23 research outputs found
A systematic review of evidence on malignant spinal metastases : natural history and technologies for identifying patients at high risk of vertebral fracture and spinal cord compression
No full textBackground: Spinal metastases can lead to significant morbidity and reduction in quality of life due to spinal cord compression (SCC). Between 5% and 20% of patients with spinal metastases develop metastatic spinal cord compression during the course of their disease. An early study estimated average survival for patients with SCC to be between 3 and 7 months, with a 36% probability of survival to 12 months. An understanding of the natural history and early diagnosis of spinal metastases and prediction of collapse of the metastatic vertebrae are important.
Objective: To undertake a systematic review to examine the natural history of metastatic spinal lesions and to identify patients at high risk of vertebral fracture and SCC.
Data sources: The search strategy covered the concepts of metastasis, the spine and adults. Searches were undertaken from inception to June 2011 in 13 electronic databases [MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations; EMBASE; Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials (CENTRAL); Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED), HTA databases (NHS Centre for Reviews and Dissemination); Science Citation Index and Conference Proceedings (Web of Science); UK Clinical Research Network (UKCRN) Portfolio Database; Current Controlled Trials; ClinicalTrials.gov].
Review methods: Titles and abstracts of retrieved studies were assessed by two reviewers independently. Disagreement was resolved by consensus agreement. Full data were extracted independently by one reviewer. All included studies were reviewed by a second researcher with disagreements resolved by discussion. A quality assessment instrument was used to assess bias in six domains: study population, attrition, prognostic factor measurement, outcome measurement, confounding measurement and account, and analysis. Data were tabulated and discussed in a narrative review. Each tumour type was looked at separately.
Results: In all, 2425 potentially relevant articles were identified, of which 31 met the inclusion criteria. No study examined natural history alone. Seventeen studies reported retrospective data, 10 were prospective studies, and three were other study designs. There was one systematic review. There were no randomised controlled trials (RCTs). Approximately 5782 participants were included. Sample sizes ranged from 41 to 859. The age of participants ranged between 7 and 92 years. Types of cancers reported on were lung alone (n= 3), prostate alone (n= 6), breast alone (n= 7), mixed cancers (n= 13) and unclear (n= 1). A total of 93 prognostic factors were identified as potentially significant in predicting risk of SCC or collapse. Overall findings indicated that the more spinal metastases present and the longer a patient was at risk, the greater the reported likelihood of development of SCC and collapse. There was an increased risk of developing SCC if a cancer had already spread to the bones. In the prostate cancer studies, tumour grade, metastatic load and time on hormone therapy were associated with increased risk of SCC. In one study, risk of SCC before death was 24%, and 2.37 times greater with a Gleason score 7 than with a score of < 7 (p= 0.003). Other research found that patients with six or more bone lesions were at greater risk of SCC than those with fewer than six lesions [odds ratio (OR) 2.9, 95% confidence interval (CI) 1.012 to 8.35, p= 0.047]. For breast cancer patients who received a computerised tomography (CT) scan for suspected SCC, multiple logistic regression in one study identified four independent variables predictive of a positive test: bone metastases 2 years (OR 3.0 95% CI 1.2 to 7.6; p= 0.02); metastatic disease at initial diagnosis (OR 3.4, 95% CI 1.0 to 11.4; p= 0.05); objective weakness (OR 3.8, 95% CI 1.5 to 9.5; p= 0.005); and vertebral compression fracture on spine radiograph (OR 2.6, 95% CI 1.0 to 6.5; p= 0.05). A further study on mixed cancers, among patients who received surgery for SCC, reported that vertebral body compression fractures were associated with presurgery chemotherapy (OR 2.283, 95% CI 1.064 to 4.898; p= 0.03), cancer type [primary breast cancer (OR 4.179, 95% CI 1.457 to 11.983; p= 0.008)], thoracic involvement (OR 3.505, 95% CI 1.343 to 9.143; p= 0.01) and anterior cord compression (OR 3.213, 95% CI 1.416 to 7.293; p= 0.005).
Limitations: Many of the included studies provided limited information about patient populations and selection criteria and they varied in methodological quality, rigour and transparency. Several studies identified type of cancer (e.g. breast, lung or prostate cancer) as a significant factor in predicting SCC, but it remains difficult to determine the risk differential partly because of residual bias. Consideration of quantitative results from the studies does not easily allow generation of a coherent numerical summary, studies were heterogeneous especially with regard to population, results were not consistent between studies, and study results almost universally lacked corroboration from other independent studies.
Conclusion: No studies were found which examined natural history. Overall burden of metastatic disease, confirmed metastatic bone involvement and immediate symptomatology suggestive of spinal column involvement are already well known as factors for metastatic SCC, vertebral collapse or progression of vertebral collapse. Although we identified a large number of additional possible prognostic factors, those which currently offer the most potential are unclear. Current clinical consensus favours magnetic resonance imaging and CT imaging modalities for the investigation of SCC and vertebral fracture. Future research should concentrate on: (1) prospective randomised designs to establish clinical and quality-of-life outcomes and cost-effectiveness of identification and treatment of patients at high risk of vertebral collapse and SCC; (2) Service Delivery and Organisation research on magnetic resonance imaging (MRI) scans and scanning (in tandem with research studies on use of MRI to monitor progression) in order to understand best methods for maximising use of MRI scanners; and (3) investigation of prognostic algorithms to calculate probability of a specified event using high-quality prospective studies, involving defined populations, randomly selected and clearly identified samples, and with blinding of investigators
Vanadium pentoxide nanoparticle mediated perturbations in cellular redox balance and the paradigm of autophagy to apoptosis
No full textThe redox-active transition metals such as copper, iron, chromium, vanadium, and silica are known for its ROS generation via mechanisms such as Haber-Weiss and Fenton-type reactions. Nanoparticles of these metals induce oxidative stress due to acellular factors owing to their small size and more reactive surface area, leading to various cellular responses. The intrinsic enzyme-like activity of nano vanadium has fascinated the scientific community. However, information concerning their cellular uptake and time-dependent induced effects on their cellular organelles and biological activity is lacking. This comprehensive study focuses on understanding the precise molecular interactions of vanadium pentoxide nanoparticles (VnNp) and evaluate their specific “nano” induced effects on MDA-MB-231 cancer cells. Understanding the mechanism behind NP-induced ROS generation could help design a model for selective NP induced toxicity, useful for cancer management. The study demonstrated the intracellular persistence of VnNp and insights into its molecular interactions with various organelles and its overall effects at the cellular level. Where triple-negative breast cancer MDA-MB-231 cells resulted in 59.6% cell death towards 48 h of treatment and the normal fibroblast cells showed only 15.4% cell death, indicating an inherent anticancer property of VnNp. It acts as an initial reactive oxygen species quencher, by serving itself as an antioxidant, while; it was also found to alter the cellular antioxidant system with prolonged incubation. The VnNp accumulated explicitly in the lysosomes and mitochondria and modulated various cellular processes including impaired lysosomal function, mitochondrial damage, and autophagy. At more extended time points, VnNp influenced cell cycle arrest, inhibited cell migration, and potentiated the onset of apoptosis.
Results are indicative of the fact that VnNp selectively induced breast cancer cell death and hence could be developed as a future drug molecule for breast cancer management. This could override the most crucial challenge of chemo-resistance that still remain as the main hurdle to cancer therapy
Down-regulation of serotonergic genes expression in the raphe nuclei of midbrain under chronic social defeat stress in male mice
No full textBackground: 
There is ample experimental evidence supporting the hypothesis that the brain serotonergic system is involved in the control of chronic social defeat stress (CSDS), depression and anxiety. The study aimed to analyze mRNA levels of the serotonergic genes in the raphe nuclei of the midbrain that may be associated with chronic social defeats consistently shown by male mice in special experimental settings. 

Methodology/Principal Findings: 
The serotonergic genes were the Tph2, Sert, Maoa and Htr1a. The Bdnf, Creb, Cphn, Gapdh, Hprt, B2M, 18S and Actb genes were also studied. The experimental groups were composed of male mice with experience of defeats in 21 daily encounters and male mice with the same track record of defeats followed by a no-defeat period without agonistic interactions (relative rest for 14 days). It has been shown that mRNA levels of the Tph2, Maoa, Sert, Htr1a, Bdnf and Creb genes in the raphe nuclei of defeated mice are decreased as compared with the controls. Under CSDS the Cphn, Gapdh, Hprt, B2M, 18S, Actb genes are also down-regulated. The expression of the serotonergic genes as well as the Cphn and Creb genes is not restored to the control level after the 2 weeks of relative rest. mRNA levels of other genes are not recovered to the control levels, although some up-regulation was observed in rested losers. Significant positive correlations were found between the total time of avoidance behavior demonstrated by the 21-day defeaters in agonistic interactions and Sert, Maoa, Bdnf, Gapdh and 18S mRNA levels. 

Conclusions: 
CSDS experience inducing the development of mixed anxious/depression-like state in male mice down-regulates the serotonergic genes expression associated with the synthesis, inactivation and reception of serotonin. The Bdnf and Creb genes as well as the cell and metabolic Cphn, Gapdh, Hprt, B2M, Actb and 18S genes in the midbrain raphe nuclei are also down-regulated under CSDS. Period of relative rest is not enough for most genes to recover expression to the control levels
Polyunsaturated fatty acid-derived lipid mediators and T cell function
No full textCopyright © 2014 Nicolaou, Mauro, Urquhart and Marelli-Berg . This is an open-
access article distributed under the terms of the
Creative Commons Attribution License
(CC BY)
. The use, distribution or reproduction in other forums is permitted, provided
the original author(s) or licensor are credited and that the original publication in this
journal is cited, in accordance with accepted academic practice. No use, distribution or
reproduction is permitted which does not comply with these terms
Probiotics and prebiotics for severe acute malnutrition (PRONUT study): a double-blind efficacy randomised controlled trial in Malawi.
No full textBACKGROUND: Severe acute malnutrition affects 13 million children worldwide and causes 1-2 million deaths every year. Our aim was to assess the clinical and nutritional efficacy of a probiotic and prebiotic functional food for the treatment of severe acute malnutrition in a HIV-prevalent setting. METHODS: We recruited 795 Malawian children (age range 5 to 168 months [median 22, IQR 15 to 32]) from July 12, 2006, to March 7, 2007, into a double-blind, randomised, placebo-controlled efficacy trial. For generalisability, all admissions for severe acute malnutrition treatment were eligible for recruitment. After stabilisation with milk feeds, children were randomly assigned to ready-to-use therapeutic food either with (n=399) or without (n=396) Synbiotic2000 Forte. Average prescribed Synbiotic dose was 10(10) colony-forming units or more of lactic acid bacteria per day for the duration of treatment (median 33 days). Primary outcome was nutritional cure (weight-for-height >80% of National Center for Health Statistics median on two consecutive outpatient visits). Secondary outcomes included death, weight gain, time to cure, and prevalence of clinical symptoms (diarrhoea, fever, and respiratory problems). Analysis was on an intention-to-treat basis. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN19364765. FINDINGS: Nutritional cure was similar in both Synbiotic and control groups (53.9% [215 of 399] and 51.3% [203 of 396]; p=0.40). Secondary outcomes were also similar between groups. HIV seropositivity was associated with worse outcomes overall, but did not modify or confound the negative results. Subgroup analyses showed possible trends towards reduced outpatient mortality in the Synbiotic group (p=0.06). INTERPRETATION: In Malawi, Synbiotic2000 Forte did not improve severe acute malnutrition outcomes. The observation of reduced outpatient mortality might be caused by bias, confounding, or chance, but is biologically plausible, has potential for public health impact, and should be explored in future studies. FUNDING: Department for International Development (DfID)
Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.
No full textImmunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events
CHARACTERISING FACTORS PREDICTIVE OF INFECTION IN SEVERELY INJURED PATIENTS
No full textInfection after trauma complicates the patients clinical course. Infection leads to longer critical care and hospital stays, has been associated with increased mortality rates and places considerable cost pressures on health economies. The predictors of infection after severe injury are not known, and the effects on outcomes other than mortality are under-reported.
The overall objective of this research was to characterise factors predictive of infection in severely injured patients admitted to critical care. A prospective cohort study of 271 patients investigated admission factors predictive of the development of infection. A second study of 280 patients evaluated post-injury immune cell changes and the association with infection. Thirdly the relationship between early coagulopathy and infections was investigated in 158 patients. Finally a study of 385 patients examined the use of Tranexamic Acid (TXA) and its association with infection and other outcomes.
Infection was a significant burden for severely injured patients. Admission hypoperfusion was the only early characteristic associated with the development of infection, and a dose dependent relationship was observed between severity of shock and increased percentage of infection (p<0.01). Lymphopenia prolonged to day four post injury was strongly predictive infection (OR 0.10, CI 0.02-0.48, p<0.01). At 24 hours, the anticoagulant Protein C was lower in those with infection (Infection: 70.2 iu/dL vs. No infection: 83.3 iu/dL p=0.02), and increased fibrinolysis was also associated with infectious complications (Infection: 6156 μg/L vs. No infection: 3324 μg/L p=0.03). There was a trend to a beneficial relationship between TXA and infection, and it was independently associated with reduced organ failure (OR 0.27, CI: 0.10 – 0.73, p=0.01) and mortality (OR 0.16 CI 0.03 - 0.86, p=0.03).
In severely injured patients, admission shock, prolonged lymphopenia and early coagulation dysfunction post severe injury were independent predictors of infection. Timely modulation of these responses after trauma may help to reduce the burden of infection
Avaliação do potencial efeito protetor do probucol em modelos experimentais da doença de Huntington
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas. Programa de Pós-Graduação em BioquímicaA doença de Huntington (DH) é uma patologia neurodegenerativa, autossômica dominante caracterizada por sintomas atribuídos à morte de neurônios estriatais e corticais no cérebro. O mecanismo de neurodegeneração na DH parece estar relacionado com excitotoxicidade, disfunção mitocondrial e estresse oxidativo. O probucol (PB) é um composto fenólico antilipêmico, que apresenta propriedades anti-inflamatória e antioxidante em diferentes modelos experimentais de toxicidade/patologia. O objetivo deste estudo foi investigar o possível efeito protetor do PB sobre a neurotoxicidade e estresse oxidativo em modelos experimentais de DH in vitro e in vivo. Inicialmente, foi avaliada a relação entre prejuízo no metabolismo energético, excitotoxicidade e estresse oxidativo em fatias de estriado de ratos expostas ao ácido quinolínico (AQ), ácido 3-nitropropiônico (3-NP) e ao modelo combinado (AQ + 3-NP). Os dados sugerem que os modelos utilizados podem gerar um padrão complexo de dano, que envolve comprometimento metabólico, formação de espécies reativas de oxigênio (ERO) e estresse oxidativo. O PB preveniu o estresse oxidativo nas três condições experimentais e foi capaz de proteger contra disfunção mitocondrial induzida pelo AQ e AQ + 3-NP. Além disso, o potencial efeito protetor do probucol foi avaliado sobre a neurotoxicidade do 3-NP em ratos. O pré-tratamento com probucol (por 60 dias) aumentou a atividade da glutationa peroxidase (GPx) no estriado e no córtex e preveniu o prejuízo motor e o estresse oxidativo induzido pelo 3-NP em ratos. O efeito do PB sobre a GPx e suas propriedades antioxidantes estão provavelmente associados ao seu efeito benéfico neste modelo. Também foi verificado o possível efeito protetor do succinobucol, um análogo do PB, sobre a toxicidade induzida pelo 3-NP em preparações mitocondriais de cérebro de ratos in vitro. O probucol e o succinobucol preveniram o estresse oxidativo induzido pelo 3-NP, mas apenas o succinobucol foi capaz de prevenir a disfunção mitocondrial induzida pela toxina. Juntos este resultados sugerem um novo papel para o probucol e seu análogo succinobucol como potenciais agentes neuroprotetores em modelos de DH
Measuring (KSK +/-)-K-0 interactions using Pb-Pb collisions at root S-NN=2.76 TeV
No full textWe present the first ever measurements of femtoscopic correlations between the K-S(0) and K-+/- particles. The analysis was performed on the data from Pb-Pb collisions at root S-NN = 2.76 TeV measured by the ALICE experiment. The observed femtoscopic correlations are consistent with final-state interactions proceeding via the a(0)(980) resonance. The extracted kaon source radius and correlation strength parameters for (KSK-)-K-0 are found to be equal within the experimental uncertainties to those for (KSK+)-K-0. Comparing the results of the present study with those from published identical-kaon femtoscopic studies by ALICE, mass and coupling parameters for the a(0) resonance are tested. Our results are also compatible with the interpretation of the a(0) having a tetraquark structure instead of that of a diquark. (c) 2017 The Author. Published by Elsevier B.V
Measurement of the production of high-p(T) electrons from heavy-flavour hadron decays in Pb-Pb collisions at root s(NN)=2.76 TeV
No full textElectrons from heavy-flavour hadron decays (charm and beauty) were measured with the ALICE detector in Pb-Pb collisions at a centre-of-mass of energy root s(NN) = 2.76 TeV. The transverse momentum (pT) differential production yields at mid-rapidity were used to calculate the nuclear modification factor R-AA in the interval 3 < p(T) < 18 GeV/c. The R-AA shows a strong suppression compared to binary scaling of pp collisions at the same energy (up to a factor of 4) in the 10% most central Pb-Pb collisions. There is a centrality trend of suppression, and a weaker suppression (down to a factor of 2) in semi-peripheral (50-80%) collisions is observed. The suppression of electrons in this broad p(T) interval indicates that both charm and beauty quarks lose energy when they traverse the hot medium formed in Pb-Pb collisions at LHC. (C) 2017 The Author. Published by Elsevier B.V
