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Journal of Neurotrauma Nov 2022Magnetic resonance spectroscopy (MRS) is a non-invasive technique used to study metabolites in the brain. MRS findings in traumatic brain injury (TBI) and subconcussive... (Meta-Analysis)
Meta-Analysis Review
Magnetic resonance spectroscopy (MRS) is a non-invasive technique used to study metabolites in the brain. MRS findings in traumatic brain injury (TBI) and subconcussive hit literature have been mixed. The most common observation is a decrease in -acetyl-aspartate (NAA), traditionally considered a marker of neuronal integrity. Other metabolites, however, such as creatine (Cr), choline (Cho), glutamate+glutamine (Glx) and -inositol (mI) have shown inconsistent changes in these populations. The objective of this systematic review and meta-analysis was to synthesize MRS literature in brain injury and explore factors (biological factors such as brain region, injury severity, time since injury, demographics and technical methodological factors such as field strength, acquisition parameters, analysis approach) that may contribute to differential findings. One hundred and thirty-eight studies met inclusion criteria for the systematic review and of those, 62 NAA, 24 Cr, 49 Cho, 18 Glx, and 21 mI studies met inclusion criteria for meta-analysis. A random effects model was used for meta-analyses with brain region as a subgroup for each of the five metabolites studied. Meta-regression was used to examine the influence of potential moderators including injury severity, time since injury, age, sex, tissue composition, and methodological factors. In this analysis of 1428 unique brain-injured subjects and 1132 controls, the corpus callosum was identified as a brain region highly susceptible to metabolite alteration. NAA was consistently decreased in TBI of all severities, but not in subconcussive hits. Cho and mI were found to be increased in moderate-to-severe TBI but not in mild TBI. Glx and Cr were largely unaffected, but did show alterations in certain conditions.
Topics: Humans; Magnetic Resonance Spectroscopy; Aspartic Acid; Magnetic Resonance Imaging; Creatine; Brain Injuries, Traumatic; Brain Concussion; Brain; Choline; Inositol
PubMed: 35838132
DOI: 10.1089/neu.2022.0125 -
PloS One 2024To systematically evaluate the safety and efficacy of antioxidant therapy in children and adolescents with attention deficit hyperactivity disorder (ADHD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically evaluate the safety and efficacy of antioxidant therapy in children and adolescents with attention deficit hyperactivity disorder (ADHD).
METHODS
Randomized controlled trials and prospective studies on antioxidant therapy in children and adolescents with ADHD were searched in PubMed, Embase, and Cochrane Library from the inception of databases to November 12, 2022. Two investigators independently screened the literature, extracted data, and evaluated the quality of the included studies. Network meta-analysis (PROSPERO registration number CRD 42023382824) was carried out by using R Studio 4.2.1.
RESULTS
48 studies involving 12 antioxidant drugs (resveratrol, pycnogenol, omega-3, omega-6, quercetin, phosphatidylserine, almond, vitamin D, zinc, folic acid, ginkgo biloba, Acetyl-L-carnitine) were finally included, with 3,650 patients. Network meta-analysis showed that omega-6 (0.18), vitamin D (0.19), and quercetin (0.24) were the top three safest drugs according to SUCRA. The omega-3 (SUCRA 0.35), pycnogenol (SUCRA 0.36), and vitamin D (SUCRA 0.27) were the most effective in improving attention, hyperactivity, and total score of Conners' parent rating scale (CPRS), respectively. In terms of improving attention, hyperactivity, and total score of Conners' teacher rating scale (CTRS), pycnogenol (SUCRA 0.32), phosphatidylserine+omega-3 (SUCRA 0.26), and zinc (SUCRA 0.34) were the most effective, respectively. In terms of improving attention, hyperactivity and total score of ADHD Rating Scale-Parent, the optimal agents were phosphatidylserine (SUCRA 0.39), resveratrol+MPH (SUCRA 0.24), and phosphatidylserine (SUCRA 0.34), respectively. In terms of improving attention, hyperactivity and total score of ADHD Rating Scale-Teacher, pycnogenol (SUCRA 0.32), vitamin D (SUCRA 0.31) and vitamin D (SUCRA 0.18) were the optimal agents, respectively. The response rate of omega-3+6 was the highest in CGI (SUCRA 0.95) and CPT (SUCRA 0.42).
CONCLUSION
The rankings of safety and efficacy of the 12 antioxidants vary. Due to the low methodological quality of the included studies, the probability ranking cannot fully explain the clinical efficacy, and the results need to be interpreted with caution. More high-quality studies are still needed to verify our findings.
Topics: Child; Humans; Adolescent; Attention Deficit Disorder with Hyperactivity; Antioxidants; Network Meta-Analysis; Resveratrol; Quercetin; Prospective Studies; Phosphatidylserines; Fatty Acids, Omega-3; Vitamin D; Zinc
PubMed: 38547138
DOI: 10.1371/journal.pone.0296926 -
Critical Reviews in Toxicology Dec 2023Metal phosphides are highly toxic pesticides that result in high morbidities and mortalities worldwide. This systematic review included 350 studies that fulfilled the... (Review)
Review
Metal phosphides are highly toxic pesticides that result in high morbidities and mortalities worldwide. This systematic review included 350 studies that fulfilled the eligibility criteria. There were significant rising trends of studies on acute aluminum phosphide (AlP) and zinc phosphide (ZnP) poisoning (-values = <.001), pointing to an increased number of phosphide-intoxicated patients. Acute AlP poisoning studies represented 81%, 89.3%, and 97.7% of all descriptive, analytical, and experimental interventional studies included in this review, respectively. High AlP poisoning mortality explains great research interest in AlP poisoning. Thus, after 2016, nearly half (49.7%) of studies on acute AlP poisoning were issued. Also, 78.82% of experimental interventional studies on AlP poisoning were published after 2016. The trends of in-vitro, animal, and clinical studies on AlP poisoning significantly increased with -values equal to .021, <.001, and <.001, respectively. Seventy-nine treatment modalities for acute AlP poisoning were pooled from 124 studies; 39 management-related case reports, 12 in-vitro studies, 39 animal studies, and 34 clinical studies. All therapeutic modalities were summarized to formulate an integrated and comprehensive overview. For clinicians, therapeutic modalities significantly decreased mortality of acute AlP poisoning in clinical trials included extracorporeal membrane oxygenation (ECMO), N-acetyl cysteine (NAC), vitamin E, glucose-insulin-potassium (GIK) infusion, fresh packed RBCs infusion, and GIT decontamination using oils. However, meta-analyses are needed to provide solid evidence regarding their efficacies. To date, there is no effective antidote nor evidence-based standardized protocol for managing acute AlP poisoning. This article outlined the potential research gaps in phosphide poisoning that might promote and direct future medical research in this context.
Topics: Animals; Pesticides; Evidence Gaps; Antidotes; Acetylcysteine; Aluminum Compounds
PubMed: 37387512
DOI: 10.1080/10408444.2023.2225539 -
Pharmacogenomics and Personalized... 2022In neonates, pharmacogenetics has an additional layer of complexity. This is because in addition to genetic variability in genes that code for proteins relevant to... (Review)
Review
In neonates, pharmacogenetics has an additional layer of complexity. This is because in addition to genetic variability in genes that code for proteins relevant to clinical pharmacology, there are rapidly maturational changes in these proteins. Consequently, pharmacotherapy in neonates has unique challenges. To provide a contemporary overview on pharmacogenetics in neonates, we conducted a systematic review to identify, describe and quantify the impact of pharmacogenetics on pharmacokinetics and -dynamics in neonates and infants (PROSPERO, CRD42022302029). The search was performed in Medline, Embase, Web of Science and Cochrane, and was extended by a PubMed search on the 'top 100 Medicines' (medicine + newborn/infant + pharmacogen*) prescribed to neonates. Following study selection (including data in infants, PGx related) and quality assessment (Newcastle-Ottawa scale, Joanna Briggs Institute tool), 55/789 records were retained. Retained records relate to metabolizing enzymes involved in phase I [cytochrome P450 (CYP1A2, CYP2A6, CYP2B6, CYP2C8/C9/C18, CYP2C19, CYP2D6, CYP3A5, CYP2E1)], phase II [glutathione-S-transferases, N-acetyl transferases, UDP-glucuronosyl-transferase], transporters [ATP-binding cassette transporters, organic cation transporters], or receptor/post-receptor mechanisms [opioid related receptor and post-receptor mechanisms, tumor necrosis factor, mitogen-activated protein kinase 8, vitamin binding protein diplotypes, corticotrophin-releasing hormone receptor-1, nuclear receptor subfamily-1, vitamin K epoxide reductase complex-1, and angiotensin converting enzyme variants]. Based on the available overview, we conclude that the majority of reported pharmacogenetic studies explore and extrapolate observations already described in older populations. Researchers commonly try to quantify the impact of these polymorphisms in small datasets of neonates or infants. In a next step, pharmacogenetic studies in neonatal life should go beyond confirmation of these associations and explore the impact of pharmacogenetics as a covariate limited to maturation of neonatal life (ie, fetal malformations, breastfeeding or clinical syndromes). The challenge is to identify the specific factors, genetic and non-genetic, that contribute to the best benefit/risk balance.
PubMed: 35795337
DOI: 10.2147/PGPM.S350205 -
European Journal of Endocrinology May 2017To summarize the current knowledge on epigenetic alterations in mother and offspring subjected to gestational diabetes (GDM) and indicate future topics for research. (Review)
Review
OBJECTIVE
To summarize the current knowledge on epigenetic alterations in mother and offspring subjected to gestational diabetes (GDM) and indicate future topics for research.
DESIGN
Systematic review.
METHODS
We performed extensive searches in PubMed, EMBASE and Google scholar, using a combination of the search terms: GDM, gestational diabetes, epigenetic(s), methylation, histone modification, histone methylation, histone acetylation, microRNA and miRNA. Studies that compared women diagnosed with GDM and healthy controls were included. Two authors independently scanned the abstracts, and all included papers were read by at least two authors. The searches were completed on October 31st, 2016.
RESULTS
We identified 236 articles, of which 43 were considered relevant for this systematic review. Studies published showed that epigenetic alterations could be found in both mothers with GDM and their offspring. However, differences in methodology, diagnostic criteria for GDM and populations studied, together with a limited number of published studies and small sample sizes, preclude clear conclusions about the role of epigenetic modifications in transmitting risk from GDM mothers to their offspring.
CONCLUSION
The current research literature suggests that GDM may have impact on epigenetic modifications in the mother and offspring. However, larger studies that include multiple cohorts of GDM patients and their offspring are needed.
Topics: Animals; Blood Glucose; Diabetes, Gestational; Endocrinology; Epigenesis, Genetic; Female; Histones; Humans; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 28232369
DOI: 10.1530/EJE-16-1017 -
Clinical Nutrition (Edinburgh, Scotland) Dec 2013Chemotherapy induced peripheral neuropathy [CIPN] is a common significant and debilitating side effect resulting from the administration of neurotoxic chemotherapeutic... (Review)
Review
Chemotherapy induced peripheral neuropathy [CIPN] is a common significant and debilitating side effect resulting from the administration of neurotoxic chemotherapeutic agents. These pharmaco-chemotherapeutics can include taxanes, vinca alkaloids and others. Moderate to severe CIPN significantly decreases the quality of life and physical abilities of cancer patients and current pharmacotherapy for CIPN e.g. Amifostine and antidepressants have had limited efficacy and may themselves induce adverse side effects. To determine the potential use of nutraceuticals i.e. vitamin E, acetyl-L-carnitine, glutamine, glutathione, vitamin B6, omega-3 fatty acids, magnesium, calcium, alpha lipoic acid and n-acetyl cysteine as adjuvants in cancer treatments a systematic literature review was conducted. Revised clinical studies comprised of randomized clinical trials that investigated the anti-CIPN effect of nutraceuticals as the adjuvant intervention in patients administered chemotherapy. Twenty-four studies were assessed on methodological quality and limitations identified. Studies were mixed in their recommendations for nutraceuticals. Currently no agent has shown solid beneficial evidence to be recommended for the treatment or prophylaxis of CIPN. The standard of care for CIPN includes dose reduction and/or discontinuation of chemotherapy treatment. The management of CIPN remains an important challenge and future studies are warranted before recommendations for the use of supplements can be made.
Topics: Acetylcarnitine; Acetylcysteine; Antineoplastic Agents; Dietary Supplements; Fatty Acids, Omega-3; Glutamine; Glutathione; Humans; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Thioctic Acid; Trace Elements; Vitamins
PubMed: 23647723
DOI: 10.1016/j.clnu.2013.04.007 -
ANZ Journal of Surgery Jun 2022Postoperative pancreatic fistula (POPF) remains a significant complication of pancreatic resection with recent evidence showing a strong association between... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postoperative pancreatic fistula (POPF) remains a significant complication of pancreatic resection with recent evidence showing a strong association between post-operative pancreatitis and subsequent development of POPF. Incidence and severity of pancreatitis following endoscopic therapy has been effectively reduced with indomethacin prophylaxis, however further agents require evaluation. We present a systematic literature review and meta-analysis of the prophylactic treatment with corticosteroids or n-acetyl cysteine (NAC) of induced pancreatitis in rodent models.
METHODS
A systematic literature search was conducted using Pubmed, Medline, Embase and Cochrane library to identify eligible randomized control trials (RCT) involving animal models that examined NAC or corticosteroids. The primary outcome was the subsequent effect on serum amylase and IL-6 and the histopathological markers of severity such as pancreatic oedema and necrosis.
RESULTS
Four RCTs (n = 178) met inclusion criteria examining NAC and eight RCTs (n = 546) examining corticosteroid agents (dexamethasone, hydrocortisone, methylprednisolone). Prophylactic administration of all corticosteroid agents showed a net effect in favour of reducing markers of severity of pancreatitis. NAC showed a significant reduction in severity of amylase and necrosis.
CONCLUSION
The RCTs examined suggest that prophylactic administration of corticosteroid agents and NAC can reduce the severity of pancreatitis as indicated by histopathologic markers, serum amylase and IL-6 levels.
Topics: Amylases; Animals; Humans; Interleukin-6; Necrosis; Pancreatitis; Postoperative Complications; Randomized Controlled Trials as Topic
PubMed: 34936178
DOI: 10.1111/ans.17417 -
Current Genomics Nov 2018Involvement of life stress in Late-Onset Alzheimer's Disease (LOAD) has been evinced in longitudinal cohort epidemiological studies, and endocrinologic evidence suggests... (Review)
Review
Involvement of life stress in Late-Onset Alzheimer's Disease (LOAD) has been evinced in longitudinal cohort epidemiological studies, and endocrinologic evidence suggests involvements of catecholamine and corticosteroid systems in LOAD. Early Life Stress (ELS) rodent models have successfully demonstrated sequelae of maternal separation resulting in LOAD-analogous pathology, thereby supporting a role of insulin receptor signalling pertaining to GSK-3beta facilitated tau hyper-phosphorylation and amyloidogenic processing. Discussed are relevant ELS studies, and findings from three mitogen-activated protein kinase pathways (JNK/SAPK pathway, ERK pathway, p38/MAPK pathway) relevant for mediating environmental stresses. Further considered were the roles of autophagy impairment, neuroinflammation, and brain insulin resistance. For the meta-analytic evaluation, 224 candidate gene loci were extracted from reviews of animal studies of LOAD pathophysiological mechanisms, of which 60 had no positive results in human LOAD association studies. These loci were combined with 89 gene loci confirmed as LOAD risk genes in previous GWAS and WES. Of the 313 risk gene loci evaluated, there were 35 human reports on epigenomic modifications in terms of methylation or histone acetylation. 64 microRNA gene regulation mechanisms were published for the compiled loci. Genomic association studies support close relations of both noradrenergic and glucocorticoid systems with LOAD. For HPA involvement, a CRHR1 haplotype with MAPT was described, but further association of only HSD11B1 with LOAD found; however, association of FKBP1 and NC3R1 polymorphisms was documented in support of stress influence to LOAD. In the brain insulin system, IGF2R, INSR, INSRR, and plasticity regulator ARC, were associated with LOAD. Pertaining to compromised myelin stability in LOAD, relevant associations were found for BIN1, RELN, SORL1, SORCS1, CNP, MAG, and MOG. Regarding epigenetic modifications, both methylation variability and de-acetylation were reported for LOAD. The majority of up-to-date epigenomic findings include reported modifications in the well-known LOAD core pathology loci MAPT, BACE1, APP (with FOS, EGR1), PSEN1, PSEN2, and highlight a central role of BDNF. Pertaining to ELS, relevant loci are FKBP5, EGR1, GSK3B; critical roles of inflammation are indicated by CRP, TNFA, NFKB1 modifications; for cholesterol biosynthesis, DHCR24; for myelin stability BIN1, SORL1, CNP; pertaining to (epi)genetic mechanisms, hTERT, MBD2, DNMT1, MTHFR2. Findings on gene regulation were accumulated for BACE1, MAPK signalling, TLR4, BDNF, insulin signalling, with most reports for miR-132 and miR-27. Unclear in epigenomic studies remains the role of noradrenergic signalling, previously demonstrated by neuropathological findings of childhood nucleus caeruleus degeneration for LOAD tauopathy.
PubMed: 30386171
DOI: 10.2174/1389202919666171229145156 -
Archives of Women's Mental Health Apr 2024We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) evaluating the effects of melatonin intake on depression and anxiety in... (Meta-Analysis)
Meta-Analysis
We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) evaluating the effects of melatonin intake on depression and anxiety in postmenopausal women. To identify RCTs examining the effect of melatonin supplementation on depression and anxiety scores in postmenopausal women, a comprehensive electronic search was conducted via the Cochrane Central Register of Controlled Trials, Science direct, Google Scholar, PubMed, Medline, Scopus and Web of Science databases using the keywords ("melatonin" OR "N-acetyl serotonin") AND ("menopause" OR "climacteric") AND ("depression" OR "anxiety"). The search strategy was applied to articles published between January 2000 and April 2023. The Cochrane tool was used to evaluate the bias risk in RCTs. For the meta-analysis, fixed effect models and random effect models were employed based on heterogeneity. Preferred Reporting Items for Systematic Reviews and Meta-Analysis in Our Study guidelines were followed. Five RCTs were included in the study, with a total sample size of 441 (experimental: 227 and control: 214). When the effect of melatonin use on depression in menopausal women was analysed, it was found that melatonin significantly reduced menopausal depression (SMD - 0.166, CI = - 0.288/ - 0.045, p < 0.05). When the effect of melatonin use on anxiety in postmenopausal women was analysed, it was found that melatonin significantly improved menopausal anxiety (SMD - 0.806, CI = 1.491/ - 0.120, p < 0.05). Melatonin is promising as a potential treatment to help depression and anxiety in the postmenopausal period. More high-quality studies are needed to determine their safety.
Topics: Female; Humans; Melatonin; Depression; Postmenopause; Anxiety; Anxiety Disorders; Randomized Controlled Trials as Topic
PubMed: 37945913
DOI: 10.1007/s00737-023-01395-0 -
Frontiers in Oncology 2021Lung cancer is the leading cause of cancer-related death worldwide and has a high incidence rate. N-Acetyltransferase 2 (NAT2) is a polymorphic xenobiotic enzyme, which...
Lung cancer is the leading cause of cancer-related death worldwide and has a high incidence rate. N-Acetyltransferase 2 (NAT2) is a polymorphic xenobiotic enzyme, which can catalyze N-acetylation and O-acetylation of various carcinogens such as aromatic, heterocyclic amines and hydrazines. At present, many studies have explored the effects of NAT2 polymorphism on lung cancer, but we found inconsistent results. We researched 18 published studies, involving 4,016 patients and 5,469 controls, to more accurately assess the effects of NAT2 polymorphism on lung cancer risk and to investigate whether smoking is associated. We used STATA software to analyze the extracted data and used STATA for subgroup analysis, sensitivity analysis, and to perform publication bias tests. To determine the correlation, we used the crude odds ratio (ORs) with 95% confidence interval (CIs). Our study was prospectively registered in PROSPERO (CRD42020159737). The odds ratio was 1.53 (95% CI: 1.211.95, I² = 45.2%, P=0.104) for the NAT2 slow + intermediate phenotype rapid phenotype. The results suggested that people with NAT2 non-rapid (slow + intermediate) phenotype have a significantly increased risk of lung cancer. In addition, NAT2 rapid phenotype was significantly associated with reduced risk of lung cancer, compared with slow phenotype or intermediate phenotype (slow phenotype . rapid phenotype: OR: 1.61, 95% CI: 1.07-2.42, I²= 50%, P= 0.075; intermediate phenotype . rapid phenotype: OR: 1.47, 95% CI: 1.15-1.88, I²= 40.3%, P= 0.137).
PubMed: 33777732
DOI: 10.3389/fonc.2021.567762