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JMIR Research Protocols Nov 2023Metabolic and bariatric surgery (MBS) is the most effective and durable obesity treatment. However, there is heterogeneity in weight outcomes, which is partially...
Transcranial Magnetic Stimulation for Reducing the Relative Reinforcing Value of Food in Adult Patients With Obesity Pursuing Metabolic and Bariatric Surgery: Protocol for a Pilot, Within-Participants, Sham-Controlled Trial.
BACKGROUND
Metabolic and bariatric surgery (MBS) is the most effective and durable obesity treatment. However, there is heterogeneity in weight outcomes, which is partially attributed to variability in appetite and eating regulation. Patients with a strong desire to eat in response to the reward of palatable foods are more likely to overeat and experience suboptimal outcomes. This subgroup, classified as at risk, may benefit from repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique that shows promise for reducing cravings and consumption of addictive drugs and food; no study has evaluated how rTMS affects the reinforcing value of food and brain reward processing in the context of MBS.
OBJECTIVE
The goal of the Transcranial Magnetic Stimulation to Reduce the Relative Reinforcing Value of Food (RESTRAIN) study is to perform an initial rTMS test on the relative reinforcing value (RRV) of food (the reinforcing value of palatable food compared with money) among adult patients who are pursuing MBS and report high food reinforcement. Using a within-participants sham-controlled crossover design, we will compare the active and sham rTMS conditions on pre- to posttest changes in the RRV of food (primary objective) and the neural modulation of reward, measured via electroencephalography (EEG; secondary objective). We hypothesize that participants will show larger decreases in food reinforcement and increases in brain reward processing after active versus sham rTMS.
METHODS
Participants (n=10) will attend 2 study sessions separated by a washout period. They will be randomized to active rTMS on 1 day and sham rTMS on the other day using a counterbalanced schedule. For both sessions, participants will arrive fasted in the morning and consume a standardized breakfast before being assessed on the RRV of food and reward tasks via EEG before and after rTMS of the left dorsolateral prefrontal cortex.
RESULTS
Recruitment and data collection began in December 2022. As of October 2023, overall, 52 patients have been screened; 36 (69%) screened eligible, and 17 (47%) were enrolled. Of these 17 patients, 3 (18%) were excluded before rTMS, 5 (29%) withdrew, 4 (24%) are in the process of completing the protocol, and 5 (29%) completed the protocol.
CONCLUSIONS
The RESTRAIN study is the first to test whether rTMS can target neural reward circuits to reduce behavioral (RRV) and neural (EEG) measures of food reward in patients who are pursuing MBS. If successful, the results would provide a rationale for a fully powered trial to examine whether rTMS-related changes in food reinforcement translate into healthier eating patterns and improved MBS outcomes. If the results do not support our hypotheses, we will continue this line of research to evaluate whether additional rTMS sessions and pulses as well as different stimulation locations produce clinically meaningful changes in food reinforcement.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05522803; https://clinicaltrials.gov/study/NCT05522803.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/50714.
PubMed: 37930756
DOI: 10.2196/50714 -
Evaluation of , a novel thromboxane receptor antagonist, in a first-in-human phase I clinical trial.Frontiers in Pharmacology 2023The thromboxane receptor (TP) antagonist is in clinical development for treatment of cardiopulmonary diseases, such as pulmonary arterial hypertension. In this...
The thromboxane receptor (TP) antagonist is in clinical development for treatment of cardiopulmonary diseases, such as pulmonary arterial hypertension. In this randomized, placebo-controlled Phase I clinical trial, , administered as the oral formulation , was evaluated for safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in healthy males. The first-in-human trial had three Parts: A, single ascending dose (SAD) study with seven groups given 0.25-243 mg or placebo; B, food effect study where one SAD group (9 mg) was also given or placebo after a high-fat breakfast; C, multiple ascending dose study with three groups given 15-135 mg or placebo once-daily for 7 days. Seventy-nine volunteers participated. No serious adverse events occurred, where any drug- or placebo-related adverse events were mild to moderate, with no correlation to dose. was rapidly absorbed, yielding dose proportional increases in exposure after single and repeat dosing. PK confirmed that, with a clearance (T) of 18.7 h, is suited to once-daily dosing, can be taken with or without food, and does not accumulate on repeat dosing. At doses ≥1 mg, led to complete and sustained inhibition of thromboxane-, but not ADP-, induced platelet aggregation , with direct correlation between exposure and duration of PD effects. Orally administered was well tolerated, with favorable PK/PD profiles and evidence of specific TP target engagement. These findings support continued clinical development of for cardiopulmonary or other relevant diseases with unmet needs. clinicaltrials.gov, identifier NCT04919863.
PubMed: 38178863
DOI: 10.3389/fphar.2023.1296188 -
Nutrients May 2024Chrono-nutrition (meal timing) aligns food consumption with one's circadian rhythm. The first meal (e.g., breakfast) likely promotes synchronization of peripheral... (Review)
Review
Chrono-nutrition (meal timing) aligns food consumption with one's circadian rhythm. The first meal (e.g., breakfast) likely promotes synchronization of peripheral circadian clocks, thereby supporting metabolic health. Time-restricted feeding (TRF) has been shown to reduce body weight (BW) and/or improve cardiovascular biomarkers. In this explorative literature assessment, 13 TRF randomized controlled trials (RCTs) were selected from PubMed and Scopus to evaluate the effects of early (eTRF: first meal before 10:30 a.m.) and late TRF (lTRF: first meal after 11:30 a.m.) on parameters of metabolic health. Although distinct variations in study design were evident between reports, TRF consistently decreased energy intake (EI) and BW, and improved insulin resistance as well as systolic blood pressure. eTRF seemed to have a greater beneficial effect than lTRF on insulin resistance (HOMA-IR). Importantly, most studies did not appear to consider chronotype in their evaluation, which may have underestimated TRF effects. TRF intervention may be a promising approach for risk reduction of human metabolic diseases. To conclusively determine benefits of TRF and identify clear differences between eTRF and lTRF, future studies should be longer-term (≥8 weeks) with well-defined (differences in) feeding windows, include participants chronotypically matching the intervention, and compare outcomes to those of control groups without any dietary limitations.
Topics: Humans; Circadian Rhythm; Insulin Resistance; Time Factors; Randomized Controlled Trials as Topic; Meals; Energy Intake; Fasting; Feeding Behavior; Male; Blood Pressure; Female; Adult; Body Weight
PubMed: 38892654
DOI: 10.3390/nu16111721 -
Microorganisms Mar 2024This study compared SARS-CoV-2 RNA loads at different anatomical sites, and the impact of self-swabbing and food intake. Adult symptomatic patients with SARS-CoV-2 or...
This study compared SARS-CoV-2 RNA loads at different anatomical sites, and the impact of self-swabbing and food intake. Adult symptomatic patients with SARS-CoV-2 or non-SARS-CoV-2 respiratory tract infection were included between 2021 and 2022. Patients performed a nasal and buccal swab before a professionally collected nasopharyngeal/oropharyngeal swab (NOPS). Buccal swabs were collected fasting and after breakfast in a subgroup of patients. SARS-CoV-2 RNA loads were determined by nucleic acid testing. Swabbing convenience was evaluated using a survey. The median age of 199 patients was 54 years (interquartile range 38-68); 42% were female and 52% tested positive for SARS-CoV-2. The majority of patients (70%) were hospitalized. The mean SARS-CoV-2 RNA load was 6.6 log copies/mL (standard deviation (SD), ±1.5), 5.6 log copies/mL (SD ± 1.9), and 3.4 log copies/mL (SD ± 1.9) in the professionally collected NOPS, and self-collected nasal and buccal swabs, respectively ( < 0.0001). Sensitivity was 96.1% (95% CI 90.4-98.9) and 75.3% (95% CI 63.9-81.8) for the nasal and buccal swabs, respectively. After food intake, SARS-CoV-2 RNA load decreased ( = 0.0006). Buccal swabbing was the preferred sampling procedure for the patients. In conclusion, NOPS yielded the highest SARS-CoV-2 RNA loads. Nasal self-swabbing emerged as a reliable alternative in contrast to buccal swabs. If buccal swabs are used, they should be performed before food intake.
PubMed: 38543642
DOI: 10.3390/microorganisms12030591 -
Implementation Science Communications Jul 2023Shared decision making (SDM) in breast cancer care improves outcomes, but it is not routinely implemented. Results from the What Matters Most trial demonstrated that...
BACKGROUND
Shared decision making (SDM) in breast cancer care improves outcomes, but it is not routinely implemented. Results from the What Matters Most trial demonstrated that early-stage breast cancer surgery conversation aids, when used by surgeons after brief training, improved SDM and patient-reported outcomes. Trial surgeons and patients both encouraged using the conversation aids in routine care. We will develop and evaluate an online learning collaborative, called the SHared decision making Adoption Implementation Resource (SHAIR) Collaborative, to promote early-stage breast cancer surgery SDM by implementing the conversation aids into routine preoperative care. Learning collaboratives are known to be effective for quality improvement in clinical care, but no breast cancer learning collaborative currently exists. Our specific aims are to (1) provide the SHAIR Collaborative resources to clinical sites to use with eligible patients, (2) examine the relationship between the use of the SHAIR Collaborative resources and patient reach, and (3) promote the emergence of a sustained learning collaborative in this clinical field, building on a partnership with the American Society of Breast Surgeons (ASBrS).
METHODS
We will conduct a two-phased implementation project: phase 1 pilot at five sites and phase 2 scale up at up to an additional 32 clinical sites across North America. The SHAIR Collaborative online platform will offer free access to conversation aids, training videos, electronic health record and patient portal integration guidance, a feedback dashboard, webinars, support center, and forum. We will use RE-AIM for data collection and evaluation. Our primary outcome is patient reach. Secondary data will include (1) patient-reported data from an optional, anonymous online survey, (2) number of active sites and interviews with site champions, (3) Normalization MeAsure Development questionnaire data from phase 1 sites, adaptations data utilizing the Framework for Reporting Adaptations and Modifications-Extended/-Implementation Strategies, and tracking implementation facilitating factors, and (4) progress on sustainability strategy and plans with ASBrS.
DISCUSSION
The SHAIR Collaborative will reach early-stage breast cancer patients across North America, evaluate patient-reported outcomes, engage up to 37 active sites, and potentially inform engagement factors affecting implementation success and may be sustained by ASBrS.
PubMed: 37452387
DOI: 10.1186/s43058-023-00453-z -
Clinical and Experimental Nephrology May 2024Idiopathic membranous nephropathy (IMN) is a leading cause of end-stage renal disease (ESRD). The purpose of this study was to evaluate whether urinary...
BACKGROUND
Idiopathic membranous nephropathy (IMN) is a leading cause of end-stage renal disease (ESRD). The purpose of this study was to evaluate whether urinary albumin-to-creatinine ratio (UACR) diurnal variation rate calculated by spot urinary protein test predicts 1-year nephrotic outcomes as a biomarker of proteinuria severity in patients with IMN.
METHODS
Patients' baseline demographics, blood and urinary biomarkers, and clinical and pathological characteristics were collected retrospectively. Urine samples were collected at 7:00 (before breakfast) and 19:00 (after dinner) to calculate the UACR diurnal variation rate. A prediction model for no remission (NR) was developed statistically based on differences between prognosis groups. Receiver operating characteristic curve (ROC) analysis was performed to evaluate prediction abilities and determine optimal cut-off points of the model and UACR diurnal variation rate alone.
RESULTS
The formula for calculating the probability of NR was exp(L)/(1 + exp(L)), where the linear predictor L = - 22.038 + 0.134 × Age (years) + 0.457 × 24-h urinary protein + 0.511 × blood urea nitrogen (BUN) + 0.014 × serum uric acid (SUA) + 2.411 if glomerular sclerosis + 0.816 × fasting blood glucose (FBG)-0.039 × UACR diurnal variation rate (%). Optimal cut-off points for NR prediction by the final model and UACR diurnal variation rate alone were 0.331 and 58.5%, respectively. Sensitivity and specificity were 0.889 and 0.859 for the final model, and 0.926 and 0.676 for UACR diurnal variation rate alone.
CONCLUSION
UACR diurnal variation using spot urinary protein is a simpler way to predict nephrotic outcomes and is a highly sensitive screening tool for identifying patients who should undergo further comprehensive risk assessment.
Topics: Humans; Glomerulonephritis, Membranous; Male; Female; Middle Aged; Creatinine; Circadian Rhythm; Retrospective Studies; Adult; Albuminuria; Biomarkers; Prognosis; ROC Curve; Predictive Value of Tests; Aged; Proteinuria; Urinalysis
PubMed: 38240880
DOI: 10.1007/s10157-023-02444-9 -
Nutrients Feb 2024The aim of the study was to explore the impact of both the macronutrient composition and snacking timing on the postprandial glycemic insulinemic responses and food...
The aim of the study was to explore the impact of both the macronutrient composition and snacking timing on the postprandial glycemic insulinemic responses and food intake. Seventeen healthy female volunteers completed the randomized crossover trials. The volunteers were provided a standard breakfast and lunch at 8:00 and 13:00, respectively, and an ad libitum dinner at 18:00. Provided at either 10:30 (midmorning) or 12:30 (preload), the glycemic effects of the three types of 70 kcal snacks, including chicken breast (mid-C and pre-C), apple (mid-A and pre-A), and macadamia nut (mid-M and pre-M), were compared with the non-snack control (CON), evaluated by continuous glucose monitoring (CGM). The mid-M showed increased insulin resistance after lunch compared with CON, while the pre-M did not. The pre-A stabilized the glycemic response in terms of all variability parameters after lunch, while the mid-A had no significant effect on postprandial glucose control. Both the mid-C and pre-C improved the total area under the glucose curve, all glycemic variability parameters, and the insulin resistance within 2 h after lunch compared with CON. The pre-C attained the lowest energy intake at dinner, while the mid-A and the mid-M resulted in the highest. In conclusion, the chicken breast snack effectively stabilized postprandial glycemic excursion and reduced insulin resistance while the macadamia snack did not, regardless of ingestion time. Only as a preload could the apple snack mitigate the glucose response after the subsequent meal.
Topics: Humans; Female; Snacks; Blood Glucose; Insulin Resistance; Healthy Volunteers; Blood Glucose Self-Monitoring; Meals; Glucose; Nutrients; Postprandial Period; Cross-Over Studies; Insulin
PubMed: 38398859
DOI: 10.3390/nu16040535 -
Journal of Diabetes Science and... Mar 2024Thirty-nine percent of people with type 1 diabetes may have lowered pancreatic elastase levels, correlated with exocrine pancreatic insufficiency (EPI or PEI). EPI is...
BACKGROUND
Thirty-nine percent of people with type 1 diabetes may have lowered pancreatic elastase levels, correlated with exocrine pancreatic insufficiency (EPI or PEI). EPI is treated with oral supplementation of pancreatic enzymes. Little is known about the glycemic impact of pancreatic enzyme replacement therapy (PERT) in people with diabetes. This article demonstrates a method of assessing glycemic variability (GV), glycemic outcomes, and other changes in an individual with type 1 diabetes using open-source automated insulin delivery (AID).
METHOD
Macronutrient, PERT intake, and EPI-related symptoms were self-tracked; diabetes data were collected automatically via an open-source AID system. Diabetes data were uploaded via Nightscout to Open Humans and downloaded for analysis alongside self-tracked data (food, PERT). Glycemic outcomes, macronutrients, PERT dosing, and a variety of GV metrics following meals were evaluated for one month before and one month after PERT commencement. Breakfast was assessed independently across both time periods.
RESULTS
In an n = 1 individual using an open-source AID, time in range was already above goal and improved further after PERT commencement. Glucose rate of change and excursions >180 mg/dL were reduced; mean high blood glucose index was reduced overall and more so specifically at breakfast following PERT commencement.
CONCLUSIONS
GV can aid in assessing response to new-onset medications, as was demonstrated in this article for n = 1 individual with type 1 diabetes (using an open-source AID) after commencing PERT for newly identified EPI. GV may be useful for evaluating the efficacy of new-onset medications for people with insulin-requiring diabetes.
Topics: Humans; Diabetes Mellitus, Type 1; Exocrine Pancreatic Insufficiency; Pancreas; Enzyme Replacement Therapy; Insulin
PubMed: 35787705
DOI: 10.1177/19322968221108414 -
BMC Nutrition Jun 2024We are not aware of studies examining the association between dietary meal intake habits (DMIH) and severity of coronary artery stenosis (CAS). This study was conducted...
BACKGROUND AND OBJECTIVE
We are not aware of studies examining the association between dietary meal intake habits (DMIH) and severity of coronary artery stenosis (CAS). This study was conducted to investigate the relationship between DMIH and the severity of CAS as well as cardiometabolic risk factors in adults undergoing coronary angiography.
METHODS
This cross-sectional study was done on 720 patients undergoing coronary angiography (aged 35-75 years) who were admitted to Afshar Hospital, a referral hospital for cardiovascular diseases in Yazd, Iran. Data on DMIH were gathered by interview. Blood samples were taken for biochemical analysis. Blood pressure, anthropometric indices, and body composition were also evaluated. The relationship between DMIH and the severity of CAS [examined by angiography based on Gensini Score (GS) and Syntax Score (SS)] and cardiometabolic risk factors were assessed using logistic regression and the analysis of covariance (ANCOVA), respectively, in crude and multivariable adjusted models.
RESULTS
After adjustment for all possible confounding variables, the study revealed that people who ate 3 meals/day had a lower risk of severe CAS compared to people who ate 2 or fewer meals (OR = 0.48, 95% CI: 0.26, 0.88, P-trend = 0.02). There was an inverse association between the number of snacks /day and the severity of CAS (OR = 0.43, 95% CI: 0.22, 0.87, P-trend = 0.02). There was also an inverse relationship between breakfast frequency/week and the severity of CAS based on both GS and SS (P < 0.05). Breakfast consumption, meal frequency, lunch consumption, snack frequency, and more food consumption on holidays were also associated with different cardiometabolic markers and anthropometric measures (P < 0.05).
CONCLUSION
According to the results of the present study, meal frequency and breakfast consumption might be inversely associated with CAS and cardiometabolic risk factors.
PubMed: 38877599
DOI: 10.1186/s40795-024-00895-1 -
The British Journal of Nutrition Mar 2024Metabolomics has been utilised in epidemiological studies to investigate biomarkers of nutritional status and metabolism in relation to non-communicable diseases....
Time-resolved concentrations of serum amino acids, one-carbon metabolites and B-vitamin biomarkers during the postprandial and fasting state: the Postprandial Metabolism in Healthy Young Adults (PoMet) Study.
Metabolomics has been utilised in epidemiological studies to investigate biomarkers of nutritional status and metabolism in relation to non-communicable diseases. However, little is known about the effect of prandial status on several biomarker concentrations. Therefore, the aim of this intervention study was to investigate the effect of a standardised breakfast meal followed by food abstinence for 24 h on serum concentrations of amino acids, one-carbon metabolites and B-vitamin biomarkers. Thirty-four healthy subjects (eighteen males and sixteen females) aged 20-30 years were served a breakfast meal (∼500 kcal) after which they consumed only water for 24 h. Blood samples were drawn before and at thirteen standardised timepoints after the meal. Circulating concentrations of most amino acids and metabolites linked to one-carbon metabolism peaked within the first 3 h after the meal. The branched-chain amino acids steadily increased from 6 or 8 hours after the meal, while proline decreased in the same period. Homocysteine and cysteine concentrations immediately decreased after the meal but steadily increased from 3 and 4 hours until 24 h. FMN and riboflavin fluctuated immediately after the meal but increased from 6 h, while folate increased immediately after the meal and remained elevated during the 24 h. Our findings indicate that accurate reporting of time since last meal is crucial when investigating concentrations of certain amino acids and one-carbon metabolites. Our results suggest a need for caution when interpretating studies, which utilise such biomarkers, but do not strictly control for time since the last meal.
Topics: Male; Female; Humans; Young Adult; Vitamin B Complex; Carbon; Fasting; Meals; Amino Acids; Biomarkers; Postprandial Period; Cross-Over Studies; Blood Glucose
PubMed: 37886826
DOI: 10.1017/S0007114523002490