Disulfide bridge-dependent dimerization triggers FGF2 membrane translocation into the extracellular space.

Fibroblast growth factor 2 (FGF2) exits cells by direct translocation across the plasma membrane, a type I pathway of unconventional protein secretion. This process is initiated by phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2)-dependent formation of highly dynamic FGF2 oligomers at the inner plasma membrane leaflet, inducing the formation of lipidic membrane pores. Cell surface heparan sulfate chains linked to glypican-1 (GPC1) capture FGF2 at the outer plasma membrane leaflet, completing FGF2 membrane translocation into the extracellular space. While the basic steps of this pathway are well understood, the molecular mechanism by which FGF2 oligomerizes on membrane surfaces remains unclear. In the current study, we demonstrate the initial step of this process to depend on C95-C95 disulfide-bridge-mediated FGF2 dimerization on membrane surfaces, producing the building blocks for higher FGF2 oligomers that drive the formation of membrane pores. We find FGF2 with a C95A substitution to be defective in oligomerization, pore formation, and membrane translocation. Consistently, we demonstrate a C95A variant of FGF2 to be characterized by a severe secretion phenotype. By contrast, while also important for efficient FGF2 secretion from cells, a second cysteine residue on the molecular surface of FGF2 (C77) is not involved in FGF2 oligomerization. Rather, we find C77 to be part of the interaction interface through which FGF2 binds to the α1 subunit of the Na,K-ATPase, the landing platform for FGF2 at the inner plasma membrane leaflet. Using cross-linking mass spectrometry, atomistic molecular dynamics simulations combined with a machine learning analysis and cryo-electron tomography, we propose a mechanism by which disulfide-bridged FGF2 dimers bind with high avidity to PI(4,5)P2 on membrane surfaces. We further propose a tight coupling between FGF2 secretion and the formation of ternary signaling complexes on cell surfaces, hypothesizing that C95-C95-bridged FGF2 dimers are functioning as the molecular units triggering autocrine and paracrine FGF2 signaling.

Bilateral transfer of motor performance as a function of motor imagery training: a systematic review and meta-analysis.

Objective: The objective of this review was to evaluate the efficacy of mental imagery training (MIT) in promoting bilateral transfer (BT) of motor performance for healthy subjects. Data sources: We searched 6 online-databases (Jul-Dec 2022) using terms: "mental practice," "motor imagery training," "motor imagery practice," "mental training," "movement imagery," "cognitive training," "bilateral transfer," "interlimb transfer," "cross education," "motor learning," "strength," "force" and "motor performance." Study selection and data extraction: We selected randomized-controlled studies that examined the effect of MIT on BT. Two reviewers independently determined if each study met the inclusion criteria for the review. Disagreements were resolved through discussion and, if necessary, by a third reviewer. A total of 9 articles out of 728 initially identified studies were chosen for the meta-analysis. Data synthesis: The meta-analysis included 14 studies for the comparison between MIT and no-exercise control (CTR) and 15 studies for the comparison between MIT and physical training (PT). Results: MIT showed significant benefit in inducing BT compared to CTR (ES = 0.78, 95% CI = 0.57-0.98). The effect of MIT on BT was similar to that of PT (ES = -0.02, 95% CI = -0.15-0.17). Subgroup analyses showed that internal MIT (IMIT) was more effective (ES = 2.17, 95% CI = 1.57-2.76) than external MIT (EMIT) (ES = 0.95, 95% CI = 0.74-1.17), and mixed-task (ES = 1.68, 95% CI = 1.26-2.11) was more effective than mirror-task (ES = 0.46, 95% CI = 0.14-0.78) and normal-task (ES = 0.56, 95% CI = 0.23-0.90). No significant difference was found between transfer from dominant limb (DL) to non-dominant limb (NDL) (ES = 0.67, 95% CI = 0.37-0.97) and NDL to DL (ES = 0.87, 95% CI = 0.59-1.15). Conclusion: This review concludes that MIT can serve as a valuable alternative or supplement to PT in facilitating BT effects. Notably, IMIT is preferable to EMIT, and interventions incorporating tasks that have access to both intrinsic and extrinsic coordinates (mixed-task) are preferred over those that involve only one of the two coordinates (mirror-task or normal-task). These findings have implications for rehabilitation of patients such as stroke survivors.

[Shenbai Jiedu Fang inhibits AOM/DSS-induced colorectal adenoma formation and carcinogenesis in mice via miRNA-22-mediated regulation of the PTEN/PI3K/AKT signaling pathway].

OBJECTIVE: To observe the inhibitory effect of Shenbai Jiedu Fang (SBJDF, a compound recipe of traditional Chinese herbal drugs) on chemically induced carcinogenesis of colorectal adenoma in mice and explore the role of PTEN/PI3K/AKT signaling pathway in mediating this effect. METHODS: Four-week-old male C57BL/6 mice were randomly divided into control group (n=10), AOM/DSS model group (n=20), low-dose (14 g/kg) SBJDF group (n=10) and high-dose (42 g/kg) SBJDF group (n= 10). In the latter 3 groups, the mice were treated with azoxymethane (AOM) and dextran sodium sulphate (DSS) to induce carcinogenesis of colorectal adenoma. In the two SBJDF treatment groups, SBJDF was administered daily by gavage during the modeling. The survival rate, body weight, general condition of the mice, and intestinal adenoma formation and carcinogenesis were observed. The expressions of proteins associated with the PTEN/PI3K/AKT signaling pathway in the intestinal tissue were detected using immunohistochemistry. RESULTS: Compared with those in the model group, the mice treated with SBJDF, especially at the high dose, showed a significantly lower incidence of intestinal carcinogenesis and had fewer intestinal tumors with smaller tumor volume. Pathological examination showed the occurrence of adenocarcinoma in the model group, while only low-grade and high-grade neoplasia were found in low-dose SBJDF group; the mice treated with high-dose SBJDF showed mainly normal mucosal tissues in the intestines with only a few lesions of low-grade neoplasia of adenoma. Compared with those in the control group, the mice in the model group had significantly elevated plasma miRNA-222 level (P < 0.05), which was obviously lowered in the two SBJDF groups (P < 0.01). The results of immunohistochemistry revealed that compared with the model group, the two SBJDF groups, especially the high-dose group, had significantly up-regulated expressions of PTEN, P-PTEN and GSK-3ß and down-regulated expressions of p-GSK-3 ß, PI3K, AKT, P-AKT, ß-catenin, c-myc, cyclinD1 and survivin in the intestinal tissues. CONCLUSION: SBJDF can significantly inhibit colorectal adenoma formation and carcino-genesis in mice possibly through regulating miRNA-222 and affecting PTEN/PI3K/AKT signaling pathway.

Elderly may benefit more from motor imagery training in gaining muscle strength than young adults: A systematic review and meta-analysis.

Objective: The current review was aimed to determine the effectiveness of mental imagery training (MIT) on the enhancement of maximum voluntary muscle contraction (MVC) force for healthy young and old adults. Data sources: Six electronic databases were searched from July 2021 to March 2022. Search terms included: "motor imagery training," "motor imagery practice," "mental practice," "mental training," "movement imagery," "cognitive training," "strength," "force," "muscle strength," "performance," "enhancement," "improvement," "development," and "healthy adults." Study selection and data extraction: Randomized controlled trials of MIT in enhancing muscle strength with healthy adults were selected. The decision on whether a study met the inclusion criteria of the review was made by two reviewers independently. Any disagreements between the two reviewers were first resolved by discussion between the two reviewers. If consensus could not be reached, then it would be arbitrated by a third reviewer. Data synthesis: Twenty-five studies including both internal MIT and external MIT were included in meta-analysis for determining the efficacy of MIT on enhancing muscle strength and 22 internal MIT were used for subgroup analysis for examining dose-response relationship of MIT on MVC. Results: MIT demonstrated significant benefit on enhancing muscle strength when compared with no exercise, Effect Size (ES), 1.10, 95% confidence interval (CI), 0.89-1.30, favoring MIT, but was inferior to physical training (PT), ES, 0.38, 95% CI, 0.15-0.62, favoring PT. Subgroup analysis demonstrated that MIT was more effective for older adults (ES, 2.17, 95% CI, 1.57-2.76) than young adults (ES, 0.95, 95% CI, 0.74-1.17), p = 0.0002, and for small finger muscles (ES, 1.64, 95% CI, 1.06-2.22) than large upper extremity muscles (ES, 0.86, 95% CI, 0.56-1.16), p = 0.02. No significant difference was found in the comparison of small finger muscles and large lower extremity muscles, p = 0.19 although the ES of the former (ES, 1.64, 95% CI, 1.06-2.22) was greater than that of the later (ES, 1.20, 95%, 0.88-1.52). Conclusion: This review demonstrates that MIT has better estimated effects on enhancing MVC force compared to no exercise, but is inferior to PT. The combination of MIT and PT is equivalent to PT alone in enhancing muscle strength. The subgroup group analysis further suggests that older adults and small finger muscles may benefit more from MIT than young adults and larger muscles.

Tributyrin supplementation in pasteurized waste milk: Effects on growth performance, health, and blood parameters of dairy calves.

This study evaluated the effects of incremental tributyrin supplementation in pasteurized waste milk on growth performance, health, and blood metabolism of dairy calves before and after weaning. Forty-eight newborn female Holstein dairy calves (39.6 ± 2.75 kg; mean ± standard deviation) were blocked by age and randomly assigned to 3 treatments: pasteurized waste milk (1) without supplementation, (2) with 1 g/L of tributyrin products (unprotected solid powder; containing 35% tributyrin), or (3) with 2 g/L of tributyrin products. The calves were weaned on d 56 and were raised until d 77. Data were analyzed for the preweaning, postweaning, and overall periods. The results showed that starter intake and hay intake were not different among treatments in any period of the trial, but the crude protein intake tended to increase linearly with tributyrin supplementation during the overall period. Although tributyrin supplementation had no effects on body weight during preweaning and overall periods, body weight increased linearly with tributyrin supplementation postweaning. The average daily gain tended to increase linearly during postweaning and overall periods. No effects were observed on feed efficiency in any period. A positive linear relationship between body length and tributyrin supplementation was observed during the postweaning period, but no differences were found for the other body structural measurements in any period. The results of diarrhea showed that tributyrin concentration had a negative linear relationship with diarrhea frequency during preweaning and overall periods. The rectal temperature did not differ among treatments in any period, but a treatment × week effect for rectal body temperature was observed. For blood metabolism, tributyrin supplementation had no effects on insulin, growth hormone, total protein, albumin, or globulin. No differences were found in serum amyloid A concentration in any of the periods, yet haptoglobin concentration decreased linearly with increasing tributyrin concentration during postweaning and overall periods. Endothelin concentration showed a tendency to decrease linearly during preweaning and postweaning periods and decreased linearly with tributyrin supplementation during the overall period. An increasing tributyrin concentration was associated with a negative linear relationship with IL-1ß concentration during the preweaning period, and no differences were found in the other periods. The concentration of IL-6 and tumor necrosis factor α were not different among treatments in any of the periods. These data suggest that increasing the concentration of tributyrin in pasteurized waste milk could increase growth performance and health of dairy calves, and incremental tributyrin supplementation could linearly reduce haptoglobin, endothelin, and IL-1ß concentrations, indicating a positive effect of tributyrin on alleviating oxidative stress and inflammatory status of dairy calves. Calves fed pasteurized waste milk supplemented with tributyrin products (containing 35% tributyrin) at 2 g/L compared with 1 g/L of milk had more improved growth and health.

[Clinical analysis of juxtapapillary retinal capillary hemangioma].

Objective: To discuss the clinical features and treatment of juxtapapillary retinal capillary hemangioma (JRCH). Methods: Retrospective study of the clinical data of 6 patients (7 eyes) who were diagnosed with JRCH, among which 2 eyes were treated by laser therapy (thermotherapy TTT or photodynamic therapy PDT), 2 eyes were treated by intravitreal anti-VEGF injection, 2 eyes with vitreous hemorrhage were treated with vitrectomy (PPV)+ anti-VEGF, and 1 eye was untreated. Results: In the 6 cases, the gender ratio of male to female is 2∶1 with average age of 46 years. Four eyes were associated with macular edema(57.1%), vitreous hemorrhage(n=2, 28.6%), and epiretinal membrane(n=1, 14.2%) in the initial examination. Three patients were associated with von Hippel-Lindau(VHL). During the follow-up period, the visual acuity of the 2 patients treated by TTT decreased. Among the 2 eyes treated by anti-VEGF, the visual acuity of 1 eye associated with macular edema increased, and the visual acuity of 1 eye with macular epiretinal membrane did not change significantly, the visual acuity of both 2 eyes treated by PPV+anti-VEGF improved, the vision of the 1 eye untreated appeared to be stable. Conclusions: Juxtapapillary retinal capillary hemangioma is the orange or red vascular hamartomas that occur on or adjacent to the optic nerve head. It is often associated with macular edema, vitreous hemorrhage, and local subretinal effusion. Symptomatic treatment of complications can effectively improve the visual acuity of patients, while long-term follow-up observation should be organized for patients without complications, laser treatment appears to be ineffective. (Chin J Ophthalmol, 2019, 55:609-615).

Biomarker of long-chain n-3 fatty acid intake and breast cancer: Accumulative evidence from an updated meta-analysis of epidemiological studies.

Objective: We aimed to summarize the up-to-date epidemiology evidence on biomarkers of long-chain (LC) n-3 fatty acid (FA) intake in relation to breast cancer (BC).Methods: Epidemiology studies determining FA levels in biospecimen (circulating blood or adipose tissue (AT)) were identified from PubMed, EMBASE, and Cochrane Library databases until March 2018. Multivariate-adjusted risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effect model. Difference in biospecimen proportions of LC n-3 FA between BC cases and non-cases were analyzed as a standardized mean difference (SMD).Results: Thirteen cohort and eleven case-control studies were eligible for the present meta-analysis. The estimated SMD was -0.14 (95% CI: -0.27, -0.11) for LC n-3 FA and -0.27 (95% CI: -0.42, -0.11) for LC n-3/n-6 FA ratio. When comparing the top tertiles with the bottom baseline levels, circulating LC n-3 FA was significantly associated with a lower risk of BC (RR: 0.84, 95% CI: 0.74, 0.96), but not AT (RR: 1.02, 95% CI: 0.70, 1.48). Significant inverse dose-response associations were observed for each 1% increment of circulating 20:5n-3 and 22:6n-3.Conclusion: This meta-analysis highlights that circulating LC n-3 FA as a biomarker of intake may be an independent predictive factor for BC, especially 20:5n-3 and 22:6n-3.

Association between blood omega-3 polyunsaturated fatty acids and the gut microbiota among breast cancer survivors.

Omega-3 polyunsaturated fatty acids (PUFAs) are essential nutrients demonstrated to have health benefits, such as decreasing the risk of coronary heart disease, improving parameters associated with metabolic syndrome, and decreasing anxiety symptoms and depression risk. Previous intervention studies indicated the association between blood or tissue PUFA levels and the gut microbiota; however, the details remain incompletely elucidated. We conducted a cross-sectional study to examine the association between PUFAs and the gut microbiota among breast cancer survivors. Adults who had been diagnosed with invasive breast cancer more than one year ago and were not currently undergoing chemotherapy were enrolled. Capillary blood and faecal samples were obtained to assess the blood PUFA levels and gut microbiota compositions. The mean age (n=124) was 58.7 years, and 46% of the participants had a history of chemotherapy. Multiple regression analysis controlling for possible confounders indicated that an increased relative abundance of Actinobacteria was significantly associated with increased levels of docosahexaenoic acid (DHA, beta=0.304, q<0.01). At the genus level, the abundance of Bifidobacterium was positively associated with the level of DHA (beta=0.307, q<0.01). No significant association between omega-6 PUFAs and the relative abundances of gut microbiota members was observed. In addition, analyses stratified by the history of chemotherapy indicated significant associations of PUFA levels with the abundance of some bacterial taxa, including the phylum Actinobacteria (DHA, beta=0.365, q<0.01) and Bacteroidetes (EPA, beta=-0.339, q<0.01) and the genus Bifidobacterium (DHA, beta=0.368, q<0.01) only among participants without a history of chemotherapy. These findings provide the first evidence of positive associations between the abundances of Bifidobacterium among the gut microbiota and the levels of omega-3 PUFAs in the blood. Further studies are required to gain additional insight into these associations in healthy subjects as well as into the causality of the relationship.

Effect of combined bifidobacteria supplementation and resistance training on cognitive function, body composition and bowel habits of healthy elderly subjects.

Physical exercise exerts favourable effects on brain health and quality of life of the elderly; some of these positive health effects are induced by the modulation of microbiota composition. We therefore conducted a randomised, double blind, placebo-controlled trial that assessed whether a combination of Bifidobacterium spp. supplementation and moderate resistance training improved the cognitive function and other health-related parameters in healthy elderly subjects. Over a 12-week period, 38 participants (66-78 years) underwent resistance training and were assigned to the probiotic Bifidobacterium supplementation (n=20; 1.25×1010 cfu each of Bifidobacterium longum subsp. longum BB536, B. longum subsp. infantis M-63, Bifidobacterium breve M-16V and B. breve B-3) or the placebo (n=18) group. At baseline and at 12 weeks, we assessed the cognitive function, using the Japanese version of the Montreal Cognitive Assessment instrument (MoCA-J); modified flanker task scores; depression-anxiety scores; body composition; and bowel habits. At 12 weeks, the MoCA-J scores showed a significant increase in both the groups, while the flanker task scores of the probiotic group increased more significantly than those of the placebo group (0.35±0.9 vs -0.29±1.1, P=0.056). Only the probiotic group showed a significant decrease in the depression-anxiety scores (5.2±6.3 to 3.4±5.5, P=0.012) and body mass index (24.0±2.8 to 23.5±2.8 kg/m2, P<0.001), with a significant increase in the defecation frequency (5.3±2.3 to 6.4±2.3 times/5 days, P=0.023) at 12 weeks. Thus, in healthy elderly subjects, combined probiotic bifidobacteria supplementation and moderate resistance training may improve the mental condition, body weight and bowel movement frequency.

Granny Smith apple procyanidin extract upregulates tight junction protein expression and modulates oxidative stress and inflammation in lipopolysaccharide-induced Caco-2 cells.

The present work is undertaken to characterize a Granny Smith apple procyanidin extract (AE) and investigate the beneficial effect of the AE in the intestine in vitro. Each AE was characterized via LC-ESI-MS. Caco-2 cells were used to study the preventive actions of the AE against the downregulation of tight junction protein expression, oxidative stress and inflammation induced by lipopolysaccharides (LPS). Phenolic compounds present in the AE, including chlorogenic acid, catechin, epicatechin, proanthocyanidin dimers, and proanthocyanidin trimers, were characterized. The expression of the tight junction protein, including occludin and zona occludens (ZO)-1, increased significantly in LPS + AE treated Caco-2 cells, compared to LPS induced Caco-2 cells. Proanthocyanidin dimers had the most potent effect on increasing tight junction protein expression. The addition of LPS to Caco-2 cells induced oxidative stress and inflammation. However, incubation with proanthocyanidin dimers prevented LPS-mediated oxidative stress, including the increase of SOD, HO-1, CAT, and GSH-Px mRNA expression, and counteracted LPS-mediated inflammation as evidenced by the down-regulation of inflammatory markers (NF-κß, IL-6, and TNF-α mRNA expression). Our findings provide evidence that AE could upregulate tight junction protein expression, probably acting via the reduction of oxidative stress and inflammation.

Different physiological properties of human-residential and non-human-residential bifidobacteria in human health.

Bifidobacteria have increasingly been shown to exert positive health benefits to humans, which are clearly reflected by their application in various commercialised dairy products and supplements. Bifidobacteria naturally inhabit a range of ecological niches and display substantial differences in their ecological adaptation among species. In general, bifidobacteria could be categorised into two major groups; bifidobacterial species of human origins as human-residential bifidobacteria (HRB) while other species which are the natural inhabitants of animals or environment as non-HRB. Current research has focused on the differential physiological features of HRB and non-HRB, such as metabolic capabilities, whilst comparative and functional genomic investigations have revealed the genetic attributes of bifidobacteria that may explain their colonisation affinities in human gut. It is becoming more apparent that distinct residential origins of bifidobacteria are likely contributed to their comparable adaptive health attributes on human host. Notably, debate still remains about the nature of bifidobacteria for use as human probiotics. Clinical evaluations involving supplementation of bifidobacteria of different origins point out the superiority of HRB in human host. Evidence also suggests that HRB especially infant-type HRB may exert better health-promoting effects and therefore serve as a better probiotic candidate for infant use. In this review, we aim to provide an overview of the genotypic and physiological differences of bifidobacteria associated with different residential origins and to shed light on the practical considerations for selection of bifidobacteria as probiotics in order to establish a healthy gut microbial community in humans.

Effectiveness of adjunctive interventions for accelerating orthodontic tooth movement: a systematic review of systematic reviews.

This study was aimed to summarise published systematic reviews (SRs) that assess the effects of adjunctive interventions on the acceleration of orthodontic tooth movement (OTM). Electronic and manual searches were performed up to August 2016. Systematic reviews investigating the impact of adjunctive techniques on the promotion of OTM were included. The methodological quality of the included reviews was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) scale. The quality of evidence for each intervention was assessed using GRADE. The Jadad decision algorithm was used to select a study to provide body evidence from discordant reviews on the same intervention. A total of 11 SRs were included in this study. AMSTAR scores ranged from 4 to 10 of 11. The quality of evidence ranged from very low to low. The short-term (1-3 months) effects of low-level laser therapy (LLLT, 5 and 8 J cm-2 ) and corticotomy were supported by low-quality evidence. The evidence regarding the efficacy of photobiomodulation, pulsed electromagnetic field, interseptal bone reduction, two vibrational devices (Tooth Masseuse and Orthoaccel) and electrical current was of very low quality. Relaxin injections and extracorporeal shock waves were reported to have no impact on OTM according to low- and very low-quality evidence, respectively. Based on currently available information, we conclude that low-quality evidence indicates that LLLT (5 and 8 J cm-2 ) and corticotomy are effective to promote OTM in the short term. Future high-quality trials are required to determine the optimal protocols, as well as the long-term effects of LLLT and corticotomy, before warranting recommendations for orthodontics clinics.

Dietary fat alters the response of hypothalamic neuropeptide Y to subsequent energy intake in broiler chickens.

Dietary fat affects appetite and appetite-related peptides in birds and mammals; however, the effect of dietary fat on appetite is still unclear in chickens faced with different energy statuses. Two experiments were conducted to investigate the effects of dietary fat on food intake and hypothalamic neuropeptides in chickens subjected to two feeding states or two diets. In Experiment 1, chickens were fed a high-fat (HF) or low-fat (LF) diet for 35 days, and then subjected to fed (HF-fed, LF-fed) or fasted (HF-fasted, LF-fasted) conditions for 24 h. In Experiment 2, chickens that were fed a HF or LF diet for 35 days were fasted for 24 h and then re-fed with HF (HF-RHF, LF-RHF) or LF (HF-RLF, LF-RLF) diet for 3 h. The results showed that chickens fed a HF diet for 35 days had increased body fat deposition despite decreasing food intake even when the diet was altered during the re-feeding period (P<0.05). LF diet (35 days) promoted agouti-related peptide (AgRP) expression compared with HF diet (P<0.05) under both fed and fasted conditions. LF-RHF chickens had lower neuropeptide Y (NPY) expression compared with LF-RLF chickens; conversely, HF-RHF chickens had higher NPY expression than HF-RLF chickens (P<0.05). These results demonstrate: (1) that HF diet decreases food intake even when the subsequent diet is altered; (2) the orexigenic effect of hypothalamic AgRP; and (3) that dietary fat alters the response of hypothalamic NPY to subsequent energy intake. These findings provide a novel view of the metabolic perturbations associated with long-term dietary fat over-ingestion in chickens.

Effects of Saccharomyces cerevisiae fermentation products on dairy calves: Ruminal fermentation, gastrointestinal morphology, and microbial community.

The aim of this study was to evaluate the effects of Saccharomyces cerevisiae fermentation products (SCFP) in the calf starter and milk on ruminal fermentation, gastrointestinal morphology, and microbial community in the first 56 d of life. Thirty Holstein bull calves were randomly assigned to 1 of 3 groups: a texturized calf starter containing 0 (CON), 0.5, or 1% SCFP (XPC, Diamond V, Cedar Rapids, IA) of dry matter from d 4 to 56. In addition, the XPC-supplemented calves were fed with 1 g/d SCFP (SmartCare, Diamond V, Cedar Rapids, IA) in milk from d 2 to 30. All calves were fed 4 L of colostrum within 1 h of birth and were subsequently fed milk twice daily until weaned on d 56. Rumen fluid was collected by an esophageal tube 4 h after the morning feeding on d 28 and 56 to determine ruminal pH, ammonia-N, and volatile fatty acids concentrations. On d 56, 15 (5 per treatment) calves were harvested and slaughter weight, gastrointestinal morphology parameters, and bacteria community were recorded. Papilla length, width, and surface area were measured from 5 locations within the rumen. Villus height, width, surface area, crypt depth, and villus height-to-crypt depth ratio were measured in the duodenum, jejunum, and ileum. Next-generation sequencing technology was used to test the microbial community of the rumen and duodenum samples on d 28 and 56. Data were analyzed by MIXED procedure in SAS (SAS Institute Inc., Cary, NC) with contrast statements to declare CON versus all SCFP and 0.5 versus 1% SCFP in starter grains. Ruminal pH, ammonia-N, and total volatile fatty acids were not altered by SCFP. However, the supplemented groups exhibited higher ruminal butyrate concentrations coinciding with higher Butyrivibrio and lower Prevotella richness than CON group. Supplementation of SCFP increased papilla length in the rumen. In the small intestine, SCFP reduced crypt depth of jejunum, and increased villus height-to-crypt depth ratio in all segments of the small intestine, especially when supplemented at a higher dosage in the starter. In conclusion, Saccharomyces cerevisiae fermentation products improved gastrointestinal morphology, possibly due to increased Butyrivibrio and decreased Prevotella richness of the rumen fluid, which resulted in an increase in butyrate production, and the effect was slightly greater with the higher dosage of SCFP in the starter.

Dietary mannitol increased the absorption of calcium and magnesium in rats.

The effect of mannitol on bone-related mineral absorption and retention and the mechanism was investigated in this study. Fourteen 8-week-old male Wistar rats in experiment 1 and same number and age cecectomized Wistar male rats in experiment 2 were divided into two subgroups of seven animals, respectively, fed diets containing 0 or 4% mannitol for 28 days. Mineral balance tests were determined twice during days 8-12 and days 22-26, and the rats were slaughtered on day 28 both in experiment 1 and experiment 2. The whole caecum and colon were collected with the content to analyse tissue weight, content weight, content's pH and moisture, organic acids' concentration and mineral levels. In experiment 1, Ca absorption and retention and Mg absorption were significantly increased by mannitol feeding during days 8-12. Caecal total weight, tissue weight and content weight were increased, the pH of caecum and colon was reduced, and the concentrations of caecal short-chain fatty acids (SCFAs) were modified by mannitol feeding. In experiment 2, during days 8-12 and days 22-26, Ca absorption and retention were significantly lowered by mannitol feeding in cecectomized rats; however, mannitol feeding decreased Mg absorption during days 8-12, but did not impact Mg retention. Colonic total weight, tissue weight and content weight were significantly increased, and colonic pH was reduced by mannitol feeding. In conclusion, dietary mannitol increased the absorption of Ca and Mg and the caecum markedly contributed to this promoting effect of mannitol.

Dexamethasone alone vs in combination with transcutaneous electrical acupoint stimulation or tropisetron for prevention of postoperative nausea and vomiting in gynaecological patients undergoing laparoscopic surgery.

BACKGROUND: Postoperative nausea and vomiting (PONV) is commonly reported after surgery and anaesthesia. We compared the effects of combinations of electrical acupoint stimulation or tropisetron with dexamethasone with the effects of dexamethasone alone, for inhibition of PONV in gynaecological patients undergoing laparoscopic surgery. METHODS: We randomized 157 patients undergoing elective gynaecological laparoscopic surgery under general anaesthesia into the following three groups: acupoint stimulation+dexamethasone (Group Acu, n=53), tropisetron+dexamethasone (Group Trp, n=53), and dexamethasone alone (Group Dxm, n=51). The incidence of nausea, vomiting, and need for rescue antiemetics was recorded 2, 6, 24, and 48 h after surgery. RESULTS: We found significant differences in the incidence of PONV during 24 h after surgery between the combination therapy groups and the dexamethasone-alone group (P=0.021). In the first 24 h, 28% of patients in Group Acu, 26% of patients in Group Trp, and 50% of patients in Group Dxm experienced nausea, vomiting, or both. The incidence of 24 h PONV in Group Acu was significantly lower than that in Group Dxm (P=0.048; odds ratio 0.389; 95% CI 0.170-0.891). The incidence of 24 h PONV in Group Trp was also significantly lower than that in Group Dxm (P=0.042; odds ratio 0.359; 95% CI 0.157-0.819). There was no significant difference between Group Acu and Group Trp (P=0.857). The need for antiemetic rescue medication was similar in the three groups. All groups expressed similar patient satisfaction. CONCLUSIONS: Combined with dexamethasone, electrical acupoint stimulation or tropisetron is more effective in PONV prophylaxis than dexamethasone alone in gynaecological patients undergoing laparoscopic surgery. CLINICAL TRIAL REGISTRATION: NCT 02096835.

Bioefficacy comparison of organic manganese with inorganic manganese for eggshell quality in Hy-Line Brown laying hens.

This study was aimed at investigating the bioefficacy of organic compared with inorganic manganese (Mn) for eggshell quality. An amino acid-Mn complex or Mn sulfate monohydrate was used as the organic or inorganic Mn source. A total of six hundred forty-eight 50-wk-old layers (Hy-Line Brown) were divided into 9 groups; each group consisted of 6 replicates with 12 layers each. The feeding trial lasted 12 wk. During the first 4 wk of the feeding trial, the groups were fed a basal diet, which met the nutrient requirements of the layers, except for Mn. During the following 8 wk, 9 levels of Mn (inorganic Mn: 0, 25, 50, 100, and 200 mg/kg; organic Mn: 25, 50, 100, and 200 mg/kg) were used to supplement, respectively, in the basal diet on an equimolar basis. An exponential regression model was applied to calculate the bioefficacy of organic Mn compared with the inorganic Mn. Dietary supplementation with either organic or inorganic Mn did not influence egg production and feed efficiency of (P > 0.05), and eggshell quality did not exhibit a significant response to dietary supplementation with Mn sources at 56 and 58 wk (P > 0.05). Dietary supplementation with either organic Mn or inorganic Mn significantly enhanced the thickness, breaking strength, and elastic modulus of the eggshells compared with the control group at the end of 62 wk (P < 0.05). At the end of 62 wk, the bioefficacy of organic Mn was 357% (shell thickness), 406% (breaking strength), 458% (elastic modulus), and 470% (eggshell Mn), as efficacious as inorganic Mn at equimolar levels. This study suggests that organic Mn enhances eggshell quality in aged laying hens compared with inorganic Mn.

Management and maintenance of the airway in cervical necrotising fasciitis: a retrospective analysis of 15 cases.

Cervical necrotising fasciitis is a progressive deep infection of the neck associated with high mortality, and skillful management of the airway is critical for operations under general anaesthesia. Tracheostomy under local anaesthesia has been considered the gold standard of airway management in patients with deep neck infections, but it may be difficult or impossible in advanced cases. We report here our experience over 6 years (January 2008 and December 2013) during which a total of 15 patients was diagnosed with cervical necrotising fasciitis. Of 6 patients, admitted between January 2008 and March 2010, 5 had routine tracheostomy under local anaesthesia, 1 had direct laryngoscopy intubation, and 9 who were admitted between Spring 2010 and December 2013 were treated with nasotracheal intubation. Postoperatively all patients were given moderate sedation and analgesia. Nasotracheal intubation was continued until the infection had been controlled. During intubation patency of the endotracheal tube was maintained by humidification with a continuous pump of 0.45% sodium chloride and suction. All 15 patients (10 men and 5 women, mean age 62 years, range 36-93) required an emergency drainage procedure under general anaesthesia. Fourteen of the 15 had evidence of compromise of the airway, but emergency intervention was not required. Since Spring 2010, 9 consecutive patients had required nasotracheal intubation, including 7 video laryngoscopies and 2 fibreoptic bronchoscopies. No other interventions were required. Patients were intubated postoperatively from 3 to 14 days, and there were no problems with the airway. Advanced techniques for control of the airway have a high rate of success in patients with necrotising fasciitis and could be an appropriate alternative to a traditional airway. Postoperative sedation and analgesia should be considered as routine management of pain and anxiety.

The reduction of circulating levels of IL-6 in pregnant women with preeclampsia by magnesium sulphate and nifedipine: In vitro evidence for potential mechanisms.

INTRODUCTION: Women with preeclampsia have elevated levels of inflammatory cytokines including IL-6. IL-6, which is known to activate endothelial cells and induce the production of necrotic trophoblastic debris from the placenta, may be important in the pathogenesis of preeclampsia. MgSO4 is a major therapy for the prevention of seizures in preeclampsia but it has been suggested to also have anti-inflammatory and vasodilatory properties. METHODS: 22 pregnant women with preeclampsia and 68 normotensive controls were recruited and circulating IL-6 levels in these women were measured before MgSO4 and nifedipine treatment and after delivery. In addition, endothelial cells were treated with IL-6 or necrotic trophoblastic debris, generated from first trimester placental explants in the presence or absence of MgSO4in vitro, and cell-surface ICAM-1 was measured by ELISA. The levels of IL-6 in the culture medium were also measured. Furthermore nitric oxide synthetase activity in endothelial cells that had been treated with IL-6 was measured using l-NAME. RESULTS: Circulating levels of IL-6 in preeclampsia were reduced significantly following administration of MgSO4. In vitro, MgSO4 reversed the activation of endothelial cells induced by IL-6 but not by necrotic trophoblastic debris. The effect of MgSO4 in reversing the IL-6 induced activation of endothelial cells was not dependent upon nitric oxide synthetase. Treating placental explants with MgSO4 prevented the production of necrotic trophoblastic debris induced by IL-6. DISCUSSION: we demonstrated that IL-6 levels drop following treatment with MgSO4 and nifedipine in vivo, and have identified several mechanisms by which this positive effect on IL-6 may occur in vitro.

Dietary polyphenols and type 2 diabetes: current insights and future perspectives.

Significant evidence suggests that polyphenol-rich diets have the ability to protect against diabetes. Since several previous reviews focused on the nutrition and health effects including type 2 diabetes of polyphenols in 2007-2008, a number of related original publications have been pulished in this field. This review summarizes important advances related to influence of dietary polyphenols and polyphenol-rich diets on preventing and managing type 2 diabetes, as well as diabetes-mediated changes in bioactivities of dietary polyphenols. It appears that anthocyanins or anthocyanin-rich food intake is related to the risk of type 2 diabetes, but there is no association for other polyphenol subclasses. It is discussed that procyanidins are more active when administered individually than when mixed with food. The benefits of dietary polyphenols for type 2 diabetes can be summarized as: protection of pancreatic ß-cells against glucose toxicity, anti-inflammatory and antioxidant effects, inhibition of α-amylases or α- glucosidases and thus decrease of starch digestion, and inhibition of advanced glycation end products formation. Moreover, type 2 diabetes also significantly influences the benefits of dietary polyphenols, although there are very limited studies have been conducted so far. How type 2 diabetes impacts the pharmacology of dietary polyphenols is not well understood. Comprehension of type 2 diabetes-mediated changes in pharmacokinetics and bioactivity of dietary polyphenols might lead to improve the benefits of these phytochemicals and subsequent clinical outcomes for type 2 diabetics.