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European Journal of Clinical... May 2020More than 30 causative genes have been identified in familial and sporadic amyotrophic lateral sclerosis (ALS). The next-generation sequencing (NGS) is a powerful and...
BACKGROUND
More than 30 causative genes have been identified in familial and sporadic amyotrophic lateral sclerosis (ALS). The next-generation sequencing (NGS) is a powerful and groundbreaking tool to identify disease-associated variants. Despite documented advantages of NGS, its diagnostic reliability needs to be addressed in order to use this technology for specific routine diagnosis.
MATERIAL AND METHODS
Literature database was explored to identify studies comparing NGS and Sanger sequencing for the detection of variants causing ALS. We collected data about patients' characteristics, disease type and duration, NGS and Sanger properties.
RESULTS
More than 200 bibliographic references were identified, of which only 14 studies matching our inclusion criteria. Only 2 out of 14 studies compared results of NGS analysis with the Sanger sequencing. Twelve studies screened causative genes associated to ALS using NGS technologies and confirmed the identified variants with Sanger sequencing. Overall, data about more 2,000 patients were analysed. The number of genes that were investigated in each study ranged from 1 to 32, the most frequent being FUS, OPTN, SETX and VCP. NGS identified already known mutations in 21 genes, and new or rare variants in 27 genes.
CONCLUSIONS
NGS seems to be a promising tool for the diagnosis of ALS in routine clinical practice. Its advantages are represented by an increased speed and a lowest sequencing cost, but patients' counselling could be problematic due to the discovery of frequent variants of unknown significance.
Topics: Amyotrophic Lateral Sclerosis; Cell Cycle Proteins; DNA Helicases; High-Throughput Nucleotide Sequencing; Humans; Membrane Transport Proteins; Multifunctional Enzymes; RNA Helicases; RNA-Binding Protein FUS; Reproducibility of Results; Sequence Analysis, DNA; Valosin Containing Protein
PubMed: 32293029
DOI: 10.1111/eci.13228 -
Gut Microbes Nov 2020In this review, we highlight the variations of gut resistome studies, which may preclude comparisons and translational interpretations. Of 22 included studies, a range...
In this review, we highlight the variations of gut resistome studies, which may preclude comparisons and translational interpretations. Of 22 included studies, a range of 12 to 2000 antibiotic resistance (AR) genes were profiled. Overall, studies defined a healthy gut resistome as subjects who had not taken antibiotics in the last three to 12 months prior to sampling. In studies with assembly, AR genes were identified based on variable nucleotide or amino acid sequence similarities. Different marker genes were used for defining resistance to a given antibiotic class. Validation of phenotypic resistance in the laboratory is frequently lacking. Cryptic resistance, collateral sensitivity and the interaction with repressors or promotors were not investigated. International consensus is needed for selecting marker genes to define resistance to a given antibiotic class in addition to uniformity in phenotypic validation and bioinformatics pipelines.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial; Gastrointestinal Microbiome; Gastrointestinal Tract; Genes, Bacterial; Humans
PubMed: 31942825
DOI: 10.1080/19490976.2019.1700755 -
Orphanet Journal of Rare Diseases Dec 2019Primary hypertrophic osteoarthropathy (PHO) is a rare disease related to HPGD and SLCO2A1 gene mutation. Gastrointestinal involvement of PHO is even rarer with unknown...
Primary hypertrophic osteoarthropathy related gastrointestinal complication has distinctive clinical and pathological characteristics: two cases report and review of the literature.
BACKGROUND
Primary hypertrophic osteoarthropathy (PHO) is a rare disease related to HPGD and SLCO2A1 gene mutation. Gastrointestinal involvement of PHO is even rarer with unknown pathogenesis. Clinical features of GI complication in PHO mimics other auto-immune based bowel entities, such as inflammatory bowel diseases and cryptogenic multifocal ulcerous stenosing enteritis (CMUSE). We aimed to analyze the clinical, genetic, radiological and pathological features of Chinese patients with PHO and determine the difference between PHO patients presenting with and without GI involvement.
METHODS
We reported two PHO cases with gastrointestinal involvement and reviewed all the studies of PHO in Chinese population published from January 1, 2000, to April 30, 2018. Clinical and genetic presentations of PHO in Chinese patients were analyzed. We compared the characteristics of those patients with gastrointestinal involvement against those without.
RESULTS
The two patients were both males with complete-form PHO for more than 10 years. GI related symptoms included diarrhea, chronic gastrointestinal hemorrhage, incomplete intestinal obstruction, anemia, and edema, which were unresponsive to etoricoxib treatment. Radiological examinations revealed segmental intestinal stenosis and thickened intestinal wall. Endoscopic findings included multiple ulcers and mucosal inflammation. Both patients had mutations of SLCO2A1 according to sequence analysis. The surgical pathology revealed chronic inflammation involving the intestinal mucosa and submucosa, similar to histological changes in CMUSE. According to the systemic review of 158 Chinese patients with PHO, 17.2% had gastrointestinal involvement, including peptic ulcer, gastric polyps, hypertrophic gastritis, and segmental intestinal stenosis. Patients with gastrointestinal involvement were more likely to have anemia (40.0% vs. 4.5%, P < 0.001), hypoalbuminemia (16.7% vs. 0.9%, P = 0.003), and myelofibrosis (19.0% vs. 0.9%, P = 0.002) than those without. Most patients with gastrointestinal complication had SLCO2A1 mutation (86.7%, 13 /15).
CONCLUSIONS
Digestive tract involvement is uncommon in patients with PHO and often presents with anemia, and hypoalbuminemia resulted from intestinal inflammation. The intestinal pathologic characteristics are distinct from Crohn's disease but similar to CMUSE. Mutations in SLCO2A1 might be the pathogenic cause of GI involvement of PHO. NSAIDs may not be effective for PHO patients with gastrointestinal complications.
Topics: Asian People; Gastrointestinal Diseases; Humans; Intramolecular Oxidoreductases; Mutation; Organic Anion Transporters; Osteoarthropathy, Primary Hypertrophic
PubMed: 31878983
DOI: 10.1186/s13023-019-1264-5 -
JAMA Neurology Mar 2020The c9orf72 repeat expansion (c9 or c9orf72RE) confers a survival disadvantage in amyotrophic lateral sclerosis (ALS); its effect on prognosis in frontotemporal dementia... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The c9orf72 repeat expansion (c9 or c9orf72RE) confers a survival disadvantage in amyotrophic lateral sclerosis (ALS); its effect on prognosis in frontotemporal dementia (FTD) remains uncertain. Data on prognostic factors in c9orf72RE disorders could inform patient care, genetic counseling, and trial design.
OBJECTIVE
To examine prognostic factors in c9ALS, c9FTD, c9ALS-FTD, and atypical phenotypes.
DATA SOURCES
The MEDLINE, Embase, Amed, ProQuest, PsychINFO, CINAHL, and LILACS databases were searched between January 2011 and January 2019. Keywords used were c9orf72 and chromosome 9 open reading frame 72. Reference lists, citations of eligible studies, and review articles were also searched by hand.
STUDY SELECTION
Studies reporting disease duration for patients with a confirmed c9orf72RE and a neurological and/or psychiatric disorder were included. A second author independently reviewed studies classified as irrelevant by the first author. Analysis began in January 2019.
DATA EXTRACTION AND SYNTHESIS
Data were extracted by 1 author; a further author independently extracted 10% of data. Data were synthesized in univariate and multivariable Cox regression and are displayed as hazard ratios (HR) and 95% confidence intervals.
MAIN OUTCOMES AND MEASURES
Survival after symptom onset.
RESULTS
Overall, 206 studies reporting on 1060 patients were included from 2878 publications identified (c9ALS: n = 455; c9FTD: n = 296; c9ALS-FTD: n = 198; atypical phenotypes: n = 111); 197 duplicate cases were excluded. The median (95% CI) survival (in years) differed significantly between patients with c9ALS (2.8 [2.67-3.00]), c9FTD (9.0 [8.09-9.91]), and c9ALS-FTD (3.0 [2.73-3.27]); survival in atypical phenotypes varied substantially. Older age at onset was associated with shorter survival in c9ALS (HR, 1.03; 95% CI, 1.02-1.04; P < .001), c9FTD (HR, 1.04; 95% CI, 1.02-1.06; P < .001), and c9ALS-FTD (HR, 1.02; 95% CI, 1.004-1.04; P = .016). Bulbar onset was associated with shorter survival in c9ALS (HR, 1.64; 95% CI, 1.27-2.08; P < .001). Age at onset and bulbar onset ALS remained significant in multivariable regression including variables indicating potential diagnostic ascertainment bias, selection bias, and reporting bias. Family history, sex, study continent, FTD subtype, or the presence of additional pathogenic sequence variants were not significantly associated with survival. Clinical phenotypes in patients with neuropathologically confirmed frontotemporal lobar degeneration-TDP-43, motor neuron disease-TDP-43 and frontotemporal lobar degeneration-motor neuron disease-TDP-43 were heterogenous and impacted on survival.
CONCLUSIONS AND RELEVANCE
Several factors associated with survival in c9orf72RE disorders were identified. The inherent limitations of our methodological approach must be considered; nonetheless, the reported prognostic factors were not significantly associated with the bias indicators examined.
Topics: Aged; Amyotrophic Lateral Sclerosis; C9orf72 Protein; DNA Repeat Expansion; Female; Frontotemporal Dementia; Humans; Male; Middle Aged; Prognosis; Risk Factors
PubMed: 31738367
DOI: 10.1001/jamaneurol.2019.3924 -
BMC Bioinformatics Nov 2019Biologically data-driven networks have become powerful analytical tools that handle massive, heterogeneous datasets generated from biomedical fields. Protein-protein...
An integrative methodology based on protein-protein interaction networks for identification and functional annotation of disease-relevant genes applied to channelopathies.
BACKGROUND
Biologically data-driven networks have become powerful analytical tools that handle massive, heterogeneous datasets generated from biomedical fields. Protein-protein interaction networks can identify the most relevant structures directly tied to biological functions. Functional enrichments can then be performed based on these structural aspects of gene relationships for the study of channelopathies. Channelopathies refer to a complex group of disorders resulting from dysfunctional ion channels with distinct polygenic manifestations. This study presents a semi-automatic workflow using protein-protein interaction networks that can identify the most relevant genes and their biological processes and pathways in channelopathies to better understand their etiopathogenesis. In addition, the clinical manifestations that are strongly associated with these genes are also identified as the most characteristic in this complex group of diseases.
RESULTS
In particular, a set of nine representative disease-related genes was detected, these being the most significant genes in relation to their roles in channelopathies. In this way we attested the implication of some voltage-gated sodium (SCN1A, SCN2A, SCN4A, SCN4B, SCN5A, SCN9A) and potassium (KCNQ2, KCNH2) channels in cardiovascular diseases, epilepsies, febrile seizures, headache disorders, neuromuscular, neurodegenerative diseases or neurobehavioral manifestations. We also revealed the role of Ankyrin-G (ANK3) in the neurodegenerative and neurobehavioral disorders as well as the implication of these genes in other systems, such as the immunological or endocrine systems.
CONCLUSIONS
This research provides a systems biology approach to extract information from interaction networks of gene expression. We show how large-scale computational integration of heterogeneous datasets, PPI network analyses, functional databases and published literature may support the detection and assessment of possible potential therapeutic targets in the disease. Applying our workflow makes it feasible to spot the most relevant genes and unknown relationships in channelopathies and shows its potential as a first-step approach to identify both genes and functional interactions in clinical-knowledge scenarios of target diseases.
METHODS
An initial gene pool is previously defined by searching general databases under a specific semantic framework. From the resulting interaction network, a subset of genes are identified as the most relevant through the workflow that includes centrality measures and other filtering and enrichment databases.
Topics: Channelopathies; Databases, Genetic; Gene Regulatory Networks; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Molecular Sequence Annotation; Protein Interaction Maps
PubMed: 31718537
DOI: 10.1186/s12859-019-3162-1 -
The Cochrane Database of Systematic... Jul 2019This is an update of the review last published in 2011. It focuses on early postoperative enteral nutrition after lower gastrointestinal surgery. Traditional management...
BACKGROUND
This is an update of the review last published in 2011. It focuses on early postoperative enteral nutrition after lower gastrointestinal surgery. Traditional management consisted of 'nil by mouth', where patients receive fluids followed by solids after bowel function has returned. Although several trials have reported lower incidence of infectious complications and faster wound healing upon early feeding, other trials have shown no effect. The immediate advantage of energy intake (carbohydrates, protein or fat) could enhance recovery with fewer complications, and this warrants a systematic evaluation.
OBJECTIVES
To evaluate whether early commencement of postoperative enteral nutrition (within 24 hours), oral intake and any kind of tube feeding (gastric, duodenal or jejunal), compared with traditional management (delayed nutritional supply) is associated with a shorter length of hospital stay (LoS), fewer complications, mortality and adverse events in patients undergoing lower gastrointestinal surgery (distal to the ligament of Treitz).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library 2017, issue 10), Ovid MEDLINE (1950 to 15 November 2017), Ovid Embase (1974 to 15 November 2017). We also searched for ongoing trials in ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (15 November 2017). We handsearched reference lists of identified studies and previous systematic reviews.
SELECTION CRITERIA
We included randomised controlled trials (RCT) comparing early commencement of enteral nutrition (within 24 hours) with no feeding in adult participants undergoing lower gastrointestinal surgery.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study quality using the Cochrane 'Risk of bias' tool tailored to this review and extracted data. Data analyses were conducted according to the Cochrane recommendations.We rated the quality of evidence according to GRADE.Primary outcomes were LoS and postoperative complications (wound infections, intraabdominal abscesses, anastomotic dehiscence, pneumonia).Secondary outcomes were: mortality, adverse events (nausea, vomiting), and quality of life (QoL).LoS was estimated using mean difference (MD (presented as mean +/- SD). For other outcomes we estimated the common risk ratio (RR) and calculated the associated 95% confidence intervals. For analysis, we used an inverse-variance random-effects model for the primary outcome (LoS) and Mantel-Haenszel random-effects models for the secondary outcomes. We also performed Trial Sequential Analyses (TSA).
MAIN RESULTS
We identified 17 RCTs with 1437 participants undergoing lower gastrointestinal surgery. Most studies were at high or unclear risk of bias in two or more domains. Six studies were judged as having low risk of selection bias for random sequence generation and insufficient details were provided for judgement on allocation concealment in all 17 studies. With regards to performance and deception bias; 14 studies reported no attempt to blind participants and blinding of personnel was not discussed either. Only one study was judged as low risk of bias for blinding of outcome assessor. With regards to incomplete outcome data, three studies were judged to be at high risk because they had more than 10% difference in missing data between groups. For selective reporting, nine studies were judged as unclear as protocols were not provided and eight studies had issues with either missing data or incomplete reporting of results.LOS was reported in 16 studies (1346 participants). The mean LoS ranged from four days to 16 days in the early feeding groups and from 6.6 days to 23.5 days in the control groups. Mean difference (MD) in LoS was 1.95 (95% CI, -2.99 to -0.91, P < 0.001) days shorter in the early feeding group. However, there was substantial heterogeneity between included studies (I = 81, %, Chi = 78.98, P < 0.00001), thus the overall quality of evidence for LoS is low. These results were confirmed by the TSA showing that the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit.We found no differences in the incidence of postoperative complications: wound infection (12 studies, 1181 participants, RR 0.99, 95%CI 0.64 to 1.52, very low-quality evidence), intraabdominal abscesses (6 studies, 554 participants, RR 1.00, 95%CI 0.26 to 3.80, low-quality evidence), anastomotic leakage/dehiscence (13 studies, 1232 participants, RR 0.78, 95%CI 0.38 to 1.61, low-quality evidence; number needed to treat for an additional beneficial outcome (NNTB) = 100), and pneumonia (10 studies, 954 participants, RR 0.88, 95%CI 0.32 to 2.42, low-quality evidence; NNTB = 333).Mortality was reported in 12 studies (1179 participants), and showed no between-group differences (RR = 0.56, 95%CI, 0.21 to 1.52, P = 0.26, I = 0%, Chi = 3.08, P = 0.96, low-quality evidence). The most commonly reported cause of death was anastomotic leakage, sepsis and acute myocardial infarction.Seven studies (613 participants) reported vomiting (RR 1.23, 95%CI, 0.96 to 1.58, P = 0.10, I = 0%, Chi = 4.98, P = 0.55, low-quality evidence; number needed to treat for an additional harmful outcome (NNTH) = 19), and two studies (118 participants) reported nausea (RR 0.95, 0.71 to 1.26, low-quality evidence). Four studies reported combined nausea and vomiting (RR 0.94, 95%CI 0.51 to 1.74, very low-quality evidence). One study reported QoL assessment; the scores did not differ between groups at 30 days after discharge on either QoL scale EORTC QLQ-C30 or EORTC QlQ-OV28 (very low-quality evidence).
AUTHORS' CONCLUSIONS
This review suggests that early enteral feeding may lead to a reduced postoperative LoS, however cautious interpretation must be taken due to substantial heterogeneity and low-quality evidence. For all other outcomes (postoperative complications, mortality, adverse events, and QoL) the findings are inconclusive, and further trials are justified to enhance the understanding of early feeding for these. In this updated review, only a few additional studies have been included, and these were small and of poor quality.To improve the evidence, future trials should address quality issues and focus on clearly defining and measuring postoperative complications to allow for better comparison between studies. However due to the introduction of fast track protocols which already include an early feeding component, future trials may be challenging. A more feasible trial may be to investigate the effect of differing postoperative energy intake regimens on relevant outcomes.
Topics: Digestive System Surgical Procedures; Enteral Nutrition; Humans; Length of Stay; Postoperative Complications; Randomized Controlled Trials as Topic; Time Factors
PubMed: 31329285
DOI: 10.1002/14651858.CD004080.pub4 -
International Journal of Biological... 2019p53 is the major mediator of the tumor suppressor response. It participates in apoptosis and senescence and can respond to DNA damage. As a crucial sequence-specific...
p53 is the major mediator of the tumor suppressor response. It participates in apoptosis and senescence and can respond to DNA damage. As a crucial sequence-specific transcription factor, p53 regulates the expression of many genes, such as small noncoding RNAs (ncRNAs), microRNAs, and long ncRNAs (lncRNAs). Given the emergence of novel and high-throughput sequencing technologies, many lncRNAs have been discovered. LncRNAs may function as vital gene regulators in a variety of biological processes through extensive mechanisms. Recently, lncRNAs have been demonstrated to be associated with the p53 regulatory pathway. In this review, we discuss the current and fast growing knowledge about the influence of lncRNAs to the p53 signaling pathway, the different mechanisms by which they affect gene expression in cancer. Our findings show that p53-associated lncRNAs may be used as biomarkers for cancer diagnosis or targets for disease therapy.
Topics: Cell Proliferation; Disease Progression; Humans; Neoplasms; Protein Processing, Post-Translational; Protein Stability; RNA, Long Noncoding; Signal Transduction; Tumor Suppressor Protein p53
PubMed: 31223287
DOI: 10.7150/ijbs.33218 -
Epigenetics Jul 2019Exercise training is continually challenging whole-body homeostasis, leading to improvements in performance and health. Adaptations to exercise training are complex and...
Exercise training is continually challenging whole-body homeostasis, leading to improvements in performance and health. Adaptations to exercise training are complex and are influenced by both environmental and genetic factors. Epigenetic factors regulate gene expression in a tissue-specific manner and constitute a link between the genotype and the environment. Moreover, epigenetic factors are emerging as potential biomarkers that could predict the response to exercise training. This systematic review aimed to identify epigenetic changes that have been reported in skeletal muscle following exercise training in healthy populations. A literature search of five databases (PUBMED, MEDLINE, CINHAL, SCOPUS and SportDiscuss) was conducted in November 2018. Articles were included if they examined epigenetic modifications (DNA methylation, histone modifications and non-coding RNAs) in skeletal muscle, following either an acute bout of exercise, an exercise intervention in a pre/post design, or a case/control type of study. Twenty-two studies met the inclusion criteria. Several epigenetic markers including DNA methylation of genes known to be differentially expressed after exercise and myomiRs were reported to be modified after exercise. Several epigenetic marks were identified to be altered in response to exercise, with potential influence on skeletal muscle metabolism. However, whether these epigenetic marks play a role in the physiological impact of exercise is unclear. Exercise epigenetics is still a very young research field, and it is expected that in the future the causality of such changes will be elucidated the utilization of emerging experimental models able to target the epigenome.
Topics: Adaptation, Physiological; Biomarkers; DNA Methylation; Epigenesis, Genetic; Exercise; Histone Code; Humans; Muscle, Skeletal; RNA, Untranslated
PubMed: 31046576
DOI: 10.1080/15592294.2019.1614416 -
The Cochrane Database of Systematic... May 2019One nutritional intervention advocated to prevent malnutrition among children is lipid-based nutrient supplements (LNS). LNS provide a range of vitamins and minerals,...
Preventive lipid-based nutrient supplements given with complementary foods to infants and young children 6 to 23 months of age for health, nutrition, and developmental outcomes.
BACKGROUND
One nutritional intervention advocated to prevent malnutrition among children is lipid-based nutrient supplements (LNS). LNS provide a range of vitamins and minerals, but unlike most other micronutrient supplements, LNS also provide energy, protein and essential fatty acids. Alternative recipes and formulations to LNS include fortified blended foods (FBF), which are foods fortified with vitamins and minerals, and micronutrient powders (MNP), which are a combination of vitamins and minerals, OBJECTIVES: To assess the effects and safety of preventive LNS given with complementary foods on health, nutrition and developmental outcomes of non-hospitalised infants and children six to 23 months of age, and whether or not they are more effective than other foods (including FBF or MNP).This review did not assess the effects of LNS as supplementary foods or therapeutic foods in the management of moderate and severe acute malnutrition.
SEARCH METHODS
In October 2018, we searched CENTRAL, MEDLINE, Embase, 21 other databases and two trials registers for relevant studies. We also checked the reference lists of included studies and relevant reviews and contacted the authors of studies and other experts in the area for any ongoing and unpublished studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs that evaluated the impact of LNS plus complementary foods given at point-of-use (for any dose, frequency, duration) to non-hospitalised infants and young children aged six to 23 months in stable or emergency settings and compared to no intervention, other supplementary foods (i.e. FBF), nutrition counselling or multiple micronutrient supplements or powders for point-of-use fortification of complementary foods.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened studies for relevance and, for those studies included in the review, extracted data, assessed risk of bias and rated the quality of the evidence using the GRADE approach. We carried out statistical analysis using Review Manager software. We used a random-effects meta-analysis for combining data as the interventions differed significantly. We set out the main findings of the review in 'Summary of findings' tables,.
MAIN RESULTS
Our search identified a total of 8124 records, from which we included 17 studies (54 papers) with 23,200 children in the review. The included studies reported on one or more of the pre-specified primary outcomes, and five studies included multiple comparison groups.Overall, the majority of trials were at low risk of bias for random sequence generation, allocation concealment, blinding of outcome assessment, incomplete outcome data, selective reporting and other sources of bias, but at high risk of bias for blinding of participants and personnel due to the nature of the intervention. Using the GRADE approach, we judged the quality of the evidence for most outcomes as low or moderate.LNS+complementary feeding compared with no intervention Thirteen studies compared LNS plus complementary feeding with no intervention. LNS plus complementary feeding reduced the prevalence of moderate stunting by 7% (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.88 to 0.98; nine studies, 13,372 participants; moderate-quality evidence), severe stunting by 15% (RR 0.85, 95% CI 0.74 to 0.98; five studies, 6151 participants; moderate-quality evidence), moderate wasting by 18% (RR 0.82, 95% CI 0.74 to 0.91; eight studies; 13,172 participants; moderate-quality evidence), moderate underweight by 15% (RR 0.85, 95% CI 0.80 to 0.91; eight studies, 13,073 participants; moderate-quality evidence), and anaemia by 21% (RR 0.79, 95% CI 0.69 to 0.90; five studies, 2332 participants; low-quality evidence). There was no impact of LNS plus complementary feeding on severe wasting (RR 1.27, 95% CI 0.66 to 2.46; three studies, 2329 participants) and severe underweight (RR 0.78, 95%CI 0.54 to 1.13; two studies, 1729 participants). Adverse effects did not differ between the groups (RR 0.86, 95% CI 0.74 to 1.01; three studies, 3382 participants).LNS+complementary feeding compared with FBF Five studies compared LNS plus complementary feeding with other FBF, including corn soy blend and UNIMIX. We pooled four of the five studies in meta-analyses and found that, when compared to other FBF, LNS plus complementary feeding significantly reduced the prevalence of moderate stunting (RR 0.89, 95% CI 0.82 to 0.97; three studies, 2828 participants; moderate-quality evidence), moderate wasting (RR 0.79, 95% CI 0.65 to 0.97; two studies, 2290 participants; moderate-quality evidence), and moderate underweight (RR 0.81, 95% CI 0.73 to 0.91; two studies, 2280 participants; moderate-quality evidence). We found no difference between LNS plus complementary feeding and FBF for severe stunting (RR 0.41, 95% CI 0.12 to 1.42; two studies, 729 participants; low-quality evidence), severe wasting (RR 0.64, 95% CI 0.19 to 2.81; two studies, 735 participants; moderate-quality evidence), and severe underweight (RR 1.23, 95% CI 0.67 to 2.25; one study, 173 participants; low-quality evidence).LNS+complementary feeding compared with MNP Four studies compared LNS plus complementary feeding with MNP. We pooled data from three of the four studies in meta-analyses and found that compared to MNP, LNS plus complementary feeding significantly reduced the prevalence of moderate underweight (RR 0.88, 95% CI 0.78 to 0.99; two studies, 2004 participants; moderate-quality evidence) and anaemia (RR 0.38, 95% CI 0.21 to 0.68; two studies, 557 participants; low-quality evidence). There was no difference between LNS plus complementary feeding and MNP for moderate stunting (RR 0.92, 95% CI 0.82 to 1.02; three studies, 2365 participants) and moderate wasting (RR 0.97, 95% CI 0.77 to 1.23; two studies, 2004 participants).
AUTHORS' CONCLUSIONS
The findings of this review suggest that LNS plus complementary feeding compared to no intervention is effective at improving growth outcomes and anaemia without adverse effects among children aged six to 23 months in low- and middle-income countries (LMIC) in Asia and Africa, and more effective if provided over a longer duration of time (over 12 months). Limited evidence also suggests that LNS plus complementary feeding is more effective than FBF and MNP at improving growth outcomes.
Topics: Child Development; Child, Preschool; Dietary Fats; Dietary Supplements; Food, Formulated; Food, Fortified; Humans; Infant; Infant Nutritional Physiological Phenomena; Nutritional Status
PubMed: 31046132
DOI: 10.1002/14651858.CD012611.pub3 -
Frontiers in Physiology 2019Endurance is not only a key factor in many sports but endurance-related variables are also associated with good health and low mortality. Twin and family studies suggest... (Review)
Review
Endurance is not only a key factor in many sports but endurance-related variables are also associated with good health and low mortality. Twin and family studies suggest that several endurance-associated traits are ≈50% inherited. However, we still poorly understand what DNA sequence variants contribute to endurance heritability. To address this issue, we conducted a systematic review to identify genes whose experimental loss or gain-of-function increases endurance capacity in mice. We found 31 genes including two isoforms of whose manipulation increases running or swimming endurance performance by up to 1800%. Genes whose gain-of-function increases endurance are , (Pepck) (both the a and b isoforms of the protein Pgc-1α), (calcineurin) & . Genes whose loss-of-function increases endurance in mice are . Of these genes, human DNA sequence variants of , , , , , , , , and are also associated with endurance capacity and/or VOmax trainability suggesting evolutionary conservation between mice and humans. Bioinformatical analyses show that there are numerous amino acid or copy number-changing DNA variants of endurance genes in humans, suggesting that genetic variation of endurance genes contributes to the variation of human endurance capacity, too. Moreover, several of these genes/proteins change their expression or phosphorylation in skeletal muscle or the heart after endurance exercise, suggesting a role in the adaptation to endurance exercise.
PubMed: 30967789
DOI: 10.3389/fphys.2019.00262