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Archives of Academic Emergency Medicine 2019There is controversy regarding the value of serum or cerebrospinal fluid (CSF) levels of S100 calcium-binding protein B (S-100B) in spinal cord injury (SCI). For... (Review)
Review
INTRODUCTION
There is controversy regarding the value of serum or cerebrospinal fluid (CSF) levels of S100 calcium-binding protein B (S-100B) in spinal cord injury (SCI). For reaching a general conclusion, the present meta-analysis was designed aiming to evaluate the value of serum and CSF levels of S-100B protein in detecting the presence of SCI in animal studies.
METHODS
An extensive search was performed in Medline, Embase, Scopus and Web of science databases. Screening articles, summarizing them and entering data to checklist and quality assessment of the mentioned articles were done by 2 independent reviewers. Data were analyzed and a pooled standardized mean difference (SMD) and 95% confidence interval (95% CI) were presented.
RESULTS
Finally, the data of 7 articles were included in the meta-analysis. Serum level of S-100B had increased as a result of SCI. During the first 6 hours after injury, the level of this protein was very high (SMD=3.8; 95% CI: 2.6 to 5.1; p<0.0001), but as time passed the serum level of the protein had decreased (SMD=0.4; 95% CI: -1.2 to 2.0; p=0.65). In addition, CSF level of the mentioned protein was very high during the initial 6 hours after injury (SMD: 5.8; 95% CI: 3.6 to 8.0), and this elevated level was still observed until 12 hours after injury (SMD: 6.5; 95% CI: 3.7 to 9.3; p<0.0001).
CONCLUSION
The results of the present systematic review and meta-analysis show that measuring the level of S-100Β protein in serum and CSF has a potential value in diagnosis of SCI in animal models. This biomarker increases during the initial 6 hours following injury and remains high until 24 hours after that. However, more than 24 hours after the injury, serum level of this protein returns to the level of animals without SCI.
PubMed: 31432029
DOI: No ID Found -
PloS One 2019New generation biologics, including interleukin (IL)-17 and IL-23 inhibitors, have delivered higher rates of skin clearance than older treatments in head-to-head... (Meta-Analysis)
Meta-Analysis
Assessing the relative efficacy of interleukin-17 and interleukin-23 targeted treatments for moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis of PASI response.
INTRODUCTION
New generation biologics, including interleukin (IL)-17 and IL-23 inhibitors, have delivered higher rates of skin clearance than older treatments in head-to-head studies. However, studies comparing these new biologics directly to one another are limited.
OBJECTIVES
To compare the short-term efficacy of available (or imminently available) biologic and non-biologic systemic therapies for treating patients with moderate-to-severe plaque psoriasis.
METHODS
A systematic review was undertaken to identify randomised controlled trials evaluating biologic treatments, apremilast and dimethyl fumarate. MEDLINE, MEDLINE In-Process, Embase and the Cochrane Library were searched from the 1st January 2000 to 22nd November 2018. A Bayesian network meta-analysis (NMA) using a random-effects multinomial likelihood model with probit link and meta-regression to adjust for cross-trial variation in placebo responses compared the efficacy of interventions at inducing different levels of Psoriasis Area and Severity Index (PASI) response during the induction period. A range of sensitivity analyses was undertaken.
RESULTS
Seventy-seven trials (34,816 patients) were included in the NMA. The base-case analysis showed that all active treatments were superior to placebo. IL-17 inhibitors, guselkumab and risankizumab were found to be more efficacious than tildrakizumab, ustekinumab, all TNF inhibitors and non-biologic systemic treatments at inducing all levels of PASI response. In addition, brodalumab, ixekizumab and risankizumab were significantly more efficacious than secukinumab; no significant difference was found in the comparison with guselkumab. The greatest benefit of brodalumab, ixekizumab, guselkumab, and risankizumab was seen for PASI 90 and PASI 100 response. Results were consistent across all analyses.
CONCLUSIONS
In the NMA brodalumab, ixekizumab, risankizumab and guselkumab showed the highest levels of short-term efficacy. There were differences in efficacy between treatments within the same class. Longer-term analyses are needed to understand differences between these drugs beyond induction in what is a life-long condition.
Topics: Biological Products; Dermatologic Agents; Humans; Interleukin-17; Interleukin-23 Subunit p19; Psoriasis; Treatment Outcome
PubMed: 31412060
DOI: 10.1371/journal.pone.0220868 -
Medicine Jun 2019The K channel, subfamily J, member-11 (KCNJ11) E23K and β1 subunit of large-conductance Ca-activated K channel (KCNMB1) E65K polymorphisms were shown to be associated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The K channel, subfamily J, member-11 (KCNJ11) E23K and β1 subunit of large-conductance Ca-activated K channel (KCNMB1) E65K polymorphisms were shown to be associated with the risk of essential hypertension (EH). However, the results were inconclusive with relatively small sample size. Thus, we carried out a meta-analysis to investigate the genetic association between KCNJ11 E23K and KCNMB1 E65K polymorphisms and essential hypertension risk.
METHODS
Relative studies were collected using PubMed, Web of Science, the Cochrane Library databases, Chinese National Knowledge Infrastructure and Embase databases. Pooled odds ratios with 95% confidence intervals were used to assess the strength of associations.
RESULTS
The dominant models of KCNJ11 E23K (P = .006, OR [95%CI] = 0.45 [0.25, 0.79]) and KCNMB1 E65K (P = .04, OR [95%CI] = 0.91 [0.83, 1.00]) were significantly associated with essential hypertension risk. No significant association was detected between the allelic and recessive models of KCNJ11 E23K and KCNMB1 E65K and the susceptibility of EH. Subgroup analysis stratified by ethnicity showed that the dominant model of KCNMB1 E65K was associated with EH risk in Asian population (P = .003, OR [95%CI] = 0.83 [0.74, 0.94]), but not in Caucasian (P = .74, OR [95%CI] = 1.02 [0.89, 1.18]).
CONCLUSIONS
The dominant model of KCNJ11 E23K and KCNMB1 E65K might be susceptible factors for essential hypertension. To confirm this result, large-scale case-control studies with more subjects are necessary.
Topics: Adult; Aged; Asian People; Essential Hypertension; Female; Genetic Predisposition to Disease; Humans; Large-Conductance Calcium-Activated Potassium Channel beta Subunits; Male; Middle Aged; Potassium Channels, Inwardly Rectifying
PubMed: 31169684
DOI: 10.1097/MD.0000000000015828 -
British Journal of Haematology Sep 2019The mechanisms by which patients with RUNX1 familial platelet disorder with propensity to myeloid malignancies (FPDMM) develop myeloid malignancies (MM) are not fully...
The mechanisms by which patients with RUNX1 familial platelet disorder with propensity to myeloid malignancies (FPDMM) develop myeloid malignancies (MM) are not fully understood. We report the results of targeted next-generation sequencing on three patients with RUNX1 FPDMM who developed acute myeloid leukaemia or myelodysplastic syndromes (AML/MDS). DNA samples were collected from bone marrow, peripheral blood and buccal swabs at different time points. One patient had clonal haematopoiesis, represented by an SRSF2 p.P95R variant, prior to his AML diagnosis, when he developed an additional NRAS p.G12D variant. His sister presented to us with MDS, with a TET2 p.S471fs and identical NRAS p.G12D variant. The third patient, from another family, had an additional RUNX1 p.R204X and an NFE2 p.Q139fs variant at AML diagnosis. This constitutes the first report of NFE2 variants in AML without extramedullary disease and NRAS variants in AML/MDS in the setting of FPDMM. A systematic review of the literature including our findings distinguishes two genetic landscapes at AML transformation from FPDMM characterized by either the presence or absence of somatic abnormalities in RUNX1 with or without variants in genes usually associated with MM. Whether clonal haematopoiesis precedes transformation only in patients without somatic abnormalities in RUNX1 needs further confirmation.
Topics: Blood Platelet Disorders; Core Binding Factor Alpha 2 Subunit; Female; Germ-Line Mutation; Humans; Longitudinal Studies; Male; Middle Aged; Myeloproliferative Disorders
PubMed: 31124578
DOI: 10.1111/bjh.15990 -
Neuropsychopharmacology Reports Sep 2019Altered trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors has been reported in postmortem studies and suggested the involvement of...
BACKGROUND AND OBJECTIVES
Altered trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors has been reported in postmortem studies and suggested the involvement of AMPA receptors in the pathophysiology underpinning addictive disorders. However, these findings seemed mixed.
METHODS
A systematic literature search was conducted, using PubMed and Embase (last search, August 2018), to identify human postmortem studies that examined the expression of proteins and mRNA of AMPA receptor subunits in patients with addictive disorders in comparison with healthy controls.
RESULTS
Twelve (18 studies) out of 954 articles were identified to be relevant. Eight studies included alcohol use disorders, and four studies included heroin/cocaine abusers. The most frequently investigated regions were the hippocampus (three studies), amygdala (three studies), and putamen (three studies). In summary, two out of the three studies showed an increase in the expression of AMPA receptors in the hippocampus, while the other study found no change. Two studies to examine the amygdala demonstrated either a decreased or no change in receptor expression or binding. Concerning putamen, two studies showed no significant change whereas an overexpression of receptors was observed in the other.
CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE
The hippocampus and amygdala may be pertinent to addictive disorders through their functions on learning and memory, whereas findings in other regions were inconsistent across the studies. Human postmortem studies are prone to degenerative changes after death. Moreover, only qualitative assessment was conducted because of the limited, heterogenous data. These limitations emphasize the need to investigate AMPA receptors in the living human brains.
Topics: Adult; Aged; Amygdala; Autopsy; Female; Hippocampus; Humans; Male; Middle Aged; Protein Binding; Protein Subunits; Putamen; RNA, Messenger; Receptors, AMPA; Substance-Related Disorders
PubMed: 31070872
DOI: 10.1002/npr2.12058 -
Brain and Behavior Jun 2019Schizophrenia is a serious mental illness with a genetic predisposition. Genome-wide association studies (GWAS) have identified the α-1C subunit of the L-type... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Schizophrenia is a serious mental illness with a genetic predisposition. Genome-wide association studies (GWAS) have identified the α-1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene as a significant risk gene for schizophrenia. However, there are inconsistent conclusions in case-control studies.
METHODS
We performed a comprehensive meta-analysis of all available samples from existing studies under four different genetic models (recessive model, dominant model, additive model and allele model) to further confirm whether CACNA1C rs1006737 is an authentic risk single nucleotide polymorphism (SNP) for schizophrenia.
RESULTS
A statistically significant difference under the four models (all p < 0.05) was observed by pooling nine Asian and European studies, including a total of 12,744 cases and 16,460 controls. For European-decent samples, a significant difference was identified between patients and controls for the four models (all p < 0.05). We observed a significant difference between patients and controls for the recessive model and allele model (GG vs. GA + AA: p < 0.00001; G vs. A: p < 0.00001) using a fixed effect model, but the dominant model (GG + GA vs. AA: OR: p = 0.15) and additive model (GG vs. AA: p = 0.11) showed no significant difference between patients and controls in the Asian samples.
CONCLUSION
Our findings provide important evidence for the establishment of CACNA1C as a susceptibility gene for schizophrenia across world populations, but its roles in the pathogenesis of schizophrenia need to be further investigated.
Topics: Alleles; Asian People; Calcium Channels, L-Type; Case-Control Studies; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Polymorphism, Single Nucleotide; Risk Factors; Schizophrenia; White People
PubMed: 31033230
DOI: 10.1002/brb3.1292 -
Frontiers in Genetics 2018This present research work reports the comparative analysis of the entire nucleotide sequence of mitochondrial genomes of and and phylogenetic analyses of their...
This present research work reports the comparative analysis of the entire nucleotide sequence of mitochondrial genomes of and and phylogenetic analyses of their protein-coding genes in order to establish their phylogenetic relationship within Cichlids. The mitochondrial genomes of and are 16,583 and 16,580 base pairs long, respectively, including 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, 22 transfer RNA genes, and one control region (D-loop) which is 888 and 887 base pairs long, respectively, showing the same gene order and identical number of gene or regions with other well-elucidated mitogenomes of Cichlids. However, with exception of cytochrome-c oxidase subunit-1 () gene, all the identified PCGs were initiated by ATG-codons. Structurally, 11 tRNA genes in species and 9 tRNA genes in species, folded into typical clover-leaf secondary structure created by the regions of self-complementarity within tRNA. All the 22 tRNA genes in both species lack variable loop. Moreover, 28 genes which include 12-protein-coding genes are encoded on the H-strand and the remaining 9 genes including one protein-coding gene are encoded on the L-strand. Thirteen sequences of concatenated mitochondrial protein-coding genes were aligned using MUSCLE, and the phylogenetic analyses performed using maximum likelihood and Bayesian inference showed that and had a broad phylogenetic relationship. These results may be a useful tool in resolving higher-level relationships in organisms and a useful dataset for studying the evolution of the Cichlidae mitochondrial genome, since Cichlids are well-known model species in the study of evolutionary biology, because of their extreme morphological, biogeographical, parental care behavior for eggs and larvae and phylogenetic diversities.
PubMed: 30894873
DOI: 10.3389/fgene.2018.00651 -
Dose-response : a Publication of... 2019Radiation therapy induces acute and chronic radiological toxicity, in particular hematological toxicity (HT). This study aimed to explore the mechanistic clue and... (Review)
Review
Analysis of mRNA Expression Patterns in Peripheral Blood Cells of 3 Patients With Cancer After the First Fraction of 2 Gy Irradiation: An Integrated Case Report and Systematic Review.
BACKGROUND
Radiation therapy induces acute and chronic radiological toxicity, in particular hematological toxicity (HT). This study aimed to explore the mechanistic clue and potential predictors at the messenger RNA (mRNA) level.
MATERIALS AND METHODS
Peripheral blood was collected from 3 patients with cervical cancer (CC), nasopharynx cancer (NC), and tongue cancer (TC) after the first 2 Gy fraction of radiotherapy (RT). High-throughput sequencing was used to assess mRNA profiles.
RESULTS
Eleven genes, such as ALAS2(5-aminolevulinate synthase), SLC4A1(solute carrier family 4 member 1), (hemoglobin subunit gamma 2), (TNF α-induced protein 3), (period circadian clock 1), (coiled-coil domain containing 136), (chromosome 9 open reading frame 84), (interleukin 1β), (FosB protooncogene), (nuclear receptor subfamily 4), (polymerase family member 15), had overlapping expression changes in all 3 cancers of which 3 (, and ) are suggested as potential predictors for the early diagnosis of HT after RT.
CONCLUSIONS
may be useful predictors of HT in patients after RT. Eleven overlapping expression mRNAs among 3 cancers might be potential predictors for early diagnosis of radiation toxicity in patients.
PubMed: 30833875
DOI: 10.1177/1559325819833474 -
Journal of Orthopaedic Surgery and... Feb 2019Recently, many studies have shown the role of hypoxia-inducible factor-1α (HIF-1α) expression in the outcome of bone tumor. However, the results remain inconclusive.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recently, many studies have shown the role of hypoxia-inducible factor-1α (HIF-1α) expression in the outcome of bone tumor. However, the results remain inconclusive. It is necessary to carry out a meta-analysis of all the current available data to clarify the relationship between HIF-1α and survival or clinicopathological features of bone tumor.
METHODS
PubMed, Cochrane Library, Web of Science, China National Knowledge Internet, and Wanfang databases were used to search the relationship between HIF-1α and bone tumor. Articles investigating clinicopathological and prognostic value of HIF-1α in bone tumor patients were enrolled in this meta-analysis. Overlapping articles, duplicate data, reviews, case reports, and letters without original data were excluded. The pooled risk ratios (RRs) and hazard ratios (HRs) were used to evaluate the clinicopathological and prognostic value of HIF-1α on bone tumor patients, respectively.
RESULTS
A total of 28 studies including 1443 patients were included in this meta-analysis, which were involved in three different types of bone tumor including 3 chondrosarcomas, 2 giant cell tumors of bone, and 23 osteosarcomas. Our results showed that high expression levels of HIF-1α were associated with poorer OS (overall survival) (HR = 2.61, 95% CI 2.11-3.23, P < 0.001) and shorter DFS (disease-free survival) (HR = 2.02, 95% CI 1.41-2.89, P < 0.001) in bone tumor. In addition, this study also analyzed the role of HIF-1α expression in clinicopathological features, which were closely related with the severity of bone tumor, including differentiation, clinical stage, metastasis, and microvessel density. Our results indicated that HIF-1α overexpression was significantly associated with differentiation (RR = 1.56, 95% CI 1.00-2.43, P = 0.049), clinical stage (RR = 1.75, 95% CI 1.25-2.45, P = 0.001), metastasis (RR = 1.78, 95% CI 1.58-2.00, P < 0.001), and microvessel density (SMD = 2.34, 95% CI 1.35-3.34, P < 0.001) of bone tumor.
CONCLUSIONS
HIF-1α overexpression indicated an unfavorable factor for OS and DFS in bone tumor, suggesting that HIF-1α may serve as a potential prognostic marker for bone tumor.
Topics: Biomarkers, Tumor; Bone Neoplasms; China; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Prognosis
PubMed: 30782196
DOI: 10.1186/s13018-019-1101-5 -
Medicine Jan 2019Parecoxib is a selective cyclooxygenase (COX)-2 inhibitor widely used as an analgesia technique in perioperative period for its potent anti-inflammatory and analgesic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Parecoxib is a selective cyclooxygenase (COX)-2 inhibitor widely used as an analgesia technique in perioperative period for its potent anti-inflammatory and analgesic effects. However, litter is known about its effect on postoperative cognitive dysfunction (POCD). The purpose of this meta-analysis of randomized controlled trials (RCTs) was to evaluate the effect of parecoxib in the treatment of postoperative cognitive dysfunction.
METHODS
We searched PubMed, Cochrane Library and Embase databases for relevant studies up to October 2017. We selected fixed-effect model for analysis of data heterogeneity. Statistical analyses were performed by using Review Manager Version 5.3 for Windows.
RESULTS
Four RCTs with 904 patients that underwent surgical operations were included. The meta-analysis demonstrated parecoxib could significantly decrease the incidence of POCD on postoperative day 1, day 3, day 5, and day 7 when compared with control treatment; IL-6 and S100β concentrations were lower up to postoperative day 2. The consumption of morphine, fentanyl and tramadol in parecoxib groups were lower than control groups.
CONCLUSION
Our meta-analysis suggested that the administration of Parecoxib was effective in treating early POCD within 7 days and reducing IL-6 and S100β concentrations within 2 days after operations. Nevertheless, our current study with some limitations such as the small sample size only provided limited quality of evidence, confirmation from further meta-analysis with large-scale, well-designed RCTs is required.
Topics: Aged; Aged, 80 and over; Cognitive Dysfunction; Cyclooxygenase 2 Inhibitors; Female; Humans; Interleukin-6; Isoxazoles; Male; Postoperative Complications; S100 Calcium Binding Protein beta Subunit; Time Factors; Treatment Outcome
PubMed: 30608392
DOI: 10.1097/MD.0000000000013812