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The Cochrane Database of Systematic... Dec 2020The introduction and advancement of enteral feeds for preterm or low birth weight infants is often delayed because of concerns that early full enteral feeding will not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The introduction and advancement of enteral feeds for preterm or low birth weight infants is often delayed because of concerns that early full enteral feeding will not be well tolerated or may increase the risk of necrotising enterocolitis. Early full enteral feeding, however, might increase nutrient intake and growth rates; accelerate intestinal physiological, metabolic, and microbiomic postnatal transition; and reduce the risk of complications associated with intravascular devices for fluid administration. OBJECTIVES: To determine how early full enteral feeding, compared with delayed or progressive introduction of enteral feeds, affects growth and adverse events such as necrotising enterocolitis, in preterm or low birth weight infants.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials; MEDLINE Ovid, Embase Ovid, Maternity & Infant Care Database Ovid, the Cumulative Index to Nursing and Allied Health Literature, and clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials to October 2020.
SELECTION CRITERIA
Randomised controlled trials that compared early full enteral feeding with delayed or progressive introduction of enteral feeds in preterm or low birth weight infants.
DATA COLLECTION AND ANALYSIS
We used the standard methods of Cochrane Neonatal. Two review authors separately assessed trial eligibility, evaluated trial quality, extracted data, and synthesised effect estimates using risk ratios (RR), risk differences, and mean differences (MD) with 95% confidence intervals (CI). We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
We included six trials. All were undertaken in the 2010s in neonatal care facilities in India. In total, 526 infants participated. Most were very preterm infants of birth weight between 1000 g and 1500 g. Trials were of good methodological quality, but a potential source of bias was that parents, clinicians, and investigators were not masked. The trials compared early full feeding (60 mL/kg to 80 mL/kg on day one after birth) with minimal enteral feeding (typically 20 mL/kg on day one) supplemented with intravenous fluids. Feed volumes were advanced daily as tolerated by 20 mL/kg to 30 mL/kg body weight to a target steady-state volume of 150 mL/kg to 180 mL/kg/day. All participating infants were fed preferentially with maternal expressed breast milk, with two trials supplementing insufficient volumes with donor breast milk and four supplementing with preterm formula. Few data were available to assess growth parameters. One trial (64 participants) reported a slower rate of weight gain (median difference -3.0 g/kg/day), and another (180 participants) reported a faster rate of weight gain in the early full enteral feeding group (MD 1.2 g/kg/day). We did not meta-analyse these data (very low-certainty evidence). None of the trials reported rate of head circumference growth. One trial reported that the mean z-score for weight at hospital discharge was higher in the early full enteral feeding group (MD 0.24, 95% CI 0.06 to 0.42; low-certainty evidence). Meta-analyses showed no evidence of an effect on necrotising enterocolitis (RR 0.98, 95% CI 0.38 to 2.54; 6 trials, 522 participants; I² = 51%; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Trials provided insufficient data to determine with any certainty how early full enteral feeding, compared with delayed or progressive introduction of enteral feeds, affects growth in preterm or low birth weight infants. We are uncertain whether early full enteral feeding affects the risk of necrotising enterocolitis because of the risk of bias in the trials (due to lack of masking), inconsistency, and imprecision.
Topics: Body Weight; Enteral Nutrition; Enterocolitis, Necrotizing; Fluid Therapy; Humans; Infant Formula; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Milk, Human; Randomized Controlled Trials as Topic; Weight Gain
PubMed: 33368149
DOI: 10.1002/14651858.CD013542.pub2 -
Nature Communications Jan 2016The domestic dog is becoming an increasingly valuable model species in medical genetics, showing particular promise to advance our understanding of cancer and...
The domestic dog is becoming an increasingly valuable model species in medical genetics, showing particular promise to advance our understanding of cancer and orthopaedic disease. Here we undertake the largest canine genome-wide association study to date, with a panel of over 4,200 dogs genotyped at 180,000 markers, to accelerate mapping efforts. For complex diseases, we identify loci significantly associated with hip dysplasia, elbow dysplasia, idiopathic epilepsy, lymphoma, mast cell tumour and granulomatous colitis; for morphological traits, we report three novel quantitative trait loci that influence body size and one that influences fur length and shedding. Using simulation studies, we show that modestly larger sample sizes and denser marker sets will be sufficient to identify most moderate- to large-effect complex disease loci. This proposed design will enable efficient mapping of canine complex diseases, most of which have human homologues, using far fewer samples than required in human studies.
Topics: Animals; Body Size; Dog Diseases; Dogs; Female; Genome-Wide Association Study; Genotype; Humans; Male; Phenotype; Quantitative Trait Loci
PubMed: 26795439
DOI: 10.1038/ncomms10460 -
Clinical Epigenetics Aug 2021In the first study of its kind, we examine the association between growth and development in early life and DNAm age biomarkers in mid-life. (Comparative Study)
Comparative Study
BACKGROUND
In the first study of its kind, we examine the association between growth and development in early life and DNAm age biomarkers in mid-life.
METHODS
Participants were from the Medical Research Council National Survey of Health and Development (n = 1376). Four DNAm age acceleration (AgeAccel) biomarkers were measured when participants were aged 53 years: AgeAccelHannum; AgeAccelHorvath; AgeAccelLevine; and AgeAccelGrim. Exposure variables included: relative weight gain (standardised residuals from models of current weight z-score on current height, and previous weight and height z-scores); and linear growth (standardised residuals from models of current height z-score on previous height and weight z-scores) during infancy (0-2 years, weight gain only), early childhood (2-4 years), middle childhood (4-7 years) and late childhood to adolescence (7-15 years); age at menarche; and pubertal stage for men at 14-15 years. The relationship between relative weight gain and linear growth and AgeAccel was investigated using conditional growth models. We replicated analyses from the late childhood to adolescence period and pubertal timing among 240 participants from The National Child and Development Study (NCDS).
RESULTS
A 1SD increase in relative weight gain in late childhood to adolescence was associated with 0.50 years (95% CI 0.20, 0.79) higher AgeAccelGrim. Although the CI includes the null, the estimate was similar in NCDS [0.57 years (95% CI - 0.01, 1.16)] There was no strong evidence that relative weight gain and linear growth in childhood was associated with any other AgeAccel biomarker. There was no relationship between pubertal timing in men and AgeAccel biomarkers. Women who reached menarche ≥ 12 years had 1.20 years (95% CI 0.15, 2.24) higher AgeAccelGrim on average than women who reached menarche < 12 years; however, this was not replicated in NCDS and was not statistically significant after Bonferroni correction.
CONCLUSIONS
Our findings generally do not support an association between growth and AgeAccel biomarkers in mid-life. However, we found rapid weight gain during pubertal development, previously related to higher cardiovascular disease risk, to be associated with older AgeAccelGrim. Given this is an exploratory study, this finding requires replication.
Topics: Adolescent; Adult; Age Factors; Aging; Biomarkers; Birth Weight; Body Height; Body Mass Index; Child; Child Development; Child, Preschool; DNA Methylation; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; United Kingdom; Weight Gain; Young Adult
PubMed: 34372922
DOI: 10.1186/s13148-021-01138-x -
Journal of Applied Physiology... Mar 2011Pentadecapeptide BPC 157, composed of 15 amino acids, is a partial sequence of body protection compound (BPC) that is discovered in and isolated from human gastric...
Pentadecapeptide BPC 157, composed of 15 amino acids, is a partial sequence of body protection compound (BPC) that is discovered in and isolated from human gastric juice. Experimentally it has been demonstrated to accelerate the healing of many different wounds, including transected rat Achilles tendon. This study was designed to investigate the potential mechanism of BPC 157 to enhance healing of injured tendon. The outgrowth of tendon fibroblasts from tendon explants cultured with or without BPC 157 was examined. Results showed that BPC 157 significantly accelerated the outgrowth of tendon explants. Cell proliferation of cultured tendon fibroblasts derived from rat Achilles tendon was not directly affected by BPC 157 as evaluated by MTT assay. However, the survival of BPC 157-treated cells was significantly increased under the H(2)O(2) stress. BPC 157 markedly increased the in vitro migration of tendon fibroblasts in a dose-dependent manner as revealed by transwell filter migration assay. BPC 157 also dose dependently accelerated the spreading of tendon fibroblasts on culture dishes. The F-actin formation as detected by FITC-phalloidin staining was induced in BPC 157-treated fibroblasts. The protein expression and activation of FAK and paxillin were determined by Western blot analysis, and the phosphorylation levels of both FAK and paxillin were dose dependently increased by BPC 157 while the total amounts of protein was unaltered. In conclusion, BPC 157 promotes the ex vivo outgrowth of tendon fibroblasts from tendon explants, cell survival under stress, and the in vitro migration of tendon fibroblasts, which is likely mediated by the activation of the FAK-paxillin pathway.
Topics: Animals; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Fibroblasts; Humans; Male; Peptide Fragments; Proteins; Rats; Rats, Sprague-Dawley; Tendon Injuries; Tendons; Treatment Outcome; Wound Healing
PubMed: 21030672
DOI: 10.1152/japplphysiol.00945.2010 -
JAMA Network Open Dec 2021Preterm birth and low birth weight are associated with brain developmental and neurocognitive outcomes in childhood; however, not much is known about the specific...
IMPORTANCE
Preterm birth and low birth weight are associated with brain developmental and neurocognitive outcomes in childhood; however, not much is known about the specific critical periods in fetal life and infancy for these outcomes.
OBJECTIVE
To examine the associations of fetal and infant growth patterns with brain morphology in children at school age.
DESIGN, SETTING, AND PARTICIPANTS
This population-based, prospective cohort study was conducted from February 1 to April 16, 2021, as a part of the Generation R Study in Rotterdam, the Netherlands. The study included 3098 singleton children born between April 1, 2002, and January 31, 2006.
EXPOSURES
Fetal weight was estimated in the second and third trimesters of pregnancy by ultrasonography. Infant weight was measured at birth and at 6, 12, and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change in SD scores greater than 0.67 between time points. Infant measurements also included peak weight velocity, and age and body mass index reached at adiposity peak.
MAIN OUTCOMES AND MEASURES
Brain structure, including global and regional brain volumes, was quantified by magnetic resonance imaging at age 10 years.
RESULTS
The study evaluated 3098 children (mean [SD] age at follow-up, 10.1 [0.6] years; 1557 girls [50.3%]; and 1753 Dutch [57.8%]). One SD score-higher weight gain until the second and third trimesters, birth, and 6, 12, and 24 months was associated with larger total brain volume independently of growth during any other age windows (second trimester: 5.7 cm3; 95% CI, 1.2-10.2 cm3; third trimester: 15.3 cm3; 95% CI, 11.0-19.6 cm3; birth: 20.8 cm3; 95% CI, 16.4-25.1 cm3; 6 months: 15.6 cm3; 95% CI, 11.2-19.9 cm3; 12 months: 11.3 cm3; 95% CI, 7.0-15.6 cm3; and 24 months: 11.1 cm3; 95% CI, 6.8-15.4 cm3). Compared with children with normal fetal and infant growth, those with fetal and infant growth deceleration had the smallest total brain volume (-32.5 cm3; 95% CI, -53.2 to -11.9 cm3). Children with fetal weight deceleration followed by infant catch-up growth had similar brain volumes as children with normal growth. Higher peak weight velocity and body mass index reached at adiposity peak were associated with larger brain volumes. Similar results were observed for cerebral and cerebellar gray and white matter volumes.
CONCLUSIONS AND RELEVANCE
This cohort study's findings suggest that both fetal and infant weight growth might be critical for cerebral and cerebellar brain volumes during childhood. Whether these associations link to neurocognitive outcomes should be further studied.
Topics: Adult; Body Mass Index; Brain; Child; Child Development; Child, Preschool; Cohort Studies; Female; Fetal Development; Humans; Infant; Infant, Newborn; Male; Netherlands; Prospective Studies; Weight Gain
PubMed: 34882181
DOI: 10.1001/jamanetworkopen.2021.38214 -
Problemy Endokrinologii Oct 2022The article presents data about short stature due to intrauterine development delay. This type of short stature - separate nosology, unites children born small for...
The article presents data about short stature due to intrauterine development delay. This type of short stature - separate nosology, unites children born small for gestation age. The majority of them in the first years of life have accelerated growth rates, allowing the child to normalize their weight-growth indicators and catch up in the development of peers. In the absence of an accelerated growth rates, children have a high risk of lagging behind in physical development throughout childhood, achieving low final growth and becoming short adults. In addition, the fact of birth with small body sizes is associated with a number of hormonal and metabolic features, a risk of metabolic syndrome in adult years.It is assumed that the absence of postnatal growth acceleration is due to various damages to the GH-IGF1 axis (partial GH deficiency, partial resistance to GH, partial resistance to IGF1). Growth hormone therapy, initiated early in life, is able to normalize growth rates in childhood and ultimately significantly improve or normalize the final growth of short stature children born small for gestational age.
Topics: Infant, Newborn; Child; Adult; Female; Humans; Fetal Growth Retardation; Body Height; Infant, Small for Gestational Age; Human Growth Hormone; Growth Hormone; Dwarfism
PubMed: 36337013
DOI: 10.14341/probl13178 -
International Journal of Nanomedicine 2023Aptamers are widely applied to diagnosis and therapy because of their targeting. However, the current progress of research into aptamers for the treatment of eye... (Review)
Review
Aptamers are widely applied to diagnosis and therapy because of their targeting. However, the current progress of research into aptamers for the treatment of eye disorders has not been well-documented. The current literature on aptamers was reviewed in this study. Aptamer-related drugs and biochemical sensors have been evaluated for several eye disorders within the past decade; S58 targeting TGF-β receptor II and pegaptanib targeting vascular endothelial growth factor (VEGF) are used to prevent fibrosis after glaucoma filtration surgery. Anti-brain-derived neurotrophic factor aptamer has been used to diagnose glaucoma. The first approved aptamer drug (pegaptanib) has been used to inhibit angiogenesis in age-related macular degeneration (AMD) and diabetic retinopathy (DR), and its efficacy and safety have been demonstrated in clinical trials. Aptamers, including E10030, RBM-007, AS1411, and avacincaptad pegol, targeting other angiogenesis-related biomarkers have also been discovered and subjected to clinical trials. Aptamers, such as C promoter binding factor 1, CD44, and advanced end products in AMD and DR, targeting other signal pathway proteins have also been discovered for therapy, and biochemical sensors for early diagnosis have been developed based on aptamers targeting VEGF, connective tissue growth factor, and lipocalin 1. Aptamers used for early detection and treatment of ocular tumors were derived from other disease biomarkers, such as CD71, nucleolin, and high mobility group A. In this review, the development and application of aptamers in eye disorders in recent years are systematically discussed, which may inspire a new link between aptamers and eye disorders. The aptamer development trajectory also facilitates the discovery of the pathogenesis and therapeutic strategies for various eye disorders.
Topics: Humans; Vascular Endothelial Growth Factor A; Ophthalmology; Macular Degeneration; Aptamers, Nucleotide; Diabetic Retinopathy; Glaucoma; Acceleration
PubMed: 37551274
DOI: 10.2147/IJN.S418115 -
Amino Acids Mar 2014Amino acids, especially glutamine (GLN) have been known for many years to stimulate the growth of small intestinal mucosa. Polyamines are also required for optimal... (Review)
Review
Amino acids, especially glutamine (GLN) have been known for many years to stimulate the growth of small intestinal mucosa. Polyamines are also required for optimal mucosal growth, and the inhibition of ornithine decarboxylase (ODC), the first rate-limiting enzyme in polyamine synthesis, blocks growth. Certain amino acids, primarily asparagine (ASN) and GLN stimulate ODC activity in a solution of physiological salts. More importantly, their presence is also required before growth factors and hormones such as epidermal growth factor and insulin are able to increase ODC activity. ODC activity is inhibited by antizyme-1 (AZ) whose synthesis is stimulated by polyamines, thus, providing a negative feedback regulation of the enzyme. In the absence of amino acids mammalian target of rapamycin complex 1 (mTORC1) is inhibited, whereas, mTORC2 is stimulated leading to the inhibition of global protein synthesis but increasing the synthesis of AZ via a cap-independent mechanism. These data, therefore, explain why ASN or GLN is essential for the activation of ODC. Interestingly, in a number of papers, AZ has been shown to inhibit cell proliferation, stimulate apoptosis, or increase autophagy. Each of these activities results in decreased cellular growth. AZ binds to and accelerates the degradation of ODC and other proteins shown to regulate proliferation and cell death, such as Aurora-A, Cyclin D1, and Smad1. The correlation between the stimulation of ODC activity and the absence of AZ as influenced by amino acids is high. Not only do amino acids such as ASN and GLN stimulate ODC while inhibiting AZ synthesis, but also amino acids such as lysine, valine, and ornithine, which inhibit ODC activity, increase the synthesis of AZ. The question remaining to be answered is whether AZ inhibits growth directly or whether it acts by decreasing the availability of polyamines to the dividing cells. In either case, evidence strongly suggests that the regulation of AZ synthesis is the mechanism through which amino acids influence the growth of intestinal mucosa. This brief article reviews the experiments leading to the information presented above. We also present evidence from the literature that AZ acts directly to inhibit cell proliferation and increase the rate of apoptosis. Finally, we discuss future experiments that will determine the role of AZ in the regulation of intestinal mucosal growth by amino acids.
Topics: Amino Acids; Animals; Apoptosis; Cell Proliferation; Intestinal Mucosa; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Polyamines; Proteins
PubMed: 23904095
DOI: 10.1007/s00726-013-1565-2 -
Scientific Reports Oct 2020Necrostatins (Necs) have been developed as a receptor-interacting protein kinase 1 (RIPK1) inhibitor, thus inhibiting necroptosis. In this current study, we have...
Necrostatins (Necs) have been developed as a receptor-interacting protein kinase 1 (RIPK1) inhibitor, thus inhibiting necroptosis. In this current study, we have investigated the possible involvement of necroptosis in the hair cycle regulation and further examined its underlying molecular mechanisms. Diverse RIPK1/3 inhibitors and siRNA were tested in the human outer-root sheath (ORS) cells and animal models. The expression and hair cycle-dependent expression of RIPK 1, respectively, were investigated in the hair follicles (HF) of human, pig, and the mouse. Resulting from the experiment, Nec-1s was most effective in the hair growth promotion among several inhibitors. Nec-1s induced the ORS cell proliferation and migration, and increased the HF length in mouse and pig organ cultures. In addition, it accelerated the telogen-to-anagen transition and elongated the anagen period in the mouse model. Both apoptosis and necroptosis were detected in hair cycle. RIPK1 and RIPK3 were highly expressed in ORS cells during the hair regression period. Nec-1s upregulated the mRNA expression of Wnt3a and Wnt5b, and the activity of β-catenin. Collectively, Nec-1s promotes hair growth through inhibiting necroptosis and activating the Wnt/β-catenin pathway. Necroptosis is involved in hair cycle regression, and Nec-1s is a promising target for hair-loss treatment.
Topics: Animals; Apoptosis; Cell Line; Cell Movement; Cell Proliferation; Hair; Hair Follicle; Humans; Imidazoles; Indoles; Male; Mice; Necroptosis; Swine; Wnt Signaling Pathway
PubMed: 33077863
DOI: 10.1038/s41598-020-74796-1 -
The Journal of General Physiology Nov 1926The human growth curve shows two (and only two) outstanding periods of accelerated growth-the circumnatal and the adolescent. The circumnatal growth cycle attains great...
The human growth curve shows two (and only two) outstanding periods of accelerated growth-the circumnatal and the adolescent. The circumnatal growth cycle attains great velocity, which reaches a maximum at the time of birth. The curve of this cycle is best fitted by a theoretical skew curve of Pearson's Type I. It has a theoretical range of 44 months and a standard deviation of 5.17 months. The modal velocity is 10.2 kilos per year. The adolescent growth cycle has less maximum velocity and greater range in time than the circumnatal cycle. The best fitting theoretical curve is a normal frequency curve ranging over about 10 years with a standard deviation of about 21 months and a modal velocity of 4.5 kilos per year. The two great growth accelerations are superimposed on a residual curve of growth which measures a substratum of growth out of which the accelerations arise. This probably extends from conception to 55 years, on the average. It is characterized by low velocity, averaging about 2 kilos per year from 2 to 12 years. It is interpreted as due to many growth operations coincident or closely blending in time. Our curve shows no third marked period of acceleration at between the 3rd and 6th years. The total growth in weight of the body is the sum of the weight of its constituent organs. In some cases these keep pace with the growth of the body as a whole; great accelerations of body growth are due to great accelerations in growth of the constituent organs. In other cases one of the organs of the body (like the thymus gland) may undergo a change in weight that is not in harmony with that of the body as a whole. The development of the weight in man is the resultant of many more or less elementary growth processes. These result in two special episodes of growth and numerous smaller, blending, growth operations. Hypotheses are suggested as to the basis of the special growth accelerations.
PubMed: 19872316
DOI: 10.1085/jgp.10.2.205