Ghrelin

ghrelin
  • 文章类型: Journal Article
    在这个分析中,我们的目的是调查COVID-19疾病对饮食行为的影响。共有55名惯用右手的成年人,<50岁,没有超重或肥胖,纳入了两项横断面研究.第一个受试者在2018年9月至2019年12月期间注册(非COVID-19组)。第二个包括2022年3月至2023年5月之间注册的受试者;对于此分析,保留有COVID-19病史的28例(COVID-19组)。饥饿,TFEQ-18血浆生长素释放肽,在禁食期间评估神经肽Y(NPY)和静息状态fMRI。通过基于体素的区域同质性(ReHo)和中心性(DC)评估区域内神经元的同步性和连通性。COVID-19组的ghrelin和NPY水平明显高于非COVID-19组(ghrelin197.5pg/mL与67.1pg/mL,p<0.001;NPY128.0pg/mL与84.5pg/mL,p=0.005)。NPY水平与左侧舌侧DC和ReHo呈正相关(分别为r=0.67785和r=0.73604)。认知克制的得分相似,根据TFEQ-18问卷结果,两组均有不受控制的进食和情绪进食(均p>0.05)。我们的数据显示食欲相关激素水平升高,与食欲调节相关的大脑区域的活动,在COVID-19感染后持续很长时间。
    In this analysis, we aimed to investigate the effect of COVID-19 disease on eating behavior. A total of 55 right-handed adults, <50 years of age, without overweight or obesity, from two cross-sectional studies were included. The first one enrolled subjects between September 2018 and December 2019 (non-COVID-19 group). The second one included subjects enrolled between March 2022 and May 2023; for this analysis, 28 with a history of COVID-19 (COVID-19 group) were retained. Hunger, TFEQ-18, plasma ghrelin, neuropeptide Y (NPY) and resting-state fMRI were assessed during fasting. Intraregional neuronal synchronicity and connectivity were assessed by voxel-based regional homogeneity (ReHo) and degree of centrality (DC). Significantly higher ghrelin and NPY levels were observed in the COVID-19 group than in the non-COVID-19 group (ghrelin 197.5 pg/mL vs. 67.1 pg/mL, p < 0.001; NPY 128.0 pg/mL vs. 84.5 pg/mL, p = 0.005). The NPY levels positively correlated with the DC and ReHo in the left lingual (r = 0.67785 and r = 0.73604, respectively). Similar scores were noted for cognitive restraint, uncontrolled eating and emotional eating in both groups according to the TFEQ-18 questionnaire results (p > 0.05 for all). Our data showed increased levels of appetite-related hormones, correlated with activity in brain regions involved in appetite regulation, persisting long after COVID-19 infection.
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  • 文章类型: Journal Article
    我们最近表明,四周的益生菌补充剂显着减少抑郁症患者的微生物和神经变化。在这里,我们通过关注免疫炎症过程进一步阐明了益生菌有益临床作用的生物学作用模式。该分析包括总共43名抑郁症患者,其中N=19接受了益生菌补充剂,N=24在四周内接受了安慰剂,除了照常治疗。在基线时收集血液和唾液,在干预后(第4周)和随访(第8周)评估免疫炎症标志物(IL-1β,IL-6,CRP,MIF),肠道相关激素(ghrelin,瘦素),和压力标记(皮质醇)。此外,进行转录组学分析以鉴定差异表达的基因。最后,我们分析了益生菌引起的临床和免疫炎症变化之间的关联.我们观察到肠道激素ghrelin的显著组x时间相互作用,表明益生菌组增加。此外,益生菌组ghrelin的增加与抑郁症状的减少相关.转录组学分析确定了51个上调基因和57个下调基因,参与与增强免疫活性相关的功能途径。我们确定了基因ELANE的益生菌依赖性上调,DEFA4和OLFM4与免疫激活和生长素释放肽浓度相关。这些结果强调了益生菌补充剂在抑郁症患者的免疫激活中产生生物学上有意义的变化的潜力。需要进一步的大规模机械试验来验证和扩展我们对免疫炎症措施作为抑郁症分层和治疗反应的潜在生物标志物的理解。试用注册:www。clinicaltrials.gov,标识符:NCT02957591。
    We recently indicated that four-week probiotic supplementation significantly reduced depression along with microbial and neural changes in people with depression. Here we further elucidated the biological modes of action underlying the beneficial clinical effects of probiotics by focusing on immune-inflammatory processes. The analysis included a total of N = 43 participants with depression, from which N = 19 received the probiotic supplement and N = 24 received a placebo over four weeks, in addition to treatment as usual. Blood and saliva were collected at baseline, at post-intervention (week 4) and follow-up (week 8) to assess immune-inflammatory markers (IL-1β, IL-6, CRP, MIF), gut-related hormones (ghrelin, leptin), and a stress marker (cortisol). Furthermore, transcriptomic analyses were conducted to identify differentially expressed genes. Finally, we analyzed the associations between probiotic-induced clinical and immune-inflammatory changes. We observed a significant group x time interaction for the gut hormone ghrelin, indicative of an increase in the probiotics group. Additionally, the increase in ghrelin was correlated with the decrease in depressive symptoms in the probiotics group. Transcriptomic analyses identified 51 up- and 57 down-regulated genes, which were involved in functional pathways related to enhanced immune activity. We identified a probiotic-dependent upregulation of the genes ELANE, DEFA4 and OLFM4 associated to immune activation and ghrelin concentration. These results underscore the potential of probiotic supplementation to produce biological meaningful changes in immune activation in patients with depression. Further large-scale mechanistic trials are warranted to validate and extend our understanding of immune-inflammatory measures as potential biomarkers for stratification and treatment response in depression. Trial Registration: www.clinicaltrials.gov , identifier: NCT02957591.
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  • 文章类型: Journal Article
    活性生长素释放肽(AG)通过翻译后添加正辛酸至氨基残基Ser-3而产生,使其成为生长素释放肽受体的天然配体。AG的合成取决于特定的膳食脂肪酸作为酰化过程的底物。先前的研究表明,AG输注可以导致肉鸡的饲料摄入量(FI)减少,这表明操纵AG可能是肉鸡饲养员定量限制饲料的替代方法。在这项研究中,我们评估了饮食中辛酸钠(辛酸)对FI,取水量(WI),BW,总生长素释放肽,和两种禽类中的β-羟基丁酸酯(BHB)浓度。按照行业的建议饲养肉鸡和火鸡。3周的时候,鸟类被随机分配到2×3阶乘。第一个因素包括两个物种(鸡和火鸡),和第二剂量(0、4和8mg/mL)的辛酸盐在饮用水中30d。每天记录饲料和WI,同时每周采集体重和血液样本。在鸡中,辛酸剂量线性增加生长素释放肽和BHB浓度,而FI和BW随辛酸盐剂量的增加呈线性下降(P<0.05)。然而,辛酸盐剂量不影响ghrelin,BHB,FI,或BW在火鸡。总之,我们的数据表明,在鸡和火鸡中,给予辛酸钠引起不同的饲料摄入量和体重增加反应。
    Active ghrelin (AG) is produced through the post-translational addition of n-octanoic acid to the amino residue Ser-3, making it the natural ligand for the ghrelin receptor. The synthesis of AG is contingent upon specific dietary fatty acids as substrates for the acylation process. Prior studies have demonstrated that AG infusion can lead to reduced feed intake (FI) in broiler chickens, suggesting that manipulating AG may serve as an alternative to quantitative feed restriction in broiler breeders. In this study, we evaluated the effect of dietary sodium octanoate (Octanoate) on FI, water intake (WI), BW, total ghrelin, and β-hydroxybutyrate (BHB) concentration in two avian species. Broiler chickens and turkeys were reared as recommended by the industry. At 3 wk of age, birds were randomly assigned to a 2 × 3 factorial. The first factor included two species (chickens and turkeys), and the second included doses (0, 4, and 8 mg/mL) of Octanoate in drinking water for 30 d. Feed and WI were recorded daily, while body weight and blood samples were obtained weekly. In chickens, Octanoate doses increased ghrelin and BHB concentrations linearly, while FI and BW decreased linearly with rising Octanoate doses (P < 0.05). However, Octanoate doses did not affect ghrelin, BHB, FI, or BW in turkeys. In conclusion, our data indicate that sodium octanoate administration elicits a differential response in feed intake and body weight gain in chickens and turkeys.
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  • 文章类型: Journal Article
    背景:咖啡消费已证明对食欲的调节有影响,导致更少的饥饿和/或更大的饱腹感;然而,它的作用在超重或肥胖的女性中并不为人所知。因此,这项研究旨在评估咖啡消费对饥饿的影响,饱腹感,感官特定欲望(SSD),超重或肥胖女性的饮食摄入量。
    方法:在3个疗程中实现了一项随机交叉临床试验:在第一个疗程中,我们进行了人体测量和身体成分分析;在第2和第3阶段,参与者随机饮用240mL含6mg/kg咖啡因/kg体重的咖啡或240mL水以及标准早餐.在禁食和早餐后每30分钟,接下来的3小时,使用视觉模拟量表记录食欲感觉和SSD。在禁食时采集血样,早餐后30和180分钟。在其余的干预日记录饮食摄入量。
    结果:在咖啡干预中,人们对甜食的渴望增加,在一天的剩余时间里摄入更多的果糖,甘油三酯水平高于水干预。没有检测到ghrelin或胆囊收缩素的差异。
    结论:咖啡消费可能导致更高的甘油三酯和更高的单糖摄入量,主要是果糖,通过SSD的变化。
    背景:https://clinicaltrials.gov/NCT05774119.
    BACKGROUND: Coffee consumption has demonstrated an effect on the regulation of appetite, causing less hunger and/or greater satiety; however, its effects are not well known in woman with overweight or obesity. Therefore, this study aimed to evaluate the effect of coffee consumption on hunger, satiety, sensory specific desire (SSD), and dietary intake in women with overweight or obesity.
    METHODS: A randomized crossover clinical trial was realized in 3 sessions: in the first session a clinical history, anthropometric measurements and body composition analysis were performed; in sessions 2 and 3 the participants randomly consumed 240mL of coffee with 6mg/caffeine/kg of weight or 240mL of water along with a standardized breakfast. At fasting and every 30min after breakfast for the next 3h, appetite sensations and SSD were recorded using visual analog scales. Blood samples were taken at fasting, 30 and 180min after breakfast. Dietary intake was recorded in the rest of the intervention days.
    RESULTS: In the coffee intervention there was an increased desire for sweet foods, higher fructose intake during the rest of the day, and higher triglyceride levels than with the water intervention. No differences were detected in ghrelin or cholecystokinin.
    CONCLUSIONS: Coffee consumption may lead to higher triglycerides and higher intake of simple sugars, mainly fructose, through changes in the SSD.
    BACKGROUND: https://clinicaltrials.gov/NCT05774119.
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  • 文章类型: Journal Article
    作为自由生活饮食的一部分,长期食用山核桃显示出调节食欲的作用,然而,对单一含山核桃膳食的生理食欲反应尚不清楚。这项研究的目的是比较急性生理,主观,以及含山核桃的膳食对能量和大量营养素匹配的对照膳食的直接食欲反应。这是一项急性进餐挑战研究,采用两个周期的双盲随机交叉设计。参与者很年轻,健康成年人(BMI:22.9±3.3kg/m2,年龄:22±3y),在单独的测试日食用含有68g山核桃(PEC;795千卡)或能量和大量营养素匹配的对照餐(CON;794千卡)。在两次测试访问中,五次餐后抽血,和视觉模拟量表(VAS)问卷(实验室内)用于确定肽YY(PYY)的差异,ghrelin,以及餐后4小时的主观食欲。参与者还在离开测试访问后完成了当天剩余时间的VAS问卷(在家)和食物记录。32名随机参与者中有31名完成了研究。总体餐后PYY反应更大(p<0.001),时间点120分钟后,餐后生长素释放肽的抑制更大(p<0.001),与PECvs.CON餐。Further,主观饱满度有更大的增加(p=0.001),和抑制在家的整体食欲(p=0.02),从用餐后240-780分钟与PECvs.CON进餐。在进餐或任何其他VAS测量之间,自我报告的EI没有差异。总之,与能量和大量营养素匹配的对照餐相比,含山核桃的早餐奶昔在食欲方面产生了更有利的生理和主观改善。该试验在clinicaltrials.gov(NCT05230212)注册。
    Longer-term pecan consumption has shown appetite-regulating effects as a part of a free-living diet, yet the physiologic appetite responses to a single pecan-containing meal are unclear. The purpose of this study was to compare the acute physiologic, subjective, and direct appetite responses of a pecan-containing meal to an energy- and macronutrient-matched control meal. This was an acute meal challenge study utilizing a double-blinded randomized crossover design with two periods. Participants were young, healthy adults (BMI: 22.9 ± 3.3 kg/m2, age: 22 ± 3 y) who consumed a meal containing either 68 g of pecans (PEC; 795 kcal) or an energy- and macronutrient-matched control meal (CON; 794 kcal) on separate testing days. At both testing visits, five postprandial blood draws, and visual analog scale (VAS) questionnaires (in-lab) were used to determine differences in peptide YY (PYY), ghrelin, and subjective appetite over a 4-h postprandial period. Participants also completed VAS questionnaires (at-home) and food records for the rest of the day after leaving the testing visits. Thirty-one out of thirty-two randomized participants completed the study. There was a greater overall postprandial PYY response (p < 0.001), and a greater suppression of postprandial ghrelin after time point 120 min (p < 0.001), with the PEC vs. CON meal. Further, there was a greater increase in subjective fullness (p = 0.001), and suppression of at-home overall appetite (p = 0.02), from time 240-780 min post-meal with PEC vs. CON meals. There were no differences in self-reported EI between meals or any other VAS measure. In conclusion, a pecan-containing breakfast shake produced more favorable physiologic and subjective improvements in appetite compared to an energy- and macronutrient-matched control meal. This trial is registered at clinicaltrials.gov (NCT05230212).
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  • 文章类型: Journal Article
    肌肉损伤可能是由于过度,高强度,或者不适当的锻炼。对于运动员和体育爱好者来说,获得加速康复和缓解不适的方法至关重要。我们先前的临床试验证明了副干酪乳杆菌PS23(PS23)的抗炎和肌肉损伤改善特性,促使我们进一步探讨这种益生菌在肌肉损伤恢复中的作用。这项随机对照研究的事后分析研究了PS23摄入量与预防肌肉损伤后力量损失之间的潜在介质。我们从一所体育大学招募了105名学生,他们参加了先前发表的临床试验。这些参与者被随机分为三组,接收封装的实时PS23(L-PS23),热处理PS23(HT-PS23),或在六周内服用安慰剂。基线和终点测量了循环ghrelin和其他血液标志物的水平,压力,心情,生活质量,和粪便微生物群。与其他组相比,L-PS23组的生长素释放肽水平显着增加。此外,L-PS23和HT-PS23干预都导致肠道微生物群组成的积极变化,特别是在升高的乳杆菌中,Blautia,和乳酸菌种群。这些细菌的丰度与运动表现呈正相关,与炎症标志物呈负相关。总之,膳食补充PS23可能通过增加生长素释放肽水平和调节肠道微生物组成来增强运动表现并影响肌肉损伤。需要进一步澄清可能的机制和临床意义。
    Muscle damage can occur due to excessive, high-intensity, or inappropriate exercise. It is crucial for athletes and sports enthusiasts to have access to ways that expedite their recovery and alleviate discomfort. Our previous clinical trial demonstrated the anti-inflammatory and muscle damage-ameliorating properties of Lacticaseibacillus paracasei PS23 (PS23), prompting us to further explore the role of this probiotic in muscle damage recovery. This post-hoc analysis of a randomized controlled study investigated potential mediators between the intake of PS23 and the prevention of strength loss after muscle damage. We recruited 105 students from a sports university who had participated in the previously published clinical trial. These participants were randomly allocated to three groups, receiving capsuled live PS23 (L-PS23), heat-treated PS23 (HT-PS23), or a placebo over a period of six weeks. Baseline and endpoint measurements were taken for the levels of circulating ghrelin and other blood markers, stress, mood, quality of life, and the fecal microbiota. A significant increase in ghrelin levels was recorded in the L-PS23 group compared to the other groups. Additionally, both L-PS23 and HT-PS23 interventions led to positive shifts in the gut microbiota composition, particularly in elevated Lacticaseibacillus, Blautia, and Lactobacillus populations. The abundance of these bacteria was positively correlated with exercise performance and inversely correlated with inflammatory markers. In conclusion, dietary supplementation with PS23 may enhance exercise performance and influence muscle damage by increasing ghrelin levels and modulating the gut microbiota composition. Further clarification of the possible mechanisms and clinical implications is required.
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  • 文章类型: Journal Article
    糖巨肽(GMP)具有独特的氨基酸谱,可能比其他饮食蛋白质的饱腹感更低。这项研究评估了富含亮氨酸的GMP饮料的可行性和可能的可接受性,并确定了老年人(OA)的食欲反应。当与水和水果冰沙混合时,招募了13个OA(11f;70±4年)用于富含亮氨酸的GMP饮料的感官评估,与乳清分离蛋白(WHEY)相比。参与者还参加了一个单一的焦点小组,探索蛋白质和补充剂的可接受性。分别,一个平衡的,进行了12个OA(8f;69±3年)的双盲研究,以确定食欲和肠道激素反应。使用视觉模拟量表记录空腹主观食欲,并收集空腹静脉血样本(以测量酰基生长素释放肽,PYY,GLP-1和CCK)在参与者食用前:GMP蛋白(27g+3g亮氨酸,350mL水),WHEY(30g,350mL水),或者水。参与者休息了240分钟,通过食欲测量和血液采样。然后食用基于意大利面食的随意膳食。感官测试表明,水中GMP的愉悦等级较低,而不是WHEY(16±14vs31±24,p=0.016)。GMP添加到冰沙降低了愉悦感(26±21vs.61±29,p=0.009),香气恶化(46±15与69±28,p=0.014)。焦点小组揭示了蛋白质需求的不确定性和对补充剂的怀疑,偏爱食物。GMP和WHEY之间的肠道激素反应没有差异(所有肠道激素的nAUCp>0.05)。随意摄入午餐的条件之间没有差异(549±171千卡,512±238千卡,GMP为460±199千卡,Whey,和水,p=0.175),或主观食欲反应。富含亮氨酸的GMP的饱腹感不亚于WHEY,以及补充剂的低适口性和怀疑性质疑GMP补充剂的可能可接受性。提供可信的营养建议和食物富集/强化可能是增加OA中蛋白质摄入的优选策略。
    Glycomacropeptide (GMP) has a unique amino acid profile which may make less satiating than other dietary proteins. This study assessed the feasibility and likely acceptability of a leucine-enriched GMP drink and determined appetite response in older adults (OA). Thirteen OA (11f; 70 ± 4 years) were recruited for sensory assessments of a leucine-enriched GMP drink when mixed with water and with fruit smoothie, compared with whey protein isolate (WHEY). Participants also partook in a single focus group exploring acceptability to protein and supplementation. Separately, a counterbalanced, double-blind study with twelve OA (8f; 69 ± 3 years) was conducted to determine appetite and gut hormone responses. Fasting subjective appetite was recorded using visual analogue scales and a fasted venous blood sample was collected (to measures acyl-ghrelin, PYY, GLP-1, and CCK) before participants consumed either: GMP protein (27g + 3g leucine, 350 mL water), WHEY (30g, 350 mL water), or water. Participants rested for 240 min, with appetite measures and blood sampling throughout. An ad libitum pasta-based meal was then consumed. Sensory testing revealed low pleasantness rating for GMP in water vs. WHEY (16 ± 14 vs 31 ± 24, p = 0.016). GMP addition to smoothie reduced pleasantness (26 ± 21 vs. 61 ± 29, p = 0.009) and worsened the aroma (46 ± 15 vs. 69 ± 28, p = 0.014). The focus group revealed uncertainty of protein needs and a scepticism of supplements, with preference for food. Gut hormone response did not differ between GMP and WHEY (nAUC for all gut hormones p > 0.05). There was no difference between conditions for lunch ad libitum intake (549 ± 171 kcal, 512 ± 238 kcal, 460 ± 199 kcal for GMP, WHEY, and water, p = 0.175), or for subjective appetite response. Leucine-enriched GMP was not less satiating than WHEY, and low palatability and scepticism of supplements question the likely acceptability of GMP supplementation. Providing trusted nutritional advice and food enrichment/fortification may be preferred strategies for increasing protein intake in OA.
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  • 文章类型: Journal Article
    背景:酒精使用障碍(AUD)是一种复发性疾病,描述为过度使用酒精。DNA甲基化在成瘾中作用的证据正在积累。Ghrelin是一种被称为食欲激素的重要肽,其在成瘾行为中的作用已被确定。在这里,我们旨在确定ghrelin信号传导中两个关键基因(GHRL和GHSR)的甲基化水平,并进一步研究甲基化比率与血浆ghrelin水平之间的关联。
    方法:本研究招募诊断有(n=71)和无(n=82)AUD的个体。通过甲基化敏感性高分辨率熔解(MS-HRM)测量DNA甲基化水平。通过ELISA检测酰化生长素释放肽水平。通过标准PCR-RFLP方法分析GHRLrs696217多态性。
    结果:GHRL在25%至50%甲基化的AUD中比对照组明显高甲基化(P<0.0022),但未观察到GHSR甲基化的显着变化。此外,GHRL的甲基化率在25%至50%之间与年龄呈显着正相关。AUD组GHSR甲基化与ghrelin水平呈显著正相关(P=0.037)。在对照组中,GHRL甲基化水平和ghrelin水平显示出显着相关性(P=0.042)。
    结论:GHSR和GHRL甲基化水平在对照组和AUD组之间没有显著变化。然而,在两组中,GHRL和GHSR甲基化似乎与血浆ghrelin水平有关。这是第一个研究AUD中GHRL和GHSR基因的DNA甲基化。
    BACKGROUND: Alcohol use disorder (AUD) is a relapsing disease described as excessive use of alcohol. Evidence of the role of DNA methylation in addiction is accumulating. Ghrelin is an important peptide known as appetite hormone and its role in addictive behavior has been identified. Here we aimed to determine the methylation levels of two crucial genes (GHRL and GHSR) in ghrelin signaling and further investigate the association between methylation ratios and plasma ghrelin levels.
    METHODS: Individuals diagnosed with (n = 71) and without (n = 82) AUD were recruited in this study. DNA methylation levels were measured through methylation-sensitive high-resolution melting (MS-HRM). Acylated ghrelin levels were detected by ELISA. The GHRL rs696217 polymorphism was analyzed by the standard PCR-RFLP method.
    RESULTS: GHRL was significantly hypermethylated (P < 0.0022) in AUD between 25 and 50% methylation than in control subjects but no significant changes of GHSR methylation were observed. Moreover, GHRL showed significant positive correlation of methylation ratio between 25 and 50% with age. A significant positive correlation between GHSR methylation and ghrelin levels in the AUD group was determined (P = 0.037). The level of GHRL methylation and the ghrelin levels showed a significant association in the control subjects (P = 0.042).
    CONCLUSIONS: GHSR and GHRL methylation levels did not change significantly between control and AUD groups. However, GHRL and GHSR methylations seemed to have associations with plasma ghrelin levels in two groups. This is the first study investigating the DNA methylation of GHRL and GHSR genes in AUD.
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  • 文章类型: Journal Article
    背景:目前的研究表明,通过人乳的能量转移会影响婴儿的营养发育并启动代谢程序,影响成年后的饮食模式。迄今为止,这项研究主要在高收入地区的妇女和/或营养不良妇女中进行.我们将调查母亲身体成分之间的关系,母乳中的代谢激素,和婴儿饱腹感,以探索发育饱腹感编程的机制以及对萨摩亚人早期婴儿生长和身体组成的影响;超重和肥胖的高危人群。我们的目标是(1)检查母体身体成分如何影响通过母乳从母体到婴儿的代谢激素转移,(2)研究母体代谢激素转移和婴儿喂养方式对婴儿早期生长和饱腹感的影响。
    方法:我们将在n=80个萨摩亚母婴二元组的前瞻性纵向队列中研究通过母乳向婴儿传递激素的时间变化。将在三个时间点(产后1、3和4个月)收集数据。在每次研究访问中,我们将从母乳喂养的母婴二元组中收集人乳和手指采血样本,以测量激素瘦素,ghrelin,和脂联素。此外,我们将从二元组获得身体成分测量值,观察母乳喂养行为,进行半结构化面试,并使用问卷记录婴儿的饥饿和喂养线索以及饱腹感反应。描述性统计,将进行单变量和多变量分析以解决每个目标。
    结论:这项研究旨在促进我们对饱腹感发育程序变化的理解以及对婴儿早期生长和身体组成的影响。使用前瞻性纵向队列以及使用混合方法方法的数据收集将使我们能够在超重和肥胖高风险人群中更准确地反映生物学和文化变量。
    BACKGROUND: Current research suggests that energy transfer through human milk influences infant nutritional development and initiates metabolic programming, influencing eating patterns into adulthood. To date, this research has predominantly been conducted among women in high income settings and/or among undernourished women. We will investigate the relationship between maternal body composition, metabolic hormones in human milk, and infant satiety to explore mechanisms of developmental satiety programming and implications for early infant growth and body composition in Samoans; a population at high risk and prevalence for overweight and obesity. Our aims are (1) to examine how maternal body composition influences metabolic hormone transfer from mother to infant through human milk, and (2) to examine the influences of maternal metabolic hormone transfer and infant feeding patterns on early infant growth and satiety.
    METHODS: We will examine temporal changes in hormone transfers to infants through human milk in a prospective longitudinal cohort of n = 80 Samoan mother-infant dyads. Data will be collected at three time points (1, 3, & 4 months postpartum). At each study visit we will collect human milk and fingerpick blood samples from breastfeeding mother-infant dyads to measure the hormones leptin, ghrelin, and adiponectin. Additionally, we will obtain body composition measurements from the dyad, observe breastfeeding behavior, conduct semi-structured interviews, and use questionnaires to document infant hunger and feeding cues and satiety responsiveness. Descriptive statistics, univariate and multivariate analyses will be conducted to address each aim.
    CONCLUSIONS: This research is designed to advance our understanding of variation in the developmental programming of satiety and implications for early infant growth and body composition. The use of a prospective longitudinal cohort alongside data collection that utilizes a mixed methods approach will allow us to capture a more accurate representation on both biological and cultural variables at play in a population at high risk of overweight and obesity.
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  • 文章类型: Journal Article
    院外心脏骤停的存活率在过去的几十年里显著上升,但神经学结果仅略有改善。尽管研究了20多种涉及心脏骤停后昏迷患者的神经保护策略,没有人表现出明确的疗效证据;然而,在心脏骤停的实验模型中,用酰基-ghrelin治疗显示出改善的功能和组织学脑恢复,并且在各种人类研究人群中是安全的。
    确定静脉注射酰基生长素释放肽改善心脏骤停后昏迷患者神经系统预后的安全性和潜在疗效。
    第二阶段,双盲,安慰剂对照,多中心,随机临床试验,Ghrelin治疗心脏骤停后昏迷患者:促进大脑恢复的临床试验(GRECO),于2019年1月18日至2022年10月17日期间进行。对心脏骤停后处于昏迷状态的18岁或以上的成年患者进行了资格评估;患者来自荷兰的3个重症监护病房。48小时内的预期死亡或12小时内开始治疗的不可行性是排除标准。
    患者随机接受静脉注射酰基生长素释放肽,600μg(干预组),或安慰剂(对照组)在心脏骤停后12小时内,持续7天,每天两次,除了标准护理。
    主要结果是6个月时的脑功能类别(CPC)量表评分。安全性结果包括任何严重不良事件。次要结果是第1天和第3天的死亡率和神经元特异性烯醇化酶(NSE)水平。
    总共对783名心脏骤停后昏迷的成年患者进行了资格评估,和160名患者(中位[IQR]年龄,68[57-75]岁;120名男性[75%])入组。共有81名患者(51%)被分配到干预组,79人(49%)被分配到对照组.干预组CPC改善的共同比值比(OR)为1.78(95%CI,0.98-3.22;P=.06)。这在所有CPC类别上都是一致的。心脏骤停后第1天的平均(SD)NSE水平在干预组(34[6]μg/L比56[13]μg/L;P=.04)和第3天(28[6]μg/L比52[14]μg/L;P=.08)显著降低。两组之间严重不良事件的发生率和类型相当。干预组的死亡率为37%(81个中的30个),对照组为51%(79个中的40个)(绝对风险降低,14%;95%CI,-2%至29%;P=.08)。
    心脏骤停后昏迷的患者,酰基-ghrelin静脉治疗是安全的,并有可能有效改善神经系统预后.需要进行3期试验才能获得确凿的证据。
    临床试验登记簿。欧盟:EUCTR2018-000005-23-NL。
    UNASSIGNED: Out-of-hospital cardiac arrest survival rates have markedly risen in the last decades, but neurological outcome only improved marginally. Despite research on more than 20 neuroprotective strategies involving patients in comas after cardiac arrest, none have demonstrated unequivocal evidence of efficacy; however, treatment with acyl-ghrelin has shown improved functional and histological brain recovery in experimental models of cardiac arrest and was safe in a wide variety of human study populations.
    UNASSIGNED: To determine safety and potential efficacy of intravenous acyl-ghrelin to improve neurological outcome in patients in a coma after cardiac arrest.
    UNASSIGNED: A phase 2, double-blind, placebo-controlled, multicenter, randomized clinical trial, Ghrelin Treatment of Comatose Patients After Cardiac Arrest: A Clinical Trial to Promote Cerebral Recovery (GRECO), was conducted between January 18, 2019, and October 17, 2022. Adult patients 18 years or older who were in a comatose state after cardiac arrest were assessed for eligibility; patients were from 3 intensive care units in the Netherlands. Expected death within 48 hours or unfeasibility of treatment initiation within 12 hours were exclusion criteria.
    UNASSIGNED: Patients were randomized to receive intravenous acyl-ghrelin, 600 μg (intervention group), or placebo (control group) within 12 hours after cardiac arrest, continued for 7 days, twice daily, in addition to standard care.
    UNASSIGNED: Primary outcome was the score on the Cerebral Performance Categories (CPC) scale at 6 months. Safety outcomes included any serious adverse events. Secondary outcomes were mortality and neuron-specific enolase (NSE) levels on days 1 and 3.
    UNASSIGNED: A total of 783 adult patients in a coma after cardiac arrest were assessed for eligibility, and 160 patients (median [IQR] age, 68 [57-75] years; 120 male [75%]) were enrolled. A total of 81 patients (51%) were assigned to the intervention group, and 79 (49%) were assigned to the control group. The common odds ratio (OR) for any CPC improvement in the intervention group was 1.78 (95% CI, 0.98-3.22; P = .06). This was consistent over all CPC categories. Mean (SD) NSE levels on day 1 after cardiac arrest were significantly lower in the intervention group (34 [6] μg/L vs 56 [13] μg/L; P = .04) and on day 3 (28 [6] μg/L vs 52 [14] μg/L; P = .08). Serious adverse events were comparable in incidence and type between the groups. Mortality was 37% (30 of 81) in the intervention group vs 51% (40 of 79) in the control group (absolute risk reduction, 14%; 95% CI, -2% to 29%; P = .08).
    UNASSIGNED: In patients in a coma after cardiac arrest, intravenous treatment with acyl-ghrelin was safe and potentially effective to improve neurological outcome. Phase 3 trials are needed for conclusive evidence.
    UNASSIGNED: Clinicaltrialsregister.eu: EUCTR2018-000005-23-NL.
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