Posterior Lumbar Interbody Fusion via a Unilateral Approach

This study sought to determine the outcomes of posterior lumbar interbody fusion (PLIF), via a unilateral approach, in selected patients who presented with unilateral leg pain and segmental instability of the lumbar spine. Patients with a single level of a herniated disc disease in the lumbar spine, unilateral leg pain, chronic disabling lower back pain (LBP), and a failed conservative treatment, were considered for the procedure. A total of 41 patients underwent a single-level PLIF using two PEEK™ (Poly-Ether-Ether-Ketone) cages filled with iliac bone, via a unilateral approach. The patients comprised 21 women and 20 men with a mean age of 41 years (range: 22 to 63 years). Two cages were inserted using a unilateral medial facetectomy and a partial hemilaminectomy. At follow-up, the outcomes were assessed using the Prolo Scale. The success of the fusion was determined by dynamic lumbar radiography and/or computerized tomography scanning. All the patients safely underwent surgery without severe complications. During a mean follow-up period of 26 months, 1 patient underwent percutaneous pedicle screw fixation due to persistent LBP. A posterior displacement of the cage was found in one patient. At the last follow up, 90% of the patients demonstrated satisfactory results. An osseous fusion was present in 85% of the patients. A PLIF, via a unilateral approach, enables a solid union with satisfactory clinical results. This preserves part of the posterior elements of the lumbar spine in selected patients with single level instability and unilateral leg pain

CmeABC multidrug efflux pump contributes to antibiotic resistance and promotes 'Campylobacter jejuni' survival and multiplication in 'Acanthamoeba polyphaga'

Campylobacter jejuni is a foodborne pathogen recognized as the leading cause of human bacterial gastroenteritis. The wide use of antibiotics in medicine and in animal husbandry has led to an increased incidence of antibiotic resistance in Campylobacter In addition to a role in multidrug resistance, the Campylobacter CmeABC RND-type efflux pump, which is associated with multidrug resistance (MDR), may also be involved in virulence. As a vehicle of pathogenic microorganisms, the protozoan Acanthamoeba is a good model for the investigation of bacterial survival in the environment and molecular mechanisms of pathogenicity. The interaction between C. jejuni 81-176 and A. polyphaga was investigated in this study by using a modified gentamicin protection assay. In addition, a possible role for the CmeABC MDR pump in this interaction was explored. Here we report that this MDR pump is beneficial for the intracellular survival and multiplication of C. jejuni in A. polyphaga, but is dispensable for biofilm formation and motility.Importance The endosymbiotic relationship between amoebae and microbial pathogens may contribute to persistence and spreading of the latter in the environment, which has significant implications to human health. In this study we found that Campylobacter jejuni was able to survive and multiply inside Acanthamoeba. polyphaga Since these microorganisms can co-exist in the same environment (e.g. in poultry farms), the latter may increase the risk of infection with Campylobacter Our data suggests that, in addition to its role in antibiotic resistance, the CmeABC MDR efflux pump also plays a role in bacterial survival within amoebae. Furthermore, we demonstrated a synergistic effect of the CmeABC MDR efflux pump and TetO on bacterial resistance to tetracycline. Due to its role both in antibiotic resistance and virulence of C. jejuni, the CmeABC MDR efflux pump could be considered as a good target for the development of antibacterial drugs against this pathogen

Patterns of variability in Be/X-ray pulsars during giant outbursts

The discovery of source states in the X-ray emission of black-hole binaries and neutron-star low-mass X-ray binaries constituted a major step forward in the understanding of the physics of accretion onto compact objects. While there are numerous studies on the correlated timing and spectral variability of these systems, very little work has been done on high-mass X-ray binaries, the third major type of X-ray binaries. The main goal of this work is to investigate whether Be accreting X-ray pulsars display source states and characterise those states through their spectral and timing properties. We have made a systematic study of the power spectra, energy spectra and X-ray hardness-intensity diagrams of nine Be/X-ray pulsars. The evolution of the timing and spectral parameters were monitored through changes over two orders of magnitude in luminosity. We find that Be/X-ray pulsars trace two different branches in the hardness-intensity diagram: the horizontal branch corresponds to a low-intensity state of the source and it is characterised by fast colour and spectral changes and high X-ray variability. The diagonal branch is a high-intensity state that emerges when the X-ray luminosity exceeds a critical limit. The photon index anticorrelates with X-ray flux in the horizontal branch but correlates with it in the diagonal branch. The correlation between QPO frequency and X-ray flux reported in some pulsars is also observed if the peak frequency of the broad-band noise that accounts for the aperiodic variability is used. The two branches may reflect two different accretion modes, depending on whether the luminosity of the source is above or below a critical value. This critical luminosity is mainly determined by the magnetic field strength, hence it differs for different sources.Comment: Complete missing words in title. Proof corrections adde

Proconvertase Furin Is Downregulated in Postural Orthostatic Tachycardia Syndrome.

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a cardiovascular autonomic disorder characterized by orthostatic intolerance and high prevalence among young women. The etiology of POTS is uncertain, though autoimmunity and inflammation may play an important role. We aimed to identify novel inflammatory biomarkers associated with POTS. Methods and Results: In the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort, we identified 396 patients (age range, 15-50 years) with either POTS (n = 113) or normal haemodynamic response during passive head-up-tilt test (n = 283). Blood samples were analyzed using antibody-based Proximity Extension Assay technique simultaneously measuring 57 inflammatory protein biomarkers. The discovery algorithm was a sequential two-step process of biomarker signature identification by supervised, multivariate, principal component analysis and verification by univariate ANOVA with Bonferroni correction. POTS patients were younger (26 vs. 31 years; p < 0.001) and there was no significant difference in sex distribution (74% vs. 67% females, p = 0.24). PCA and Bonferroni-adjusted ANOVA identified proconvertase furin as the most robust biomarker signature for POTS. Plasma level of proconvertase furin was lower (6.38 vs. 6.58 of normalized protein expression units (NPX); p < 0.001 in POTS, compared with the reference group. Proconvertase furin met Bonferroni-adjusted significance criteria in both uni- and multivariable regression analyses. Conclusion: Patients with POTS have lower plasma level of proconvertase furin compared with individuals with normal postural hemodynamic response. This finding suggests the presence of a specific autoimmune trait with disruption of immune peripheral tolerance in this hitherto unexplained condition. Further studies are needed for external validation of our results.This study was supported by grants from the Swedish Heart-Lung Foundation, the Swedish Heart and Lung Association, the Medical Faculty of Lund University, ALF funds, Skne University Hospital Funds, Crafoord Foundation, Ernhold Lundstrms Research Foundation, Region Skåne, Hulda and Conrad Mossfelt Foundation, and Anna-Lisa and Sven Eric Lundgrens Foundation for Medical Research

Tuberculosis diagnostics and biomarkers: needs, challenges, recent advances, and opportunities

Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostics

Predictive Models for Assessing Patients’ Response to Treatment in Metastatic Prostate Cancer : A Systematic Review

Peer reviewe

A change in the optical polarization associated with a gamma-ray flare in the blazar 3C 279

It is widely accepted that strong and variable radiation detected over all accessible energy bands in a number of active galaxies arises from a relativistic, Doppler-boosted jet pointing close to our line of sight. The size of the emitting zone and the location of this region relative to the central supermassive black hole are, however, poorly known, with estimates ranging from light-hours to a light-year or more. Here we report the coincidence of a gamma-ray flare with a dramatic change of optical polarization angle. This provides evidence for co-spatiality of optical and gamma-ray emission regions and indicates a highly ordered jet magnetic field. The results also require a non-axisymmetric structure of the emission zone, implying a curved trajectory for the emitting material within the jet, with the dissipation region located at a considerable distance from the black hole, at about 10^5 gravitational radii.Comment: Published in Nature issued on 18 February 2010. Corresponding authors: Masaaki Hayashida and Greg Madejsk

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection

The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown. Here we show that anatomically distinct human granulomas contain clonally expanded CD8+ T cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific T cells with extreme TCRß bias. Using a retro genic model of TB10.44-11-specific CD8+ Tcells, we show that TCR dominance can arise because of competition between clonotypes driven by differences in affinity. Finally, we demonstrate that TB10.4-specific CD8+ T cells mediate protection against tuberculosis, which requires interferon-? production and TAP1-dependent antigen presentation in vivo. Our study of how immunodominance, biased TCR repertoires, and protection are inter-related, provides a new way to measure the quality of T cell immunity, which if applied to vaccine evaluation, could enhance our understanding of how to elicit protective T cell immunity.This work was supported by the Portuguese Foundation for Science and Technology individual fellowship (CNA) www.fct.pt, a National Institutes of Health Grant R01 AI106725 (SMB) www.nih.gov, and a Center for AIDS Research Grant P30 AI 060354 (SMB) www.nih.gov. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript