ABSTRACT
After three publications defining an updated guidance on the diagnostic criteria for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (pwCFTR-RDs), establishing its relationship to CFTR-dysfunction and describing the individual disorders, this fourth and last paper in the series addresses some critical challenges facing health care providers and pwCFTR-RD. Topics included are: 1) benefits and obstacles to collect data from pwCFTR-RD are discussed, together with the opportunity to integrate them into established CF-registries; 2) the potential of infants designated CRMS/CFSPID to develop a CFTR-RD and how to communicate this information; 3) a description of the challenges in genetic counseling, with particular regard to phenotypic variability, unknown long-term evolution, CFTR testing and pregnancy termination 4) a proposal for the assessment of potential barriers to the implementation and dissemination of the produced documents to health care professionals involved in the care of pwCFTR-RD and a process to monitor the implementation of the CFTR-RD recommendations; 5) clinical trials investigating the efficacy of CFTR modulators in CFTR-RD and how endpoints and outcomes might be adapted to the heterogeneity of these disorders.
Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator , Cystic Fibrosis , Standard of Care , Humans , Cystic Fibrosis/therapy , Cystic Fibrosis/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Genetic Counseling , Genetic Testing/methods , Infant, NewbornABSTRACT
Deflation is an efficient numerical technique for identifying new branches of steady state solutions to nonlinear partial differential equations. Here, we demonstrate how to extend deflation to discover new periodic orbits in nonlinear dynamical lattices. We employ our extension to identify discrete breathers, which are generic exponentially localized, time-periodic solutions of such lattices. We compare different approaches to using deflation for periodic orbits, including ones based on Fourier decomposition of the solution, as well as ones based on the solution's energy density profile. We demonstrate the ability of the method to obtain a wide variety of multibreather solutions without prior knowledge about their spatial profile.
ABSTRACT
We perform a bifurcation analysis of the steady states of Rayleigh-Bénard convection with no-slip boundary conditions in two dimensions using a numerical method called deflated continuation. By combining this method with an initialization strategy based on the eigenmodes of the conducting state, we are able to discover multiple solutions to this nonlinear problem, including disconnected branches of the bifurcation diagram, without the need for any prior knowledge of the solutions. One of the disconnected branches we find contains an S-shaped curve with hysteresis, which is the origin of a flow pattern that may be related to the dynamics of flow reversals in the turbulent regime. Linear stability analysis is also performed to analyze the steady and unsteady regimes of the solutions in the parameter space and to characterise the type of instabilities.
Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis , Medical Overuse/prevention & control , Monitoring, Physiologic , Neonatal Screening , Sweat/chemistry , Cystic Fibrosis/diagnosis , Cystic Fibrosis/genetics , Cystic Fibrosis/metabolism , Diagnosis, Differential , False Positive Reactions , Family Health , Heterozygote , Humans , Infant, Newborn , International Classification of Diseases/trends , Monitoring, Physiologic/methods , Monitoring, Physiologic/psychology , Neonatal Screening/methods , Neonatal Screening/standards , Sodium Chloride/analysis , Terminology as TopicABSTRACT
The formal evaluation of scientific literature by invited referees (peer reviewers) is a relatively recent phenomenon and now is considered a cornerstone of modern science. However, its roots can be traced back to antiquity. As the speed and complexity of scientific information and publishing increases in the digital age, peer review must continue to evolve. To understand the future direction of peer review, we must understand its past. Here, we briefly explore the history of scientific peer review. This may help us predict and design appropriate peer review for the new era. This work was originally presented at the Pediatric Academic Societies Annual Meeting in Baltimore, Maryland in the Spring of 2016.
Subject(s)
Peer Review/methods , Peer Review/trends , Publications/history , Congresses as Topic , History, 15th Century , PubMed/historyABSTRACT
This study aimed to estimate the frequency of the SNPs (+45T>G and +276G>T) genotypes and investigate the association between the two SNPs and adiponectin concentration, metabolic parameters and risk of T2DM in the Bahraini population. We genotyped the two ADIPOQ SNPs in 140 unrelated T2DM patients and 66 nondiabetic controls using the polymerase chain reaction-restriction fragment length polymorphism assay. Lipid profile was measured by enzymatic methods. Total serum adiponectin levels were measured by immunoassay. T2DM patients had reduced adiponectin levels compared with controls. +45T>G was more prevalent in patients than controls. The rare G allele of +45T>G occurred more frequently than the common T allele in T2DM patients compared with controls, and was associated with lower serum adiponectin levels. There was no significant difference in allele and genotype frequencies of +276G>T between type T2DM patients and controls. There was no association between both SNPs and metabolic parameters.
Subject(s)
Adiponectin/blood , Diabetes Mellitus, Type 2/genetics , Polymorphism, Single Nucleotide/genetics , Adiponectin/genetics , Bahrain , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Risk AssessmentABSTRACT
The design of slice selective pulses for magnetic resonance imaging can be cast as an optimal control problem. The Fourier synthesis method is an existing approach to solve these optimal control problems. In this method the gradient field as well as the excitation field are switched rapidly and their amplitudes are calculated based on a Fourier series expansion. Here, we provide a novel insight into the Fourier synthesis method via representing the Bloch equation in spherical coordinates. Based on the spherical Bloch equation, we propose an alternative sequence of pulses that can be used for slice selection which is more time efficient compared to the original method. Simulation results demonstrate that while the performance of both methods is approximately the same, the required time for the proposed sequence of pulses is half of the original sequence of pulses. Furthermore, the slice selectivity of both sequences of pulses changes with radio frequency field inhomogeneities in a similar way. We also introduce a measure, referred to as gradient complexity, to compare the performance of both sequences of pulses. This measure indicates that for a desired level of uniformity in the excited slice, the gradient complexity for the proposed sequence of pulses is less than the original sequence.
Subject(s)
Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Algorithms , Computer Simulation , Fourier Analysis , Magnetics , Models, Theoretical , Radio WavesABSTRACT
Clinical heterogeneity in cystic fibrosis (CF) often causes diagnostic uncertainty in infants without symptoms and in older patients with milder phenotypes. We performed a cross-sectional evaluation of a comprehensive set of clinical and laboratory descriptors in a physician-defined cohort (N = 376; Children's Hospital of Wisconsin and the American Family Children's Hospital CF centers in Milwaukee and Madison, WI, USA) to determine the robustness of categorizing CF (N = 300), cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (N = 19), and CFTR-related (CRMS) metabolic syndrome (N = 57) according to current consensus guidelines. Outcome measures included patient demographics, clinical measures, sweat chloride levels, CFTR genotype, age at diagnosis, airway microbiology, pancreatic function, infection, and nutritional status. The CF cohort had a significantly higher median sweat chloride level (105 mmol/l) than CFTR-related disorder patients (43 mmol/l) and CFTR-related metabolic syndrome patients (35 mmol/l; p ≤ 0.001). Patient groups significantly differed in pancreatic sufficiency, immunoreactive trypsinogen levels, sweat chloride values, genotype, and positive Pseudomonas aeruginosa cultures (p ≤ 0.001). An automated classification algorithm using recursive partitioning demonstrated concordance between physician diagnoses and consensus guidelines. Our analysis suggests that integrating clinical information with sweat chloride levels, CFTR genotype, and pancreatic sufficiency provides a context for continued longitudinal monitoring of patients for personalized and effective treatment.
Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis/genetics , Genetic Testing/methods , Mutation , Neonatal Screening/methods , Adolescent , Child , Chlorides/metabolism , Cohort Studies , Cross-Sectional Studies , Cystic Fibrosis/classification , Cystic Fibrosis/diagnosis , Female , Genotype , Hospitals, Pediatric , Humans , Infant , Infant, Newborn , Male , Pancreas/physiology , Pancreas/physiopathology , Pseudomonas aeruginosa/isolation & purification , Pseudomonas aeruginosa/physiology , Sweat/chemistry , Sweat/microbiologyABSTRACT
Antithrombin III (ATIII) deficiency offers unique challenges to the anaesthetist in the perioperative setting due to the inherent thrombophilia, the anticoagulant therapies instituted and replacement of the deficient intrinsic natural anticoagulant. A particular challenge is the use of intrathecal anaesthesia, which requires a safe level of coagulation at the time of subarachnoid puncture. We describe the use of intrathecal anaesthesia on two occasions in a patient with ATIII deficiency who received human-derived ATIII concentrate as part of a perioperative anticoagulant regimen. The patient sustained no thrombotic or bleeding events. Our experience suggests that ATIII deficiency does not preclude the use of regional anaesthetic techniques so long as there is timely referral to a multidisciplinary perioperative service for anticoagulant management and that ATIII concentrate is used to ensure safe levels of ATIII throughout the perioperative period.
Subject(s)
Anesthesia, Spinal/methods , Antithrombin III Deficiency/drug therapy , Humans , Male , Middle Aged , Perioperative CareABSTRACT
BACKGROUND: Prolyl hydroxylation is a post-translational modification that affects the structure, stability and function of proteins including collagen by catalysing hydroxylation of proline to hydroxyproline through action of collagen prolyl hydroxylases3 (C-P3H) and 4 (C-P4H). Three C-P3Hs (nomenclature was amended according to approval by the HGNC symbols and names at http://www.genenames.org/ and Entrez database at http://www.ncbi.nlm.nih.gov/gene) leucineproline-enriched proteoglycan (leprecan) 1 (Lepre1), leprecan-like 1 (Leprel1), leprecan-like 2 (Leprel2) and two paralogs Cartilage-Related Protein (CRTAP) and leprecan-like 4 (Leprel4) are found in humans. The C-P4Hs are tetrameric proteins comprising a variable α subunit, encoded by the P4HA1, P4HA2 and P4HA3 genes and a constant ß subunit encoded by P4HB. METHODS: We used RT-PCR, qPCR, pyrosequencing, methylation-specific PCR, western blotting and immunohistochemistry to investigate expression and regulation of the C-P3H and C-P4H genes in B lymphomas and normal bone marrow. RESULTS: C-P3H and C-P4H are downregulated in lymphoma. Down-regulation is associated with methylation in the CpG islands and is detected in almost all common types of B-cell lymphoma, but the CpG islands are unmethylated or methylated at lower levels in DNA isolated from normal bone marrow and lymphoblastoid cell lines. Methylation of multiple C-P3H and C-P4H genes is present in some lymphomas, particularly Burkitt's lymphoma. CONCLUSIONS: Methylation of C-P3H and C-P4H is common in B lymphomas and may have utility in differentiating disease subtypes.
Subject(s)
Collagen/genetics , Lymphoma, B-Cell/genetics , Procollagen-Proline Dioxygenase/genetics , Cell Line, Tumor , Collagen/metabolism , CpG Islands/genetics , Gene Expression Regulation , Gene Silencing , Humans , Lymphoma, B-Cell/metabolism , Methylation , Procollagen-Proline Dioxygenase/metabolismABSTRACT
Invasions by alien plants are a significant threat to the biodiversity and functioning of ecosystems and the services they provide. The South African Working for Water program was established to address this problem. It needs to formulate objective and transparent priorities for clearing in the face of multiple and sometimes conflicting demands. This study used the analytic hierarchy process (a multi-criteria decision support technique) to develop and rank criteria for prioritising alien plant control operations in the Western Cape, South Africa. Stakeholder workshops were held to identify a goal and criteria and to conduct pair-wise comparisons to weight the criteria with respect to invasive alien plant control. The combination of stakeholder input (to develop decision models) with data-driven model solutions enabled us to include many alternatives (water catchments), that would otherwise not have been feasible. The most important criteria included the capacity to maintain gains made through control operations, the potential to enhance water resources and conserve biodiversity, and threats from priority invasive alien plant species. We selected spatial datasets and used them to generate weights that could be used to objectively compare alternatives with respect to agreed criteria. The analysis showed that there are many high priority catchments which are not receiving any funding and low priority catchments which are receiving substantial allocations. Clearly, there is a need for realigning priorities, including directing sufficient funds to the highest priority catchments to provide effective control. This approach provided a tractable, consensus-based solution that can be used to direct clearing operations.
Subject(s)
Ecosystem , Plants , Conservation of Natural Resources , South AfricaABSTRACT
INTRODUCTION: Preeclampsia is a disorder related to an imbalance in the angiogenesis axis manifesting as endothelial dysfunction. Animal and human studies have shown that sFLT-1 (soluble fms like tyrosine kinase 1) is increased and PlGF (placental growth factor) reduced during the disease state. There are a paucity of studies investigating the clinical significance of normalising angiogenic axis. OBJECTIVES: To use a non-human primate uteroplacental ischemic (UPI) model of preeclampsia to assess if reversing the angiogenic imbalance, by increasing circulating PlGF, is able to ameliorate the hypertension and proteinuria. METHODS: Hypertensive proteinuria was induced in a non-human primate (Papio hamadryas) by ligation of a unilateral uterine artery at 130days of an 182day pregnancy. After two weeks of UPI, PlGF was administered by subcutaneous injection (100mg/kg/day) for 5 days (n=3) or normal saline in an equivalent volume (n=3). Blood pressure was monitored via intra-arterial radiotelemetry, sFLT-1 measured via ELISA and spot urinary protein:creatinine ratios were measured to monitor proteinuria. Data was analysed using SPSS by t-tests and analysis of repeated measures. Significance was set at p<0.05 and data expressed as the mean ±SEM. RESULTS: After two weeks of UPI both groups demonstrated a significant elevation in blood pressure, proteinuria (p<0.05) and sFLT-1 (p<0.001). The systolic BP increased by 12.4±2.3mmHg and 11.7±2.9mmHg in the PlGF and control groups respectively compared to baseline (p<0.005). After PlGF administration, there was a significant reduction in blood pressure in the treated group (-5.2s±0.8mmHg) compared to the increase in BP in the control group (+6.5±3mmHg). Proteinuria also reduced in the treated group from 112±51mg/mmol to 38±12mg/mmol whilst proteinuria in the control group was unchanged. The total circulating sFLT-1 was not significantly affected by the administration of PlGF after 5days. Although this study was not designed to assess fetal safety or outcomes, there was no adverse fetal outcome attributable to the administration of the PlGF. CONCLUSION: Administration of PlGF resulted in a reduction in BP and proteinuria without significantly affecting total sFLT-1 levels. Correcting the angiogenic axis imbalance may improve the clinical parameters in a non-human primate animal model of preeclampsia.
ABSTRACT
OBJECTIVE: To determine whether the activation of innate immune responses, which can be elicited by pathogenic and endogenous triggers, is associated with the presence of Epstein-Barr virus (EBV) infection in the multiple sclerosis (MS) brain. METHODS: White matter postmortem MS (n = 10) and control tissue (n = 11) was analyzed for the expression of the proinflammatory cytokine interferon α (IFNα) by immunohistochemistry and for EBV by using the highly sensitive method of EBV-encoded RNA (EBER) in situ hybridization. RESULTS: We detected overexpression of IFNα in active areas of white matter MS lesions but not in inactive MS lesions, normal-appearing white matter, or normal brains. The presence of IFNα in macrophages and microglia (expressing human leukocyte antigen class II) is suggestive of local production as part of an acute inflammatory process. Interestingly, EBERs were also specifically detected in areas where IFNα was overexpressed in these preselected active MS lesions. EBER+ cells were also found in CNS lymphoma and stroke cases, but were absent in other control brains. We next addressed a potential mechanism, e.g., the role of EBERs in eliciting IFNα production, and transfected EBERs into human embryonic kidney (HEK) cells. We used HEK cells that stably expressed Toll-like receptor-3, which recognizes double-stranded RNAs, associated with many viral infections. EBERs elicited IFNα production in vitro. CONCLUSION: These findings suggest that latent EBV infection may contribute to the inflammatory milieu in active MS lesions by activating innate immune responses, e.g., IFNα production. Unraveling the underlying mechanisms may help in uncovering causal pathways and developing better treatment strategies for MS and other neuroinflammatory diseases.
Subject(s)
Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human/pathogenicity , Immunity, Innate , Multiple Sclerosis/immunology , Multiple Sclerosis/virology , Virus Activation/immunology , Virus Latency/immunology , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/pathology , HEK293 Cells , Herpesvirus 4, Human/immunology , Humans , Inflammation/immunology , Inflammation/pathology , Inflammation/virology , Interferon-alpha/biosynthesis , Multiple Sclerosis/pathologyABSTRACT
Most newborn screening (NBS) laboratories use second-tier molecular tests for cystic fibrosis (CF) using dried blood spots (DBS). The Centers for Disease Control and Prevention's NBS Quality Assurance Program offers proficiency testing (PT) in DBS for CF transmembrane conductance regulator (CFTR) gene mutation detection. Extensive molecular characterization on 76 CF patients, family members or screen positive newborns was performed for quality assurance. The coding, regulatory regions and portions of all introns were sequenced and large insertions/deletions were characterized as well as two intronic di-nucleotide microsatellites. For CF patient samples, at least two mutations were identified/verified and four specimens contained three likely CF-associated mutations. Thirty-four sequence variations in 152 chromosomes were identified, five of which were not previously reported. Twenty-seven of these variants were used to predict haplotypes from the major haplotype block defined by HapMap data that spans the promoter through intron 19. Chromosomes containing the F508del (p.Phe508del), G542X (p.Gly542X) and N1303K (p.Asn1303Lys) mutations shared a common haplotype subgroup, consistent with a common ancient European founder. Understanding the haplotype background of CF-associated mutations in the U.S. population provides a framework for future phenotype/genotype studies and will assist in determining a likely cis/trans phase of the mutations without need for parent studies.
Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis/genetics , DNA Mutational Analysis , Haplotypes/genetics , Adolescent , Adult , Cystic Fibrosis/diagnosis , Dried Blood Spot Testing , Female , Genetic Testing , Humans , Linkage Disequilibrium , Male , Microsatellite Repeats , Population , Reference Standards , United StatesABSTRACT
Several diseases have been clinically or genetically related to cystic fibrosis (CF), but a consensus definition is lacking. Here, we present a proposal for consensus guidelines on cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (CFTR-RDs), reached after expert discussion and two dedicated workshops. A CFTR-RD may be defined as "a clinical entity associated with CFTR dysfunction that does not fulfil diagnostic criteria for CF". The utility of sweat testing, mutation analysis, nasal potential difference, and/or intestinal current measurement for the differential diagnosis of CF and CFTR-RD is discussed. Algorithms which use genetic and functional diagnostic tests to distinguish CF and CFTR-RDs are presented. According to present knowledge, congenital bilateral absence of vas deferens (CBAVD), acute recurrent or chronic pancreatitis and disseminated bronchiectasis, all with CFTR dysfunction, are CFTR-RDs.
Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis/classification , Cystic Fibrosis/genetics , Medicine/standards , Practice Guidelines as Topic , Cystic Fibrosis/physiopathology , Europe , HumansABSTRACT
BACKGROUND: With newborn screening (NBS) for cystic fibrosis (CF), eradication of Pseudomonas aeruginosa (PA) is possible if PA detection occurs early. A serological response to infection likely precedes culture positivity in CF patients, so PA serological testing is very appealing in this population. However, controversies continue to exist about serology testing, titer cutoffs for enzyme-linked immunosorbent assay (ELISA) antibody tests, and their value in children with CF. METHODS: This longitudinal, prospective study collected respiratory secretions as oropharyngeal swabs or expectorated sputum for culture and also sera over 6 years in 69 patients diagnosed by NBS. Serology assessed PA antibody titers against cell lysate, exotoxin A, and elastase. A novel statistical approach with weighted receiver operating characteristic (ROC) curves was used to determine best antibody titer cutoff values to predict subsequent PA positive cultures. RESULTS: Using these weighted ROC curves, the order of sensitivity was found to be cell lysate, exotoxin A, and then elastase while age-specific cutoffs were better than fixed cutoffs previously used. Age-specific serological cutoffs both predict and detect PA respiratory infections with a higher sensitivity and specificity. Serological responses to the PA antigens determined that a response to cell lysate occurs significantly earlier than culture positivity. CONCLUSIONS: Age-specific serological cutoffs rather than fixed values against common PA antigens improve early PA identification in infants and young children diagnosed with NBS. Regular serological assessment with age-specific cutoffs in these children appears to be a worthy diagnostic tool.
Subject(s)
Cystic Fibrosis/complications , Neonatal Screening/methods , Pseudomonas Infections/diagnosis , Pseudomonas aeruginosa/immunology , ADP Ribose Transferases/immunology , Age Factors , Bacterial Toxins/immunology , Child , Child, Preschool , Cystic Fibrosis/diagnosis , Cystic Fibrosis/immunology , Cystic Fibrosis/microbiology , Enzyme-Linked Immunosorbent Assay/methods , Exotoxins/immunology , Female , Humans , Immunoglobulins/immunology , Infant , Infant, Newborn , Longitudinal Studies , Male , Pancreatic Elastase/immunology , Predictive Value of Tests , Prognosis , Prospective Studies , Pseudomonas Infections/complications , Pseudomonas Infections/microbiology , ROC Curve , Sensitivity and Specificity , Sputum/microbiology , Virulence Factors/immunology , Pseudomonas aeruginosa Exotoxin AABSTRACT
Research into the use of unstructured mesh methods in oceanography has been growing steadily over the past decade. The advantages of this approach for domain representation and non-uniform resolution are clear. However, a number of issues remain, in particular those related to the computational cost of models produced using unstructured mesh methods compared with their structured mesh counterparts. Mesh adaptivity represents an important means to improve the competitiveness of unstructured mesh models, where high resolution is only used when and where necessary. In this paper, an optimization-based approach to mesh adaptivity is described where emphasis is placed on capturing anisotropic solution characteristics. Comparisons are made between the results obtained with uniform isotropic resolution, isotropic adaptive resolution and fully anisotropic adaptive resolution.
ABSTRACT
Burkitt lymphoma (BL) is an aggressive B-cell malignancy with endemic, sporadic and immunodeficiency-associated variants. It has been known for many years that the fundamental transforming event in BL is the translocation of the MYC gene, and the events that bring about this translocation and those that allow cells to survive with the constitutive expression of MYC have been the subject of intense investigation. Epstein-Barr virus (EBV) infection, malaria, immunodeficiency and spontaneous, somatic mutation can all contribute to the origin and maintenance of this cancer and their mechanisms are the subject of this review.
Subject(s)
Burkitt Lymphoma/genetics , Burkitt Lymphoma/virology , Epstein-Barr Virus Infections/genetics , Genes, myc/genetics , Cell Survival , Epstein-Barr Virus Infections/complications , Humans , Malaria/complications , Translocation, GeneticABSTRACT
It is often challenging for the clinician interested in cystic fibrosis (CF) to interpret molecular genetic results, and to integrate them in the diagnostic process. The limitations of genotyping technology, the choice of mutations to be tested, and the clinical context in which the test is administered can all influence how genetic information is interpreted. This paper describes the conclusions of a consensus conference to address the use and interpretation of CF mutation analysis in clinical settings. Although the diagnosis of CF is usually straightforward, care needs to be exercised in the use and interpretation of genetic tests: genotype information is not the final arbiter of a clinical diagnosis of CF or CF transmembrane conductance regulator (CFTR) protein related disorders. The diagnosis of these conditions is primarily based on the clinical presentation, and is supported by evaluation of CFTR function (sweat testing, nasal potential difference) and genetic analysis. None of these features are sufficient on their own to make a diagnosis of CF or CFTR-related disorders. Broad genotype/phenotype associations are useful in epidemiological studies, but CFTR genotype does not accurately predict individual outcome. The use of CFTR genotype for prediction of prognosis in people with CF at the time of their diagnosis is not recommended. The importance of communication between clinicians and medical genetic laboratories is emphasized. The results of testing and their implications should be reported in a manner understandable to the clinicians caring for CF patients.
Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis/genetics , DNA Mutational Analysis , Humans , Nutritional Status/genetics , Polymorphism, Genetic , Prognosis , Protein Splicing , Quality Control , Respiratory Function Tests , Terminology as TopicABSTRACT
Burkitt lymphoma (BL) is an aggressive B-cell malignancy with endemic, sporadic and immunodeficiency-associated variants. It has been known for many years that the fundamental transforming event in BL is the translocation of the MYC gene, and the events that bring about this translocation and those that allow cells to survive with the constitutive expression of MYC have been the subject of intense investigation. Epstein-Barr virus (EBV) infection, malaria, immunodeficiency and spontaneous, somatic mutation can all contribute to the origin and maintenance of this cancer and their mechanisms are the subject of this review.