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International Journal of Molecular... Apr 2023This systematic review and meta-analysis summarize the difference in the methylation of the gene in patients with abnormal versus normal conventional sperm parameters.... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis summarize the difference in the methylation of the gene in patients with abnormal versus normal conventional sperm parameters. It also evaluates the effects of age and sperm concentration on methylation in spermatozoa using meta-regression analysis. It was performed according to the MOOSE guidelines for meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The quality of the evidence reported in the studies included was assessed using the Cambridge Quality Checklists. A total of 11 articles met our inclusion criteria. Quantitative analysis showed that methylation levels were significantly lower in the group of infertile patients than in fertile controls. The reduction in methylation was much more pronounced in patients with oligozoospermia (alone or associated with other sperm parameter abnormalities) and in those with recurrent pregnancy loss. Meta-regression analysis showed the results to be independent of both patient age and sperm concentration. Therefore, the methylation pattern should be evaluated among couples accessing assisted reproductive techniques (ART), in order to gain prognostic information on ART outcome and offspring health.
Topics: Female; Humans; Male; Pregnancy; DNA Methylation; Genomic Imprinting; Histones; Infertility, Male; Meta-Analysis as Topic; Semen; Spermatozoa
PubMed: 37108386
DOI: 10.3390/ijms24087224 -
Journal of Affective Disorders Apr 2023Growing evidence suggests that epigenetic modification is vital in biological processes of depression. Findings from studies exploring the associations between DNA... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Growing evidence suggests that epigenetic modification is vital in biological processes of depression. Findings from studies exploring the associations between DNA methylation and depression have been inconsistent.
METHODS
A systematical search of EMBASE, PubMed, Web of Science, and PsycINFO databases was conducted to include studies focusing on the associations between DNA methylation and depression (up to November 1st 2021) according to PRISMA guidelines with registration in PROSPERO (CRD42021288664).
RESULTS
A total of 47 studies met inclusion criteria and 31 studies were included in the meta-analysis. This meta-analysis found that genes hypermethylation, including BDNF (OR: 1.15, 95%CI: 1.01-1.32, I = 90 %), and NR3C1 (OR: 1.43, 95%CI: 1.09-1.87, I = 88 %) was associated with increased risk of depression. Significant association of SLC6A4 hypermethylation with depression was only found in the subgroup of using original data (OR: 1.09, 95%CI: 1.01-1.19, I = 52 %). BDNF hypermethylation could increase the risk of depression only in the Asian population (OR: 1.18, 95%CI: 1.01-1.40, I = 91 %), and significant associations of NR3C1 hypermethylation with depression were found in the group for depressive symptoms (OR: 1.34, 95%CI: 1.08-1.67, I = 85 %), but not for depressive disorder (OR: 1.89, 95%CI: 0.54-6.55, I = 94 %).
LIMITATIONS
More studies are needed to explore the factors that might influence the estimates owing to the contextual heterogeneity of the pooling of included studies.
CONCLUSIONS
It is noted that DNA hypermethylation, namely BDNF and NR3C1, is associated with increased risk of depression. The findings in this study could provide some material evidence for preventing and diagnosing of depression.
Topics: Humans; Brain-Derived Neurotrophic Factor; Depression; DNA Methylation; Epigenesis, Genetic; Serotonin Plasma Membrane Transport Proteins
PubMed: 36717033
DOI: 10.1016/j.jad.2023.01.079 -
Lifestyle Genomics 2023DNA methylation patterns are directly associated with diverse metabolic disorders. The status of methyl-donor micronutrients has been associated with DNA methylation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
DNA methylation patterns are directly associated with diverse metabolic disorders. The status of methyl-donor micronutrients has been associated with DNA methylation levels, and altered ingestion of folate, choline, betaine, B vitamins and methionine may impact genes both globally and at the level of promoter regions. Despite this, the role of methyl-donor micronutrient supplementation on DNA methylation profiles is currently unclear.
OBJECTIVES
The aims of this systematic review and meta-analysis were to identify and synthesize the evidence about methyl-donor nutrient supplementation on DNA methylation.
METHODS
A systematic literature search was performed in Medline, Embase, Scopus, and Web of Science databases with a combination of terms related to DNA methylation assessment, supplementation, and methyl-donor nutrients. Studies (in vitro, animal models, or human clinical trials) were included if DNA methylation levels after any kind of methyl-donor micronutrient supplementation or treatment was investigated. Studies were assessed for bias using Revised Cochrane risk-of-bias tool for randomized trials, risk-of-bias in Non-randomized Studies of Interventions or Systematic Review Centre for Laboratory Animal Experimentation tools. Data were extracted from studies measuring DNA methylation levels in any sample or tissue, following any kind of methyl-donor micronutrient supplementation or treatment. Separate random-effects meta-analyses were performed for animal model studies and human clinical trials that examined the effects of folic acid supplementation on DNA methylation.
RESULTS
Fifty-seven studies were included in this systematic review: 18 human clinical trials, 35 in animal model, and 4 in vitro studies. Concerning overall risk of bias, most of the studies were classified as "high risk" or "some concerns." Meta-analysis with meta-regression from studies in animal models showed that folic acid dose significantly affected DNA methylation and that high and very high doses showed increases in DNA methylation when compared to low doses. However, meta-analysis of human clinical trials showed that folic acid supplementation did not promote significant changes in DNA methylation when compared to placebo.
CONCLUSION
Folic acid supplementation may change global DNA methylation levels in animals supplemented with high, as compared to low, doses. Heterogeneity in studies and supplementation protocols make it difficult to establish clinical recommendations. However, these effects, even if small, might be of clinical importance in the management of patients with diseases related to DNA hypomethylation.
Topics: Humans; Animals; DNA Methylation; Folic Acid; Dietary Supplements; Vitamin B Complex; Micronutrients
PubMed: 37935134
DOI: 10.1159/000533193 -
European Journal of Midwifery 2023Cannabis and its derivatives are becoming increasingly popular in women's preferences during pregnancy in order to relieve nausea. The present study examines cannabis... (Review)
Review
INTRODUCTION
Cannabis and its derivatives are becoming increasingly popular in women's preferences during pregnancy in order to relieve nausea. The present study examines cannabis use during pregnancy and its effects on the fetus, newborn and later childhood.
METHODS
All primary studies were searched in the databases: PubMed, Scopus, Medline during the period June 2019 to August 2020. The keywords used were 'pregnancy', 'pregnant women', 'cannabis', 'marijuana', 'fetus', 'newborn', 'childhood', and combined with 'AND' and 'OR' Boolean operators. Inclusion criteria were: pregnant users of cannabis as the study group and pregnant non-users of cannabis as the control group; the articles could be in English or in Greek. The exclusion criteria were: unpublished studies, reviews, presentations at conferences, and animal studies.
RESULTS
From the systematic review of the literature, the study included 13 primary research studies in which it was found that the children of mother-user faced: disorders in the sleep cycle, memory problems, hyperactivity, increased chances of low birth weight, prematurity with lower Apgar score in the 1st and 5th minutes and hospitalization in an NICU, DNA methylation at the position CpG.32, and modifications in the brain, especially in the amygdala. In addition, girls had more aggressive behavior at the age of 18 months, shorter breastfeeding period, and neonatal death.
CONCLUSIONS
The use of cannabis during the gestation period by the mother, aggravates the physical and mental development of the fetus, the newborn and the later childhood.
PubMed: 37547668
DOI: 10.18332/ejm/168727 -
The Journal of the Association of... Jan 2022Though systemic corticosteroid is used for treatment of COVID 19, questions regarding the appropriate dose, duration and type of corticosteroid use still remain... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Though systemic corticosteroid is used for treatment of COVID 19, questions regarding the appropriate dose, duration and type of corticosteroid use still remain unanswered. This study aimed to address, whether choice of systemic corticosteroid significantly influences the clinical outcome of COVID 19 patients.
MATERIALS AND METHODS
Studies reporting the comparison between clinical outcome of dexamethasone and methylprednisolone in treatment of COVID 19 were searched from inception till April, 2021. Random-effect model was used. Odd's ratio (OR) and 95% confidence interval was expressed. I2 statistics used for test of heterogeneity.
RESULT
Three studies with 373 patients (160 in dexamethasone group and 213 in methyl prednisolone group) were included. Though, statistically significant reduction in all-cause mortality with methyl prednisolone group in comparison to dexamethasone group (OR=1.80, 95%CI: 1.08 to 3.01, P=0.02) estimated, sub group analysis of observational studies did not support the finding (OR=1.60, 95% CI: 0.88 to 2.92, P=0.12). No significant difference in terms of need for invasive ventilator or intensive care unit (ICU) between the 2 groups. The grade of evidence was very low for both the outcomes. Conclusion and Relevance: In the present context, both dexamethasone and methyl prednisolone are equally effective in the management of COVID 19.
Topics: Dexamethasone; Humans; Methylprednisolone; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35062806
DOI: No ID Found -
Therapeutic Drug Monitoring Oct 2021The utility of measuring thiopurine metabolites (TM) to individualize therapy in autoimmune hepatitis (AIH) has not been defined, and the evidence regarding its use in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The utility of measuring thiopurine metabolites (TM) to individualize therapy in autoimmune hepatitis (AIH) has not been defined, and the evidence regarding its use in clinical practice is heterogeneous. This systematic review and meta-analysis aimed to compare the mean concentration of TM between patients in biochemical remission and those not in remission.
METHODS
A systematic literature search was conducted using PubMed, Scopus, the Cochrane Library, and Google Scholar for keywords related to TM and AIH. Two reviewers independently searched and selected studies comparing the levels of 6-methyl mercaptopurine (6-MMP) and 6-thioguanine nucleotide (6-TGN) and their ratio in cases of AIH in remission and otherwise. Meta-analysis was performed by calculating the weighted mean difference using the inverse variance heterogeneity model.
RESULTS
A total of 1066 records were identified through systematic search; of which, 7 (n = 3 pediatric, n = 4 adults) were considered for inclusion, and 442 TM measurements (n = 128 in children) were analyzed. Mean 6-TGN levels were significantly higher among patients in remission than in those who were not, with a pooled weighted mean difference (WMD) of 15.67 [95% confidence interval (CI), 6.68-24.66] pmol/8 × 108 red blood cells (RBC). The difference was higher in the pediatric age group (WMD, 56.11; 95% CI, 13.60-98.62) than in adults (WMD, 13.77; 95% CI, 4.58-22.97). There was no significant difference in the 6-MMP levels (WMD, -431.7; 95% CI, -1237.4 to 373.9 pmol/8 × 108 RBC; I2 = 82%; n = 3 studies) or 6-MMP/6-TGN ratio among the patients who were in biochemical remission and those who were not (WMD, -0.97; 95% CI, -5.77 to 3.84; I2 = 82%; n = 3 studies).
CONCLUSIONS
This meta-analysis suggests a link between 6-TGN levels and biochemical remission in AIH. Further high-quality studies are required to determine the therapeutic cutoff of 6-TGN.
Topics: Adult; Azathioprine; Child; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Mercaptopurine; Thioguanine
PubMed: 33346628
DOI: 10.1097/FTD.0000000000000848 -
The Cochrane Database of Systematic... Nov 2022Newborn infants affected by hypoxic-ischemic encephalopathy (HIE) undergo therapeutic hypothermia. As this treatment seems to be associated with pain, and intensive and... (Review)
Review
BACKGROUND
Newborn infants affected by hypoxic-ischemic encephalopathy (HIE) undergo therapeutic hypothermia. As this treatment seems to be associated with pain, and intensive and invasive care is needed, pharmacological interventions are often used. Moreover, painful procedures in the newborn period can affect pain responses later in life, impair brain development, and possibly have a long-term negative impact on neurodevelopment and quality of life.
OBJECTIVES
To determine the effects of pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia. Primary outcomes were analgesia and sedation, and all-cause mortality to discharge.
SEARCH METHODS
We searched CENTRAL, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the trial register ISRCTN in August 2021. We also checked the reference lists of relevant articles to identify additional studies.
SELECTION CRITERIA
We included randomized controlled trials (RCT), quasi-RCTs and cluster-randomized trials comparing drugs used for the management of pain or sedation, or both, during therapeutic hypothermia: any opioids (e.g. morphine, fentanyl), alpha-2 agonists (e.g. clonidine, dexmedetomidine), N-Methyl-D-aspartate (NMDA) receptor antagonist (e.g. ketamine), other analgesics (e.g. paracetamol), and sedatives (e.g. benzodiazepines such as midazolam) versus another drug, placebo, no intervention, or non-pharmacological interventions. Primary outcomes were analgesia and sedation, and all-cause mortality to discharge.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies identified by the search strategy for inclusion. We planned to use the GRADE approach to assess the certainty of evidence. We planned to assess the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomization, blinding, loss to follow-up, and handling of outcome data). We planned to evaluate treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data. MAIN RESULTS: We did not find any completed studies for inclusion. Amongst the four excluded studies, topiramate and atropine were used in two and one trial, respectively; one study used dexmedetomidine and was initially reported in 2019 to be a randomized trial. However, it was an observational study (correction in 2021). We identified one ongoing study comparing dexmedetomidine to morphine.
AUTHORS' CONCLUSIONS
We found no studies that met our inclusion criteria and hence there is no evidence to recommend or refute the use of pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia.
Topics: Infant, Newborn; Humans; Dexmedetomidine; Clonidine; Hypothermia, Induced; Pain; Morphine Derivatives; Observational Studies as Topic
PubMed: 36354070
DOI: 10.1002/14651858.CD015023.pub2 -
Pain Physician Jul 2023S-ketamine is the S-enantiomer of ketamine, which exerts anesthetic and analgesic effects through noncompetitive antagonism of N-methyl-D-aspartate (NMDA) receptors. (Meta-Analysis)
Meta-Analysis
BACKGROUND
S-ketamine is the S-enantiomer of ketamine, which exerts anesthetic and analgesic effects through noncompetitive antagonism of N-methyl-D-aspartate (NMDA) receptors.
OBJECTIVE
We aimed to define the relative risk of post-abdominal surgery pain in adults who were administered perioperative S-ketamine.
STUDY DESIGN
Systematic review and meta-analysis.
METHODS
Two reviewers independently screened the articles from the titles and abstracts based on our eligibility criteria, evaluated the risk of bias by using the Cochrane Collaboration Risk of Bias tool in randomized controlled trials, and extracted the data from the included studies according to a prespecified protocol; any disagreements were solved by consultation. The level of certainty for the main results were evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.
RESULTS
Of the 1,621 studies identified, 9 studies were included; they were published from 2004 through 2022. Only one study involved epidural anesthesia, whereas the other 8 studies included general anesthesia. The pain at rest scores at 4 and 24 hours post-abdominal surgery were significantly lower in the S-ketamine group, respectively. However, there was no significant difference between the 2 groups in the pain at rest scores at 48 hours post-abdominal surgery. S-ketamine infusion reduced pain during movement 24 hours post-abdominal surgery, but not at 48 hours, respectively. The incidence of postoperative nausea and vomiting, as well as psychotomimetic adverse effects post-abdominal surgery were similar between the 2 groups, respectively. A subgroup analysis revealed that the pain at rest score at 4 hours post-abdominal surgery in patients in the intraoperative use group was remarkably reduced, compared with the patients who received S-ketamine perioperatively. Otherwise, the pain at rest score at 24 hours post-abdominal surgery in the perioperative use group was significantly reduced versus intraoperative use group.
LIMITATION
The number of trials included was small. The remarkable heterogeneity found in the pooled results at each time point post-abdominal surgery might affect the credibility of the results.
CONCLUSIONS
S-ketamine is effective in reducing the early postoperative pain of patients who received abdominal surgery, and may not increase the incidence of postoperative complications.
Topics: Humans; Adult; Ketamine; Pain, Postoperative; Postoperative Nausea and Vomiting; Abdomen; Analgesics, Opioid
PubMed: 37535771
DOI: No ID Found -
The Cochrane Database of Systematic... Oct 2004Alzheimer's disease, vascular and mixed dementia are the three commonest forms of dementia affecting older people. There is evidence that the excitatory activity of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alzheimer's disease, vascular and mixed dementia are the three commonest forms of dementia affecting older people. There is evidence that the excitatory activity of L-glutamate plays a role in the pathogenesis of Alzheimer's disease and in the damage from an ischaemic stroke. A low affinity antagonist to N-Methyl-D-aspartate (NMDA) type receptors, such as memantine, may prevent excitatory amino acid neurotoxicity without interfering with the physiological actions of glutamate required for memory and learning.
OBJECTIVES
To determine the clinical efficacy and safety of memantine for people with Alzheimer's disease, or vascular or mixed dementia.
SEARCH STRATEGY
Trials were identified from a search of the Trial-based Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 April 2004 using the terms: memantin*, namenda*, ebixa*, axura*, D-145, DMAA, DRG-0267. All major health care databases and many ongoing trial databases are searched regularly to keep this Register up to date.
SELECTION CRITERIA
Double-blind, parallel group, placebo-controlled, randomised and unconfounded trials in which memantine was administered to people with dementia.
DATA COLLECTION AND ANALYSIS
Data were extracted, pooled where possible, and weighted mean differences, standardized mean differences or odds ratios were estimated. Intention-to-treat (ITT) and observed cases (OC) analyses are reported, where data were available.
MAIN RESULTS
The evidence suggests that memantine has a positive effect on cognition, mood and behaviour and the ability to perform activities of daily living in patients with moderate to severe Alzheimer's disease. The results in patients with mild to moderate vascular dementia, suggest a beneficial effect of 20mg/day of memantine on cognitive function measured at 28 weeks. However, these results are neither supported by an effect on ability to perform activities of daily living nor by an effect on the clinical impression of change. This suggests that, in patients with mild to moderate vascular dementia, the effect on cognitive function is not translated into clinically detectable changes.
REVIEWERS' CONCLUSIONS
:Memantine 20 mg/day caused a clinically noticeable reduction in deterioration over 28 weeks in patients with moderate to severe Alzheimer disease. This was supported by less functional and cognitive deterioration. Patients taking memantine were less likely to become agitated. The effect in mild to moderate AD is unknown. Patients with mild to moderate vascular dementia receiving memantine 20 mg/day had less cognitive deterioration at 28 weeks but the effects were not clinically discernible. There is an early beneficial effect on cognition, mood, behaviour and clinical impression for memantine at 6 weeks. The drug is well tolerated in general and the incidence of adverse effects is low.
Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease; Cognition Disorders; Dementia; Dementia, Vascular; Excitatory Amino Acid Antagonists; Humans; Memantine; Randomized Controlled Trials as Topic
PubMed: 15495043
DOI: 10.1002/14651858.CD003154.pub2 -
The Cochrane Database of Systematic... 2001Bronchiectasis is characterised by chronic sputum production,bronchial wall dilation,recurrent infection and airflow limitation. Methylxanthines are used in the... (Review)
Review
BACKGROUND
Bronchiectasis is characterised by chronic sputum production,bronchial wall dilation,recurrent infection and airflow limitation. Methylxanthines are used in the management of airflow limitation associated with asthma and COPD, where they are also purported to have anti-inflammatory properties. In theory they may be of use in bronchiectasis.
OBJECTIVES
To determine the efficacy of methylxanthines in the treatment of bronchiectasis.
SEARCH STRATEGY
The Cochrane Airways Group clinical trials register derived from MEDLINE,EMBASE and hand searches using the terms bronchiectasis, aminophylline, theophylline and methyl- xanthine
SELECTION CRITERIA
Only randomised controlled trials were to be considered.
DATA COLLECTION AND ANALYSIS
The results of the searches were reviewed by two authors. Searches yielded seven trials none of which met the inclusion criteria.
MAIN RESULTS
No randomised controlled trials were identified.
REVIEWER'S CONCLUSIONS
Further research is required to establish if the methylxanthines have a role in the treatment of bronchiectasis.
Topics: Administration, Oral; Aminophylline; Bronchiectasis; Bronchodilator Agents; Humans; Randomized Controlled Trials as Topic; Theophylline
PubMed: 11279764
DOI: 10.1002/14651858.CD002734