Fasting State Research Articles

Progress Toward Estimating the Minimal Clinically Important Difference of Intelligibility: A Crowdsourced Perceptual Experiment.

The purpose of the current study was to estimate the minimal clinically important difference (MCID) of sentence intelligibility in control speakers and in speakers with dysarthria due to multiple sclerosis (MS) and Parkinson's disease (PD). Sixteen control speakers, 16 speakers with MS, and 16 speakers with PD were audio-recorded reading aloud sentences in habitual, clear, fast, loud, and slow speaking conditions. Two hundred forty nonexpert crowdsourced listeners heard paired conditions of the same sentence content from a speaker and indicated if one condition was more understandable than another. Listeners then used the Global Ratings of Change (GROC) Scale to indicate how much more understandable that condition was than the other. Listener ratings were compared with objective intelligibility scores obtained previously via orthographic transcriptions from nonexpert listeners. Receiver operating characteristic (ROC) curves and average magnitude of intelligibility difference per level of the GROC Scale were evaluated to determine the sensitivity, specificity, and accuracy of potential cutoff scores in intelligibility for establishing thresholds of important change. MCIDs derived from the ROC curves were invalid. However, the average magnitude of intelligibility difference derived valid and useful thresholds. The MCID of intelligibility was determined to be about 7% for a small amount of difference and about 15% for a large amount of difference. This work demonstrates the feasibility of the novel experimental paradigm for collecting crowdsourced perceptual data to estimate MCIDs. Results provide empirical evidence that clinical tools for the perception of intelligibility by nonexpert listeners could consist of three categories, which emerged from the data ("no difference," "a little bit of difference," "a lot of difference"). The current work is a critical step toward development of a universal language with which to evaluate changes in intelligibility as a result of neurological injury, disease progression, and speech-language therapy.

The Feasibility of an Experimental Hypobaric Simulation to Evaluate the Safety of Closed-Loop Insulin Delivery Systems in Flight-Related Atmospheric Pressure Changes.

Hybrid closed-loop (HCL) systems remain underexplored within aviation, and as atmospheric pressure changes can independently affect insulin pumps and continuous glucose monitoring readings, this preliminary study assessed the feasibility of HCL safety evaluation, in both fasting and post-prandial states, by using hypobaric chamber to simulate flights. Participants with type 1 diabetes and on HCL were studied: Medtronic Guardian 4-Medtronic 780G-SmartGuard (n = 4), Dexcom G6-Omnipod DASH-Android APS (n = 1), and Dexcom G6-Ypsomed Pump-CamAPS (n = 1). Flight cabin pressures of 550 mmHg and 750 mmHg were simulated in a hypobaric chamber. Seven-hundred-50 glucose measurements were taken, with glucose levels demonstrating a stable decline to 4 mmol/L during fasting. To maintain a tight fasting and post-prandial glucose range across the different pressure settings, the HCL administered insulin as expected. While not demonstrating any apparent issues, repeating flight simulation protocol with other systems, examining longer flights, and undertaking larger, powered randomised controlled trials can confirm their safety in aviation.

Exploring the Etiology and Clinical Diagnosis and Treatment of Upper Gastrointestinal Bleeding

Upper gastrointestinal bleeding refers to bleeding caused by the digestive tract above the flexor ligament, including diseases of the esophagus, stomach, duodenum, pancreas, biliary tract, and lesions after gastrojejunostomy. It is a common and critical condition in internal medicine. In recent years, with the continuous development of medical technology and the improvement of treatment methods, the diagnosis and treatment level of this disease has been greatly improved. However, this disease has the characteristics of fast onset, complex condition, and certain mortality rate. Therefore, exploring and analyzing the etiology, causes, and treatment plans of this disease is of great significance for improving the cure rate and prognosis of patients with this disease. Due to inflammation, mechanical injury, vascular disease, or adjacent organ lesions, the choice of treatment plan varies depending on the cause. Based on the above situation, this article, The etiology and diagnosis and treatment plan of upper gastrointestinal bleeding have been explored, which can provide reference for improving the treatment level of this disease

Bioequivalence study of eltrombopag 75 mg film-coated tablets under fasting conditions during the Covid-19 pandemic in healthy Caucasian male subjects

This study aims to determine the bioequivalence of the reference preparation and the test preparation containing eltrombopag when both were given during the COVID-19 pandemic while fasting. Participants in the research were healthy male Caucasian subjects. One film-coated tablet of the test preparation or one film tablet of the reference preparation, equivalent to 75 mg of eltrombopag, was given to the participants in a randomized order throughout each treatment session. At pre determined blood sampling points, blood samples were taken to determine the pharmacokinetics of eltrombopag. Eltrombopag concentrations in the samples were determined using an LC-MS/MS technique verified using ESI(−). The study results were used to calculate the rate (the maximum plasma concentration, or Cmax) and extent (area under the concentration-time curve of plasma, or AUC(0−72) and AUC(0−t) of eltrombopag absorption from the test preparation and reference preparation. The 90% confidence intervals (CI) of the ln-transformed AUC(0−72), AUC(0−t), and Cmax of eltrombopag met the bioequivalence requirements of 80.00–125.00%. Both trial preparations had a similar and very satisfactory safety profile.

Bioequivalence and Pharmacokinetic Evaluation of Regorafenib Tablets in Healthy Chinese Volunteers.

This was a single-center, randomized, open-label, 2-formulation, and 2-cycle crossover trial conducted in 48 healthy Chinese volunteers, under fasting and fed conditions. The participants received oral doses of the test formulation (regorafenib) and reference formulation (40mg) during each study period. Blood samples were collected before and up to 144hours after the formulations were administered to determine changes in the pharmacokinetic parameters and adverse reactions, which were then used to evaluate bioequivalence and safety. The geometric mean ratios of maximum blood concentration, area under the plasma concentration-time curve from time 0 to the last quantifiable concentration, and area under the plasma concentration-time curve from time 0 to infinity for regorafenib were as follows: 94.7%, 91.4%, and 91.7%, respectively, under fasting conditions; and 94.6%, 97.7%, and 98.8%, respectively, under fed conditions. The 90% confidence intervals for the geometric mean ratios were within the 80%-125% equivalence interval for both the fasting and fed tests. Ingesting high-fat and high-calorie foods increases exposure to regorafenib, leading to slower rates of absorption. The safety profiles of the 2 preparations were similar.

Reproducibility of ultrasound-derived fat fraction in measuring hepatic steatosis

PurposeSteatotic liver disease (SLD) has become the most common cause of chronic liver disease. Nevertheless, the non-invasive quantitative diagnosis of steatosis is still lacking in clinical practice. This study aimed to evaluate the reproducibility of the new parameter for steatosis quantification named ultrasound-derived fat fraction (UDFF).Materials and methodsThe UDFF values were independently executed by two operators in two periods. In the process, repeated measurements of the same patient were performed by the same operator under different conditions (liver segments, respiration, positions, and dietary). Finally, the results of some subjects (28) were compared with the MRI-derived proton density fat fraction (PDFF). The concordance analysis was mainly achieved by the intraclass correlation coefficient (ICC) and Bland–Altman.ResultsOne hundred-five participants were included in the study. UDFF had good reliability in measuring the adult liver (ICCintra-observer = 0.96, ICCinter-observer = 0.94). Meanwhile, the ICC of the two operators increased over time. The variable measurement states did not influence the UDFF values on the surface, but they affected the coefficient of variation (Cov) of the results. Segment 8 (S8), end-expiratory, supine, and fasting images had the most minor variability. On the other hand, the UDFF value of S8 displayed satisfied consistency with PDFF (mean difference, −0.24 ± 1.44), and the results of both S5 (mean difference: −0.56 ± 3.95) and S8 (mean difference: 0.73 ± 1.87) agreed well with the whole-liver PDFF.ConclusionUDFF measurements had good reproducibility. Furthermore, the state of S8, end-expiration, supine, and fasting might be the more stable measurement approach.Critical relevance statementUDFF is the quantitative ultrasound parameter of hepatic steatosis and has good reproducibility. It can show more robust performance under specific measurement conditions (S8, end-expiratory, supine, and fasting).Trial registrationThe research protocol was registered at the Chinese Clinical Trial Registry on October 9, 2023 (http://www.chictr.org.cn/). The registration number is ChiCTR 2300076457.Key PointsThere is a lack of non-invasive quantitative measurement options for hepatic steatosis.UDFF demonstrated excellent reproducibility in measuring hepatic steatosis.S8, end-expiratory, supine, and fasting may be the more stable measuring condition.Training could improve the operators’ measurement stability.Variable measurement state affects the repeatability of the UDFF values (Cov).Graphical

Pharmacokinetics and Bioequivalence of Two Powders of Azithromycin for Suspension: A Nonblinded, Single-Dose, Randomized, Three-Way Crossover Study in Fed and Fasting States Among Healthy Chinese Volunteers.

Azithromycin, a macrolide antibiotic, is commonly used to treat mild-to-moderate bacterial infections. This research aimed to evaluate the pharmacokinetics (PK) properties and bioequivalence (BE) of two azithromycin (EQ 100 mg base/packet) powders for suspension in Chinese healthy participants in fed and fasting conditions. A total of 90 Chinese healthy participants were enrolled in this nonblinded, single-dose, randomized, semireplicate, three-period, three-sequence, crossover study. Of them, 42 and 40 were categorized to the fed and fasting conditions, respectively. The washout period between doses was 21 days. Blood specimens were harvested prior to administering the drug and 194 h following administration. The plasma levels of azithromycin were analyzed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach. PK parameters were measured using noncompartmental analysis. This research compared BE between the reference and test products using the average bioequivalence (ABE) or reference-scaled average bioequivalence (RSABE) method, considering the within-subject variability (SWR) of the reference preparation. Adverse events (AEs) were monitored to examine safety and tolerability. The RSABE method (SWR ≥ 0.294) was used to determine the BE of maximal plasma concentration (Cmax) in both fed and fasting conditions. In the ABE approach, (SWR < 0.294) was adopted to assess the BE of the area under the plasma concentration-time curve from time zero to the last measurable time point (AUC0-t) and determine the area under the plasma concentration time curve from time zero to time infinity (AUC0-inf). In the fasting condition, the point estimate of the test/reference ratio for Cmax was 1.08, with a 95% upper confidence bound of - 0.05 < 0.00. The geometric mean ratio (GMRs) for AUC0-t and AUC0-inf was 115.21% [90% confidence interval (CI) 107.25-123.27%] and 113.07% (90% CI 105.14-121.61%), respectively. In the fed condition, the point estimate of the test/reference ratio for Cmax was 0.94, with a 95% upper confidence bound of - 0.10 < 0.00. The GMR for AUC0-t and AUC0-inf was 99.51% (90% CI of 91.03-108.78%) and 99.43% (90% CI 91.73-107.78%), respectively. These data all satisfied the BE criteria for drugs with high variability. All AEs were transient and mild, and no severe AEs were observed. Our study indicated that the test and reference products of azithromycin (EQ 100 mg base/packet) powder for suspension were bioequivalent and safe in healthy Chinese participants, irrespective of the feeding condition. CLINICAL TRIAL REGISTRATION (CHINADRUGTRIALS.ORG.CN): CTR20232646, registered on 25 August 2023.

Breakfast Habits in Patients Using Levothyroxine: Patient Experiences and Preferences.

Levothyroxine (LT4) is recommended to be ingested in a fasting state, 30-60 minutes before breakfast to avoid interactions with food and drugs. In clinical practice, we noticed that this instruction may be inconvenient for patients. Therefore, we aimed to evaluate patient experiences and preferences concerning the recommended fasting administration of LT4. Patients using LT4 were invited to complete a questionnaire. Regression analyses were performed to identify patient characteristics associated with taking LT4 close to or together with food and/or interfering drugs, feeling burdened with postponing breakfast, and preferring nonfasting LT4 ingestion. Of 463 invited patients, 410 completed the questionnaire (88.6%). Of these, 76.8% was female and median age was 57 years (interquartile range: 43-67). Nearly all patients (97.3%) reported to have received instruction on fasting LT4 ingestion, but only 30% adhered to this. Nonfasting LT4 intake was associated with use of co-medication (odds ratio [OR], 2.82; 95% CI, 1.77-4.47), treatment duration >1 year (OR, 1.76; 95% CI, 1.02-3.04), and male sex (OR, 1.67; 95% CI, 1.03-2.70). Approximately half of the patients reported being burdened with postponing breakfast and the majority (60.5%) expressed their preference for nonfasting LT4 ingestion. Interestingly, 25% omitted breakfast and 13.4% forgot their medication because of the fasting requirement. Furthermore, the majority (68.2%) of patients that used interfering drugs stated not to be instructed to separate these drugs from LT4. This study highlights the burden associated with fasting LT4 ingestion, leading to nonadherence, irregular LT4 intake, and omitting breakfast. Given the clear preferences towards nonfasting LT4 ingestion, further research into alternative nonfasting administration methods is warranted.

Retraction Note: FFcPsA: a fast finite conventional state using prefix pattern gene search algorithm for large sequence identification

Retraction Note: FFcPsA: a fast finite conventional state using prefix pattern gene search algorithm for large sequence identification

Efficient Multi-floor Indoor Mapping with A Versatile Rotating LiDAR System

Abstract. Light Detection And Ranging (LiDAR) technology has provided an impactful way to capture 3D environmental map. However, consistent mapping in sensing-degenerated and perceptually-limited scenes (e.g. multi-story buildings) or under high dynamic sensor motion (e.g. rotating platform) remains a significant challenge. To this end, an efficient multi-floor indoor mapping system is proposed in this paper utilizing a versatile rotating LiDAR platform. In the front end, measurements from motor, IMU and LiDAR are tightly integrated to track the fast motion state of system, based on iterative Error State Kalman Filter (ESKF). Then linear and planar features are extracted from the point cloud map voxelized with adaptive resolutions. A sliding-window-based batch optimization is performed to simultaneously optimize the states of local frames with reference to the map consistency. In the experiments, we investigated the influence of rotating speed on the mapping performance as well as the superiority of rotating mechanism when compared to standard LiDAR setup. Moreover, comparative studies with one of the SOTA work, FAST-LIO2, have shown the competitive mapping results in multi-floor indoor environments.

A Bioequivalence Study of Azilsartan in Healthy Chinese Subjects.

Azilsartan is an angiotensin II receptor blocker used for treating adult hypertension. It significantly improves cardiovascular outcomes in patients with high-risk hypertension, heart failure, and diabetic nephropathy. A single-center, randomized, open-label, single-dose, dual-cycle, dual-crossover clinical trial was conducted to evaluate the bioequivalence of azilsartan under fasting and postprandial conditions in 60 Chinese healthy volunteers. Thirty healthy subjects were enrolled in each test group, with random cross-administration for fasting and postprandial tests. The concentration of azilsartan in human plasma was evaluated using liquid chromatography-tandem mass spectrometry after a single oral administration of test and reference preparations, each at a dose of 20mg (1 tablet). Pharmacokinetic parameters were determined using WinNonlin8.2 software, and bioequivalence was evaluated using SAS 9.4 software. The geometric mean ratios and 90% confidence intervals for maximum concentration, area under the plasma concentration-time curve from time 0 to the time of last measurable concentration, and area under the plasma concentration-time curve from time 0 to infinity of the test and reference preparations in the fasting and postprandial test groups were in the range of 80%-125%. The incidence of adverse events in the fasting and postprandial test groups was 30% (9/30) and 33.3% (10/30), respectively. No serious adverse events or unexpected adverse drug reactions were observed. In conclusion, the test and reference preparations of azilsartan tablets demonstrate bioequivalence and good safety in healthy Chinese subjects under fasting and postprandial conditions.

Serum concentrations of lipids, ketones and acylcarnitines during the postprandial and fasting state: the Postprandial Metabolism (PoMet) study in healthy young adults.

To improve the interpretation and utilisation of blood lipids, ketones and acylcarnitine concentrations as biomarkers in clinical assessments, more information is needed on their dynamic alterations in response to dietary intake and fasting. The aim of this intervention study was to characterise the changes in serum lipid, ketone and acylcarnitine concentrations 24 h after a standardised breakfast meal. Thirty-four healthy subjects (eighteen males and sixteen females) aged 20-30 years were served a breakfast meal (∼500 kcal, 36 E% fat, 46 E% carbohydrates, 16 E% protein, 2E% fibre), after which they consumed only water for 24 h. Blood samples were drawn before and at thirteen standardised timepoints after the meal. Metabolite concentrations were plotted as a function of time since the completion of the breakfast meal. Results demonstrated that concentrations of HDL-cholesterol and LDL-cholesterol decreased until ∼2 h (-4 % for both), while TAG concentrations peaked at 3 h (+27 %). Acetoacetate and β-hydroxybutyrate were highest 24 h after the meal (+433 and +633 %, respectively). Acetylcarnitine, butyrylcarnitine, hexanoylcarnitine, octanoylcarnitine, decanoylcarnitine and dodecanoylcarnitine reached the lowest values at 60 min (decreases ranging from -47 to -70 %), before increasing and peaking at 24 h after the meal (increases ranging from +86 to +120 %). Our findings suggest that distinguishing between fasting and non-fasting blood samples falls short of capturing the dynamics in lipid, ketone, carnitine and acylcarnitine concentrations. To enhance the utility of serum acylcarnitine analyses, we strongly recommend accounting for the specific time since the last meal at the time of blood sampling.

Oral Administration of a Novel, Synthetic Ketogenic Compound Elevates Blood β-Hydroxybutyrate Levels in Mice in Both Fasted and Fed Conditions.

Elevating ketone levels with therapeutic nutritional ketosis can help to metabolically manage disease processes associated with epilepsy, diabetes, obesity, cancer, and neurodegenerative disease. Nutritional ketosis can be achieved with various dieting strategies such as the classical ketogenic diet, the modified Atkins diet, caloric restriction, periodic fasting, or the consumption of exogenous ketogenic supplements such as medium-chain triglycerides (MCTs). However, these various strategies can be unpleasant and difficult to follow, so that achieving and sustaining nutritional ketosis can be a major challenge. Thus, investigators continue to explore the science and applications of exogenous ketone supplementation as a means to further augment the therapeutic efficacy of this metabolic therapy. Here, we describe a structurally new synthetic triglyceride, glycerol tri-acetoacetate (Gly-3AcAc), that we prepared from glycerol and an acetoacetate precursor that produces hyperketonemia in the therapeutic range (2-3 mM) when administered to mice under both fasting and non-fasting conditions. Animal studies were undertaken to evaluate the potential effects of eliciting a ketogenic response systemically. Acute effects (24 h or less) were determined in male VM/Dk mice in both fasted and unfasted dietary states. Concentration levels of β-hydroxybutyrate in blood were elevated (βHB; 2-3 mM) under both conditions. Levels of glucose were reduced only in the fasted state. No detrimental side effects were observed. Pending further study, this novel compound could potentially add to the repertoire of methods for inducing therapeutic nutritional ketosis.

Pharmacokinetics and bioequivalence of two formulations of mifepristone tablets in healthy Chinese subjects under fasting conditions: a single-center, open, randomized, single-dose, double-period, two-sequence, crossover trial.

A bioequivalence (BE) study was performed to evaluate the pharmacokinetics, safety, and bioequivalence of two formulations of mifepristone tablets in healthy Chinese volunteers under fasting conditions. A single-center, open, randomized, single-dose, double-period, two-sequence, crossover study in healthy subjects under fasting conditions was performed. The subjects received a single fasting dose of mifepristone (10mg/tablet) during the first and second periods, followed by a 14-day washout period, during which frequent pharmacokinetic (PK) sampling occurred up to 120h. The pharmacokinetic parameters of mifepristone were calculated based on the plasma drug concentration-time profile. Primary endpoints were the BE of major pharmacokinetic parameters (AUC0-t and AUC0-∞) and the maximum observed serum concentration (Cmax). Secondary endpoints were safety parameters. Forty subjects (34 male and 6 female subjects) were randomly assigned to treatment, with 39 completing the two-period study. After the single administration of mifepristone tablets (test preparation vs. reference preparation) under fasting conditions, the geometric mean ratios (GMRs) of Cmax, AUC0-t, and AUC0-∞ were 98.76%, 104.28%, and 104.83%, respectively. The primary metabolites of mifepristone (RU42633 and RU42698),the GMRs of Cmax, AUC0-t, AUC0-∞ were 102.33% and 100.97%, 103.17% and 103.71%, 104.02% and 103.84%, respectively. Similarly, for another metabolite of mifepristone (RU42698), the GMRs of Cmax, AUC0-t, and AUC0-∞ were 100.97%, 103.71%, and 103.84%, respectively. All 90% confidence intervals (CIs) for the test/reference AUC ratio and Cmax ratio were within the acceptable range (80%-125%) for BE, which met the requirements of bioequivalence. No serious adverse events (AEs) occurred, and all AEs were classified as level 1 or 2. The PK parameters of mifepristone and its metabolites (RU42633 and RU42698) were measured using the (GMRs) of AUC0-t, AUC0-∞, and Cmax and were similar between the test and reference drug. The two formulations of mifepristone showed good tolerability and a similar safety profile. chinadrugtrials.org.cn, identifier CTR20182413.

Discriminative Power of the Flow through Cell Dissolution Tester in Predicting the In Vivo Performance of Pentoxifylline SR Product under Fed and Fasting Conditions

This study explored, for the first time the role of different designs of the Flow-Through-Cell (FTC, USP IV) dissolution Tester in predicting the in-vivo performance of Pentoxifylline (PTX) sustained-release (SR) market product, under fed & fasting conditions. Release studies of Trental® SR 400 mg (Sanofi, Egypt), were carried-out in the FTC under different conditions, including: different volumes / compositions of release media, variable FTC flow patterns as well as applying open / closed loop configuration setups. Pharmacokinetic (PK) data, obtained from literature, were converted to in-vivo fraction-absorbed [FA] using Wagner-Nelson (WN) method. A 1:1 IVIVC was investigated by comparing PTX fraction-dissolved [FD] under different FTC release designs versus calculated [FA]. Predicted PK parameters were evaluated, and compared with actual data, with estimation of prediction-error (PE%). The suggested FTC design; a closed-loop setup, with turbulent-flow pattern of the dissolution medium; provided the most acceptable PTX release according to USP labeled limits (USP 27). Also, results showed that PTX release was pronouncedly increased in a finite-volume of gradient-buffer system rather than water, which guarantee complete resemblance to GIT environment. This release design presented the most predictive IVIVC model with PTX in-vivo performance under fasting / fed states, with acceptable PE% values in terms of Cmax and AUCs. A suggested FTC design is proposed as an alternative dissolution model in the official USP-monograph for PTX SR products.Graphical

A metabolic dysfunction-associated steatotic liver acinus biomimetic induces pancreatic islet dysfunction in a coupled microphysiology system

Preclinical and clinical studies suggest that lipid-induced hepatic insulin resistance is a primary defect that predisposes to dysfunction in islets, implicating a perturbed liver-pancreas axis underlying the comorbidity of T2DM and MASLD. To investigate this hypothesis, we developed a human biomimetic microphysiological system (MPS) coupling our vascularized liver acinus MPS (vLAMPS) with pancreatic islet MPS (PANIS) enabling MASLD progression and islet dysfunction to be assessed. The modular design of this system (vLAMPS-PANIS) allows intra-organ and inter-organ dysregulation to be deconvoluted. When compared to normal fasting (NF) conditions, under early metabolic syndrome (EMS) conditions, the standalone vLAMPS exhibited characteristics of early stage MASLD, while no significant differences were observed in the standalone PANIS. In contrast, with EMS, the coupled vLAMPS-PANIS exhibited a perturbed islet-specific secretome and a significantly dysregulated glucose stimulated insulin secretion response implicating direct signaling from the dysregulated liver acinus to the islets. Correlations between several pairs of a vLAMPS-derived and a PANIS-derived factors were significantly altered under EMS, as compared to NF conditions, mechanistically connecting MASLD and T2DM associated hepatic-factors with islet-derived GLP-1 synthesis and regulation. Since vLAMPS-PANIS is compatible with patient-specific iPSCs, this platform represents an important step towards addressing patient heterogeneity, identifying disease mechanisms, and advancing precision medicine.

Pyruvate dehydrogenase kinase 1 controls triacylglycerol hydrolysis in cardiomyocytes.

Pyruvate dehydrogenase kinase (PDK) 1 is one of four isozymes that inhibit the oxidative decarboxylation of pyruvate to acetyl-CoA via pyruvate dehydrogenase. PDK activity is elevated in fasting or starvation conditions to conserve carbohydrate reserves. PDK has also been shown to increase mitochondrial fatty acid utilization. In cardiomyocytes, metabolic flexibility is crucial for the fulfillment of high energy requirements. The PDK1 isoform is abundant in cardiomyocytes, but its specific contribution to cardiomyocyte metabolism is unclear. Here we show that PDK1 regulates cardiomyocyte fuel preference by mediating triacylglycerol turnover in differentiated H9c2 myoblasts using lentiviral shRNA to knockdown Pdk1 . Somewhat surprisingly, PDK1 loss did not affect overall PDH activity, basal glycolysis, or glucose oxidation revealed by oxygen consumption rate experiments and 13 C 6 glucose labelling. On the other hand, we observed decreased triacylglycerol turnover in H9c2 cells with PDK1 knockdown, which was accompanied by decreased mitochondrial fatty acid utilization following nutrient deprivation. 13 C 16 palmitate tracing of uniformly labelled acyl chains revealed minimal acyl chain shuffling within triacylglycerol, indicating that the triacylglycerol hydrolysis, and not re-esterification, was dysfunctional in PDK1 suppressed cells. Importantly, PDK1 loss did not significantly impact the cellular lipidome or triacylglycerol accumulation following palmitic acid treatment, suggesting that effects of PDK1 on lipid metabolism were specific to the nutrient-deprived state. We validated that PDK1 loss decreased triacylglycerol turnover in Pdk1 knockout mice. Together, these findings implicate a novel role for PDK1 in lipid metabolism in cardiomyocytes, independent of its canonical roles in glucose metabolism.

Evaluating the Net Energy Requirements for Maintenance Based on Indirect Calorimetry and Heart Rate Monitoring in Gestating Sows

The objectives of this study were (1) to determine the net energy requirements for the maintenance of gestating sows based on indirect calorimetry, and (2) to explore the feasibility of predicting the net energy requirements for the maintenance of gestating sows based on daily heart rate monitoring. In Exp. 1, six Landrace × Yorkshire crossbred reproductive sows with an initial body weight of 229.5 ± 14.9 kg at d 56 of gestation were randomly assigned to six diverse energy feeding levels using a 6 × 6 Latin square design. The experimental diet was formulated using corn, soybean meal, and wheat bran as major ingredients, and the six feeding levels were set as 1.2, 1.4, 1.6, 1.8, 2.0, and 2.2 times metabolizable energy for maintenance (100 kcal ME/kg BW0.75·d−1), respectively. The animal trial lasted for six periods with 9 days per period, encompassing 5 days of adaptation, 3 days of calorimetry in fed state, and 1 day of calorimetry in fasting state. In Exp. 2, six Landrace × Yorkshire crossbred pregnant sows with an initial body weight of 232.5 ± 12.5 kg at d 64 were fed a corn–soybean meal diet. All sows were tested in a respiratory calorimetry chamber for a 4 day calorimetry test. The heat production of the gestation sows was measured every 5 min using indirect calorimetry, and the heart rate of the gestating sows was recorded every minute using a belt-shape monitor. The results showed that the net energy requirements for the maintenance of gestating sows significant increased as the gestational stage progressed (p &lt; 0.05), and a linear regression model revealed the average net energy requirement for the maintenance of gestating sows was 410 kJ/BW0.75 d−1 during late gestation (days 70–110). Moreover, the average heart rate of the gestating sows was 84 bpm, and the mathematical model developed to predict the net energy requirements for the maintenance of gestating sows was NEm(kcal/h)=19901+exp⁡[136−HR(bpm)43]. In conclusion, the average net energy requirement for the maintenance of sows during late gestation was 410 kJ/BW0.75 d−1, and the utilization of the heart rate monitoring method was found to provide a relevant, accurate prediction for the net energy requirements of sows.

Investigating premotor corticospinal excitability in fast and slow voluntary contractions of the elbow flexors.

Corticospinal excitability (CSE) increases prior to a voluntary contraction; however, the relative contributions of premotor cortical and spinal mechanisms are poorly understood. It is unknown whether the intended voluntary contractile rate affects CSE. Eighteen young, healthy participants (nine females) completed isometric elbow flexion contractions targeting 50% maximal voluntary contraction (MVC) torque, at either fast (fast as possible) or slow (25% MVC/s) contractile rates. Participants were cued to contract with warning (red) and "GO" (green) visual signals. Magnetic and electric stimulations were applied to elicit motor evoked potentials (MEPs), cervicomedullary evoked potentials (CMEPs), and M-waves, in the surface electromyogram (EMG) recorded over the biceps brachii. MEPs and CMEPs were collected at 0, 25, 50 and 75% premotor reaction time (RT - defined as the time between the "GO" cue and onset of biceps brachii EMG) and compared to a resting baseline. MEP amplitude was greater than baseline at 75% RT (p=0.009), and CMEP amplitude was significantly increased at all RT points relative to baseline (p≤0.001). However, there were no differences in MEP and CMEP amplitudes when compared between fast and slow conditions (p≥0.097). Normalized to the CMEP, there was no difference in MEP amplitude from baseline in either contractile condition (p≥0.264). These results indicate that increased premotor CSE is a spinally-mediated response. Furthermore, premotor CSE is not influenced by the intended voluntary contractile rate. CMEP amplitudes were larger for females than males within the premotor RT period (p=0.038), demonstrating that premotor spinal excitability responses may be influenced by sex.

The effect of Oleoylethanolamide supplementation on lipid profile, fasting blood sugar and dietary habits in obese people: a randomized double-blind placebo-control trial.

Abnormalities in biochemical parameters and changes in eating habits are considered complications of obesity. Oleoylethanolamide (OEA), an endocannabinoid-like compound, has been shown to have protective effects on many metabolic disorders. Given this evidence, the present study aimed to assess the effects of OEA on lipid profile parameters, fasting blood sugar (FBS), and dietary habits in healthy obese people. In this randomized, double-blind, placebo-controlled clinical trial, which was carried out in 2016 in Tabriz, Iran, 60 obese people were enrolled in the study based on inclusion criteria. The intervention group consumed 125mg of OEA capsules, and the placebo group received the same amount of starch twice for 8 weeks. Blood samples (5 mL) were taken at baseline and the end of the study in a fasting state. Serum concentrations of FBS, triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC) were measured by enzymatic methods using commercial kits. The low-density lipoprotein cholesterol (LDL-C) concentration was obtained using the Friede-Wald formula. To assess dietary habits, a food frequency questionnaire (147 items) was used at baseline and the end of the study. A value less than < 0.05 was considered to indicate statistical significance. The TG concentration decreased significantly in the intervention group (mean (SD): 166.29 (70.01) mg/dL to 142.22 (48.05) mg/dL, p = 0.047). Changes in the placebo group were not significant (p > 0.05). After adjusting for baseline values and demographic characteristics, the difference in TG between groups remained significant (p = 0.044). Changes in other biochemical parameters were not significant. There was no significant difference between or within groups in terms of food groups. OEA, as a complementary agent, plays a protective role in TG regulation. However, future studies with longer durations are needed to explore the impact of OEA on regulating dietary habits and to identify the mechanisms related to metabolic abnormalities in obese people. The study was registered in the Iranian Registry of Clinical Trials (IRCT) center as IRCT201607132017N30 with URL. www.IRCT.IR in date 03/10/2016.