Anterior Cervical Discectomy with Arthroplasty versus Arthrodesis for Single-Level Cervical Spondylosis: A Systematic Review and Meta-Analysis

Objective

To estimate the effectiveness of anterior cervical discectomy with arthroplasty (ACDA) compared to anterior cervical discectomy with fusion (ACDF) for patient-important outcomes for single-level cervical spondylosis.

Data sources

Electronic databases (MEDLINE, EMBASE, Cochrane Register for Randomized Controlled Trials, BIOSIS and LILACS), archives of spine meetings and bibliographies of relevant articles.

Study selection

We included RCTs of ACDF versus ACDA in adult patients with single-level cervical spondylosis reporting at least one of the following outcomes: functionality, neurological success, neck pain, arm pain, quality of life, surgery for adjacent level degeneration (ALD), reoperation and dysphonia/dysphagia. We used no language restrictions. We performed title and abstract screening and full text screening independently and in duplicate.

Data synthesis

We used random-effects model to pool data using mean difference (MD) for continuous outcomes and relative risk (RR) for dichotomous outcomes. We used GRADE to evaluate the quality of evidence for each outcome.

Results

Of 2804 citations, 9 articles reporting on 9 trials (1778 participants) were eligible. ACDA is associated with a clinically significant lower incidence of neurologic failure (RR  = 0.53, 95% CI  = 0.37–0.75, p = 0.0004) and improvement in the Neck pain visual analogue scale (VAS) (MD  = 6.56, 95% CI  = 3.22–9.90, p = 0.0001; Minimal clinically important difference (MCID)  = 2.5. ACDA is associated with a statistically but not clinically significant improvement in Arm pain VAS and SF-36 physical component summary. ACDA is associated with non-statistically significant higher improvement in the Neck Disability Index Score and lower incidence of ALD requiring surgery, reoperation, and dysphagia/dysphonia.

Conclusions

There is no strong evidence to support the routine use of ACDA over ACDF in single-level cervical spondylosis. Current trials lack long-term data required to assess safety as well as surgery for ALD. We suggest that ACDA in patients with single level cervical spondylosis is an option although its benefits and indication over ACDF remain in question.     

A network synthesis model for generating protein interaction network families

In this work, we introduce a novel network synthesis model that can generate families of evolutionarily related synthetic protein-protein interaction (PPI) networks. Given an ancestral network, the proposed model generates the network family according to a hypothetical phylogenetic tree, where the descendant networks are obtained through duplication and divergence of their ancestors, followed by network growth using network evolution models. We demonstrate that this network synthesis model can effectively create synthetic networks whose internal and cross-network properties closely resemble those of real PPI networks. The proposed model can serve as an effective framework for generating comprehensive benchmark datasets that can be used for reliable performance assessment of comparative network analysis algorithms. Using this model, we constructed a large-scale network alignment benchmark, called NAPAbench, and evaluated the performance of several representative network alignment algorithms. Our analysis clearly shows the relative performance of the leading network algorithms, with their respective advantages and disadvantages. The algorithm and source code of the network synthesis model and the network alignment benchmark NAPAbench are publicly available at http://www.ece.tamu.edu/bjyoon/NAPAbench/.     

Possible transmission of human immunodeficiency virus-1 infection from an elite controller to a patient who progressed to acquired immunodeficiency syndrome: a case report

ABSTRACT: INTRODUCTION: Most individuals infected with human immunodeficiency virus-1, in the absence of antiretroviral therapy, exhibit persistent virus replication and declining CD4+ cell numbers, and progress to acquired immunodeficiency syndrome within 10 years of infection. Elite controllers are rare individuals with human immunodeficiency virus-1 infection who can maintain undetectable plasma virus levels and remain asymptomatic without antiretroviral therapy. It has been proposed that elite controllers benefit from being infected with attenuated human immunodeficiency virus-1 variants. CASE PRESENTATION: A 31-year-old African woman presented with human immunodeficiency virus-1 infection during pregnancy and was diagnosed with acquired immunodeficiency syndrome. Subsequently, her husband, a 31-year-old African man, was tested and found to be seropositive for human immunodeficiency virus-1. His plasma human immunodeficiency virus-1 ribonucleic acid level was found to be below the limit of detection of the clinical assay. CONCLUSION: This report provides evidence for the first described case of human immunodeficiency virus-1 infection possibly transmitted from an elite controller to a patient who progressed to acquired immunodeficiency syndrome. This observation strengthens the case against avirulence as a mechanism that protects elite controllers.     

Prediction of membrane protein types by means of wavelet analysis and cascaded neural networks

In this study, membrane proteins were classified using the information hidden in their sequences. It was achieved by applying the wavelet analysis to the sequences and consequently extracting several features, each of them revealing a proportion of the information content present in the sequence. The resultant features were made normalized and subsequently fed into a cascaded model developed in order to reduce the effect of the existing bias in the dataset, rising from the difference in size of the membrane protein classes. The results indicate an improvement in prediction accuracy of the model in comparison with similar works. The application of the presented model can be extended to other fields of structural biology due to its efficiency, simplicity and flexibility.     

A simple and inexpensive on-column frit fabrication method for fused-silica capillaries for increased capacity and versatility in LC-MS/MS applications

A modified sol-gel method for a one-step on-column frit preparation for fused-silica capillaries and its utility for peptide separation in LC-MS/MS is described. This method is inexpensive, reproducible, and does not require specialized equipments. Because the frit fabrication process does not damage polyimide coating, the frit-fabricated column can be tightly connected on-line for high pressure LC. These columns can replace any capillary liquid transfer tubing without any specialized connections up-stream of a spray tip column. Therefore multiple columns with different phases can be connected in series for one- or multiple-dimensional chromatography.     

Regulation of I(kappa)B kinase complex by phosphorylation of (gamma)-binding domain of I(kappa)B kinase (beta) by Polo-like kinase 1

IkappaB kinase (IKK) complex is a key regulator of NF-kappaB pathways. Signal-induced interaction of the IKKgamma (NEMO) subunit with the C-terminal IKKgamma/NEMO-binding domain (gammaBD) of IKKbeta is an essential interaction for IKK regulation. Underlying regulatory mechanism(s) of this interaction are not known. Phosphorylation of gammaBD has been suggested to play a regulatory role for IKK activation. However, a kinase that phosphorylates gammaBD has not been identified. In this study, we used a C-terminal fragment of IKKbeta as substrate and purified Polo-like kinase 1 (Plk1) from HeLa cell extracts by standard chromatography as a gammaBD kinase. Plk1 phosphorylates serines 733, 740, and 750 in the gammaBD of IKKbeta in vitro. Phosphorylating gammaBD with Plk1 decreased its affinity for IKKgamma in pulldown assay. We generated phosphoantibodies against serine 740 and showed that gammaBD is phosphorylated in vivo. Expressing a constitutively active Plk1 in mammalian cells reduced tumor necrosis factor (TNF)-induced IKK activation, resulting in decreased phosphorylation of endogenous IkappaBalpha and reduced NF-kappaB activation. To activate endogenous Plk1, cells were treated with nocodazole, which reduced TNF-induced IKK activation, and increased the phosphorylation of gammaBD. Knocking down Plk1 in mammalian cells restored TNF-induced IKK activation in nocodazole-treated cells. Activation of Plk1 inhibited TNF-induced expression of cyclin D1. In cells in which Plk1 was knocked down, TNFalpha increased expression of cyclin D1 and the proportion of cells in the S phase of the cell cycle. Taken together, this study shows that phosphorylation regulates the interaction of gammaBD of IKKbeta with IKKgamma and therefore plays a critical role for IKK activation. Moreover, we identify Plk1 as a gammaBD kinase, which negatively regulates TNF-induced IKK activation and cyclin D1 expression, thereby affecting cell cycle regulation. Untimely activation of cyclin D1 by TNFalpha can provide a potential mechanism for an involvement of TNFalpha in inflammation-induced cancer.     

Mendelian randomization: can genetic epidemiology help redress the failures of observational epidemiology?

Establishing causal relationships between environmental exposures and common diseases is beset with problems of unresolved confounding, reverse causation and selection bias that may result in spurious inferences. Mendelian randomization, in which a functional genetic variant acts as a proxy for an environmental exposure, provides a means of overcoming these problems as the inheritance of genetic variants is independent of—that is randomized with respect to—the inheritance of other traits, according to Mendel’s law of independent assortment. Examples drawn from exposures and outcomes as diverse as milk and osteoporosis, alcohol and coronary heart disease, sheep dip and farm workers’ compensation neurosis, folate and neural tube defects are used to illustrate the applications of Mendelian randomization approaches in assessing potential environmental causes of disease. As with all genetic epidemiology studies there are problems associated with the need for large sample sizes, the non-replication of findings, and the lack of relevant functional genetic variants. In addition to these problems, Mendelian randomization findings may be confounded by other genetic variants in linkage disequilibrium with the variant under study, or by population stratification. Furthermore, pleiotropy of effect of a genetic variant may result in null associations, as may canalisation of genetic effects. If correctly conducted and carefully interpreted, Mendelian randomization studies can provide useful evidence to support or reject causal hypotheses linking environmental exposures to common diseases.     

Birth weight of offspring and insulin resistance in late adulthood: cross sectional survey

ObjectiveTo investigate the association between birth weight of offspring and mothers'' insulin resistance in late adulthood.DesignCross sectional survey.SettingGeneral practitioner''s surgeries in 23 towns in Great Britain.Participants4286 women aged 60-79 years.ResultsBirth weight of offspring was inversely related to maternal insulin resistance in late adulthood. For each 1 kg higher birth weight of offspring, women had a 15% reduction in the odds of being in the fourth with highest insulin resistance, compared to other fourths (odds ratio 0.85; 95% confidence interval 0.71 to 1.00). This increased to 27% (0.73; 0.60 to 0.90) after adjusting data for potential confounders. A U shaped relation between birth weight of offspring and diabetes in older age was found; women with the lightest and heaviest offspring had the highest prevalence of diabetes.ConclusionsBirth weight of offspring is inversely related to the mother''s insulin resistance in late adulthood, despite the association of glucose intolerance during pregnancy with heavier offspring at birth. Common genetic factors contribute to the relation between birth weight and risk of cardiovascular disease and diabetes in adults.

What is already known on this topic

Small birth weight is related to increased risk of cardiovascular disease and diabetes in adulthood; the underlying mechanisms are unclearSmall birth weight of offspring is related to parental cardiovascular disease, suggesting that common genetic factors affect birth weight and the risk of disease in adulthoodGenetic factors associated with the metabolism of insulin are plausible in linking birth weight and cardiovascular disease (the fetal insulin hypothesis)

What this study adds

Birth weight of offspring is inversely related to maternal insulin resistance in older ageGenetic factors related to both insulin resistance and birth weight explain at least part of the association between birth weight and risk of cardiovascular disease and diabetes in adulthood     

Neurotransmitter Specific,Cellular-Resolution Functional Brain Mapping Using Receptor Coated Nanoparticles: Assessment of the Possibility

Receptor coated resonant nanoparticles and quantum dots are proposed to provide a cellular-level resolution image of neural activities inside the brain. The functionalized nanoparticles and quantum dots in this approach will selectively bind to different neurotransmitters in the extra-synaptic regions of neurons. This allows us to detect neural activities in real time by monitoring the nanoparticles and quantum dots optically. Gold nanoparticles (GNPs) with two different geometries (sphere and rod) and quantum dots (QDs) with different sizes were studied along with three different neurotransmitters: dopamine, gamma-Aminobutyric acid (GABA), and glycine. The absorption/emission spectra of GNPs and QDs before and after binding of neurotransmitters and their corresponding receptors are reported. The results using QDs and nanorods with diameter 25nm and aspect rations larger than three were promising for the development of the proposed functional brain mapping approach.