title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
|---|---|---|---|---|
Control analyses/manipulation checks | RVT | Analysis of the control variables (respiratory frequency, RVT, and tracking error) is summarized in | PMC10295813 | |
Effects of attention on respiration rate and respiratory volume | RVT | The study-wide average respiration frequency was 0.21 Hz (Estimated marginal means for respiration frequencyData are displayed in Hz, SE = standard error of the estimate, df = degrees of freedom, CI = confidence interval.Tukey-adjusted pairwise comparisons of respiration frequencyActExt = Active Exteroception; ActInt = Active Interoception; ActMatch = Active Matching; PasExt = Passive Exteroception; PasInt = Passive Interoception. * indicates Condition had a large impact on RVT, Estimated marginal means for respiration volume/time (RVT)Data are reported in respiratory volume/time, in terms of respiratory belt stretch (arbitrary units) integrated over time.Tukey-adjusted pairwise comparisons of respiration volume/time (RVT)Data are reported in respiratory volume/time, in terms of respiratory belt stretch (arbitrary units) integrated over time. ActExt = Active Exteroception; ActInt = Active Interoception; ActMatch = Active Matching; PasExt = Passive Exteroception; PasInt = Passive Interoception. * indicates A frequency/RVT trade-off was also evident as negative within-participant correlations, | PMC10295813 | |
Interoceptive and exteroceptive tracking accuracy | Participant tracking of the sensory stimuli (respiration and visual circle) was analyzed in terms of error (in milliseconds) between key presses and the peaks and troughs of stimulus waveforms within each of the active task blocks. Stimulus waveforms were first phase-corrected to maximally match peaks and troughs with keypresses. Error was then measured as the average time difference between stimulus peaks/troughs and key presses (Participants accurately and reliably tracked both the respiratory and visual stimuli (Estimated marginal means for target tracking errorTarget indicates the target for which button tracking accuracy is calculated; for Active Exteroception, this is always the circle, and for Active Interoception, this is always the breath, but for the Active Matching condition, both targets are required to align with keypresses, so both accuracies can be computed. Data reported are in milliseconds lag relative to the target inflection points.Tukey-adjusted pairwise comparisons of target tracking errorData reported are in milliseconds lag relative to the target inflection points. * indicates | PMC10295813 | ||
Effects of attentional and reporting demand | INTERACTIONS, CORTEX | A whole-brain interaction analysis between Reporting Demand [Active vs Passive] and Attentional Target [Exteroception vs Interoception] implicated the sensorimotor, temporoparietal, striatum, and prefrontal cortex (Task interactions and simple effectsActExt = Active Exteroception; ActInt = Active Interoception; ActMatch = Active Matching; PasExt = Passive Exteroception; PasInt = Passive Interoception.Interactions and simple effects of task. A follow-up simple effects contrast of [Active Exteroception > Active Interoception] largely replicated the interaction effect ( | PMC10295813 | |
Covariates of self-reported interoceptive awareness | SEPARATION, ANTERIOR, POSITIVE | To better understand the nature of the deactivation observed during Active Interoception relative to Active Exteroception, a focal analysis was conducted to investigate the potential moderating role of self-reported interoceptive awareness (MAIA scores). Interoceptive awareness was significantly related to the level of deactivation observed across a subset of the cortical regions implicated in interoception-related deactivation (Positive covariates of MAIA scale on [ActExt > ActInt] contrastActExt = Active Exteroception; ActInt = Active Interoception; ActMatch = Active Matching; PasExt = Passive Exteroception; PasInt = Passive Interoception.Covariates of self-reported interoceptive awareness. MAIA scale and anterior cingulate (ACC) activation with all five task conditions. The relationship between interoceptive sensibility/awareness scores (MAIA) and anterior cingulate activity across all five task conditions. Signal was extracted from each experimental condition and plotted above, demonstrating the same reduced separation between conditions, including within the passive conditions. ActExt = Active Exteroception, ActInt = Active Interoception, ActMatch = Active Matching, PasExt = Passive Exteroception, PasInt = Passive Interoception. Download MAIA covariates of the [Active Interoception – Active Exteroception] contrast, corrected using threshold-free cluster estimation (TFCE) to the familywise MAIA covariates of the [Active Interoception – Active Exteroception] contrast, corrected using the joint thresholds of MAIA Scale subfactor intercorrelations and reliabilities. Download Factor loadings for a single factor solution of the eight MAIA subfactors. Download Univariate Correlations of Anterior Cingulate ROI with MAIA total score and subscales. Download MAIA subscales generally showed comparable correlations with the region of interest (ROI) as the total score (MAIA subscale correlates with MAIA covariate ROI: means, SDs, and correlations with confidence intervalsM and SD are used to represent mean and standard deviation, respectively. Values in square brackets indicate the 95% confidence intervals. * indicates correlations with As the largest and most powerfully moderated cluster, the ACC region, k = 1205, | PMC10295813 | |
Endogenous versus exogenous sources of interoceptive control | The next planned comparison contrasted Active Matching against Active Interoception to explore endogenous and exogenous sources of respiratory control. To contextualize Active Matching, we first compared it to Active Exteroception. Active Matching showed even more pronounced and widespread patterns of deactivation than Active Interoception (Endogenous versus exogenous sources of interoceptive control. | PMC10295813 | ||
Psychophysiological interaction (PPI) analysis | CORTEX | The final contrast examined changes in functional connectivity between Active Exteroception and Active Interoception. The anterior cingulate cortex (ACC) region of interest (Comparisons between active effects and active matchActExt = Active Exteroception; ActInt = Active Interoception; ActMatch = Active Matching.PPI effectsThe PPI was defined by the interaction of the [ActInt – ActExt] contrast * ACC activity.Psychophysiological interaction (PPI) analysis. Test-retest reliability of neuroimaging findings. To demonstrate the robustness and replicability of the results, conjunction analysis for the four main contrasts reported in this paper was conducted. As the TFCE algorithm does not currently perform conjunction analysis, and halving the sample size reduces experimental power, the baseline and postintervention sessions were each analyzed separately at | PMC10295813 | |
Test-retest reliability | A conjunction analysis of the main H1–H4 contrasts estimated separately at each of the two timepoints successfully reproduced the results described above ( | PMC10295813 | ||
Discussion | RVT | Relative to visual Exteroception, respiratory Interoception was characterized by pervasive neural deactivation in prefrontal, somatomotor, striatum, and temporoparietal regions. This finding deviates from previous respiratory interoception studies (Alternatively, slower and deeper breathing during the Active Interoception condition could suggest that neural activation differences may be predicated on gross physiological changes driven by different respiration rates, RVT, and spontaneous end-tidal COThe right anterior insula, commonly implicated in investigations of interoceptive accuracy ( | PMC10295813 | |
The moderating influence of self-reported interoceptive awareness | A second aim of the study was to explore the potential moderating effects of subjective interoceptive awareness (MAIA scores) on interoceptive network engagement, with the hypothesis that greater subjective interoceptive awareness would be supported by increased SLN activity in the ACC and anterior insula, commensurate with their established role in supporting interoceptive accuracy (Despite the surprising widespread pattern of cortical deactivation during interoception of the breath, the ACC was spared from deactivation in participants who generally reported greater interoceptive awareness via the MAIA total score. Exploratory analyses of the MAIA subfactors suggested that this moderating effect was driven primarily by the Emotion Awareness, Self-Regulation, and Body Listening subfactors, which were intended to assess “Mind-Body Integration” during the scale’s construction ( | PMC10295813 | ||
Characterizing the network supporting interoceptive awareness | The final aim of the study was to characterize an interoceptive attention network supporting adaptive interoceptive sensibility. The rostral ACC was identified as a seed region for psychophysiological interaction (PPI) analysis, convolving the activity in the region implicated as a MAIA covariate with the Active Interoception versus Active Exteroception contrast.Breath interoception led to increased connectivity between the ACC and the frontoparietal dorsal attention network (DAN; The idea of an “always on” interoceptive state is consistent with contemporary theories that place interoception as the background of consciousness, such as Damasio’s “Proto Self” ( | PMC10295813 | ||
Limitations and constraints on generalizability | somatic disorders, anxiety, interoceptive dysfunction, Thomas, RVT | EVENTS, BRAIN, CORTEX | The IEAT should be improved by introducing a circle motion to the Passive Interoception condition, as the stationary target described here led to a motion confound between passive interoception and the other four experimental conditions. In its current form, Passive Interoception showed relative deactivation in the middle temporal (MT or V5) region of the visual cortex, which is well-established for its sensitivity to motion (Additionally, while we corrected for both respiration frequency and RVT, we did not measure PSeveral constraints on generalizability are also apparent. We present unexpected and exploratory findings from a small sample; replication is therefore needed, especially given the paucity of studies in this area. The community sample may also not generalize to people with clinical conditions associated with interoceptive dysfunction, nor advanced contemplative practitioners with extensive interoceptive training. Respiration is also only one of many interoceptive signals that each vary in their reportability and controllability, and so may possess distinct neural dynamics. Multimodal interoceptive research is needed to determine the generalizability of the patterns discussed here, to clarify the impact of active reporting versus passive engagement, the role sensory signal salience, and the influence of participant expertise/dysfunction.A further limitation to the present findings is that all practices were conducted with eyes-open, which may be dissimilar to many meditation practices. Following repeated evidence that opening one’s eyes decreases the functional connectivity between the SLN and the DMN, it was theorized that reducing the connectivity between these networks reflects an orientation to external rather than internal events (In conclusion, relative to Exteroception, Interoception of the breath reduced somatomotor and prefrontal activity, offset by enhanced connectivity between the ACC and the DAN. Greater self-reported interoceptive awareness was linked to sparing of the ACC and language processing regions from this deactivation pattern. Together, these processes may allow sensory signals from the body to be better discerned. The ACC deactivation observed in the IEAT paradigm may serve as a candidate biomarker of individual differences in interoceptive processing, one that distinguishes adaptive representations engendered by contemplative training from the avoidance and catastrophizing observed in anxiety and somatic disorders. Larger, more diverse samples and replication of effects are needed to test these emerging ideas.Acknowledgments: We thank Natalie Koh and Sophie Xie for their coordination and data collection efforts and to Dr. Thomas Grabowski, Dr. Chris Gatenby, and Liza Young at the Integrated Brain Research Center at the University of Washington for their collaboration. | PMC10295813 |
References | PMC10295813 | |||
Synthesis | respiratory interoceptive attention, interoceptive sensations, ’ | MINOR, CORTEX | Reviewing Editor: Erica Glasper, The Ohio State UniversityDecisions are customarily a result of the Reviewing Editor and the peer reviewers coming together and discussing their recommendations until a consensus is reached. When revisions are invited, a fact-based synthesis statement explaining their decision and outlining what is needed to prepare a revision will be listed below. The following reviewer(s) agreed to reveal their identity: NONE. Note: If this manuscript was transferred from JNeurosci and a decision was made to accept the manuscript without peer review, a brief statement to this effect will instead be what is listed below.Overview: The authors of this manuscript describe a new fMRI task that utilizes respiratory interoceptive attention, with the goal of using it to probe the neural basis of interoception in studies that could follow. The authors selected a small sample of health individuals from a larger clinical trial using a mindfulness intervention that focused on body awareness. These individuals reported higher levels of stress during this task. The authors report that, despite their initial predictions, participants demonstrated widespread deactivations, rather than activations, of the insular cortex and other brain regions. The task is sound and the study, overall, is meritorious. There are a few minor concerns, that require further attention that are described, in detail, below. When needed, exact reviewer comments can be found in quotations.Overall CommentsThe authors are encouraged to reduce, or remove, the many leading statements within the manuscript. Please see the following as examples and consider phrasing that mentions an association between 2 variables:1. Abstract - ‘attention towards...may lead to a low activity, high connectivity state’2. Discussion - ‘Interoception led to increased connectivity in the frontoparietal dorsal attention network’Remaining ConcernsStatistics1. It is unclear why the authors used a global MAIA score instead of conducting analyses on the validates subscales. If a multiple comparison issue is of concern, this analysis could be included in the supplemental material to highlight “whether the observed brain-behavior relationships could be further refined”.2. 22 participants in a small N size, and not a ‘relatively small’ N like the author’s state. This should be explicitly emphasized in the revised manuscript and the authors should state that replication is needed given this small N.Discussion1. It is suggested that the authors reconsider the “notion of MAIA scores simply as a measure of ‘interoceptive sensibility’ in the discussion”. The authors should focus on the most relevant subscale processes.2. It is suggested that the authors reduce, or narrow, the respiratory interoceptive network inferences. The full extent to which these findings may apply to other interoceptive sensations was not studied. | PMC10295813 |
Author Response | interoceptive sensations, ’ | CORTEX | Dear Professor Glasper,Thank you for your efforts in reviewing our manuscript entitled “Interoceptive Awareness of the Breath Preserves Dorsal Attention Network Activity amidst Widespread Cortical Deactivation: A Within-Participant Neuroimaging Study“, submitted for consideration in eNeuro.We appreciate your supportive synthesis of the paper, reviews, and response to reviews. We are grateful to the reviewers for their suggestions, which we believe have helped us to substantially improve the paper. We respond to each of the comments below.Overall Comments. The authors are encouraged to reduce, or remove, the many leading statements within the manuscript. Please see the following as examples and consider phrasing that mentions an association between 2 variables:1. Abstract - ‘attention towards...may lead to a low activity, high connectivity state’We have replaced this general statement with more specific language: “attention towards accessible body sensations such as the breath may lead to greater ACC-Dorsal Attention Network connectivity state in a context of widespread cortical deactivation.”2. Discussion - ‘Interoception led to increased connectivity in the frontoparietal dorsal attention network’We clarify that “Breath interoception led to increased connectivity between the ACC and the frontoparietal dorsal attention network”.Remaining ConcernsStatistics1. It is unclear why the authors used a global MAIA score instead of conducting analyses on the validates subscales. If a multiple comparison issue is of concern, this analysis could be included in the supplemental material to highlight “whether the observed brain-behavior relationships could be further refined”.We appreciate the suggestion to delve deeper than a blanket ‘sensibility’ description of the MAIA, and the reviewer is correct that we shouldn’t equivocate- we have revised the description of MAIA to be an assessment of subjective interoceptive awareness and attention tendency throughout the manuscript.We also agree that greater specificity of our findings could be supported by reviewing the interoceptive subscales. We initially created a second supplement to the paper (“Supplementary MAIA Analyses”), but learned that eNeuro does not allow supplemental materials, so we have placed extensive analyses within a document on the Open Science Framework for your reference (https://osf.io/d3uzw), with the highlights of these analyses added to the manuscript text.The supplement reviews the creation of the MAIA and its conceptual and empirical subfactors, and explains why we chose to use the single total score given limitations with the original version of the MAIA that was available at the time of data acquisition. We support this decision via exploratory factor analysis of the observed data, showing an optimal single-factor solution, and also that many of the subfactors show similar correlations with anterior cingulate cortex (ACC) region of interest (ROI).We did take to heart the need to go deeper than a blanket total score; we therefore explored each of the eight MAIA subfactors at both the TFCE familywise-error corrected and a more liberal threshold (p<.005, k{greater than or equal to}200), we now attach figures of these analyses as extended data to the MAIA analysis figure (The reviewer was correct that these analyses show more directly how whole-brain covariates might be supported by the subscales. The MAIA total score covariate map is similar to reduced- threshold maps for the subfactors of Emotion Awareness, Self-Regulation, Body Listening, and to a lesser extant Attention Regulation and Noticing. These whole brain analyses suggest a particular role of the “Mind-Body Integration” conceptual domain in supporting the covariation effect. Intriguingly, Attention Regulation implicated only the ACC component of the total score map, whereas Noticing implicated only language regions. By contrast the Not Distracting, Not Worrying, Trusting, and Noticing subfactors show little of this covariation effect, suggesting that self-reported integration/use of interoceptive information may be driving the total score finding. We make note of these ideas in the revised discussion section.2. 22 participants in a small N size, and not a ‘relatively small’ N like the author’s state. This should be explicitly emphasized in the revised manuscript and the authors should state that replication is needed given this small N.We appreciate the need to be clear about small sample size and have removed the word ‘relatively’ from the sentence, which now reads “We present unexpected and exploratory findings from a small sample; replication is therefore needed, especially given the paucity of studies in this area.” (p.32)Discussion1. It is suggested that the authors reconsider the “notion of MAIA scores simply as a measure of ‘interoceptive sensibility’ in the discussion”. The authors should focus on the most relevant subscale processes.We agree that the subscales add nuance, and also that ‘sensibility’ may not be the appropriate term for what the MAIA measures- we have revised the manuscript to emphasize ‘attention tendency’ rather than ‘sensibility’ per se, which seems to be a narrower term focusing on appraisal. As noted above, the suggested subscale analyses provide supporting evidence that these effects are driven primarily by the integration subscales (Emotion Awareness, Self-Regulation, and Body Listening), and we now dedicate a paragraph of the results and discussion to reviewing these findings, in addition to a more lengthy discussion of these findings in the MAIA Analysis Supplement found on the Open Science Framework (https://osf.io/d3uzw) as eNeuro will not allow supplemental materials beyond additional tables and figures.2. It is suggested that the authors reduce, or narrow, the respiratory interoceptive network inferences. The full extent to which these findings may apply to other interoceptive sensations was not studied.This suggestion is well-received given the multimodal nature of interoception. We have revised the manuscript language to be more specific about respiratory interoception / attention to the breath rather than implying that the findings generalize to interoception more broadly.We are grateful for the opportunity to improve our work and hope that the revisions satisfy the constructive suggestions offered by the editor and reviewers.Thank you for time and consideration. We look forward to your feedback!Best regards, | PMC10295813 |
Introduction | MFDM, diabetes | CROSS, DIABETES | Edited by: John L. Sievenpiper, St. Michael’s Hospital, CanadaReviewed by: Rongshao Tan, Guangzhou Red Cross Hospital, China; Lalita Tantisira, University of California, San Diego, United States; Evelyn Parr, Australian Catholic University, AustraliaWe developed a novel rice-based medical food for diabetes (MFDM) powder formula, using locally available ingredients in Thailand, which can potentially improve patient access to diabetes-specific formula (DSF) by reducing cost and improving availability. | PMC10244629 |
Purpose | gastrointestinal (GI) hormone responses, MFDM, prediabetes | TYPE 2 DIABETES, PREDIABETES | The goals of our studies were to 1) measure the glycemic index (GI) and glycemic load (GL) of the MFDM powder formula in healthy individuals, and 2) assess postprandial glucose, insulin, satiety, hunger, and gastrointestinal (GI) hormone responses in adults with prediabetes or early type 2 diabetes after consuming MFDM in comparison with a commercially available standard formula (SF) and a DSF. | PMC10244629 |
Methods | MFDM, prediabetes | TYPE 2 DIABETES, PREDIABETES | In Study 1, glycemic responses were assessed using the area under the curve (AUC), which was used to calculate GI and GL. Study 2 was a double-blinded multi-arm randomized crossover trial enrolling participants with either prediabetes or type 2 diabetes of ≤6 years. At each study visit, participants consumed either MFDM, SF, or DSF which contained 25 g of carbohydrates. Hunger and satiety were assessed using a visual analog scale (VAS). Glucose, insulin, and GI hormones were assessed using AUC. | PMC10244629 |
Results | ADVERSE EVENTS | All participants tolerated the MFDM well with no adverse events. In Study 1, the measured GI was 39 ± 6 (low GI) and GL was 11 ± 2 (medium GL). In Study 2, glucose and insulin responses were significantly lower after MFDM compared with SF ( | PMC10244629 | |
Conclusions | prediabetes, MFDM | HYPERGLYCEMIA, TYPE 2 DIABETES, PREDIABETES | MFDM had a low GI and a low-to-medium GL. In people with prediabetes or early type 2 diabetes, MFDM elicited reduced glucose and insulin responses when compared with SF. Rice-based MFDM may be an option for patients who are at risk for postprandial hyperglycemia. | PMC10244629 |
Clinical Trial Registration | PMC10244629 | |||
Introduction | hyperglycemia, satiety, MFDM, diabetes | HYPERGLYCEMIA, DIABETES MELLITUS, DIABETES | Diabetes-specific enteral nutrition formulas (DSFs) are an integral part of the management of patients with diabetes. In inpatient settings, oral and enteral nutrition often result in hyperglycemia which has been associated with adverse outcomes including increased mortality (Meta-analyses have shown that DSFs can reduce postprandial glucose responses, improve HbA1c and lipid profile, and promote satiety due to their low glycemic index (GI) and glycemic load (GL), increased fiber and protein content, and the use of healthy lipid blends (Despite its benefits, patient access to DSF remains limited in many clinical settings, particularly in low- and middle-income countries such as Thailand, with cost and lack of reimbursement being important barriers. For this reason, the development of novel DSFs using locally available ingredients can potentially improve patient access to DSFs by reducing cost and improving availability.Rice (The objectives of this study were twofold. The first objective was to measure the glycemic index and glycemic load of a novel rice-based diabetes-specific formula (MFDM, medical food for diabetes mellitus, powder formula) in healthy individuals. The second objective was to compare postprandial responses in glucose, insulin, gastrointestinal hormones, satiety, and hunger after consumption of the MFDM with commercially available formulas, including a non-diabetes-specific standard formula (SF) and a diabetes-specific formula (DSF) in adults with recent-onset diabetes or those who were at risk for diabetes. | PMC10244629 |
Materials and methods | PMC10244629 | |||
Development of the rice-based diabetes-specific formula (medical food for diabetes mellitus) | MFDM, diabetes | DIABETES MELLITUS, DIABETES | The novel rice-based MFDM was developed by SC and CH from the Department of Nutrition, Faculty of Public Health, Mahidol University and manufactured by DOD Biotech Public Company Limited (Samut Sakhon, Thailand). The ingredients of the MFDM are shown in Ingredients of the novel rice-based medical food for diabetes (MFDM powder formula).MFDM, medical food for diabetes mellitus.The macronutrient composition of the MFDM, SF, and DSF.NA, data not available; SFA, saturated fatty acids; MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids.Data is shown as the amount per usual serving size and the amount per serving used in Study 2. In Study 2, serving sizes were matched so that 25 g of carbohydrates would be available from each formula. | PMC10244629 |
Study 1: Glycemic index and glycemic load in healthy individuals | PMC10244629 | |||
Study design and setting | MFDM | This study was designed in compliance with ISO 26642:2010 (E) (In this study, each participant presented to the study center for 3 study visits which included (in the order of occurrence):Visits 1 and 2: consuming 50 g of glucose dissolved in 300 ml of water which served as the standard foodVisit 3: consuming MFDM which contained 50 g of glucose, prepared by dissolving 95.42 g of MFDM powder in water to reconstitute a 300 mL solutionAll participants had the same study visit sequences since the interventions were unlikely to have any period or order effects. The washout period used was between 1 to 30 days, since it was unlikely that the effects of the interventions would be carried over beyond one day ( | PMC10244629 | |
Participants | Inclusion criteria included age 18-60 years, BMI 18.5-23 kg/m | PMC10244629 | ||
Interventions | MFDM | PATHOLOGY | Participants were recruited from online advertisements and billboards. After an initial telephone screening interview, eligible participants presented to the study center for screening blood tests which included fasting plasma glucose and HbA1c. These tests were measured from the venous blood by the clinical pathology laboratory at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (Cobas 8000 Analyzer Series, Roche Diagnostics, Indianapolis, United States). HbA1c was measured according to the standards of the National Glycohemoglobin Standardization Program (NGSP). Those who met all the inclusion criteria were enrolled in the study. Subjects were asked to fast after 8 pm and avoid exercises before attending each study visit.At the first study visit, participants’ baseline data including sex, age, body weight, body mass index, waist circumference, hip circumference, blood pressure, medical history, and current medications were collected. Height was measured using a calibrated stadiometer. Body weight (BW) was measured, using a calibrated weighing scale (TANITA BC-587, Tanita Corporation, Tokyo, Japan). Body mass index (BMI) was calculated by BW (kg)/(height [m]Participants were asked to consume the glucose solution or MFDM at an even pace and to finish within 15 mins. After finishing, drinking up to 250 ml of water was allowed. For each subject, a blood sample was taken in the fasting state and used as the baseline blood glucose concentration. After consumption of the reference food or test food, blood samples were collected at 15, 30, 45, 60, 90, and 120 mins, and assayed for glucose. Precautions were taken during the screening, enrollment, and intervention periods to minimize the risk of SARS-CoV-2 transmission including avoiding crowding, determining a history of high-risk exposure, and asking participants to perform SARS-CoV-2 rapid testing before coming in for study visits. | PMC10244629 |
Sample size | At least ten participants were included in the study to comply with the ISO 26642:2010(E) standards. A participant may be considered an outlier if the glycemic index measured from that participant was 2 standard deviations below or above the mean of the group of 10 participants or more. Outliers may be excluded if at least 10 participants remain available for analysis. | PMC10244629 | ||
Outcomes and statistical analysis | The area under the curve (AUC) of glucose was calculated using the trapezoidal rule. Only positive areas under the curve were considered. The glycemic index and glycemic load for each participant were calculated as follows:
The glycemic index and glycemic load of each test product were reported as the mean ± standard error of the mean (SEM). | PMC10244629 | ||
Study 2: Glycemic, insulin, and gastrointestinal hormone responses in adults with diabetes or at risk for diabetes | PMC10244629 | |||
Study design and setting | MFDM, A. Rice-based diabetes-specific formula | The study was designed as a four-arm randomized double-blinded crossover clinical trial. This trial was prospectively registered at the Thai Clinical Trials Registry (A. Rice-based diabetes-specific formula, powder (MFDM)B. Rice-based diabetes-specific formula, liquid (MFDM-liquid)C. Commercially available standard non-diabetes formula (SF)D. Commercially available diabetes-specific formula (DSF)This report focuses on the data from the MFDM, SF, and DSF interventions. Data from the MFDM-liquid intervention will be published in a future report.These interventions were chosen to allow for the comparison of the MFDM with either a commercially available diabetes-specific formula or a standard, non-diabetes-specific formula, with an assumption that the MFDM would elicit glycemic and hormonal responses similar to the commercially available DSF, but would elicit less glycemic responses and more favorable hormonal responses compared with commercially available SF. Each intervention was separated by a washout period of between 7 to 14 days, because the effects of study products on the primary outcome, postprandial glucose response, were unlikely to carry over beyond such a period ( | PMC10244629 | |
Randomization and blinding | The participants were randomized to receive interventions in one of the following orders 1) ABCD, 2) BCDA, 3) CDAB, and 4) DABC, in a ratio of 1:1:1:1 using randomization with a permuted block of four. Study personnel (pharmacists) who were not involved in subject enrollment or data collection performed randomization and blinding. All other personnel and all participants were blinded to the order of the intervention. The pharmacists utilized an online program (sealedenvelope.com) to generate a randomization list ( | PMC10244629 | ||
Participants | Inclusion criteria included age 18-60 years, BMI 25-35 kg/m | PMC10244629 | ||
Formulas | The comparison of composition between the MFDM, SF, and DSF formulas is shown in Standard non-diabetes formula (SF, commercial formula 1, Fresubin 2 kcal Fibre, Fresenius Kabi, Bad Homburg, Germany): usual serving size = 200 ml, serving size in Study 2 = 114.7 ml diluted to 300 mlDiabetes-specific formula (DSF, commercial formula 2, Glucerna SR Triple Care, Abbott Laboratories, Chicago, Illinois, United States): usual serving size = 230 ml, serving size in Study 2 = 287.5 ml diluted to 300 mlRice-based diabetes-specific formula, powder (MFDM): usual serving size = 55g diluted to 250 ml, serving size in Study 2 = 47.7 g diluted to 300 mlThe amount of carbohydrates of 25g was chosen to allow serving sizes to be reasonable and not too large for a single meal. We chose to administer the formulas orally instead of through a feeding tube since both methods would likely induce similar physiological responses and oral administration was more comfortable for the study participants. | PMC10244629 | ||
Interventions | Satiety | BLOOD | Participants were recruited from posters and online advertisements. After a screening phone interview, eligible participants were selected and asked to visit the study center for screening blood tests (fasting plasma glucose and HbA1c). Those who met all the inclusion criteria were enrolled in the study. Subjects were asked to fast after 8 pm and avoid exercises before attending each study visit.At the first study visit, participants’ baseline data including sex, age, body weight, body mass index, waist circumference, hip circumference, blood pressure, medical history, and current medications were collected similarly as in Study 1. All products were diluted to the same final volume of 300 ml. Participants were asked to consume study products at an even pace within 15 mins with up to 250 ml of water afterward. Blood samples were collected at baseline and 15, 30, 45, 60, 90, and 120 mins after consuming study products. Blood samples were assayed for glucose, insulin, and gastrointestinal hormones as discussed below. Satiety and hunger were assessed at each time point using visual analog scales (VAS). Similar precautions were taken as in Study 1 to reduce the risk of SARS-CoV-2 transmission during the study. | PMC10244629 |
Hunger and satiety | hunger and satiety | A visual analog scale (VAS) was used to assess hunger and satiety at baseline, and then at 15, 30, 45, 60, 90, 120, and 180 mins after consuming study products. The participants self-reported their hunger and satiety using the VAS which comprises ten 1-centimeter segments, representing a score from 0 to 10. All volunteers were asked not to discuss their feelings or ratings with their counterparts. | PMC10244629 | |
Gastrointestinal hormones | Gastrointestinal hormones, including active ghrelin, glucose-dependent insulinotropic peptide (GIP), active glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) were measured using a bead-based multiplex assay kit (MILLIPLEX | PMC10244629 | ||
Sample size | TYPE 2 DIABETES | The sample size was calculated using nQuery Advisor version 6.01 (Statsols (Statistical Solutions Ltd), Cork, Ireland). Previously, Garcia-Rodriguez et al. demonstrated that the mean ± SEM of AUC of glucose in participants with type 2 diabetes after consuming Glucerna SR was 415 ± 71 mmol/l*min ( | PMC10244629 | |
Outcomes and statistical analysis | satiety, gastrointestinal hormones | There was no significant change to trial outcomes after trial commencement. Characteristics of participants at baseline were described using standard descriptive statistics. Data were presented as the median and interquartile range (IQR). The area under the curve (AUC) of glucose, insulin, other gastrointestinal hormones, and satiety or hunger visual analog scale (VAS) score were calculated using the trapezoidal rule. Only positive areas under the curve above the baseline value were considered, except for ghrelin for which only negative areas under the baseline were considered. AUC of glucose, insulin and other gastrointestinal hormones were compared between interventions using paired | PMC10244629 | |
Results | PMC10244629 | |||
Study 1: Glycemic index and glycemic load in healthy individuals | diabetes mellitus, MFDM | DIABETES MELLITUS | The participant flow is illustrated in Participant flow diagram for Study 1.Baseline characteristics of healthy subjects in Study 1. Data are presented as the median and interquartile range (IQR) unless noted otherwise.Glycemic response in healthy subjects to MFDM powder formula compared with glucose in Study 1. Error bars represent SEM.Measured glycemic index and glycemic load of the novel rice-based medical food for diabetes mellitus (MFDM) powder formula.*Calculated based on available carbohydrates per serving; MFDM contained 28.82 g of carbohydrates per serving (55g).**Glycemic index is considered low if ≤ 55, medium if >55 and ≤70, and high if >70.***Glycemic load is considered low if ≤ 10, medium if 11-19, and high if ≥20. | PMC10244629 |
Study 2: Glycemic, insulin, and gastrointestinal hormone responses in adults with diabetes or at risk for diabetes | The participant flow diagram is shown in Participant flow diagram for Study 2.Baseline characteristics of participants in Study 2. Data are shown as the median and interquartile range (IQR) unless noted otherwise. | PMC10244629 | ||
Glucose and insulin responses | The MFDM powder formula elicited significantly lower glycemic response compared with SF (Response curves and AUC of glycemic responses | PMC10244629 | ||
Hunger | The MFDM formula suppressed hunger over the course of 180 minutes ( | PMC10244629 | ||
Satiety | The MFDM formula promoted satiety over the course of 180 minutes ( | PMC10244629 | ||
Gastrointestinal hormone responses | After consumption of the MFDM powder formula, stimulation of active GLP-1, PYY, and GIP and suppression of ghrelin were noted (Response curves and AUC of active GLP-1 | PMC10244629 | ||
Tolerability and adverse events | ADVERSE EVENTS | There was no adverse events or side effects during the study. All participants tolerated the new MFDM powder formula well without any gastrointestinal side effects. | PMC10244629 | |
Discussion | satiety, postprandial gastrointestinal hormones, MFDM, diabetes | TYPE 2 DIABETES, DIABETES | In the first study, we demonstrated that the novel rice-based MFDM powder formula had attenuated postprandial glycemic response compared with glucose in a healthy population, resulting in a low GI and a low-to-intermediate GL. In the second study performed in adults with diabetes or at risk for diabetes, when compared with the commercially available standard formula (SF), the MFDM powder formula had significantly lower postprandial glycemic and insulin responses even when the serving sizes were matched for the carbohydrate content and macronutrient distribution (We also demonstrated in the second study that the MFDM powder formula had similar glucose and insulin responses when compared with a commercially available diabetes-specific formula (DSF) in adults at risk for or diagnosed with early diabetes. The carbohydrate sources differed significantly between the two formulas. Commercial product 2 contained maltodextrin (40%), Fibersol 2 (25%), and sucromalt (20%), while the MFDM powder formula contained physically modified rice flour (22.3%), fructose (11.5%), and isomaltulose (15.6%) (In Study 2 we showed that the novel MFDM powder formula produced suppressed hunger and maintained satiety throughout the course of each intervention day. The formula also stimulated the release of active GLP-1, GIP, and PYY, and suppressed active ghrelin over the course of 180 minutes. However, such effects on hunger, satiety and postprandial gastrointestinal hormones did not differ significantly from the commercially available SF and DSF. Some previous studies demonstrated the ability of diabetes-specific formulas to stimulate greater postprandial GLP-1 release compared with control foods or standard formulas (The limitations of our studies included a short-term study design. Although we were able to assess postprandial glycemic and hormonal responses after consumption of the novel rice-based MFDM powder formula, long-term studies are required to investigate the effects of the MFDM formula on glycemic control, body weight, and other health outcomes over a longer period. The generalizability of our study may also be limited as the study was single-center and enrolled only healthy individuals, those at risk for diabetes, and those with early-onset type 2 diabetes. The effects of the MFDM powder on people with long-standing diabetes must be assessed in another study. The strengths of our studies, primarily Study 2, included a double-blinded multi-arm randomized crossover design, and matching of macronutrient distribution and carbohydrate content per serving in the three formulas tested.To conclude, we showed in this study that in healthy participants, the rice-based MFDM powder formula had a low glycemic index and a low-to-intermediate glycemic load. We also showed that in adults at risk for diabetes or with early type 2 diabetes, the MFDM powder formula produced significantly less glucose and insulin responses compared with a commercially available standard formula (SF). The MFDM powder formula may be an option for patients who require diabetes-specific formulas, particularly those who are vegan as all of its ingredients are plant-based. The use of locally sourced ingredients has lowered the cost of the MFDM to 18-24 THB (0.5-0.7 USD) per 250 ml serving compared with 70-170 THB (2-5 USD) per 250 ml serving for other commercial formulas. This likely would improve patient access and reduce the barrier to care in resource-limited settings such as in Thailand. | PMC10244629 |
Data availability statement | The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author. | PMC10244629 | ||
Ethics statement | The studies involving human participants were reviewed and approved by Human Research Protection Unit, Faculty of Medicine Siriraj Hospital, Mahidol University. The patients/participants provided their written informed consent to participate in this study. | PMC10244629 | ||
Author contributions | SC and CH developed and oversaw the production of the MFDM powder formula. The study was conceived and designed by PP, SC, and CH. NKe, CC, NKh, WD, PW, TS, and PP enrolled participants and conducted the study visits. NKe and CC performed measurements of the gastrointestinal hormones. NKe, CC, and PP performed the statistical analysis and wrote the first draft of the manuscript. All authors contributed to the manuscript revision and approved the submitted version. | PMC10244629 | ||
Acknowledgments | We want to thank our advisors, including Professor Dr. Prasit Watanapa, Ph.D., Associate Professor Dr. Watana Watanapa, Ph.D., Associate Professor Dr. Suebwong Chuthapisith, Ph.D., and Ms.Songsri Keawtanom for their kind guidance throughout our journey. We also want to thank Ms. Julaporn Pooliam from the Clinical Epidemiology Unit, Faculty of Medicine Siriraj Hospital, Mahidol University for her assistance with sample size calculation and data analysis. Lastly, we thank the Siriraj Institute of Clinical Research (SiCRES) at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok for their assistance with double-blinding and conducting the study visits. | PMC10244629 | ||
Conflict of interest | The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. | PMC10244629 | ||
Publisher’s note | All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. | PMC10244629 | ||
References | PMC10244629 | |||
Background | hyperpigmentation | HYPERPIGMENTATION | Physiologic gingival hyperpigmentation is a common esthetic concern that affects individuals of various ethnicities, and can have a significant impact on individual’s self-confidence and overall quality of life. Thus, this study aimed to clinically assess the effectiveness of intra-mucosal injection of vitamin C versus 980 nm diode laser for the management of physiologic gingival hyperpigmentation. | PMC10662509 |
Methods | hyperpigmentation, pain | PIGMENTATION, HYPERPIGMENTATION | Twenty-six healthy non-smoker individuals with physiologic gingival hyperpigmentation were randomly assigned to two groups. Group I received intra-mucosal injection of vitamin C (L-Ascorbic acid 1000 mg/5 ml), and group II was managed using diode laser (980 nm, 1.5 W, continuous wave mode). Clinical evaluation of pigmentation intensity and distribution was performed preoperatively, and at 1, 2 and 3 months postoperatively using two different color assessment indices; Dummett-Gupta Oral Pigmentation Index (DOPI), and Gingival Pigmentation Index (GPI). Additionally, the study assessed pain intensity and patients’ satisfaction. | PMC10662509 |
Results | PIGMENTATION | Pigmentation scores decreased significantly between pre-operative visit and different follow-up visits for both treatment modalities | PMC10662509 | |
Conclusions | HYPERPIGMENTATION | Vitamin C mesotherapy and diode laser are both effective in the management of physiologic gingival hyperpigmentation. While diode laser yields better and earlier results, vitamin C mesotherapy offers a cost-effective, safe and minimally invasive approach that is equally satisfying for the patients seeking esthetic enhancements. | PMC10662509 | |
Trial registration | The study was registered on ClinicalTrials.gov (NCT05608057) on (01/11/2022). | PMC10662509 | ||
Keywords | Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB). | PMC10662509 | ||
Background | depigmentation, Efficient coagulation, hyperpigmentation, pain | DEPIGMENTATION, HYPERPIGMENTATION, MELANIN HYPERPIGMENTATION | In today’s world, patients’ esthetic demands and expectations have greatly risen, with all current trends focusing on facial esthetics and smile design. A smile plays a vital role in non-verbal communication, and greatly influences an individual’s self-esteem. It holds significant value in social interactions impacting relationships, professional image, and personality development. Studies have consistently shown that individuals who are satisfied with their physical appearance, particularly their smile, tend to be more confident and successful. Conversely, a compromised smile negatively impacts personal image and overall quality of life [The role of pink esthetics in smile design cannot be overlooked, as the harmony of a smile is not solely determined by the shade, shape and arrangement of teeth, but also by the appealing and healthy appearance of the surrounding gingival tissues [Healthy gingival color is generally described as coral pink [Gingival hyperpigmentation is defined as increased intensity of gingival color through excessive melanin deposition by the melanocytes found within the basal and supra-basal cell layers of the gingival epithelium [A wide range of depigmentation techniques have been proposed with the surgical approaches being the most widely employed such as conventional scalpel surgery, bur abrasion, electrosurgery, cryosurgery, radiosurgery & more recently, the application of lasers of different types & wavelengths [Laser-tissue interaction is dependent on the laser light’s affinity for specific chromophores found within the tissue [Efficient coagulation, short treatment line, accelerated healing, and excellent esthetic outcomes are laser’s known advantages. However, the expensive and sophisticated equipment limits its use, and significantly raises the cost of treatment [Vitamin C, also known as Ascorbic acid, has been introduced as a promising therapeutic agent for reducing melanin hyperpigmentation due to its ability to suppress the activity of tyrosinase, the rate-limiting enzyme in melanin biosynthesis [In the field of dermatology, vitamin C has gained significant popularity and has been widely employed as a safe depigmenting agent. It has shown promising results in the treatment of various dermatological problems associated with hyperpigmentation [However, a recent systematic review indicated that studies investigating the application of vitamin C for gingival depigmentation are scarce, with the majority being experimental studies [The aim behind introducing vitamin C mesotherapy in clinical practice was to develop a novel approach that enables targeted and localized delivery of the therapeutic agent, vitamin C, to the site of concern, maximizing its efficacy and ensuring a more potent and focused effect. On the financial aspect, vitamin C mesotherapy stands out as a cost-effective treatment modality, allowing successful drug delivery using inexpensive equipment, and requiring short learning curve for the general practitioner [To the best of our knowledge, no clinical trial has exclusively compared the clinical effect of vitamin C mesotherapy with laser ablation therapy for gingival depigmentation. Therefore, the aim of this study was to compare the effectiveness of vitamin C mesotherapy with diode laser ablation therapy for the management of physiologic gingival hyperpigmentation in terms of clinical outcome, pain perception and patients’ satisfaction. | PMC10662509 |
Methods | PMC10662509 | |||
Study design | A randomized, parallel double-blinded clinical trial was carried out in accordance with the modified Helsinki’s code for human clinical studies 2013 [This clinical trial received approval from the Research Ethics Committee at the Faculty of Dentistry, Alexandria University (IRB 00010556)-(IORG 0008839), and was registered on ClinicalTrials.gov (NCT05608057) on (01/11/2022). The study protocol was thoroughly explained to each participant, and a written informed consent was obtained. | PMC10662509 | ||
Study setting and patient selection | hypersensitivity | PERIODONTAL DISEASE, HYPERSENSITIVITY | Patients were recruited from the outpatient clinic of the Department of Oral Medicine, Periodontology, Oral Diagnosis and Oral Radiology, Faculty of Dentistry, Alexandria University. After conducting an initial assessment that included reviewing medical and dental histories and performing clinical examinations to determine subject eligibility, 26 subjects met the following inclusion criteria: adults of either sex between 18 and 40 years old with physiologic melanin pigmentation in the anterior esthetic zone of the maxillary or mandibular gingiva, and who were free from any systemic diseases or conditions.On the other hand, the exclusion criteria included: smokers, pregnant and lactating women, drugs intake which associate with gingival melanin pigmentation such as antimalarials drugs, phenothiazines and oral contraceptives, patients with periodontal disease, and patients with known hypersensitivity to ascorbic acid. | PMC10662509 |
Study sample and sample size estimation | PIGMENTATION | Sample size was estimated assuming 5% alpha error and 80% study power. The mean (SD) Pigmentation score after 3 months is assumed to be 0.90 (0.55) for the Vitamin C Mesotherapy [ | PMC10662509 | |
Randomization, allocation concealment and blinding | Participants were randomly allocated into two groups using computer generated random list. The lists were placed in opaque, sealed envelopes, and organized in sequential manner by a dental assistant who was not involved in the study. Subsequently, each envelope was opened at the time of intervention [This study was double-blinded, where both the evaluator of the outcomes and the statistician were blinded to the type of intervention used. Given the differences in the intervention techniques utilized in the two groups, blinding of both the operator and the patient could not be possibly achieved. | PMC10662509 | ||
Patient preparation | Pre-operative preparation phase was performed which included phase I therapy; this involved professional scaling using ultrasonic scalers and comprehensive oral hygiene instructions for all patients ensuring optimal oral health conditions prior to any procedure. | PMC10662509 | ||
Operative procedures | hyperpigmentation, strokes | DEPIGMENTATION, INFILTRATION, HYPERPIGMENTATION, STROKES | Eligible participants were randomly allocated into test group (G1. Mesotherapy) and control group (G2. Diode laser). All interventions were performed by the same operator (S.E.), thereby minimizing any potential variations in operator skills.In both groups, infiltration anesthesia was administered at the target area using a local anesthetic agent; Alexandricaine 1:100000 (1.7 ml Articaine hydrochloride with 1:100000 Adrenaline, Alexandria Co. for Pharmaceuticals & Chemical Industries, Alexandria, Egypt). Group 1 [Vitamin C intra-mucosal injection (G1. Mesotherapy)] received intra-mucosal field injections of 1–1.5 ml Cevarol (L-Ascorbic acid 1000 mg/5 ml, Memphis Pharmaceuticals & Chemical Industries, Cairo, Egypt) using insulin syringe (30 Gauge 1 cc 0.33 mm × 8 mm 5/16″ needle) [The intra-mucosal injection procedure involved inserting the needle just beneath the surface of the gingival epithelium, aligning it parallel to the junction between the epithelium & connective tissue. While ensuring that the bevel of the needle faced upward, an injection volume of 0.1 ml was administered at each point until the tissues blanched. This process was repeated across the entire pigmented area, while maintaining a distance of 2 to 3 mm between injection sites (Fig. Illustration of Vitamin C intramucosal injection (Mesotherapy technique)Each patient underwent four treatment sessions, with a one-week interval between each session. Follow-up evaluations were conducted during each visit, and gingival depigmentation was assessed at 1 month, 2 months, and 3 months following the completion of the treatment procedure. Group 2 [Diode laser ablation (G2. Diode Laser)] was managed using 980 nm Diode laser (MEDENCY Primo Dental Laser, Italy). A comprehensive overview of the laser parameters can be found in (Table Laser parametersTo prevent overheating of the tissues, the tip was moved using small brush strokes in a back and forth motion. Throughout the procedure, the fiber tip was regularly cleaned using gauze soaked in saline solution. To ensure the preservation of the delicate gingival margin and interdental papilla, and to minimize the risk of gingival recession, the elimination of gingival hyperpigmentation was performed with a 1 mm distance maintained from the free gingiva. Epithelial remnants were cleared using gauze soaked in normal saline, serving to enhance visualization and to provide a cooling effect on the tissues. The ablation process was concluded when a whitish pink color was attained throughout the treated area. | PMC10662509 |
Post-operative care | trauma | All patients were given the following postoperative instructions: to refrain from consuming hot, spicy, hard, or rough foods for the first 24-hours, and to avoid any actions that may cause trauma to the treated area during the healing process. No medications were prescribed. | PMC10662509 | |
Assessment | PIGMENTATION | Clinical assessment was conducted at multiple time points, including the baseline examination and follow-up evaluations at 1, 2, & 3 months after completion of the treatment.The following parameters were evaluated:Dummett- Gupta Oral Pigmentation Index (DOPI): [Gingival Pigmentation Index (GPI): [Visual Analogue Scale (VAS): [Patient satisfaction and acceptability questionnaire: [Dummet-Gupta Oral Pigmentation Index (DOPI)Gingival Pigmentation Index (GPI)Satisfaction & Acceptability Questionnaire | PMC10662509 | |
Statistical analysis | Data were analyzed using IBM SPSS version 25, Armonk, NY, USA. DOPI, GPI, and VAS were non-normally distributed and presented mainly using median, minimum, and maximum in addition to mean and standard deviation. Comparisons between groups was done using Mann Whitney U test with Bonferroni correction for multiple comparison adjustment while changes across time intervals were assessed using Friedman test followed by post hoc test with Bonferroni correction. Differences in patient satisfaction were assessed using Pearson Chi Square and Fisher’s Exact tests. Intra-examiner and inter-examiner reliability was calculated using Kappa Statistics. All tests were two tailed and the significance level was set at | PMC10662509 | ||
Results | PMC10662509 | |||
Demographic data | ADVERSE EFFECTS | A total of 26 participants were enrolled in the study and equally randomized into two groups: Group I, the Mesotherapy Group, and Group II, the Laser Group, with 13 participants in each group. Group I received intra-mucosal injection of vitamin C, while Group II was treated with the 980 nm diode laser. The mean age of participants in Group I was 23.00 years, while in Group II it was 21.62 years. The gender distribution in both groups was similar, with 15.4% males and 84.6% females. There was no statistically significant difference observed in terms of mean age or gender distribution between the two groups, as indicated in (Table Demographic variablesStatistically significant difference at All eligible participants included in the study adhered to the treatment protocol without any instances of dropouts or significant adverse effects, as illustrated in the study flowchart. (Fig. CONSORT flowchart of the study | PMC10662509 | |
Inter- and intra-examiner reliability | The inter- & intra-examiner reliability for DOPI & GPI scores were assessed using Kappa statistics, and the results ranged from 0.90 to 1.00 indicating an excellent level of agreement between examiners, and for repeated measurements by the same examiner across time. | PMC10662509 | ||
Dummett-Gupta Oral pigmentation index (DOPI) (Table | PMC10662509 | |||
Comparison within group (intragroup comparison) | In terms of intragroup comparison, the Mesotherapy group showed a significant reduction in DOPI scores across time (Intergroup and intragroup comparison of DOPI scores at different time intervals2 monthsafter completion of Tx3 monthsafter completion of Tx*Statistically significant difference at However, no significant difference was detected in DOPI scores between the 1, 2, and 3 months follow-up visits in either group. | PMC10662509 | ||
Comparison between the two groups (intergroup comparison) | At baseline, there was no statistically significant difference in pigmentation intensity between the two groups ( | PMC10662509 | ||
Gingival Pigmentation Index (GPI) (Table | PMC10662509 | |||
Comparison within group (intragroup comparison) | In the Mesotherapy group, there was a statistically significant reduction (Intergroup and intragroup comparison of GPI scores at different time intervals*Statistically significant difference at Nevertheless, there was no statistically significant difference between the follow up visits scores at 1, 2 and 3 months in both groups. | PMC10662509 | ||
Comparison between the two groups (intergroup comparison) | At Baseline, no significant difference was found in preoperative distribution of pigmentation area between the two groups (However, at 1, 2 & 3 months follow up, there was a statistically significant difference (Intraoral photographs of a patient from Group 1 at baseline ( | PMC10662509 | ||
Visual analogue scale (VAS): (intergroup comparison) | A statistically significant difference (Comparison of Visual Analogue Scale (VAS) between groups immediately postoperative, at 1st and 7th days postoperatively | PMC10662509 | ||
Patient satisfaction and acceptability questionnaire | The study’s results revealed no notable difference in patients’ satisfaction and acceptance of the treatment method between the two groups, as demonstrated in (Fig. Satisfaction Questionnaire | PMC10662509 | ||
Discussion | depigmentation, inflammation, pain | DEPIGMENTATION, INFLAMMATION, RECURRENCE, HYPERPIGMENTATION | The role of pink (gingival) esthetics in enhancing the overall appearance, self-confidence, and personality of an individual cannot be overstated. Recent advances in esthetic dentistry aim to harmonize the functional and esthetic aspects of a smile, while taking into consideration patients’ unique values and needs. Therefore, there is a need to investigate cost-effective yet efficient techniques to ensure the accessibility of these esthetic treatments for all those who desire them.A variety of treatment modalities have been proposed and presented in the literature for the management of gingival hyperpigmentation, with lasers being the prevailing choice in contemporary practice. In spite of the overall advantages of laser depigmentation, it remains a technique sensitive procedure that requires expensive equipment and proper training before usage. Conversely, while vitamin C has gained widespread recognition as a depigmenting agent in dermatology, its application for gingival depigmentation has been sparsely documented [Hence, this study was conducted to evaluate and compare the clinical performance, pain perception and patient satisfaction of vitamin C mesotherapy and diode laser ablation therapy in managing physiologic gingival hyperpigmentation. To the best of our knowledge, this is the first randomized clinical trial to compare between these two treatment modalities.Our findings indicate that both treatment modalities were successful in effectively managing gingival hyperpigmentation, highlighting the efficacy of both approaches in managing this common esthetic concern.In the diode laser group, there was a significant reduction in pigmentation indices following treatment. These results were consistent with several other published studies [With laser depigmentation, the absorption of the laser light by melanocytes is influenced by the wavelength of the laser used, and its depth of penetration. Melanin, being the target chromophore, has an absorption spectrum ranging between 351 and 1064 nm. Hence, 980 nm diode laser was chosen as it is highly absorbed by soft tissue with a particular affinity for chromophores, like melanin and oxyhemoglobin. Additionally, it offers great tissue penetration, reaching depths of up to 10 mm [In the vitamin C mesotherapy group, the pigmentation indices (DOPI and GPI) showed a decrease in indices’ scores with a significant statistical difference between baseline scores and follow-up visits’ scores, confirming the effectiveness of vitamin C as a depigmenting agent. These findings aligned with other clinical studies that revealed significant improvement in gingival color with the vitamin C mesotherapy technique [There are various mechanisms by which vitamin C reduces the gingival hyperpigmentation. Firstly, it suppresses the tyrosinase activity, the rate-limiting enzyme in melanin biosynthesis, through cytoplasmic acidification. Given that vitamin C is an acidic compound, it causes intracellular acidification of melanocytes, which reduces melanin production since the activity of tyrosinase is generally minimal in an acidic environment [As a result of the aforementioned mechanisms, vitamin C has a significant impact on hyperpigmentation, although its effects may take longer to manifest compared to the rapid outcomes achieved through laser therapy.Furthermore, previous studies have demonstrated the synergistic effects of vitamin C injection on the enhancement of the overall gingival health and reduction of inflammation [Although the two treatment modalities have proven to be statistically significant in reducing the intensity and areas of gingival pigmentation, the intergroup comparison showed statistically significant difference in favor of the Laser group.This could be attributed to the fact that the mechanism of gingival depigmentation by diode laser and vitamin C is entirely distinct. As diode laser therapy involves the complete removal of the surface epithelium, along with the melanocytes contained within it [Hence, we may conclude that the choice of the gingival depigmentation technique should be driven by multiple factors; including the patient’s financial status, the patient’s compliance to treatment, the operator’s skills, the overall health of the gingival tissue, the intensity of the gingival pigments and the gingival biotype.In terms of pain perception, the participants in the Laser group reported less levels of pain immediately after treatment than those in the Mesotherapy group. This could be attributed to several factors. The pain scores reported just after treatment in the Mesotherapy group were probably only due to the discomfort associated with the multiple injections required for that treatment method. In contrast, the reduction in pain reported by laser group could be explained by the protein coagulum that forms on the treated surface, acting as a biologic barrier that seals sensory nerves endings. Additionally, the photobiomodulation effects of laser therapy can play a role in reducing pain [In our study, a questionnaire was used to evaluate the patients’ satisfaction with the esthetic outcome achieved after 3 months, as well as their acceptability of the treatment method employed in both groups. Overall, the patients expressed high levels of satisfaction, indicating positive esthetic outcomes for both treatment modalities. Notably, there was no statistically significant difference observed between the two groups in terms of satisfaction and acceptability of the treatment method.While the present study provides valuable insights into the research topic, there are some limitations that should be taken into consideration. Longer follow up periods may be required to assess the recurrence rate following each depigmentation technique. Besides, the mesotherapy technique involves multiple injections, which can be uncomfortable for some patients. This can limit the use of this technique in certain patient populations, such as those with needle phobia. In addition, the requirement for multiple visits for vitamin C mesotherapy can pose a drawback as it increases the need for patient’s compliance.Another consideration involves the random treatment assignment of both maxillary and mandibular gingiva to either vitamin C mesotherapy or diode laser ablation, which could be seen as a limitation, as the maxillary gingiva has a relatively thick phenotype compared to that of the mandibular region. Therefore, it is advised that future studies take into consideration the gingival phenotype and consider its potential influence on the outcomes. | PMC10662509 |
Conclusion | HYPERPIGMENTATION | Based on the favorable outcomes reported in this study, it could be concluded that vitamin C mesotherapy is an effective and safe approach for managing gingival hyperpigmentation. Although diode laser yields better and earlier results, vitamin C mesotherapy offers a minimally invasive and applicable treatment option that is both cost-effective and esthetically satisfying for the patients. | PMC10662509 | |
Authors’ contributions | S.E. Conceptualization, Methodology, Data Curation, Formal Analysis, Investigation, Validation, Resources, Visualization, Writing - Original Draft, N.E. Methodology, Supervision, Writing – Review & Editing, R.F. Methodology, Supervision, Writing – Review & Editing. | PMC10662509 | ||
Funding | Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB). No funding is subjected to the research reported in this manuscript. | PMC10662509 | ||
Availability of data and materials | All data included in this study are available from the corresponding author upon request. | PMC10662509 | ||
Declarations | PMC10662509 | |||
Consent to participate | A written informed consent was obtained from all participants. | PMC10662509 | ||
Ethics approval | Ethics approval was granted by the Research Ethics Committee at the Faculty of Dentistry, Alexandria University (IRB 00010556 - IORG 0008839), and the study was carried out in accordance with the principles of the modified Helsinki code for human clinical studies. | PMC10662509 | ||
Consent for publication | A written informed consent for publication was obtained. | PMC10662509 | ||
Competing interests | The authors declare no competing interests. | PMC10662509 | ||
References | PMC10662509 | |||
Subject terms | artery atherosclerosis, stroke, acute stroke, disability | STROKE, ACUTE STROKE | We aim to explore the effect of head-down position (HDP), initiated within 24 hours of onset, in moderate anterior circulation stroke patients with probable large artery atherosclerosis (LAA) etiology. This investigator-initiated, multi-center trial prospective, randomized, open-label, blinded-endpoint, multi-center and phase-2 trial was conducted in China and completed in 2021. Eligible patients were randomly assigned (1:1) into the HDP group receiving −20° Trendelenburg, or control group receiving standard care according to national guideline. The primary endpoint was proportion of modified Rankin Scale (mRS) of 0 to 2 at 90 days, which is a scale for measuring the degree of disability after stroke. 90-day mRS was assessed by a certified staff member who was blinded to group assignment. A total of 96 patients were randomized (47 in HDP group and 49 in control group) and 94 (97.9%) patients were included in the final analysis: 46 in HDP group and 48 in control group. The proportion of favorable outcome was 65.2% (30/46) in the HDP group versus 50.0% (24/48) in the control group (unadjusted: OR 2.05 [95%CI 0.87-4.82], The effect of head positioning in acute stroke is controversial. Here, the authors report the results of a clinical trial suggesting that the procedure, initiated within 24 hours of onset, is safe and feasible, but does not improve functional outcome in acute moderate stroke patients with large artery atherosclerosis. | PMC10163013 |
Introduction | stroke, acute ischemic stroke, AIS | STROKE | To date, there is a paucity of effective neuroprotective treatments for acute ischemic stroke (AIS), other than reperfusion therapy such as intravenous thrombolysis and mechanical thrombectomy, which is limited by a strict therapeutic time window and requirement for a highly developed stroke system of careIn theory, compared with the supine or lying-flat position, the steeper head-down position (i.e., fully supine with TrendelenburgIn this work, we undertook the prospective, multicenter, randomized, open-label, blinded-endpoint trial to explore the effect of HDP, initiated within 24 h of symptom onset, in moderate AIS patients with LAA who were not eligible for intravenous thrombolysis or endovascular therapy. | PMC10163013 |
Results | PMC10163013 | |||
Trial population | Between Nov 16, 2018, and Aug 28, 2021, 113 consecutive patients were screened and 96 eligible patients were randomly assigned to the HDP group ( | PMC10163013 | ||
Distribution of modified Rankin scale scores at 90 days by treatment groups in the modified intention-to-treat population. | death, disability | SECONDARY | Raw distribution of scores is shown. Scores range from 0 to 6: 0 = no symptoms, 1 = symptoms without clinically significant disability, 2 = slight disability, 3 = moderate disability, 4 = moderately severe disability, 5 = severe disability, and 6 = death. HDP head-down position. Source data are provided as a Source Data file.For the secondary outcome, the proportion of mRS score 0–1 at 90 days was 45.7% (21/46) in HDP group and 25.0% (12/48) in the control group (unadjusted OR 2.66 [95% CI 1.10–6.44], | PMC10163013 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.