Mechanical ventilation settings during weaning from venovenous extracorporeal membrane oxygenation.

BACKGROUND: The optimal timing of weaning from venovenous extracorporeal membrane oxygenation (VV ECMO) and its modalities have been rarely studied. METHODS: Retrospective, multicenter cohort study over 7 years in two tertiary ICUs, high-volume ECMO centers in France and Italy. Patients with ARDS on ECMO and successfully weaned from VV ECMO were classified based on their mechanical ventilation modality during the sweep gas-off trial (SGOT) with either controlled mechanical ventilation or spontaneous breathing (i.e. pressure support ventilation). The primary endpoint was the time to successful weaning from mechanical ventilation within 90 days post-ECMO weaning. RESULTS: 292 adult patients with severe ARDS were weaned from controlled ventilation, and 101 were on spontaneous breathing during SGOT. The 90-day probability of successful weaning from mechanical ventilation was not significantly different between the two groups (sHR [95% CI], 1.23 [0.84-1.82]). ECMO-related complications were not statistically different between patients receiving these two mechanical ventilation strategies. After adjusting for covariates, older age, higher pre-ECMO sequential organ failure assessment score, pneumothorax, ventilator-associated pneumonia, and renal replacement therapy, but not mechanical ventilation modalities during SGOT, were independently associated with a lower probability of successful weaning from mechanical ventilation after ECMO weaning. CONCLUSIONS: Time to successful weaning from mechanical ventilation within 90 days post-ECMO was not associated with the mechanical ventilation strategy used during SGOT. Further research is needed to assess the optimal ventilation strategy during weaning off VV ECMO and its impact on short- and long-term outcomes.

High casein concentration induces diarrhea through mTOR signal pathway inhibition in post-weaning piglets.

Weaning is one of the most challenging periods in a pig's life, during which piglets suffer from nutrition and other issues. Post-weaning diarrhea is one of the major health problems in the pig industry, leading to high morbidity and mortality rates. Previous studies have demonstrated that both the source and concentration of proteins are closely associated with post-weaning diarrhea in piglets. This study was conducted to prevent and control post-weaning diarrhea by selecting different dietary protein concentrations. To eliminate interference from other protein sources, casein was used as the only protein source in this study. Fourteen piglets (weighing 8.43 ± 0.3 kg, weaned on the 28th day) were randomly assigned to two dietary protein groups: a low-protein group (LP, containing 17% casein) and a high-protein group (HP, containing 30% casein). The experiment lasted 2 weeks, during which all piglets had ad libitum access to food and water. Diarrhea was scored on a scale from 1 to 3 (where 1 indicates normal stools and 3 indicates watery diarrhea), and growth performance measurements were recorded daily. The results showed that the piglets in the HP group had persistent diarrhea during the whole study, whereas no diarrhea was observed among piglets in the control group. The body weights and feed intake were significantly lower in piglets in the HP group compared to those in the LP group (p < 0.05). The gastrointestinal pH was significantly higher in piglets in the HP group than those in the LP group (p < 0.05). The intestinal tract microorganisms of the piglets in both groups were significantly affected by the protein concentration of the diet. A diet with high casein concentration significantly reduced the microbiota diversity. Compared to the LP group, the 30% casein diet decreased the abundance of Firmicutes, Bacteroidetes, and Actinobacteria at the phylum level and the relative abundance of Ruminococcus at the genus level. Diarrhea-related mRNA abundances were analyzed by the real-time polymerase chain reaction (PCR) in the intestine of piglets, and the results showed that the HP concentration markedly decreased the expression of solute carriers (SLC, p < 0.05). The mammalian target of rapamycin-mTOR signaling pathway (p < 0.01) was activated in the HP group. In conclusion, a high-protein diet induced post-weaning diarrhea, decreased growth performance, increased gastrointestinal pH, and reduced expression of solute carrier proteins. However, the relationship between high dietary casein feed and post-weaning diarrhea remains unclear and needs to be explored further.

Turkish validity and reliability study of the Baby-Led Weaning Scale.

AIM: The aim of this study was to test the psychometric properties of the Turkish version of the Baby-Led Weaning Scale for parents with babies/children aged from 6 to 30 months. METHODS: The sample for this methodological research consisted of parents with babies aged 6 to 30 months between March and June 2024 in a city in eastern Turkey. The data were collected from 354 parents for exploratory factor analysis, from 213 parents for confirmatory factor analysis, and from 70 for the test-retest reliability study. The data were collected using the "Descriptive Information Form", the "Baby-Led Weaning Scale" and the "Transition to Complementary Feeding Behaviors Scale" (TCFBS). RESULTS: The total content validity index score of the Baby Led Weaning Scale was 0.92 and the content validity rate score was 0.92. The TCBFS was used for the concordance of the scale with similar scales. During the measurements, the intra-observer reliability of the Baby Led Weaning Scale was statistically significant (p < 0.001). The Exploratory Factor Analysis revealed a three-factor structure, explaining 611.5 % of the variance. The fix index values were χ2/df = 3.036, RMSEA = 0.069, GFI = 0.902, CFI = 0.907 and AGFI = 0.857, IFI = 0.928, and TLI = 0.921.The Cronbach alpha values of the scale were in the range of 0.706 and 0.831. CONCLUSION: As a result, the Turkish adaptation of the Baby Led Weaning Scale is a valid and reliable measurement tool. PRACTICAL IMPLICATIONS: The Baby-Led Weaning Scale can be used as a simple and objective tool to measure the knowledge level of parents with babies/children aged 6 to 30 months.

Respiratory effort in mechanical ventilation weaning Prediction: An observational, case-control study.

BACKGROUND: The diaphragm is crucial for ventilator weaning, but its specific impact on weaning indicators needs further clarification. This study investigated the variability in weaning outcomes across different diaphragm function populations and the value of respiratory drive and inspiratory effort in weaning. METHODS: This observational case-control study enrolled patients on mechanical ventilation for more than 48 h and completed a 30-minute spontaneous breathing trial (SBT) with pressure-support ventilation for the first time. After the SBT, airway pressure at 100 ms during occlusion (P0.1), inspiratory effort, and diaphragmatic ultrasound were evaluated to predict weaning outcomes. Weaning failure was defined as re-intubation within 48 h of weaning, the need for therapeutic non-invasive ventilation, or death. RESULTS: 68 patients with a mean age of 63.21 ± 15.15 years were included. In patients with diaphragm thickness (DT) ≥ 2 mm, P0.1 (P=0.002), pressure-muscle index (PMI) (P=0.012), and occluded expiratory airway pressure swing (ΔPocc) (P=0.030) were significantly higher in those who failed weaning. Conversely, for patients with DT<2 mm, PMI (P=0.003) and ΔPocc (P=0.002) were lower in the weaning failure group. Additionally, within the DT≥2 mm group, P0.1 demonstrated a higher area under the curve (AUC) for weaning prediction (0.889 vs. 0.739) compared to those with DT<2 mm. CONCLUSIONS: PMI and ΔPocc are predictive of weaning outcomes in patients with diaphragm thickness ≥ 2 mm, where the assessment value of P0.1 is notably higher. Diaphragm function significantly influences the accuracy of weaning predictions based on respiratory drive and inspiratory effort. IMPLICATIONS FOR CLINICAL PRACTICE: Our findings indicate that the effectiveness of respiratory drive and inspiratory effort in predicting successful weaning from mechanical ventilation may vary across different patient populations. Diaphragm function plays a crucial role in weaning assessments, particularly when using P0.1, the pressure-muscle index (PMI), and occluded expiratory airway pressure swing (ΔPocc).

The effect of different weaning strategies on piglet growth, feed intake and gut health.

The present study evaluated the effects of weaning strategy on piglet growth performance, onset of feed intake, and intestinal health. A total of 254 crossbred piglets were used and the experimental period lasted 45 days. The piglets were assigned to the fallowing treatments: early strategic weaning (ESW, n = 85), piglets weaned at 16 days of age and transferred to the pre-nursery unit; strategic segregated weaning (SSW, n = 85), piglets weaned at 21 days of age and kept in the farrowing crate until 24 days of age; and conventional weaning (CW, n = 84), piglet weaned at 24 days of age and transferred directly to the nursery unity; this experimental group was used as a control. Piglets from all treatments were transferred to the nursery unit at 24 days of age. For the nursery phase three periods of evaluation was considered: nursery phase I (0-7 d), nursery phase II (7-14 d), and nursery phase III (14-21 days). Piglets from the ESW and CW had greater (P < 0.001) ADG in the lactation period 16-21 days. The BW at 24 day of age was higher (P < 0.001) for piglets in the ESW and CW groups. In the nursery phase I, the ESW group had higher (P = 0.003) daily feed intake. Piglets from the ESW group had higher (P = 0.004) BW at the end of the experimental period. The ESW and SSW groups had a higher percentage of piglets (88% and 92%, respectively; P < 0,001) consuming feed in the first 24 h after transference to the nursery facility. When the total experimental period is considered, a reduction (P < 0.001) in the incidence of diarrhea was observed for ESW piglets. Overall, there was no effect of weaning strategy on intestinal permeability. In conclusion, the results of our study showed that the Segregated Strategic Weaning management can be used to mitigate the deleterious effects of early weaning.

Time course of electrical activity of the diaphragm (EAdi) in the peri extubation period and its role as predictor of extubation failure in difficult to wean patients.

INTRODUCTION: Weaning patients from mechanical ventilation is crucial in the management of acute respiratory failure (ARF). Spontaneous breathing trials (SBT) are used to assess readiness for extubation, but extubation failure remains a challenge. Diaphragmatic function, measured by electrical activity of the diaphragm (EAdi), may provide insights into weaning outcomes. MATERIALS AND METHODS: This prospective, observational study included difficult-to-wean patients undergoing invasive mechanical ventilation. EAdi was recorded before, during, and after extubation. Patients were categorized into extubation success and failure groups based on reintubation within 48 h. Statistical analysis assessed EAdi patterns and predictive value. RESULTS: Thirty-one patients were analyzed, with six experiencing extubation failure. Overall, EAdi increased significantly between the phases before the SBT, the SBT and post-extubation period, up to 24 h (p < 0.001). EAdi values were higher in the extubation failure group during SBT (p = 0.01). An EAdi > 30 µV during SBT predicted extubation failure with 92% sensitivity and 67% specificity. Multivariable analysis confirmed EAdi as an independent predictor of extubation failure. CONCLUSIONS: In difficult-to-wean patients, EAdi increases significantly between the phases before the SBT, the SBT and post-extubation period and is significantly higher in patients experiencing extubation failure. An EAdi > 30 µV during SBT may enhance extubation failure prediction compared to conventional parameters. Advanced monitoring of diaphragmatic function could improve weaning outcomes in critical care settings.

Gene co-expression network and differential expression analyses reveal key genes for weaning weight in Simmental-Holstein crossbred cattle.

Weaning weight is a key indicator of the early growth performance of cattle. An understanding of the genetic mechanisms underlying weaning weight will help increase the accuracy of selection of breeding animals. In order to identify candidate genes associated with weaning weight in Simmental-Holstein crossbred cattle, this study generated RNA-Sequencing (RNA-seq) data from 86 crossbred calves (37 males and 49 famales) and measured their weaning weight and body size traits (wither height, body length, chest girth, rump width, and rump length). Differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) were performed. A total of 498 differentially expressed genes (DEGs) were identified between the low weaning weight (LWW) group and the high weaning weight (HWW) group. Weaning weight was transcriptionally correlated (FDR < 0.05) with four of the eleven co-expression gene modules. By intersecting DEGs and hub genes of the four modules, we identified a final set of 37 candidate genes enriched in growth, development, or immune-related processes. In addition, one co-expression module was significantly correlated with all the five body size traits (P < 0.05), from which MX1 was identified as a key candidate gene through protein-protein interaction (PPI) analysis of hub genes. Further evidence from cattle transcriptome-wide association study analysis (TWAS) and human phenome-wide association study (PheWAS) validated significant associations of CACNA1S, SEMA7A, VCAN, CD101, CD19, and CSF2RB with growth and development traits (P < 0.05). Notably, CACNA1S and CD19 were also associated with typical immune traits such as B cell proliferation, differentiation, and activation. In conclusion, this study reveals new candidate genes significantly associated with weaning weight in Simmental-Holstein crossbred cattle, providing a basis for further exploration of the genetic mechanisms behind growth traits of cattle.

Early weaning damages the intestinal epithelial barrier of squabs through toll-like receptor signaling pathways.

Stress damage caused by early weaning and its possible mechanism have been studied mainly in young mammals, but rarely in altrices, especially in squabs. The study aimed to investigate the possible molecular mechanism of intestinal epithelial barrier damage caused by early weaning in squabs through determining the intestinal permeability, the ultrastructure of villous epithelium, the contents of ileal cytokines, and the protein relative expression of tight-junction proteins, TLRs and their mediated key factors in inflammatory signaling pathways. A total of 192 newly hatched squabs were randomly divided into 2 groups, 1 group was weaned and fed artificial pigeon milk from d 7, and the other group continued to be fed by the parent pigeons. The ileal mucosa and serum of 8 replicates were collected at 1, 4, 7, 10, and 14 d after weaning. The results indicated that early weaning could reduce the growth performance of squabs and damage the intestinal epithelial barrier, which is characterized by down-regulating the protein expression of claudin-1/3, up-regulating the protein expression of claudin-2, promoting the secretion of pro-inflammatory factors, inhibiting the secretion of anti-inflammatory factors, and increasing the permeability of the intestinal barrier. The specific mechanism of stress damage might be the activation of TLR2/4-MyD88-ERK/JNK inflammatory signaling pathway leading to the increase levels of IL-6 and TNF-α.

Dietary supplementation with a blend composed of carvacrol, tannic acid derived from Castanea sativa and Glycyrrhiza glabra, and glycerides of medium chain fatty acids for weanling piglets raised in commercial farm.

This study aimed to evaluate the dietary administration of a blend composed of carvacrol, tannic acid derived from Castanea sativa mill and Glycyrrhiza glabra, medium chain fatty acids (MCFAs) glycerides for weanling piglets. An in vitro digestion followed by total phenolic content (TPC) and total antioxidant activity (TAC) assessment was performed before the in vivo application. At weaning, a total of 210 piglets were randomly allocated to two experimental treatments (7 replicates/15 piglets for each replicate). Control group (CTR) was fed a standard basal diet while the treated group (T) was fed the basal diet mixed with 1.500 mg/kg of blend. After in vitro digestion, TPC and TAC evidenced peaks at the end of oral and gastric phases in comparison to the intestinal one in line with the high content of phenolic compound (P < 0.05). Treatment conditioned body weight and average daily gain (P < 0.05), fecal score on 6, 7, and 8 d after weaning (P < 0.05). At 35d, the T group showed a decrease in salivary cortisol compared to CTR (P < 0.05). Duodenum and jejunum sections of T piglets revealed higher villi (P < 0.05), deeper crypts (P < 0.01), and increased V/C ratio (P < 0.01). CTR showed a higher expression of duodenal Occludin (P < 0.05). Jejunal E-cadherin and Occludin were more expressed in T jejunum sections (P < 0.05). Twelve differentially abundant genera were identified in T group caecal samples. Potentially harmful Clostridium sensu stricto 13 was reduced by the treatment (P < 0.05). In conclusion, the tested blend positively affected salivary stress markers and the gut health of weaned piglets.

Short Communication: Artificially reared ewes cannot be distinguished from natural reared ewes based on observed maternal behavior or lamb weaning weights.

Artificially rearing lambs is an important component of United States sheep production as some flocks select for increasing litter size to boost productivity. However, there is a conception among shepherds that artificially reared ewe lambs will ultimately result in poor mothers since they were not naturally raised. The objective of this study was to determine if differences in maternal behavior could be detected between ewes raised artificially and those raised naturally and if dam rearing type had an impact on lamb growth performance. Forty-eight ewes were enrolled comprised of four equal sized groups: artificially reared primiparous, naturally reared primiparous, artificially reared multi-parous, and naturally reared multi-parous. Ewes were observed using remote cameras to record maternal behaviors toward the lambs during and shortly after parturition. Behavior of twenty-nine ewes during the first hour after parturition was analyzed. Independent multivariable regression models were evaluated for: proportion of time spent grooming, proportion of time spent helping the lambs nurse, number of helpful bouts, and the number of negative bouts. No statistically significant difference (p<0.05) was detected between artificially reared and naturally reared ewes for the proportion of time spent grooming and the proportion of time spent helping the lambs nurse. Historical flock data was utilized to evaluate lamb growth between artificially and naturally reared ewes. No detrimental associations between artificially reared ewes and lamb weaning weights were observed. This study shows that artificially reared ewes are no different in terms of mothering behaviors and may be used as potential replacement candidates.

Effects of forage feeding level on ruminal pH and metabolic adaptation of the rumen epithelium in pre-weaned Jersey calves.

The objective of this study was to determine the effect of limiting forage provision in pre-weaned calves on ruminal pH and short chain fatty acid (SCFA) transport capacity during the pre-weaning period. Twelve Jersey bull calves (age = 1.9 ± 0.8 d) were housed individually on sand. All calves were fed milk replacer at 1,200 g/d and texturized grain-based starter ad libitum from birth. Calves were randomly assigned one of two treatments: ad libitum forage (ALF) or limited forage provision, where forage was limited to 90 g/d as-fed (LFP). Individual feed intake was recorded daily, calf weights, and jugular blood samples were collected weekly. Once calves consumed 680 g/d of calf starter, ruminal pH was measured for seven days after which calves were humanely killed and rumen fluid sampled. During the pre-weaning period, starter intake, feed efficiency, plasma glucose and ß-hydroxybutyrate (BHB) concentration, SCFA concentration, average daily gain, and body weight were not different between treatments. Forage intake for ALF calves was greater than LFP beginning at wk 9 (255 ± 34 vs. 71 ± 40 g/d, respectively). Compared to ALF, LFP decreased mean ruminal pH (6.38 ± 0.16 vs. 5.98 ± 0.23) and duration of time where rumen pH was below 5.8 (796 ± 145 vs. 261 ± 133 min/d). Epithelial markers of SCFA transport and cell homeostasis (MCT1, NBC1, NHE3) were not affected by treatment. In conclusion, incidence of sub-acute ruminal acidosis in limited forage-fed calves did not have the same effects on intake and nutrient transporters seen in adult cows.

An algorithm for discontinuing mechanical ventilation in boys with x-linked myotubular myopathy after positive response to gene therapy: the ASPIRO experience.

X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital myopathy. Most (80%) children with XLMTM have profound muscle weakness and hypotonia at birth resulting in severe respiratory insufficiency, the inability to sit up, stand or walk, and early mortality. At birth, 85-90% of children with XLMTM require mechanical ventilation, with more than half requiring invasive ventilator support. Historically, ventilator-dependent children with neuromuscular-derived respiratory failure of this degree and nature, static or progressive, are not expected to achieve complete independence from mechanical ventilator support. In the ASPIRO clinical trial (NCT03199469), participants receiving a single intravenous dose of an investigational gene therapy (resamirigene bilparvovec) started showing significant improvements in daily hours of ventilation support compared with controls by 24 weeks post-dosing, and 16 of 24 dosed participants achieved ventilator independence between 14 and 97 weeks after dosing. At the time, there was no precedent or published guidance for weaning chronically ventilated children with congenital neuromuscular diseases off mechanical ventilation. When the first ASPIRO participants started showing dramatically improved respiratory function, the investigators initiated efforts to safely wean them off ventilator support, in parallel with primary protocol respiratory outcome measures. A group of experts in respiratory care and physiology and management of children with XLMTM developed an algorithm to safely wean children in the ASPIRO trial off mechanical ventilation as their respiratory muscle strength increased. The algorithm developed for this trial provides recommendations for assessing weaning readiness, a stepwise approach to weaning, and monitoring of children during and after the weaning process.

Lactiplantibacillus argentoratensis AGMB00912 protects weaning mice from ETEC infection and enhances gut health.

Maintaining a healthy intestinal environment, optimal epithelial barrier integrity, and balanced gut microbiota composition are essential for the growth performance of weaning pigs. We identified Lactiplantibacillus argentoratensis AGMB00912 (LA) in healthy porcine feces as having antimicrobial activity against pathogens and enhanced short-chain fatty acid (SCFA) production. Herein, we assess the protective role of LA using a weaning mouse model with enterotoxigenic Escherichia coli (ETEC) infection. LA treatment improves feed intake and weight gain and alleviates colon shortening. Furthermore, LA inhibits intestinal damage, increases the small intestine villus height compared with the ETEC group, and enhances SCFA production. Using the Kyoto Encyclopedia of Genes and Genomes and other bioinformatic tools, including InterProScan and COGNIZER, we validated the presence of SCFA-producing pathways of LA and Lactiplantibacillus after whole genome sequencing. LA mitigates ETEC-induced shifts in the gut microbiota, decreasing the proportion of Escherichia and Enterococcus and increasing SCFA-producing bacteria, including Kineothrix, Lachnoclostridium, Roseuburia, Lacrimispora, Jutongia, and Blautia. Metabolic functional prediction analysis revealed enhanced functions linked to carbohydrate, amino acid, and vitamin biosynthesis, along with decreased functions associated with infectious bacterial diseases compared to the ETEC group. LA mitigates the adverse effects of ETEC infection in weaning mice, enhances growth performance and intestinal integrity, rebalances gut microbiota, and promotes beneficial metabolic functions. These findings validate the functionality of LA in a small animal model, supporting its potential application in improving the health and growth performance of weaning pigs.

Effect of various flavors in starter diets on growth, behavior, and blood parameters of Holstein calves.

This study investigated the effect of adding various flavors to calf starter concentrates on the performance, behavior, and blood parameters of Holstein dairy calves. The hypothesis was that an optimal flavor enhancer would increase starter intake, improve growth performance, and possibly enable earlier weaning without adverse physiological effects. In Experiment 1, a cafeteria test was conducted with 80 pre-weaned calves to evaluate four synthetic flavor enhancers (salty, sweet, sour, bitter) at levels of 3.3, 6.6, and 9.9 g/kg dry matter (DM), and a control without a flavor enhancer. Experiment 2 tested higher levels (9.9, 19.8, 29.7 g/kg DM) of the sweet flavor enhancer sodium saccharin in a single cafeteria test with 20 calves. Experiment 3 compared three sweet flavor enhancers (sodium saccharin, stevia, sucralose) at 9.9 g/kg DM in another cafeteria test with 20 calves. After selecting sodium saccharin at 9.9 g/kg DM as the optimal flavor enhancer, Experiment 4 was conducted with 40 calves divided into a treatment group receiving the flavored starter and a control group without flavor. In Experiment 1, sodium saccharin at 9.9 g/kg DM resulted in the highest dry matter intake (DMI) of 347 g/d, significantly higher than the control (173 g/d). Experiment 2 revealed a quadratic effect with DMI peaking at 9.9 g/kg DM sodium saccharin (201.0 g/d) and declining at higher levels. Experiment 3 confirmed that sodium saccharin outperformed other sweet flavor enhancers, increasing DMI to 350 g/d compared to 251 g/d for the control. In Experiment 4, calves fed the starter concentrate with 9.9 g/kg DM sodium saccharin showed significantly higher DMI (1749 g/d), average daily gain (ADG; 730 g/d), and feed conversion ratio (FCR; 2.05) compared to the control group (DMI 1470 g/d, ADG 650 g/d, FCR 2.36). Furthermore, calves in the flavored treatment were weaned earlier (59 days) than the control group (64 days). Behavioral observations showed that the sweet flavor treatment increased the time spent on solid feed intake, rumination, and standing behavior. Calves fed the flavored starter had lower levels of cholesterol, triglycerides, and blood urea nitrogen, suggesting improved nutrient utilization. Overall, the results demonstrated the potential benefits of incorporating sodium saccharin as a sweet flavor enhancer in calf starter concentrates, leading to improved feed intake, growth performance, feed efficiency, final body weight (FBW), and behavioral patterns during the critical pre-weaning and post-weaning periods.

Korean Red Ginseng and Rb1 restore altered social interaction, gene expressions in the medial prefrontal cortex, and gut metabolites under post-weaning social isolation in mice.

Background: Post-weaning social isolation (SI) reduces sociability, gene expressions including myelin genes in the medial prefrontal cortex (mPFC), and alters microbiome compositions in rodent models. Korean Red Ginseng (KRG) and its major ginsenoside Rb1 have been reported to affect myelin formation and gut metabolites. However, their effects under post-weaning SI have not been investigated. This study investigated the effects of KRG and Rb1 on sociability, gene expressions in the mPFC, and gut metabolites under post-weaning SI. Methods: C57BL/6J mice were administered with water or KRG (150, 400 mg/kg) or Rb1 (0.1 mg/kg) under SI or regular environment (RE) for 2 weeks during the post-weaning period (P21-P35). After this period, mice underwent a sociability test, and then brains and ceca were collected for qPCR/immunohistochemistry and non-targeted metabolomics, respectively. Results: SI reduced sociability compared to RE; however, KRG (400 mg/kg) and Rb1 significantly restored sociability under SI. In the mPFC, expressions of genes related to myelin, neurotransmitter, and oxidative stress were significantly reduced in mice under SI compared to RE conditions. Under SI, KRG and Rb1 recovered the altered expressions of several genes in the mPFC. In gut metabolomics, 313 metabolites were identified as significant among 3027 detected metabolites. Among the significantly changed metabolites in SI, some were recovered by KRG or Rb1, including metabolites related to stress axis, inflammation, and DNA damage. Conclusion: Altered sociability, gene expression levels in the mPFC, and gut metabolites induced by two weeks of post-weaning SI were at least partially recovered by KRG and Rb1.

Position Statement of ISCCM Committee on Weaning from Mechanical Ventilator.

Background and purpose: Weaning from a mechanical ventilator is a milestone in the recovery of seriously ill patients in Intensive care. Failure to wean and re-intubation adversely affects the outcome. The method of mechanical ventilation (MV) varies between different ICUs and so does the practice of weaning. Therefore, updated guidelines based on contemporary literature are designed to guide intensivists in modern ICUs. This is the first ISCCM Consensus Statement on weaning complied by a committee on weaning. The recommendations are intended to be used by all the members of the ICU (Intensivists, Registrars, Nurses, and Respiratory Therapists). Methods: A Committee on weaning from MV, formed by the Indian Society of Critical Care Medicine (ISCCM) has formulated this statement on weaning from mechanical ventilators in intensive care units (ICUs) after a review of the literature. Literature was first circulated among expert committee members and allotted sections to each member. Sections of the statement written by sectional authors were peer-reviewed on multiple occasions through virtual meetings. After the final manuscript is accepted by all the committee members, it is submitted for peer review by central guideline committee of ISCCM. Once approved it has passed through review by the Editorial Board of IJCCM before it is published here as "ISCCM consensus statement on weaning from mechanical ventilator". As per the standard accepted for all its guidelines of ISCCM, we followed the modified grading of recommendations assessment, development and evaluation (GRADE) system to classify the quality of evidence and strength of recommendation. Cost-benefit, risk-benefit analysis, and feasibility of implementation in Indian ICUs are considered by the committee along with the strength of evidence. Type of ventilators and their modes, ICU staffing pattern, availability of critical care nurses, Respiratory therapists, and day vs night time staffing are aspects considered while recommending for or against any aspect of weaning. Result: This document makes recommendation on various aspects of weaning, namely, definition, timing, weaning criteria, method of weaning, diagnosis of failure to wean, defining difficult to wean, Use of NIV, HFOV as adjunct to weaning, role of tracheostomy in weaning, weaning in of long term ventilated patients, role of physiotherapy, mobilization in weaning, Role of nutrition in weaning, role of diaphragmatic ultrasound in weaning prediction etc. Out of 42 questions addressed; the committee provided 39 recommendations and refrained from 3 questions. Of these 39; 32 are based on evidence and 7 are based on expert opinion of the committee members. It provides 27 strong recommendations and 12 weak recommendations (suggestions). Conclusion: This guideline gives extensive review on weaning from mechanical ventilator and provides various recommendations on weaning from mechanical ventilator. Though all efforts are made to make is as updated as possible one needs to review any guideline periodically to keep it in line with upcoming concepts and standards. How to cite this article: Clerk AM, Shah RJ, Kothari J, Sodhi K, Vadi S, Bhattacharya PK, et al. Position Statement of ISCCM Committee on Weaning from Mechanical Ventilator. Indian J Crit Care Med 2024;28(S2):S233-S248.

Current Evidence on Nutrient Intakes and Infant Growth: A Narrative Review of Baby-Led Weaning vs. Conventional Weaning.

Throughout infancy, changes in growth and development are observed, including changes in nutritional requirements; at approximately 6 months of age, when complementary feeding begins, breastmilk and/or formula are no longer the sole source of energy and nutrients. Little is known about the impact of complementary feeding (CF) approaches used during this time on infant nutrition and growth. Baby-led weaning (BLW) has continued to gain popularity over the last two decades, emphasizing the importance of examining the adequacy of different CF methods. This narrative review of 19 studies from January 2010 to April 2024 aims to discuss the differences between BLW and conventional weaning (CW). The definition of BLW varied across studies, and no standard definition has been established. Though no differences in energy were reported, macronutrient and micronutrient intakes were variable between approaches, including for micronutrients such as iron and zinc. Of the few studies with growth data, results comparing BLW and CW were conflicting. Differences were seen in the demographics of parents who chose to follow BLW and breastfeeding prevalence and duration prior to complementary feeding. Additional research is needed to understand the impacts of BLW and CW on nutrient intakes and growth to inform recommendations for infant complementary feeding approaches.

A Microencapsulated Blend Of Botanicals Supports Weaning Piglets During An Lps Challenge By Modulating Liver Inflammation And Intestinal Integrity.

This study examined the action of a blend of botanicals (BOT) against LPS-induced inflammation on cultured hepatocytes and weaning piglets. In vitro studies examined HepG2 cells treated with BOT and challenged with E. coli lipopolysaccharide (LPS) for 8 days. BOT treatment reduced IL-6 concentration in cell culture media across time (p < 0.05) and decreased pro-inflammatory cytokine expression on day 1 and 8 of experiment (TNFα, IL-1ß; p < 0.05). BOT also increased the expression of antioxidant enzymes (GPX-2, SOD, CAT) on day 8 (p < 0.05), which was supported by lowered reactive oxygen species concentration after LPS challenge (p < 0.1). The in vivo study was conducted with 72 weaning pigs, allotted into 24 pens and divided into 3 groups: a negative control (CTR-, basal diet), a challenged control (CTR+) that received an intraperitoneal injection of E. coli O55:B5 LPS on day 14 and 16, and a challenged treated group which received a diet containing 1.5 g/Kg of microencapsulated BOT (BOT+) for the whole duration of the study. Growth performance was determined weekly and, on days 21 (one animal per pen) and 28 (remaining animals), pigs were sacrificed to collect liver and jejunal tissues. After challenge, BOT+ pigs had increased BW on day 21 (p < 0.05) and 28 (p < 0.1) compared to CTR+. Similar improvements in ADG and FCR on day 14-21 (p < 0.05) and 21-28 (p < 0.1) were also seen in BOT+ group. In the liver, compared to CTR+ pigs, BOT+ pigs downregulated the expression of TLR-4, IL-6, IFN-γ on day 21 (p < 0.05), and TLR-4, TNF-α, IL-8 on day 28 (p < 0.05). BOT+ also increased GPX-2 expression on day 21 and 28 (p < 0.05), while also upregulating SOD-1 and SOD-2 on day 21 (p < 0.05) and CAT on day 28 (p < 0.05) compared to CTR+. In the jejunum, BOT+ reduced inflammation by affecting cytokine expression (p < 0.05) and increasing the expression of tight-junction proteins, ZO-1 on day 21 and CLD-1 on day 28 (p < 0.05). Furthermore, BOT+ pigs had lower crypt depth on day 21 (p < 0.1) and day 28 (p < 0.05), and increased villi to crypt ratio on day 21 and 28 (p < 0.05). By day 28, BOT+ intestinal measurements were restored to values similar to the CTR-. Finally, BOT+ also reduced mast cell activation on day 21 (p < 0.05) compared to CTR+. Considering all the findings, BOT controlled inflammatory activation and the oxidative stress in liver cells, enhanced intestinal integrity, and as a result improved the growth performance of weaning piglets challenged with LPS.

Pathogenic mechanisms in the evolution of food allergy.

The early development of the neonatal immune system is profoundly influenced by exposure to dietary and microbial antigens, which shapes mucosal tolerance. Successful oral tolerance induction is crucially dependent on microbially imprinted immune cells, most notably the RORγt+ regulatory T (Treg) and antigen presenting cells and is essential for preventing food allergy (FA). The development of FA can be envisioned to result from disruptions at key checkpoints (CKPTs) that govern oral tolerance induction. These include gut epithelial sensory and effector circuits that when dysregulated promote pro-allergic gut dysbiosis. They also include microbially imprinted immune regulatory circuits that are disrupted by dysbiosis and pro-allergic immune responses unleashed by the dysregulation of the aforementioned cascades. Understanding these checkpoints is essential for developing therapeutic strategies to restore immune homeostasis in FA.

Machine learning-based risk prediction model construction of difficult weaning in ICU patients with mechanical ventilation.

In intensive care unit (ICU) patients undergoing mechanical ventilation (MV), the occurrence of difficult weaning contributes to increased ventilator-related complications, prolonged hospitalization duration, and a significant rise in healthcare costs. Therefore, early identification of influencing factors and prediction of patients at risk of difficult weaning can facilitate early intervention and preventive measures. This study aimed to strengthen airway management for ICU patients by constructing a risk prediction model with comprehensive and individualized offline programs based on machine learning techniques. This study involved the collection of data from 487 patients undergoing MV in the ICU, with a total of 36 variables recorded. The dataset was divided into a training set (70% of the data) and a test set (30% of the data). Five machine learning models, namely logistic regression, random forest, support vector machine, light gradient boosting machine, and extreme gradient boosting, were compared to predict the risk of difficult weaning in ICU patients with MV. Significant influencing factors were identified based on the results of these models, and a risk prediction model for ICU patients with MV was established. When evaluating the models using AUC (Area under the Curve of ROC) and Accuracy as performance metrics, the Random Forest algorithm exhibited the best performance among the five machine learning algorithms. The area under the operating characteristic curve for the subjects was 0.805, with an accuracy of 0.748, recall (0.888), specificity (0.767) and F1 score (0.825). This study successfully developed a risk prediction model for ICU patients with MV using a machine learning algorithm. The Random Forest algorithm demonstrated the highest prediction performance. These findings can assist clinicians in accurately assessing the risk of difficult weaning in patients and formulating effective individualized treatment plans. Ultimately, this can help reduce the risk of difficult weaning and improve the quality of life for patients.