Circadian rhythms in humans are biological rhythms that regulate various physiological processes within a 24-hour time frame. Critical illness can disrupt the circadian rhythm, as can environmental and clinical factors, including altered light exposure, organ replacement therapies, disrupted sleep-wake cycles, noise, continuous enteral feeding, immobility, and therapeutic interventions. Nonpharmacological interventions, controlling the ICU environment, and pharmacological treatments are among the treatment strategies for circadian disruption. Nutrition establishes biological rhythms in metabolically active peripheral tissues and organs through appropriate synchronization with endocrine signals. Therefore, adhering to a feeding schedule based on the biological clock, a concept known as \"chrononutrition,\" appears to be vitally important for regulating peripheral clocks. Chrononutritional approaches, such as intermittent enteral feeding that includes overnight fasting and consideration of macronutrient composition in enteral solutions, could potentially restore circadian health by resetting peripheral clocks. However, due to the lack of evidence, further studies on the effect of chrononutrition on clinical outcomes in critical illness are needed. The purpose of this review was to discuss the role of chrononutrition in regulating biological rhythms in critical illness, and its impact on clinical outcomes.

OBJECTIVE: For growth of methylotrophic yeast, glycerol is usually used as a carbon source. Glucose is used in some cases, but not widely consumed due to strong repressive effect on AOX1 promoter. However, glucose is still considered as a carbon source of choice since it has low production cost and guarantees growth rate comparable to glycerol.
RESULTS: In flask cultivation of the recombinant yeast, Pichia pastoris GS115(pPIC9K-appA38M), while methanol induction point(OD600) and methanol concentration significantly affected the phytase expression, glucose addition in induction phase could enhance phytase expression. The optimal flask cultivation conditions illustrated by Response Surface Methodology were 10.37 OD600 induction point, 2.02 h before methanol feeding, 1.16% methanol concentration and 40.36μL glucose feeding amount(for 20 mL culture volume) in which the expressed phytase activity was 613.4 ± 10.2U/mL, the highest activity in flask cultivation. In bioreactor fermentation, the intermittent glucose feeding showed several advantageous results such as 68 h longer activity increment, 149.2% higher cell density and 200.1% higher activity compared to the sole methanol feeding method. These results implied that remaining glucose at induction point might exhibit a positive effect on the phytase expression.
CONCLUSIONS: Glucose intermittent feeding could be exploited for economic phytase production and the other recombinant protein expression by P. pastoris GS115.

This study evaluated the effect of feeding ergot contaminated grain continuously or intermittently through backgrounding (BG) and finishing (FN) in a mash or pelleted supplement on the growth performance, health and welfare parameters, and carcass characteristics of feedlot beef steers. Sixty black Angus steers (300 ± 29.4 kg BW) were used in a complete randomized 238-d study. Steers were stratified by weight and randomly assigned to four different diets (15 steers/treatment) and individually housed. Treatments included: (1) control [CON; no added ergot alkaloids (EA)], (2) continuous ergot mash (CEM; fed continuously at 2 mg total EA/kg of DM), (3) intermittent ergot mash (IEM; fed at 2 mg total EA/kg of DM, during the first week of each 21-d period and CON for the remaining 2 wk, this feeding pattern was repeated in each period), and (4) intermittent ergot pellet (IEP; fed at 2 mg of total EA/kg of DM as a pellet during the first week of each 21-d period and CON for the remaining 2 wk as described for IEM). Steers were fed barley based BG diets containing 40% concentrate:60% silage (DM basis) for 84 d (four 21-d periods), transitioned over 28 d (no ergot fed) to an FN diet (90% concentrate:10% silage DM basis) and fed for 126 d (six 21-d periods) before slaughter. In the BG phase, steer DMI (P < 0.01, 7.45 vs. 8.05 kg/d) and ADG (P < 0.01) were reduced for all EA diets compared to CON. The CEM fed steers had lower ADG (P < 0.01, 0.735 vs. 0.980 kg) and shrunk final BW (P < 0.01, 350 vs. 366 kg) than CON. CEM had lower gain:feed (P < 0.07, 0.130 vs. 0.142) than CON. In the FN phase, steer DMI (P < 0.01, 9.95 vs. 11.05 kg/d) and ADG (P = 0.04) were also decreased for all EA fed steers compared to CON. Total shrunk BW gain (P = 0.03, 202.5 vs. 225.2 kg), final BW (P = 0.03, 617.9 vs. 662.2 kg), and carcass weight (P = 0.06) decreased for all EA fed steers compared to CON. The percentage of AAA carcasses decreased for all EA fed steers (P < 0.01, 46.7 vs. 93.3%) compared to CON. EA fed steers had increased rectal temperatures (P < 0.01, 39.8 vs. 39.4 °C) compared to CON. Pelleting ergot contaminated grain did not reduce the impact of ergot alkaloids on any of the measured parameters during BG or FN. Continuously or intermittently feeding ergot contaminated diets (2 mg total EA/kg of DM) significantly reduced intake, growth performance, and carcass weight, with minimal impact on blood parameters in feedlot steers. Pelleting was not an effective method of reducing ergot toxicity.
Produced by the fungus Claviceps purpurea, ergot alkaloids (EA) are toxic to beef cattle when consumed and can lead to reduction in feed intake and growth performance, vasoconstriction of the blood vessels, hyperthermia, damage to extremities (ears, tails, and hooves) and in severe cases, death. Grain is often cleaned to meet quality standards, and the resulting screenings are often utilized for feeding livestock and can have high concentrations of EA. The application of heat during pelleting of EA contaminated grain has been suggested to reduce its toxicity. Backgrounding and finishing beef cattle feeding experiments were conducted to assess the effect of continuously or intermittently feeding EA contaminated grain (2 mg/kg of diet DM) either as a pellet or as mash on growth performance, health, and animal welfare. Feeding EA grain continuously or intermittently either as a mash or pellet drastically reduced growth performance of steers, with no difference between treatments.

暂无摘要。

OBJECTIVE: The prevalence of obesity and overweight in children has been increasing rapidly worldwide and threatens society with various chronic diseases that these children are born with. High-protein ketogenic diets and intermittent nutrition are thought to be protective against obesity and metabolic syndrome MetS. However, the exact effects and results, insulin resistance, and the role of leptin in the functioning mechanism of these diets have not been fully elucidated. The aim of this study was to investigate the roles of insulin resistance and leptin hormone on the effects of body composition with a high-protein ketogenic diet and intermittent nutrition combination.
METHODS: Thirty-two young non-obese rats were randomly divided into four equal groups. Both the standard diet and the high-protein ketogenic diet were given ad libitum and intermittently to the rats for 6 wk. The body weight and fat mass of the rats were measured at the end of the experiment. The fasting glucose, leptin, insulin, high- and low-density lipoprotein, and triacylglycerols were measured with the blood samples.
RESULTS: The lowest body weight was observed in the intermittent and high-protein ketogenic diet group, followed by the free high-protein ketogenic diet and standard intermittent diet group, respectively. Also, the lowest body fat mass was observed in the intermittent and high-protein ketogenic diet group, followed by the standard intermittent diet group. Although there was no change in leptin, insulin, high- and low-density lipoprotein, and triacylglycerol levels in any group, the lowest blood glucose rate was observed in the intermittent and high-protein ketogenic diet group.
CONCLUSIONS: The results of the present study revealed that an intermittent high-protein ketogenic diet is more effective than others in weight loss without disrupting biochemical health parameters, and the applied diets do not prevent growth and development.

Critically ill children are fed day and night, assuming this improves enteral tolerance and the probability of achieving nutritional goals. It was previously shown that a fasting response, reflected by increased ketosis, at least partly explained the beneficial outcome of delayed initiation of supplemental parenteral nutrition. This study aims to investigate whether an overnight fast increases ketosis and is feasible and safe in critically ill children.
The Continuousversus Intermittent Nutrition in Paediatric Intensive Care (ContInNuPIC) study is a randomised controlled trial in a tertiary referral Paediatric Intensive Care Unit (PICU) in the Netherlands. Critically ill children (term newborn-18 years) with an expected PICU stay ≥48 h, dependent on artificial nutrition, were eligible. Participants were randomly assigned (1:1, stratified for age group) to intermittent feeding, with interruption of feedings during an age-dependent overnight period of eight to 12 h, or to continuous feeding, with the administration of feedings day and night. In both groups, similar daily caloric targets were pursued. For children younger than one year, mandatory minor glucose infusions were provided during fasting. The primary outcome was the feasibility, defined as two conditions (1): a significant difference in the patients\' highest daily ketone (3-β-hydroxybutyrate, BHB) levels during each overnight period, and (2): non-inferiority regarding daily caloric intake, examined using a two-part mixed-effects model with a predefined non-inferiority margin of 33%, in an intention-to-treat analysis. The study is registered in the Netherlands Trial Register (NL7877).
Between May 19, 2020, and July 13, 2022, 140 critically ill children, median (first quartile; third quartile) age 0.3 (0.1; 2.7) years, were randomised to intermittent (n = 67) or continuous feeding (n = 73). In the intermittent feeding group, BHB levels were significantly higher (median 0.4 (0.2; 1.0) vs. 0.3 (0.1; 0.7) mmol/L, p < 0.001). The ratio of total caloric intake in the intermittent feeding group to the intake in the continuous feeding group was not consistently significantly more than 0.67, thus not proving non-inferiority. No severe, resistant hypoglycaemic events, nor severe gastrointestinal complications related to the intervention occurred, and feeding intolerance did not occur more often in the intermittent than in the continuous feeding group.
Compared with day and night feeding, intermittent feeding with an overnight fast and mandatory glucose infusion for children younger than one year marginally increased ketosis and did not lead to more hypoglycaemic incidents in critically ill children. Because non-inferiority regarding daily caloric intake was not proven, the feasibility of an overnight fast could not be shown in the current study. However, as feeding intolerance did not increase during the condensed feeding periods, the nutritional intake was probably limited by the prescription of nutrition and interruptions. More research is needed to determine the optimal level and duration of clinically relevant ketosis and the best method to achieve this.

Although numerous observational studies associated underfeeding with poor outcome, recent randomized controlled trials (RCTs) have shown that early full nutritional support does not benefit critically ill patients and may induce dose-dependent harm. Some researchers have suggested that the absence of benefit in RCTs may be attributed to overrepresentation of patients deemed at low nutritional risk, or to a too low amino acid versus non-protein energy dose in the nutritional formula. However, these hypotheses have not been confirmed by strong evidence. RCTs have not revealed any subgroup benefiting from early full nutritional support, nor benefit from increased amino acid doses or from indirect calorimetry-based energy dosing targeted at 100% of energy expenditure. Mechanistic studies attributed the absence of benefit of early feeding to anabolic resistance and futile catabolism of extra provided amino acids, and to feeding-induced suppression of recovery-enhancing pathways such as autophagy and ketogenesis, which opened perspectives for fasting-mimicking diets and ketone supplementation. Yet, the presence or absence of an anabolic response to feeding cannot be predicted or monitored and likely differs over time and among patients. In the absence of such monitor, the value of indirect calorimetry seems obscure, especially in the acute phase of illness. Until now, large feeding RCTs have focused on interventions that were initiated in the first week of critical illness. There are no large RCTs that investigated the impact of different feeding strategies initiated after the acute phase and continued after discharge from the intensive care unit in patients recovering from critical illness.

The current study investigated the effects of intermittent feeding (IF) and fasting strategies at different times post-hatch on muscle growth and white striping (WS) breast development. In the first trial, 32 one-day-old Abor Acre broilers were fed ad libitum (AL) for 3 d post-hatch and then randomly allotted into 4 feeding strategies including AL, 1h-IF group (1 h IF, 4 times feeding/d, 1 h each time), 1.5h-IF (1.5 h IF, 4 times feeding/d, 1.5 h each time), and fasting (1d acute fasting, 6 d free access to feed) groups and fed for 7 d. Although angiogenic genes including VEGFA, VEGFR1, and VEGFR2, and myogenic genes including MYOG and MYOD were upregulated (P < 0.05), the breast muscle satellite cell (SC) number and PAX7, MYF5 expression were decreased by the IF strategies (P < 0.05). One-day fasting at 6 d of age also upregulated angiogenic genes and MYOD expression (P < 0.05), downregulated MYF5 expression (P < 0.05), but did not change SC number (P > 0.05). In the second trial, 384 one-day-old birds were fed AL for 1 wk and then randomly allotted to the above 4 feeding strategies starting at 8 d of age until 42 d of age. Similarly, IF and fasting strategies upregulated the expression of angiogenic and myogenic genes (P < 0.05). Both 1h-IF and 1.5h-IF increased breast muscle SC number (P < 0.05). At slaughter, breast muscle fiber diameter of 1.5h-IF was smaller but the SC number was larger than that of the birds fed AL (P < 0.05). The IF and fasting strategies prevented WS development, and reduced breast WS scores and triglyceride content (P < 0.05) without changing the body weight (P > 0.05). Fasting and 1h-IF reduced the expression of adipogenic genes ZNF423 and PDGFRα (P < 0.05). Moreover, IF and fasting strategies reduced fibrosis in breast muscle and reduced skeletal muscle-specific E3 ubiquitin ligases (TRIM63 and MAFBX) (P < 0.05). Fasting significantly reduced CASPASE-3 in breast muscle (P < 0.05). In conclusion, IF starting in the first week decreases SC number. Compared to AL, IF or fasting promotes muscular angiogenesis, increases SC number, prevents muscle degeneration, and prevents the development of WS without impairing the growth performance of broiler chickens.

The main purpose of this study was to evaluate the impact of drip versus intermittent feeding on splanchnic oxygenation in preterm infants with intrauterine growth restriction. The second objective was to assess the relationship between fetal splanchnic circulation parameters and splanchnic oxygenation during the first week of life. A single-center, prospective, randomized study with 51 fetuses/infants was conducted. Fetal Doppler measurements including umbilical artery, middle cerebral artery, and superior mesenteric artery (SMA) were recorded in IUGR fetuses. After preterm delivery, the infants were randomly assigned to one of two feeding modalities: drip (3-h continuous) or intermittent (bolus in 10 min). Continuous regional splanchnic saturation (rSO2S) monitoring was carried out during the first week of life, simultaneously with continuous oxygen arterial saturation (SaO2) monitoring, and the infants\' fractional oxygen extractions (FOE) were calculated. These parameters were evaluated as means on a daily basis for the first week of life, as well as pre-prandial and post-prandial measurements on the seventh day. Fetal Doppler flow velocimetry disturbances were present in 72.5% of the study cohort. The drip (26 infants) and intermittent (25 infants) groups were similar in demographic and clinical characteristics, as well as the prevalence of feeding intolerance and necrotizing enterocolitis. During the first week of life, there was no difference in daily mean rSO2S and FOE values between the drip and intermittent groups, whereas unfed infants had mostly lower rSO2S values. Pre-prandial and post-prandial rSO2S values remained stable in both groups. Also, no association was detected between fetal splanchnic circulation parameters and neonatal splanchnic oxygenation. RSO2S values were strongly correlated to gestational age and birth weight. During the whole week, except for the first 2 days, infants with umbilical catheters had significantly lower rSO2S values than infants without.  Conclusion: Our data suggest that the key factor in splanchnic oxygenation is feeding, not the feeding modality. In addition, the umbilical vein catheter had a negative impact on splanchnic oxygenation.  Clinical Trial Registration: The Effect of Neonatal Feeding Modalities on Splanchnic Oxygenation, NCT05513495,  https://clinicaltrials.gov/ct2/results cond=&term=NCT05513495&cntry=TR&state=&city=&dist= . Retrospectively registered, date of registration: August 2022. What is Known: • It is known that preterm infants with IUGR are at increased risk of hypoxic-ischemic intestinal damage and impaired splanchnic oxygenation. What is New: • The key factor in splanchnic oxygenation of preterm infants with IUGR is feeding, not the feeding modality (drip or intermittent). • In addition, the umbilical vein catheter had a negative impact on splanchnic oxygenation.

1. A field assessment was performed to map the extent of crop usage and thus retention time in broiler chickens. In addition, a broiler experiment was carried out to study the short-term effect of acid addition on phytase efficacy in the crop.2. In the field assessment, the crop content of 40 ad libitum fed broiler chickens from four different farms were sampled at 10, 20 and 30 d of age. The dry matter (DM) content varied from zero to 32 g.3. From 11 d of age, 120 individually caged chickens were intermittently fed a high phytate-P diet with either no addition or 500 FYT C. braakii-derived phytase added or both phytase and 1.4 % formic acid added. Excreta were collected for assessment of phosphorus (P) retention. At 20 and 21 d of age, starved birds were fed for 1 h, and thereafter crop and gizzard contents were collected every 20 min until 140 min after start of the feeding. At 60 and 140 min, the contents from the jejunum and ileum were collected.4. All diets reduced the concentration of phytate in the crop, however the combination of acid and phytase resulted in a higher degradation (P<0.05) than the other diets from 20 min after the start of feeding. Simultaneously, the concentration of the smaller inositol phosphate isomers, such as inositol-5-phosphate, increased (P<0.05). Phytase increased (P<0.05) P retention, and the combination of acid and phytase increased jejunal P digestibility (P<0.05) compared to the other diets.5. The results indicated that lower pH in the crop due to acid addition improved phytase efficacy and increased P digestibility in the anterior digestive tract, even with short retention times.