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Journal of Psychiatry & Neuroscience :... Nov 2013Endophenotypes in genetic psychiatry may increase our understanding of the molecular mechanisms underlying disease risk and its manifestations. We sought to investigate... (Review)
Review
BACKGROUND
Endophenotypes in genetic psychiatry may increase our understanding of the molecular mechanisms underlying disease risk and its manifestations. We sought to investigate the link between neuropsychological impairments and brain structural abnormalities associated with the COMT Val(158)Met polymorphism in patients with schizophrenia to improve understanding of the pathophysiology of this disorder.
METHODS
We performed a systematic review using studies identified in PubMed and MEDLINE (from the date of the first available article to July 2012). Our review examined evidence of an association between the COMT Val(158)Met polymorphism and both neuropsychological performance and brain structure in patients with psychosis, in their relatives and in healthy individuals (step 1). The review also explored whether the neuropsychological tasks and brain structures identified in step 1 met the criteria for an endophenotype (step 2). Then we evaluated evidence that the neuropsychological endophenotypes identified in step 2 are associated with the brain structure endophenotypes identified in that step (step 3). Finally, we propose a neurobiological interpretation for this evidence.
RESULTS
A poorer performance on the n-back task and the Continuous Performance Test (CPT) and smaller temporal and frontal brain areas were associated with the COMT Val allele in patients with schizophrenia and their relatives and met most of the criteria for an endophenotype. It is possible that the COMT Val(158)Met polymorphism therefore contributes to the development of these neuropsychological and brain structural endophenotypes of schizophrenia, in which the prefrontal cortex may represent the neural substrate underlying both n-back and CPT performances.
LIMITATIONS
The association between a single genetic variant and an endophenotype does not necessarily imply a causal relationship between them.
CONCLUSION
This evidence and the proposed interpretation contribute to explain, at least in part, the biological substrate of 4 important endophenotypes that characterize schizophrenia.
Topics: Atrophy; Brain; Catechol O-Methyltransferase; Endophenotypes; Frontal Lobe; Genetic Predisposition to Disease; Humans; Neuropsychological Tests; Polymorphism, Single Nucleotide; Psychomotor Performance; Schizophrenia; Schizophrenic Psychology; Temporal Lobe
PubMed: 23527885
DOI: 10.1503/jpn.120178 -
PloS One 2013To describe the frequency of MLH1 promoter methylation in colorectal cancer (CRC); to explore the associations between MLH1 promoter methylation and clinicopathological... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To describe the frequency of MLH1 promoter methylation in colorectal cancer (CRC); to explore the associations between MLH1 promoter methylation and clinicopathological and molecular factors using a systematic review and meta-analysis.
METHODS
A literature search of the PubMed and Embase databases was conducted to identify relevant articles published up to September 7, 2012 that described the frequency of MLH1 promoter methylation or its associations with clinicopathological and molecular factors in CRC. The pooled frequency, odds ratio (OR) and 95% confidence intervals (95% CI) were calculated.
RESULTS
The pooled frequency of MLH1 promoter methylation in unselected CRC was 20.3% (95% CI: 16.8-24.1%). They were 18.7% (95% CI: 14.7-23.6%) and 16.4% (95% CI: 11.9-22.0%) in sporadic and Lynch syndrome (LS) CRC, respectively. Significant associations were observed between MLH1 promoter methylation and gender (pooled OR = 1.641, 95% CI: 1.215-2.215; P = 0.001), tumor location (pooled OR = 3.804, 95% CI: 2.715-5.329; P<0.001), tumor differentiation (pooled OR = 2.131, 95% CI: 1.464-3.102; P<0.001), MSI (OR: 27.096, 95% CI: 13.717-53.526; P<0.001). Significant associations were also observed between MLH1 promoter methylation and MLH1 protein expression, BRAF mutation (OR = 14.919 (95% CI: 6.427-34.631; P<0.001) and 9.419 (95% CI: 2.613-33.953; P = 0.001), respectively).
CONCLUSION
The frequency of MLH1 promoter methylation in unselected CRC was 20.3%. They were 18.7% in sporadic CRC and 16.4% in LS CRC, respectively. MLH1 promoter methylation may be significantly associated with gender, tumor location, tumor differentiation, MSI, MLH1 protein expression, and BRAF mutation.
Topics: Adaptor Proteins, Signal Transducing; Colorectal Neoplasms; DNA Methylation; Female; Humans; Male; Microsatellite Instability; MutL Protein Homolog 1; Mutation; Neoplasm Grading; Neoplasm Staging; Nuclear Proteins; Promoter Regions, Genetic; Proto-Oncogene Proteins B-raf; Publication Bias; Sex Factors; ras Proteins
PubMed: 23555617
DOI: 10.1371/journal.pone.0059064 -
PloS One 2017Avian influenza or bird flu is a highly contagious acute viral disease that can occur in epidemics and cross-border forms in poultry and wild birds. The characteristics... (Review)
Review
Avian influenza or bird flu is a highly contagious acute viral disease that can occur in epidemics and cross-border forms in poultry and wild birds. The characteristics of avian influenza viruses (AIVs) allow the emergence of new viral variants, some with zoonotic and pandemic potential. AIVs have been identified in Latin America; however, there is a lack of understanding of these viruses at the regional level. We performed a systematic literature review on serological or molecular evidence of AIVs circulation in Latin America. Methods were designed based on the PRISMA and STROME guidelines. Only peer-reviewed studies published between 2000 to 2015 and data was analysed based on country, viral subtype, avian species, and phylogenetic origins. From 271 studies initially found only twenty-six met our inclusion criteria. Evidence of AIVs infection was found in most Latin American countries, with Mexico as the country with the largest number of conducted studies and reported cases during the period analysed, followed by Chile and Argentina. Most of the AIVs were early reported through surveillance systems and at least 14 different subtypes of influenza viruses were reported in birds, and the presence of both low (92.9%) and high (7.1%) pathogenic AIVs was shown in Latin America. Of the reported AIVs in Latin America, 43.7% belong to migratory birds, 28.1% to local wild birds, and 28.1% to poultry. The migratory bird population mainly comprises families belonging to the orders Anseriformes and Charadriformes. We highlight the importance of epidemiological surveillance systems and the possible role of different migratory birds in the transmission of AIVs within the Americas. Our findings demonstrate the limited information on AIVs in Latin America and highlight the need of more studies on AIVs at the regional level, particularly those focused on identifying the endemic subtypes in regional wild birds.
Topics: Animal Migration; Animals; Animals, Wild; Genotype; Influenza A virus; Influenza in Birds; Latin America; Poultry
PubMed: 28632771
DOI: 10.1371/journal.pone.0179573 -
Oxidative Medicine and Cellular... 2015Because the function and mechanisms of sleep are partially clear, here we applied a meta-analysis to address the issue whether sleep function includes antioxidative... (Meta-Analysis)
Meta-Analysis Review
Because the function and mechanisms of sleep are partially clear, here we applied a meta-analysis to address the issue whether sleep function includes antioxidative properties in mice and rats. Given the expansion of the knowledge in the sleep field, it is indeed ambitious to describe all mammals, or other animals, in which sleep shows an antioxidant function. However, in this paper we reviewed the current understanding from basic studies in two species to drive the hypothesis that sleep is a dynamic-resting state with antioxidative properties. We performed a systematic review of articles cited in Medline, Scopus, and Web of Science until March 2015 using the following search terms: Sleep or sleep deprivation and oxidative stress, lipid peroxidation, glutathione, nitric oxide, catalase or superoxide dismutase. We found a total of 266 studies. After inclusion and exclusion criteria, 44 articles were included, which are presented and discussed in this study. The complex relationship between sleep duration and oxidative stress is discussed. Further studies should consider molecular and genetic approaches to determine whether disrupted sleep promotes oxidative stress.
Topics: Animals; Databases, Factual; Glutathione; Lipid Peroxidation; Models, Animal; Nitric Oxide; Oxidative Stress; Oxidoreductases; Reactive Oxygen Species; Sleep Deprivation
PubMed: 25945148
DOI: 10.1155/2015/234952 -
Journal of Cancer Research and... 2020Development of human genetic and proteomic research has increased the interest in alternative head-and-neck cancer (HNC) detection methods. The aim of this article, the... (Meta-Analysis)
Meta-Analysis
Development of human genetic and proteomic research has increased the interest in alternative head-and-neck cancer (HNC) detection methods. The aim of this article, the second of two-part series, was to review the scientific literature about novel HNC genetic and proteomic biomarkers. A comprehensive review of the current literature was conducted according to the Preferred Reporting Item for Systematic Review and Meta-analyses guidelines by accessing the NCBI PubMed database. Authors conducted the search of articles in English language published from 2004 to 2015. A total of 50 relevant studies were included in the review. Thirty of them concerned proteomic and twenty genetic alterations in HNC. The present systematic review discovered 242 genes and 44 proteins associated with HNC. Due to inconsistent and sparse results, novel biomarkers cannot be firmly established. Prognostic capacity of genetic markers was not evaluated. Proteins (14-3-3γ, extracellular matrix metalloproteinase inducer, and PA28γ) were described as most valuable for prognostic observation of HNC. A strict methodological protocol for molecular studies must be established.
Topics: Biomarkers, Tumor; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Mutation; Prognosis; Proteomics
PubMed: 32719245
DOI: 10.4103/jcrt.JCRT_145_17 -
Annals of Palliative Medicine Oct 2015The morbidity and mortality associated with metastatic disease to brain make this problem a formidable challenge faced by health care providers and caregivers. The aim... (Review)
Review
BACKGROUND
The morbidity and mortality associated with metastatic disease to brain make this problem a formidable challenge faced by health care providers and caregivers. The aim of this review is to summarize management for patients with brain metastases with a particular focus on symptom management.
METHODS
A systematic review of the literature was performed. Outcomes of interest included survival, brain control (local in field and whole brain). In particular, symptom control (quality of life, neurological function and neurocognition) was examined.
RESULTS
Steroids provide relief of symptoms due to intra-cerebral edema. The steroid of choice is dexamethasone. Anti-seizure medications should not be given as prophylaxis but instead be given for treatment of seizures. Depending on patient, tumour and treatment factors, management for brain metastases range from optimal supportive care including the use of steroids, whole brain radiotherapy (WBRT), radiosurgery, surgery alone or in combination. Surgery or radiosurgery improves survival for selected patients with single brain metastasis as compared to WBRT alone. Ongoing research topics include focal postoperative cavity radiation, focal fractionated regimens, molecular targeted therapies, chemoprevention of brain metastases and neurocognitive protection (such as neuro-protective drugs and radiation techniques such as hippocampal sparing).
CONCLUSIONS
The management of brain metastases has evolved over the decades. Other than survival and brain control (local in-field and whole brain), the outcomes of quality of life and neurocognition are becoming increasingly important.
Topics: Brain Neoplasms; Breast Neoplasms; Humans; Lung Neoplasms; Melanoma; Meta-Analysis as Topic; Multicenter Studies as Topic; Palliative Care; Prognosis; Randomized Controlled Trials as Topic
PubMed: 26541403
DOI: 10.3978/j.issn.2224-5820.2015.09.01 -
Diagnostics (Basel, Switzerland) Mar 2022Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men, with an increasing incidence. Pathology diagnosis complemented with... (Review)
Review
Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men, with an increasing incidence. Pathology diagnosis complemented with prognostic and predictive biomarker information is the first step for personalized treatment. The increased diagnostic load in the pathology laboratory, combined with the reported intra- and inter-variability in the assessment of biomarkers, has prompted the quest for reliable machine-based methods to be incorporated into the routine practice. Recently, Artificial Intelligence (AI) has made significant progress in the medical field, showing potential for clinical applications. Herein, we aim to systematically review the current research on AI in CRC image analysis. In histopathology, algorithms based on Deep Learning (DL) have the potential to assist in diagnosis, predict clinically relevant molecular phenotypes and microsatellite instability, identify histological features related to prognosis and correlated to metastasis, and assess the specific components of the tumor microenvironment.
PubMed: 35453885
DOI: 10.3390/diagnostics12040837 -
Cancer May 2022H3G34-mutant diffuse hemispheric glioma (DHG) is recognized as a new, distinct entity in the latest World Health Organization classification for central nervous system... (Review)
Review
BACKGROUND
H3G34-mutant diffuse hemispheric glioma (DHG) is recognized as a new, distinct entity in the latest World Health Organization classification for central nervous system tumors and is associated with a particularly aggressive course. The authors performed a systematic review and pooled analysis to investigate the frequency of genetic events in these tumors and to determine whether these events were associated with survival trends.
METHODS
Two electronic databases were accessed to search for relevant data. Included criteria were studies that had individual patient data on H3.3 G34-mutant gliomas. To analyze the impact of genetic events on overall survival, Kaplan-Meier analysis and Cox regression models were used, and corresponding hazard ratios and 95% confidence intervals were computed.
RESULTS
In total, 20 studies with 257 H3G34-mutant DHGs were included for integrated analyses. The H3 glycine-to-valine (H3G34V) mutation showed a significantly worse prognosis than the glycine-to-arginine (H3G34R) mutation (median overall survival, 9.9 vs 14.8 months; hazard ratio, 3.040; 95% confidence interval, 1.208-7.651; P = .018), and this result remained statistically significant in the multivariate Cox regression model. Among H3G34 DHGs, TP53 mutation was the most common genetic alteration (94.9%), followed by ATRX alterations (87.5%), MGMT methylation (79.5%), and PDGFRA alterations (33.2%). The presence of PDGFRA amplification or EGFR amplification conferred poor survival. After adjusting for age and sex, these alterations were still independent indicators for adverse outcomes.
CONCLUSIONS
The authors highlight the important role of molecular stratification of H3G34 DHGs, which may help refine our understanding of the natural history of this group of malignant tumors.
Topics: Brain Neoplasms; Genotype; Glioma; Glycine; Humans; Prognosis
PubMed: 35195909
DOI: 10.1002/cncr.34156 -
Journal of Neuroinflammation Sep 2015Research focus in neuro-oncology has shifted in the last decades towards the exploration of tumor infiltration by a variety of immune cells and their products. T cells,... (Review)
Review
BACKGROUND
Research focus in neuro-oncology has shifted in the last decades towards the exploration of tumor infiltration by a variety of immune cells and their products. T cells, macrophages, B cells, and mast cells (MCs) have been identified.
METHODS
A systematic review of the literature was conducted by searching PubMed, EMBASE, Google Scholar, and Turning Research into Practice (TRIP) for the presence of MCs in meningiomas using the terms meningioma, inflammation and mast cells.
RESULTS
MCs have been detected in various tumors of the central nervous system (CNS), such as gliomas, including glioblastoma multiforme, hemangioblastomas, and meningiomas as well as metastatic brain tumors. MCs were present in as many as 90 % of all high-grade meningiomas mainly found in the perivascular areas of the tumor. A correlation between peritumoral edema and MCs was found.
INTERPRETATION
Accumulation of MCs in meningiomas could contribute to the aggressiveness of tumors and to brain inflammation that may be involved in the pathogenesis of additional disorders.
Topics: Animals; Databases, Bibliographic; Encephalitis; Humans; Mast Cells; Meningeal Neoplasms; Meningioma
PubMed: 26377554
DOI: 10.1186/s12974-015-0388-3 -
Parasites & Vectors Jan 2022Sensitive, reliable and fast diagnostic tools that are applicable in low-resource settings, at the point of care (PoC), are seen as crucial in the fight against visceral... (Meta-Analysis)
Meta-Analysis Review
Sensitive, reliable and fast diagnostic tools that are applicable in low-resource settings, at the point of care (PoC), are seen as crucial in the fight against visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL). Addressing the need for a PoC test, several diagnostic tests, including serological and molecular methods, have been developed and evaluated in the past. One promising molecular method, already implemented for diagnosis of a range of diseases, is the loop-mediated isothermal amplification (LAMP) protocol. In this systematic review and meta-analysis, using a comprehensive search strategy, we focus on studies evaluating the performance of LAMP for the diagnosis of leishmaniasis in humans and other mammals such as dogs, compared with microscopy and/or any other molecular diagnostic method. A meta-analysis, pooling sensitivity and specificity rates and calculating areas under the curve (AUCs) in summary receiver operating characteristic (SROC) plots, was conducted on datasets extracted from studies, grouped by clinical condition and sample type. We found high sensitivity and specificity for LAMP when compared with microscopy and PCR using blood samples, with pooled estimate values of > 90% for all subgroups, corresponding to calculated AUC values > 0.96, except for LAMP compared to microscopy for diagnosis of CL. However, only a limited number of studies were truly comparable. Most of the observed heterogeneity is likely based on true differences between the studies rather than sampling error only. Due to simple readout methods and low laboratory equipment requirements for sample preparation compared to other molecular methods, LAMP is a promising candidate for a molecular (near-)PoC diagnostic method for VL and CL.
Topics: Animals; Dogs; Genes, Protozoan; Humans; Leishmania; Leishmaniasis, Visceral; Molecular Diagnostic Techniques; Neglected Diseases; Nucleic Acid Amplification Techniques; Pathology, Molecular
PubMed: 35073980
DOI: 10.1186/s13071-021-05133-2