suffering from chronic diarrhea or other gastrointestinal infections; (3) Patients diagnosed with malignant tumors in the body; (4) Patients with diseases affecting vital organs su...
PMC10291993
General data
The study was approved by Ethics Committee of the People's Hospital Affiliated to Fujian University of TCM. Written informed consent was obtained from all participants. (2020‐048‐02). Patients were randomly assigned to either the Zibai ointment group (Comparison of Gender and Age between the Two Groups.
PMC10291993
Methods
PMC10291993
Treatment methods
MYZZ, Z06106031, fistula
Surgical method: First, use a probe to gently probe along the direction of the fistula from the outer opening, pass through the entire fistula, and reach the inner opening. Cut all fistulas along the direction of the probe and open the entire length of the fistula. Make incisions on both sides of the skin of the open f...
PMC10291993
Experimental methods
We collected granulation tissue samples from both groups on Days 7, 14, and 21 postsurgery to analyze Bcl‐2 and Bax levels using enzyme‐linked immunosorbent assay (ELISA) and to measure granulation tissue apoptosis using the TUNEL assay.We used Human B lymphocytoma‐2 (Bcl‐2) ELISA kit (enzyme immunoassay, MM‐0381H1) B ...
PMC10291993
ELISA method for detecting the expression of Bcl‐2 and Bax
An appropriate amount of tissue was collected for later use after removal of blood, and weighed and transferred into a glass homogenizer. The tissue was rinsed with 5–10 mL of precooled PBS (0.01 M, pH = 7.4) to eliminate any residual blood and then ground thoroughly. The prepared homogenate was centrifuged at 5000
PMC10291993
TUNEL assay for assessing cell apoptosis in granulation tissue postsurgery
The granulation tissue was prepared for apoptosis detection by fixing it, embedding in paraffin, and sectioning and dewaxing with xylene. It was then digested with trypsin, incubated with the TUNEL reaction solution at 37°C for 1 h, then incubated with peroxidase antibody at 37°C for 30 min; diamine benzidine (DAB) was...
PMC10291993
Statistical analysis
We used SPSS 25.0 software for the data analysis. Measurement data are expressed as mean values and the means of two samples were compared using the
PMC10291993
RESULTS
PMC10291993
Levels of Bcl‐2 and Bax in the two groups after surgery
The levels of Bcl‐2 gradually decreased and those of Bax gradually increased in both groups over time. On Day 21 post‐surgery, there were significant differences in the expression levels of Bcl‐2 and Bax between the groups (Expression Levels of Bcl‐2 and Bax in the postoperative tissues of the two groups.The expression...
PMC10291993
TUNEL assay results on cell apoptosis in wound granulation tissue
On Day 14 post‐surgery, samples from the Zibai ointment group showed signs of apoptosis (brown‐yellow cells with nuclei) under light microscopy, including chromatin condensation (arrangement close to the karyotheca in a hemisphere‐shaped, crescent‐shaped or sickle‐shaped manner), cytoplasmic pyknosis, reduced cell volu...
PMC10291993
Comparison of postoperative healing time and clinical efficacy between the two groups
There was no significant difference in clinical efficacy between the two groups (Comparison of Postoperative Healing Time and Clinical Efficacy between the Two Groups.
PMC10291993
DISCUSSION
postoperative pain, fever, swelling, toxicity, edema, anorectal disorder, necrotic, pain, anorectal disorders, pruritus, fistula, dryness, sores
HEAT, EDEMA, ANORECTAL DISORDER, NECROTIC, ANORECTAL DISORDERS, PERIANAL ABSCESS, STASIS, DISEASES, COMPLICATIONS, INFLAMMATORY RESPONSE
Anal fistula is an anorectal disorder with high incidence, characterized by the formation of an abnormal tunnel between the rectum or anal canal and surrounding skin. Perianal abscess, pruritus, and pain are some of its clinical signs. Systemic inflammatory reactions, fever, and other symptoms may also be present in mo...
PMC10291993
AUTHOR CONTRIBUTIONS
PMC10291993
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
PMC10291993
ETHICS STATEMENT
The study was conducted in accordance with the Declaration of Helsinki(as was revised in 2013). The study was approved by Ethics Committee of the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine. Written informed consent was obtained from all participants (2020‐048‐02).
PMC10291993
ACKNOWLEDGMENTS
We are particularly grateful to all the people who have given us help on our article. Special project of the Chinese medicine clinical research base of the People's Hospital affiliated to the Fujian University of Traditional Chinese Medicine, project number: JDZX201938.
PMC10291993
REFERENCES
PMC10291993
1. Introduction
hedonic sensations, dyspepsia, functional gut disorders, satiety, fullness
These authors contributed equally to this work.Background. Meal ingestion induces a postprandial experience that involves homeostatic and hedonic sensations. Our aim was to determine the effect of aversive conditioning on the postprandial reward of a comfort meal. Methods: A sham-controlled, randomised, parallel, singl...
PMC10221585
2. Material and Methods
PMC10221585
2.1. Experimental Design
A sham-controlled, randomised, parallel, single-blind study on the effect of aversive conditioning on the responses to a comfort meal in healthy women was performed in a tertiary referral centre between February and August 2021. The research was conducted according to the Declaration of Helsinki. The protocol for the s...
PMC10221585
2.2. Participants
gastrointestinal symptoms, non-obese
Twelve, non-obese, non-dieting and weight-stable women (6 per group), without history of gastrointestinal symptoms were recruited by public advertising to participate in the study. For this pilot, proof-of-concept study, only women were included for the sake of homogeneity and because some data indicate that they are m...
PMC10221585
2.3. Experimental Paradigm
Participants were informed that the aim of the study was to investigate the effect of meal composition on the postprandial responses and that a nasoduodenal tube was used to evaluate gastric outflow. Participants were informed that two recipes of a tasty humus with different compositions would be tested; however, the s...
PMC10221585