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Sleep and Microdialysis: An Experiment and a Systematic Review of Histamine and Several Amino Acids.Journal of Circadian Rhythms Jul 2019Sleep seems essential to proper functioning of the prefrontal cortex (PFC). The role of different neurotransmitters has been studied, mainly the catecholamines and...
Sleep seems essential to proper functioning of the prefrontal cortex (PFC). The role of different neurotransmitters has been studied, mainly the catecholamines and serotonin. Less attention has been paid to the amino acid transmitters and histamine. Here, we focus on the activity of these molecules in the PFC during sleep and sleep deprivation (SD). We determined extracellular concentrations of histamine and 8 amino acids in the medial PFC before, during and after SD. Additionally, we systematically reviewed the literature on studies reporting microdialysis measurements relating to sleep throughout the brain. In our experiment, median concentrations of glutamate were higher during SD than during baseline (p = 0.013) and higher during the dark-active than during the resting phase (p = 0.003). Glutamine was higher during post-SD recovery than during baseline (p = 0.010). For other compounds, no differences were observed between light and dark circadian phase, and between sleep deprivation, recovery and baseline. We retrieved 13 papers reporting on one or more of the molecules of interest during naturally occurring sleep, 2 during sleep deprivation and 2 during both. Only two studies targeted PFC. Histamine was low during sleep, but high during sleep deprivation and wakefulness, irrespective of brain area. Glu (k = 11) and GABA (k = 8) concentrations in different brain areas were reported to peak during sleep or wakefulness or to lack state-dependency. Aspartate, glycine, asparagine and taurine were less often studied (1-2 times), but peaked exclusively during sleep. Sleep deprivation increased glutamate and GABA exclusively in the cortex. Further studies are needed for drawing solid conclusions.
PubMed: 31303885
DOI: 10.5334/jcr.183 -
Hypertension (Dallas, Tex. : 1979) Aug 2022Confirmatory tests are recommended for diagnosing primary aldosteronism, but the supporting evidence is unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Confirmatory tests are recommended for diagnosing primary aldosteronism, but the supporting evidence is unclear.
METHODS
We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials. Studies evaluating any guideline-recommended confirmatory test (ie, saline infusion test, salt loading test, fludrocortisone suppression test, and captopril challenge test), compared with a reference standard were included. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the risk of bias. Meta-analyses were conducted using hierarchical summary receiver operating characteristic models.
RESULTS
Fifty-five studies were included, comprising 26 studies (3654 participants) for the recumbent saline infusion test, 4 studies (633 participants) for the seated saline infusion test, 2 studies (99 participants) for the salt loading test, 7 studies (386 participants) for the fludrocortisone suppression test, and 25 studies (2585 participants) for the captopril challenge test. Risk of bias was high, affecting more than half of studies, and across all domains. Studies with case-control sampling overestimated accuracy by 7-fold (relative diagnostic odds ratio, 7.26 [95% CI, 2.46-21.43]) and partial verification or use of inconsistent reference standards overestimated accuracy by 5-fold (5.12 [95% CI, 1.48-17.77]). There were large variations in how confirmatory tests were conducted, interpreted, and verified. Under most scenarios, confirmatory testing resulted in an excess of missed cases. The certainty of evidence underlying each test (Grading of Recommendations, Assessment, Development, and Evaluations) was very low.
CONCLUSIONS
Recommendations for confirmatory testing in patients with abnormal screening tests and high probability features of primary aldosteronism are based on very low-quality evidence and their routine use should be reconsidered.
Topics: Captopril; Fludrocortisone; Humans; Hyperaldosteronism; ROC Curve; Sensitivity and Specificity
PubMed: 35652330
DOI: 10.1161/HYPERTENSIONAHA.122.19377 -
Caries Research 2022Salivary proteins play an important role in repairing mechanisms of damaged tissues and the maintenance of oral health. However, there is a dearth of information in the...
Salivary proteins play an important role in repairing mechanisms of damaged tissues and the maintenance of oral health. However, there is a dearth of information in the literature regarding the concentrations of salivary proteins in caries-free (CF) and caries-active (CA) subjects. Hence, this systematic review was conducted to update our previous systematic review published in 2013 that aimed to assess the association between caries and salivary proteins by comparing CF and CA individuals. Thereby, evaluating the possibility of whether salivary proteins can be regarded as biomarkers for caries. An extensive search of studies was conducted using PubMed, EMBASE, Clarivate Analytics' Web of Science, and Elsevier's Scopus between July 2012 and January 2022, without any language restriction. Manual searching in Google Scholar and evaluation of bibliographies of the included studies were also undertaken. The Newcastle-Ottawa Scale was used to assess the risk of bias (RoB) within the included studies. Of 22 included studies, 1,551 human subjects (range: 30-213 participants) were recruited, of which 848 individuals (54.7%) were CA and 703 (45.3%) were CF. Regarding the utilization of DMFT as the caries index, high variability was observed across different articles. A statistically significant increase in the salivary levels of alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, and mucin-1 was found in CA patients, while the salivary levels of carbonic anhydrase 6, proteinase-3, and statherin were observed to be significantly increased in CF subjects. Conflicting results were found regarding the salivary levels of immunoglobulin A and total proteins among CA and CF subjects. The included studies were categorized as low RoB (n = 15), medium RoB (n = 4), and high RoB (n = 3). Due to significant heterogeneity among the included studies, no meta-analysis could be performed. In conclusion, the salivary levels of protein(s) might be a useful biomarker for caries diagnosis, especially alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, mucin-1, carbonic anhydrase 6, proteinase-3, and statherin. However, their diagnostic value must be verified by large-scale prospective studies.
Topics: Humans; Mucin-1; Dental Caries; Histatins; Lactoperoxidase; Prospective Studies; Salivary Proteins and Peptides; Biomarkers; Proline; alpha-Amylases; Peptide Hydrolases
PubMed: 36116431
DOI: 10.1159/000526942 -
BMC Endocrine Disorders Nov 2020We aimed to explore metabolite biomarkers that could be used to identify pre-diabetes and type 2 diabetes mellitus (T2DM) using systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
We aimed to explore metabolite biomarkers that could be used to identify pre-diabetes and type 2 diabetes mellitus (T2DM) using systematic review and meta-analysis.
METHODS
Four databases, the Cochrane Library, EMBASE, PubMed and Scopus were selected. A random effect model and a fixed effect model were applied to the results of forest plot analyses to determine the standardized mean difference (SMD) and 95% confidence interval (95% CI) for each metabolite. The SMD for every metabolite was then converted into an odds ratio to create an metabolite biomarker profile.
RESULTS
Twenty-four independent studies reported data from 14,131 healthy individuals and 3499 patients with T2DM, and 14 included studies reported 4844 healthy controls and a total of 2139 pre-diabetes patients. In the serum and plasma of patients with T2DM, compared with the healthy participants, the concentrations of valine, leucine, isoleucine, proline, tyrosine, lysine and glutamate were higher and that of glycine was lower. The concentrations of isoleucine, alanine, proline, glutamate, palmitic acid, 2-aminoadipic acid and lysine were higher and those of glycine, serine, and citrulline were lower in prediabetic patients. Metabolite biomarkers of T2DM and pre-diabetes revealed that the levels of alanine, glutamate and palmitic acid (C16:0) were significantly different in T2DM and pre-diabetes.
CONCLUSIONS
Quantified multiple metabolite biomarkers may reflect the different status of pre-diabetes and T2DM, and could provide an important reference for clinical diagnosis and treatment of pre-diabetes and T2DM.
Topics: Biomarkers; Diabetes Mellitus, Type 2; Humans; Metabolome; Prediabetic State; Prognosis
PubMed: 33228610
DOI: 10.1186/s12902-020-00653-x -
The Cochrane Database of Systematic... Feb 2023IgA vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is the most common vasculitis of childhood but may also occur in adults. This small vessel... (Review)
Review
BACKGROUND
IgA vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is the most common vasculitis of childhood but may also occur in adults. This small vessel vasculitis is characterised by palpable purpura, abdominal pain, arthritis or arthralgia and kidney involvement. This is an update of a review first published in 2009 and updated in 2015.
OBJECTIVES
To evaluate the benefits and harms of different agents (used singularly or in combination) compared with placebo, no treatment or any other agent for (1) the prevention of severe kidney disease in people with IgAV with or without kidney involvement at onset, (2) the treatment of established severe kidney disease (macroscopic haematuria, proteinuria, nephritic syndrome, nephrotic syndrome with or without acute kidney failure) in IgAV, and (3) the prevention of recurrent episodes of IgAV-associated kidney disease.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 2 February 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing interventions used to prevent or treat kidney disease in IgAV compared with placebo, no treatment or other agents were included.
DATA COLLECTION AND ANALYSIS
Two authors independently determined study eligibility, assessed the risk of bias and extracted data from each study. Statistical analyses were performed using the random-effects model, and the results were expressed as risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Twenty studies (1963 enrolled participants) were identified; one three-arm study has been assessed as two studies. Nine studies were at low risk of bias for sequence generation (selection bias), and nine studies were at low risk of bias for allocation concealment (selection bias). Blinding of participants and personnel (performance bias) and outcome assessment (detection bias) was at low risk of bias in four and seven studies, respectively. Nine studies reported complete outcome data (attrition bias), while 10 studies reported expected outcomes, so were at low risk of reporting bias. Five studies were at low risk of other bias. Eleven studies evaluated therapy to prevent persistent kidney disease in IgAV with or without kidney involvement at presentation. There was probably no difference in the risk of persistent kidney disease any time after treatment (5 studies, 746 children: RR 0.74, 95% CI 0.42 to 1.32) or at one, three, six and 12 months in children given prednisone for 14 to 28 days at presentation of IgAV compared with placebo or supportive treatment (moderate certainty evidence). There may be no differences in the risk of any persistent kidney disease with antiplatelet therapy (three studies) or heparin (two studies) in children with or without any kidney disease at study entry, although heparin may reduce the risk of proteinuria by three months compared with placebo or no specific treatment (2 studies, 317 children: RR 0.47, 95% CI 0.31 to 0.73). One study comparing montelukast with placebo found no differences in outcomes as assessed by severity scale scores. Nine studies examined the treatment of severe IgAV-associated kidney disease. In two studies (one involving 56 children and the other involving 54 adults), there may be no differences in efficacy outcomes or adverse effects with cyclophosphamide compared with placebo or supportive treatment. In two studies, there may be no differences in the numbers achieving remission of proteinuria with intravenous (IV) cyclophosphamide compared with mycophenolate mofetil (MMF) (65 children evaluated) or tacrolimus (142 children evaluated). In three small studies comparing cyclosporin with methylprednisolone (15 children), MMF with azathioprine (26 children), or MMF with leflunomide (19 children), it is unclear whether the treatment had any effect on the numbers in remission or the degree of proteinuria between treatment groups because of small numbers of included participants. In one study comparing plasmapheresis, cyclophosphamide and methylprednisolone with cyclophosphamide and methylprednisolone, there may be no difference in the numbers achieving remission. One study compared fosinopril with no specific therapy and reported fosinopril reduced the number of participants with proteinuria. No studies were identified that evaluated the efficacy of therapy on kidney disease in participants with recurrent episodes of IgAV.
AUTHORS' CONCLUSIONS
There are no substantial changes in conclusions from this update compared with the initial review or the previous update despite the addition of five studies. From generally low to moderate certainty evidence, we found that there may be little or no benefit in the use of corticosteroids or antiplatelet agents to prevent persistent kidney disease in children with IgAV in participants with no or minimal kidney involvement at presentation. We did not find any studies which evaluated corticosteroids in children presenting with IgAV and nephritic and/or nephrotic syndrome, although corticosteroids are recommended in such children in guidelines. Though heparin may be effective in reducing proteinuria, this potentially dangerous therapy is not justified to prevent serious kidney disease when few children with IgAV develop severe kidney disease. There may be no benefit of cyclophosphamide compared with no specific treatment or corticosteroids. While there may be no benefit in the efficacy of MMF or tacrolimus compared with IV cyclophosphamide in children or adults with IgAV and severe kidney disease, adverse effects, particularly infections, may be lower in MMF or tacrolimus-treated children. Because of small patient numbers and events leading to imprecision in results, it remains unclear whether cyclosporin, MMF or leflunomide have any role in the treatment of children with IgAV and severe kidney disease. We did not identify any studies which evaluated corticosteroids.
Topics: Adult; Child; Humans; Fosinopril; IgA Vasculitis; Kidney Diseases; Leflunomide; Proteinuria; Tacrolimus; Vasculitis
PubMed: 36853224
DOI: 10.1002/14651858.CD005128.pub4 -
Heliyon Jan 2024Triple-negative breast cancer stands out as the most aggressive subtype of breast malignancy and is characterized by an unfavourable prognosis. : This systematic review...
Triple-negative breast cancer stands out as the most aggressive subtype of breast malignancy and is characterized by an unfavourable prognosis. : This systematic review summarizes the insights gleaned from metabolomic analyses of individuals afflicted with this cancer variant. The overarching goal was to delineate the molecular alterations associated with triple-negative breast cancer, pinpointing potential therapeutic targets and novel biomarkers. We systematically searched for evidence using the PubMed database and followed the PRISMA and STARLITE guidelines. The search parameters were delimited to articles published within the last 13 years. From an initial pool of 148 scrutinized articles, 17 studies involving 1686 participants were deemed eligible for inclusion. The current body of research shows a paucity of studies, and the available evidence presents conflicting outcomes. Notwithstanding, Pathway Enrichment Analysis identified the urea and glucose-alanine cycles as the most affected metabolic pathways, followed by arginine, proline, and aspartate metabolism. Future investigations need to focus on elucidating which of those metabolites and/or pathways might be reliable candidates for novel therapeutic interventions or reliable biomarkers for diagnosis and prognosis of this subtype of breast cancer.
PubMed: 38187259
DOI: 10.1016/j.heliyon.2023.e23628 -
Metabolites Sep 2023Response to radiotherapy (RT) includes tissue toxicity, which may involve inflammatory reactions. We aimed to compare changes in metabolic patterns induced at the... (Review)
Review
Response to radiotherapy (RT) includes tissue toxicity, which may involve inflammatory reactions. We aimed to compare changes in metabolic patterns induced at the systemic level by radiation and inflammation itself. Patients treated with RT due to head and neck cancer and patients with inflammation-related diseases located in the corresponding anatomical regions were selected. PubMed and Web of Science databases were searched from 1 January 2000 to 10 August 2023. Twenty-five relevant studies where serum/plasma metabolic profiles were analyzed using different metabolomics approaches were identified. The studies showed different metabolic patterns of acute and chronic inflammatory diseases, yet changes in metabolites linked to the urea cycle and metabolism of arginine and proline were common features of both conditions. Although the reviewed reports showed only a few specific metabolites common for early RT response and inflammatory diseases, partly due to differences in metabolomics approaches, several common metabolic pathways linked to metabolites affected by radiation and inflammation were revealed. They included pathways involved in energy metabolism (e.g., metabolism of ketone bodies, mitochondrial electron transport chain, Warburg effect, citric acid cycle, urea cycle) and metabolism of certain amino acids (Arg, Pro, Gly, Ser, Met, Ala, Glu) and lipids (glycerolipids, branched-chain fatty acids). However, metabolites common for RT and inflammation-related diseases could show opposite patterns of changes. This could be exemplified by the lysophosphatidylcholine to phosphatidylcholine ratio (LPC/PC) that increased during chronic inflammation and decreased during the early phase of response to RT. One should be aware of dynamic metabolic changes during different phases of response to radiation, which involve increased levels of LPC in later phases. Hence, metabolomics studies that would address molecular features of both types of biological responses using comparable analytical and clinical approaches are needed to unravel the complexities of these phenomena, ultimately contributing to a deeper understanding of their impact on biological systems.
PubMed: 37755280
DOI: 10.3390/metabo13091000 -
Frontiers in Genetics 2021Schizophrenia is a disorder that is characterized by delusions, hallucinations, disorganized speech or behavior, and socio-occupational impairment. The duration of...
Schizophrenia is a disorder that is characterized by delusions, hallucinations, disorganized speech or behavior, and socio-occupational impairment. The duration of observation and variability in symptoms can make the accurate diagnosis difficult. Identification of biomarkers for schizophrenia (SCZ) can help in early diagnosis, ascertaining the diagnosis, and development of effective treatment strategies. Here we review peripheral blood-based gene expression studies for identification of gene expression biomarkers for SCZ. A literature search was carried out in PubMed and Web of Science databases for blood-based gene expression studies in SCZ. A list of differentially expressed genes (DEGs) was compiled and analyzed for overlap with genetic markers, differences based on drug status of the participants, functional enrichment, and for effect of antipsychotics. This literature survey identified 61 gene expression studies. Seventeen out of these studies were based on expression microarrays. A comparative analysis of the DEGs ( = 227) from microarray studies revealed differences between drug-naive and drug-treated SCZ participants. We found that of the 227 DEGs, 11 genes () also showed genetic and epigenetic changes associated with SCZ. Functional enrichment analysis of the DEGs revealed dysregulation of proline and 4-hydroxyproline metabolism. Also, arginine and proline metabolism was the most functionally enriched pathway for SCZ in our analysis. Follow-up studies identified effect of antipsychotic treatment on peripheral blood gene expression. Of the 27 genes compiled from the follow-up studies , and had no effect on their expression status as a result of antipsychotic treatment. Despite the differences in the nature of the study, ethnicity of the population, and the gene expression analysis method used, we identified several coherent observations. An overlap, though limited, of genetic, epigenetic and gene expression changes supports interplay of genetic and environmental factors in SCZ. The studies validate the use of blood as a surrogate tissue for biomarker analysis. We conclude that well-designed cohort studies across diverse populations, use of high-throughput sequencing technology, and use of artificial intelligence (AI) based computational analysis will significantly improve our understanding and diagnostic capabilities for this complex disorder.
PubMed: 34721526
DOI: 10.3389/fgene.2021.736483 -
Shoulder & Elbow Apr 2021The EVOLVE implant (Wright Medical Technology, Arlington, TN, USA) is a modular loose-fitting radial head prosthesis. The primary objective was to synthesize all... (Review)
Review
INTRODUCTION
The EVOLVE implant (Wright Medical Technology, Arlington, TN, USA) is a modular loose-fitting radial head prosthesis. The primary objective was to synthesize all available literature investigating the midterm clinical outcomes of the EVOLVE implant.
MATERIALS AND METHODS
An electronic literature search in Pubmed/Medline, Scopus, EMBASE, and Cochrane library was performed querying for studies published in 2000-2017. Articles describing clinical and radiographical outcomes as well as reoperation were included. Outcomes of interest included range of motion, Mayo Elbow Performance Score, Disabilities of the Arm Shoulder and Hand, radiographic outcome, and reason for reoperation.
RESULTS
A total of five articles consisting of 146 patients with EVOLVE implants were included. Mean patient age was 57.4 years (range 22-84), and 43.8% were males (n = 64). Mean follow-up was 4.8 years (range 1-14). Mean Mayo Elbow Performance Score and Disabilities of the Arm Shoulder and Hand score were 87.6 (range 30-100) and 18.9 (range 0-82), respectively. Midterm clinical results were good or excellent (Mayo Elbow Performance Score > 74) in 94 patients. Reoperation was observed in 12 patients, with implant revision required in 2 patients. The primary reason for reoperation was persistent stiffness (n = 9).
CONCLUSION
Midterm outcomes of EVOLVE radial head prosthesis are satisfactory, and associated complication rates are low. Loose-fit implant method appears to be a reliable approach to avoid failure of radial head prosthesis by painful loosening.
PubMed: 33897852
DOI: 10.1177/1758573219850111 -
Investigative Ophthalmology & Visual... Dec 2020Age-related macular degeneration (AMD) is one of the leading causes of blindness among the elderly, and the exact pathogenesis of the AMD remains unclear. The purpose of...
PURPOSE
Age-related macular degeneration (AMD) is one of the leading causes of blindness among the elderly, and the exact pathogenesis of the AMD remains unclear. The purpose of this review is to summarize potential metabolic biomarkers and pathways of AMD that might facilitate risk predictions and clinical diagnoses of AMD.
METHODS
We obtained relevant publications of metabolomics studies of human beings by systematically searching the MEDLINE (PubMed) database before June 2020. Studies were included if they performed mass spectrometry-based or nuclear magnetic resonance-based metabolomics approach for humans. In addition, AMD was assessed from fundus photographs based on standardized protocols. The metabolic pathway analysis was performed using MetaboAnalyst 3.0.
RESULTS
Thirteen studies were included in this review. Repeatedly identified metabolites including phenylalanine, adenosine, hypoxanthine, tyrosine, creatine, citrate, carnitine, proline, and maltose have the possibility of being biomarkers of AMD. Validation of the biomarker panels was observed in one study. Dysregulation of metabolic pathways involves lipid metabolism, carbohydrate metabolism, nucleotide metabolism, amino acid metabolism, and translation, which might play important roles in the development and progression of AMD.
CONCLUSIONS
This review summarizes the potential metabolic biomarkers and pathways related to AMD, providing opportunities for the construction of diagnostic or predictive models for AMD and the discovery of new therapeutic targets.
Topics: Biomarkers; Humans; Macular Degeneration; Metabolic Networks and Pathways; Metabolomics; Risk Factors
PubMed: 33315052
DOI: 10.1167/iovs.61.14.13