To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The association of leishmaniasis and malignancies in human and animal models has been highlighted in recent years. The misdiagnosis of coexistence of leishmaniasis and cancer and the use of common drugs in the treatment of such diseases prompt us to further survey the molecular biology of Leishmania parasites and cancer cells. The information regarding common expressed proteins, as possible therapeutic targets, in Leishmania parasites and cancer cells is scarce. Therefore, the current study reviews proteins, and investigates the regulation and functions of several key proteins in Leishmania parasites and cancer cells. The up- and down-regulations of such proteins were mostly related to survival, development, pathogenicity, metabolic pathways and vital signalling in Leishmania parasites and cancer cells. The presence of common expressed proteins in Leishmania parasites and cancer cells reveals valuable information regarding the possible shared mechanisms of pathogenicity and opportunities for therapeutic targeting in leishmaniasis and cancers in the future.
"The migration process is impeded by different challenges. Refugees must deal with their own traumatic experiences, which are intimate and personal but also relate to collective trauma that can destroy a sense of belonging to a community and weaken shared values. In addition to multiple traumas experienced in their country, refugees face the trauma of migration itself and the dramatic events that occur during migration. We argue that every migration process constitutes a traumatic experience marked by a rupture with the country of origin, by the modification of relational links, and by difficulties in cultural identification. In these situations, the parent-child relationship might be severely compromised. Children in migration are exposed to a particular vulnerability described by the concept of “exposed child”. We address the sequelae of the disruption of cultural meaning systems and cultural belonging invoked by collective violence and by migration itself, focusing on a specific therapeutic device for families. We illustrate the theoretical elaboration of this device with a clinical vignette."
The DHVI Division of Structural Biology seeks to use atomic level structural information for design of an effective HIV-1 vaccine. Through visualization of the HIV-1 envelope (Env) and its interactions with the human immune system, we obtain structural information that we translate into the rational development vaccine immunogens
We use negative stain electron microscopy (NSEM), cryo-electron microscopy (cryo-EM), and x-ray crystallography as the major structural techniques for visualization of HIV-1 Env, and combine these with biochemical and biophysical studies, as well as computational methods to obtain a basic understanding of the functions and interactions of the HIV-1 Env.
1.The DHVI NSEM pipeline runs on a daily basis to quality control vaccine immunogens for animal studies and other applications. Offering rapid sample turnover and economical operations, the NSEM pipeline is the most widely utilized resource of the DHVI Division of Structural Biology. Over the last year, the NSEM team has focused efforts on improving operational speed and data processing allowing high-quality visualization of a large variety of samples including HIV-1 Env immunogens, antibodies, nanoparticles, and VLPs. In the last year we have also expanded our NSEM studies to the analyses of serum samples and mucosal fluids.
2. To understand the mechanism of HIV-1 entry we have determined structures of HIV-1 entry intermediates. We have determined a 3.8 Å resolution structure of a single CD4 bound to a closed HIV-1 Env trimer revealing new contacts of CD4 with Env. We have also structurally characterized an Env designed to prevent CD4-induced rearrangements by targeted disruption of an allosteric network modulating Env conformational changes.
3. We have structurally characterized the HIV-1 glycan-V3 targeting DH270 Broadly Neutralizing Antibody Lineage. The structures revealed movements in the V1 loop and interactive glycans, shifts in antibody orientations, antibody VH-VL orientations, and antibody elbow angles, as the lineage progressed to maturation.
4. We have solved a structure in complex with the HIV-1 Env immunogen Man5-enriched CH505.N279K.G458Y.SOSIP.664 of the unmutated common ancestor (UCA) of the HIV-1 CD4-binding site targeting CH235 Broadly Neutralizing Antibody Lineage. The structure revealed interactions of the N279K and G458Y mutations with the CDR L3 loop of CH235 UCA thus providing a structural understanding of the role of these mutations in facilitating binding to the CH235 UCA. (see also Henderson et al abstract)
5. Using NSEM and cryo-EM we have characterized the structural properties of a novel class of 2G12-mimetic, yet non domain-swapped Fab dimer glycan-reactive (FDG) antibodies. These studies showed that the Fab-dimerized 2G12-like motif is more common than previously thought, and that creation of a Fab-dimerized paratope for an HIV-1 neutralizing antibody does not require VH domain-swapping.
6. Finally, the structural team is an integral part of the CHAVD Kalma Immunogen Design Team, wherein we are defining the structural basis of bnAb affinity maturation to guide sequential immunogen design.
These results highlight the power of structural information on HIV-1 vaccine design, from leveraging a basic understanding of HIV-1 entry mechanism for immunogen design, to rapid visualization of Env immunogens by NSEM for quality control, discovery of novel antibody interactions, and atomic level visualization of antibody/Env interactions.
Plasmodium falciparum is the main cause of severe malaria in humans that can lead to death. There is growing evidence of drug-resistance in P. falciparum treatment, and the design of effective vaccines remains an ongoing strategy to control the disease. On the other hand, the recognition of specific diagnostic markers for P. falciparum can accelerate the diagnosis of this parasite in the early stages of infection. Therefore, the identification of novel antigenic proteins especially by proteomic tools is urgent for vaccination and diagnosis of P. falciparum. The proteome diversity of the life cycle stages of P. falciparum, the altered proteome of P. falciparum-infected human sera and altered proteins in P. falciparum-infected erythrocytes could be proposed as appropriate proteins for the aforementioned aims. Accordingly, this review highlights and proposes different proteins identified using proteomic approaches as promising markers in the diagnosis and vaccination of P. falciparum. It seems that most of the candidates identified in this study were able to elicit immune responses in the P. falciparum-infected hosts and they also played major roles in the life cycle, pathogenicity and key pathways of this parasite.
High-grade gliomas (HGGs) are aggressive tumors that inevitably recur due to their diffusely infiltrative nature. Intraoperative adjuncts such as 5-aminolevulinic acid (5-ALA) have shown promise in increasing extent of resection. As the prospect of increased use of 5-ALA rises, a systematic overview of the health economics of this adjunct is critical.
Medline, EMBASE, Centre for Reviews and Dissemination, EconPapers, and Cochrane databases were searched for keywords relating to glioma, cost-effectiveness, and 5-ALA. Primary studies reporting on the health economics or cost-effectiveness of 5-ALA compared to white light surgery in HGG were included. Quality was assessed using the British Medical Journal guidelines.
Three studies were identified. All were European and conducted from the perspective of national healthcare systems. Two studies demonstrated the cost-utility of 5-ALA compared to white light (C$12,817 and C$13,508/quality-adjusted life-years (QALYs)). One assessed the cost-utility per gross total resection (C$6,813). Both these values were below the national cost-effectiveness thresholds for each respective study. The third study demonstrated no significant difference in cost of 5-ALA in glioblastoma resection (C$14,732) compared to prior to its routine use (C$15,936). The quality of these studies ranged from moderate to average. None of these studies considered patient perspective or indirect costs in their analysis.
Growing evidence exists examining the health economic benefit of 5-ALA as an intraoperative adjunct for HGG resection. Additional studies within the Canadian context using 5-ALA, specifically incorporating patient and societal perspectives into the cost-utility analyses, are necessary to solidify this line of evidence.
HAJRI M., HALAYEM S., LAKHAL M.H., MANSOURI A., ABBES Z., OTHMAN S., BOUDEN A.
Advancements in human genetics are revealing a large number of genetic variants involved in Autism spectrum disorder (ASD). This genetic variability affects mostly proteins involved in synaptic function.
The Medline database was searched using the following keywords: ‘synapses’; ‘autism’. Animal as well as human models of ASD were included.
Nowadays, ASD are considered genetically influenced neurodevelopmental disorders, with abundant evidence pointing to dysfunction at the level of the synapse in the early stages of cerebral development. Potential mechanisms underlying ASD are neuroanatomical abnormalities, extracellular factors, excitatory and inhibitory imbalance and synaptic signaling.
I. Neuroanatomical abnormalities
Mutations of Tsc1 (tuberous sclerosis 1) and nlgn3 (neuroligin3) lead to alterations of synapses in the cerebellum and could explain signs of autism in mice.
II. Extracellular factors
Growth factors and neurotrophic factors are associated with ASD such as: HGF, BDNF and WNT2.
III. Excitatory and inhibitory imbalance
Defects in synaptic proteins would lead to defective transmissions at excitatory and inhibitory synapses, a key mechanism implicated in ASD. Synaptic molecules involved: neuroligin, neurexin, shank, but also Glutamatergic system, GABAergic system and Serotonergic system.
IV. Synaptic signaling
NF1 (Neurofibromin 1), TSC1/TSC2 (tuberous sclerosis complex 1 and 2), and PTEN(phosphatase end tensin homolog) are tumor suppressors genes associated with ASD.
An alternative but not mutually exclusive hypothesis is that environmental factors interact with genetic susceptibilities to influence ASD risk, clinical phenotype and/or treatment outcome.
About 60 % of the subjects with a first episode of major depression will present a second episode lifetime. Thus, it is important to determine the risk factors of recurrence.
To identify the risk factors of depressive recurrence.
It is a retrospective study conducted in university hospital of Mahdia including 150 patients hospitalized in psychiatric ward for major depressive disorder according to DSM-IV-TR. Data were collected using a questionnaire of 89 items. Statistical analysis was done using the Kaplan-Meier method. The Cox test was used to check for recurrence risk factors.
The sample was divided into:
Group 1: diagnosed with major depressive disorder, single episode (MDD, n = 63)
Group 2: diagnosed with recurrent major depressive disorder (MDDr, n = 87)
Family history of mood disorders were found in 25,4% and 59,7% of patients in respectively group 1 and 2. The age of onset was less than 25 years in 34.48% of Group 2 against 22.2% in group 1. Residual symptoms were similar in both groups. The mean time to recurrence was 109 months. Multivariate analysis retained 5 risk factors: early age of onset disorders (p = 0.02), family history of mood disorder (p = 0.04), the severity of depressive index episode (p = 0.03), the persistence of residual symptoms (p = 0.02) and early interruption of the treatment (p = 0.04).
The identification of risk factors for recurrence before a first depressive episode is very important to prevent recurrence and chronicity.
Pegmatites and associated granitoids are integral parts of the Alvand plutonic complex in the Sanandaj–Sirjan zone, Iran. Whole rock major- and trace-element lithogeochemistry together with zircon U–Pb geochronology and zircon geochemistry are examined to evaluate the petrogenesis of sapphire-bearing pegmatites and other peraluminous pegmatites in the region. Pegmatites vary in their chemical compositions from mostly peraluminous, high-K calc-alkaline to shoshonitic signatures. A rare variety of extremely peraluminous sapphire-bearing syenitoid pegmatite (Al2O3 > 30 wt %; A/CNK > 2) exists. This silica-undersaturated pegmatite and its sapphire crystals have a primary igneous origin. U–Pb zircon geochronology of three separate samples from this pegmatite indicates the following ages: 168 ± 1 Ma, 166 ± 1 Ma and 164 ± 1 Ma. The zircon grains have notable amounts of Hf (up to 17 200 ppm), U (up to 13 580 ppm), Th (up to 5148 ppm), Y (up to 4764 ppm) and ∑REE (up to 2534 ppm). There is a positive correlation between Hf and Th, Nb and Ta, U and Th, and Y and HREE and a negative correlation between Hf and Y values in the zircons. These zircons exhibit pronounced positive Ce anomalies (Ce/Ce* = 1.15–68.06) and negative Eu anomalies (Eu/Eu* = 0.001–0.56), indicative of the relatively oxidized conditions of the parent magma. Ti-in-zircon thermometry reveals temperatures from as low as ~683 °C up to ~828 °C (average = 755° ± 73 °C). Zircon and monazite saturation equilibria are also consistent with these temperatures. Zircon grains are magmatic (average La < 1.5, (Sm/La)N > 100 and Th/U > 0.7), with chemical characteristics similar to zircons from continental crust.
To examine detail depth dose characteristics of ideal proton beams using the GATE Monte Carlo technique.
In this study, in order to improve simulation efficiency, we used pencil beam geometry instead of parallel broad-field geometry. Depth dose distributions for beam energies from 5 to 250 MeV in a water phantom were obtained. This study used parameters named Rpeak, R90, R80, R73, R50, full width at half maximum (FWHM), width of 80–20% distal fall-off (W(80–20)) and peak-to-entrance ratio to represent Bragg peak characteristics. The obtained energy–range relationships were fitted into third-order polynomial formulae. The present study also used the GATE Monte Carlo code to calculate the stopping power of proton pencil beams in a water cubic phantom and compared results with the National Institute of Standards and Technology (NIST) standard reference database.
The study results revealed deeper penetration, broader FWHM and distal fall-off and decreased peak-to-entrance dose ratio with increasing beam energy. Study results for monoenergetic proton beams showed that R73 can be a good indicator to characterise a range of incident beams. These also suggest FWHM is more sensitive than W(80–20) distal fall-off in finding initial energy spread. Furthermore, the difference between the obtained stopping power from simulation and NIST data almost in all energies was lower than 1%.
Detail depth dose characteristics for monoenergetic proton beams within therapeutic energy ranges were reported. These results can serve as a good reference for clinical practitioners in their daily practice.
Background: Molecular signatures are being increasing used to classify central nervous system (CNS) tumors with incorporation into World Health Organization (WHO) classifications. A recently published genome-wide DNA methylation-based CNS tumor classifier assisted in diagnostically challenging cases. However its impact on patient care has not been reported, limiting translation to other centres. Methods: All 55 challenging CNS tumour diagnoses over three years underwent DNA methylation profiling. Tumor classification along with copy number variant (CNV) plot results were integrated with histopathological findings to determine final diagnoses and corresponding clinical impact was assessed. Results: After methylation profiling 46/55 (84%) received clinically relevant diagnostic changes, 30 (55%) with a new diagnosis or resolved differential diagnosis and 16 (29%) with clinically important molecular diagnostic or subtyping changes. WHO grade changed in 15 (27%), with two-thirds upgraded. Nine new IDH mutations in gliomas, four new molecular subtypes in medulloblastomas/ependymomas, and three false positive 1p/19q codeletions were identified. Patient care was directly changed by methylation profiling in 7/47 (15%) followed-up cases to avoid unnecessary treatment in three, insufficient treatment in three, and medically assisted death in one. Conclusions: This real-world use of methylation-based CNS tumor classification substantially impacts patient care for diagnostically challenging tumors and also avoids misdiagnosis-related uncessary resource use.
Background: Challenges in predicting risk of recurrence for individual patients with meningioma limits appropriate selection of patients who may benefit from adjuvant radiation therapy to delay recurrence. Here, we aimed to develop and validate a combined clinicomolecular predictor of early recurrence for individual patients with meningiomas. Methods: A methylation-based predictor of 5-year recurrence-free-survival (RFS) was developed using DNA-methylation profiles from a training cohort of 228 patients. Model performance was compared to a standard-of-care histological-based model using three independent cohorts (N=54 ;N=140; N=64 patients). Subsequently, a nomogram that integrated the methylome-based predictor with prognostic clinical factors was developed and validated. Results: The methylome-based predictor of 5-year RFS performed favorably compared to a grade-based predictor when tested using the three validation cohorts (ΔAUC=0.10, 95%CI 0.03 – 0.018) and was independently associated with RFS on multivariable Cox regression analysis (HR=3.6, 95%CI 1.8–7.2, P<0.001). A nomogram combining the methylome-predictor with clinical factors demonstrated greater discrimination for recurrence than a nomogram using clinical factors alone (ΔAUC=0.25, 95%CI 0.22–0.27) and resulted in two risk groups with distinct recurrence patterns (HR=7.7, 95%CI 5.3–11.1, P<0.001) and clinical implications. Conclusions: Our validated models provide important novel prognostic information that could be used to individualize decisions regarding post-operative therapeutic interventions in meningioma.
Objective: To summarize the findings of randomized controlled trials (RCTs) on the efficacy and safety of vitamins and minerals for migraine prophylaxis. Methods: We systematically searched bibliographic databases and relevant websites for parallel and crossover RCTs reporting efficacy and/or safety of vitamins and/or minerals for migraine prophylaxis. Our primary outcomes were migraine frequency (number of attacks) and duration (hours). Secondary outcomes were severity (intensity), days with migraine, and adverse events. Meta-analysis was conducted when analyzable data were available from at least two trials. Results: Eighteen placebo-controlled trials met our eligibility criteria. Only coenzyme Q10 and magnesium contributed to meta-analyses. In adults, compared with placebo, coenzyme Q10 did not significantly decrease migraine frequency (mean difference (MD) −0.44 (−2.14 to 1.26); I2 53%; 2 trials; 97 participants; moderate strength of the evidence), duration (MD −1.97 (−4.82 to 0.87); I2 0%; 2 trials; 97 participants; moderate strength of the evidence), or severity (ratio of means (RoM) −0.05 (−0.20 to 0.11); I2 0%; 2 trials; 97 participants). In adults, compared with placebo, magnesium did not significantly decrease migraine severity (RoM −0.17 (−0.36 to 0.02); I2 48%; 3 trials; 226 participants; low strength of the evidence). Meta-analysis of other vitamins and minerals, and other outcomes were not feasible due to a lack of sufficiently reported data. Conclusions: Based on insufficient evidence, it is unknown if coenzyme Q10 and magnesium are effective for migraine prophylaxis in adults. High-quality, adequately powered RCTs are needed to fully evaluate the efficacy and safety of vitamins and minerals for migraine prophylaxis.
In this study, polyploidy level was determined by flow cytometry analysis. The effect of polyploidy by colchicine treatment was examined on the growth parameters, malondealdehyde (MDA), as well as activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) in response to different levels of salinity in Dunaliella salina. The results of algal growth indicated that 3 M NaCl was the optimal concentration of salt, since the highest enhancement in fresh and dry weight, chlorophyll and carotenoids, soluble sugar, glycerol, protein and starch content was observed in comparison to other concentrations. The amount of these metabolites declined in the concentrations under optimum salinity. The least and highest amounts of MDA were observed at 1 and 4 M NaCl respectively. Polyploidy in optimum concentration of salt, caused further increment of the above growth parameters. In relation to this, in most cases, treatment of 0.1% colchicine was most effective. The beneficial effects of polyploidy in non-optimal conditions were also found in some parameters such as biomass, chlorophyll, carotenoids, proteins and starch. Furthermore, the activity of antioxidant enzymes CAT, SOD and POD showed a positive significant correlation with salt stress and these were maximized at 4 M NaCl. Polyploidy (especially colchicine 0.1%) affected activity of these antioxidant enzymes in some concentrations of salt. Overall, our results suggest that the microalgae has significantly different responses to salt stress based on ploidy levels.
To validate the Geant4 Application for Tomographic Emission (GATE) Monte Carlo simulation code by calculating the proton beam range in the therapeutic energy range.
Materials and methods
In this study, the GATE code which is based on Geant4 was used for simulation. The proton beams in the therapeutic energy range (5–250 MeV) were simulated in a water medium, and then compared with the data from National Institute of Standards and Technology (NIST) in order to investigate the accuracy of different physics list available in the GATE code. In addition, the optimal value of SetCut was assessed.
In all energy ranges, the QBBC physics had a greater deviation in the ranges relative to the NIST data. With respect to the range calculation accuracy, the QGSP_BIC_EMY and QGSP_BERT_HP_EMY physics were in the range of statistical uncertainty; however, QGSP_BIC_EMY produced better results using the least squares. Based on an investigation into the range calculation precision and simulation efficiency, the optimal SetCut was set at 0·1 mm.
Based on an investigation into the range calculation precision and simulation yield, the QGSP_BIC_EMY physics and the optimal SetCut was recommended to be 0·1 mm.
A time-optimal problem for redundantly actuated robots moving on a specified path is a challenging problem. Although the problem is well explored and there are proposed solutions based on phase plane analysis, there are still several unresolved issues regarding calculation of solution curves. In this paper, we explore the characteristics of the maximum velocity curve and propose an efficient algorithm to establish the solution curve. Then we propose a straightforward method to calculate the maximum or minimum possible acceleration on the path based on the pattern of saturated actuators, which substantially reduces the computational cost. Two numerical examples are provided to illustrate the issues and the solutions.
The present study proposed and tested a revision of the self-guides outlined in the L2 motivational self system (Dörnyei, 2005, 2009). Covering the previous conceptualization and measurement issues, ideal L2 self and ought-to L2 self were bifurcated by own and other standpoints, and reoperationalized based on the fundamental tenets of self-discrepancy theory (Higgins, 1987) and regulatory focus theory (Higgins, 1997). Confirmatory factor analysis supported the fitness of the model and its superiority over three alternative models based on data collected from 257 international students learning English as a second language at a major North American university. Multiple regression results showed that ought L2 self/own was the strongest predictor of motivated behavior. Ideal L2 self/own, ought L2 self/other, and ideal L2 self/other were the next predictors in order of strength. Furthermore, ideal L2 self/own predicted an eager strategic inclination in L2 behavior, whereas ought L2 self/own predicted a vigilant strategic inclination, supporting the core principle of the regulatory focus theory that individuals with different regulatory orientations pursue their goals in qualitatively different manners.
BACKGROUND: Meningiomas are the most common primary benign brain tumors in adults. Given the extended life expectancy of most meningiomas, consideration of quality of life (QOL) is important when selecting the optimal management strategy. There is currently a dearth of meningioma-specific QOL tools in the literature. OBJECTIVE: In this systematic review, we analyze the prevailing themes and propose toward building a meningioma-specific QOL assessment tool. METHODS: A systematic search was conducted, and only original studies based on adult patients were considered. QOL tools used in the various studies were analyzed for identification of prevailing themes in the qualitative analysis. The quality of the studies was also assessed. RESULTS: Sixteen articles met all inclusion criteria. Fifteen different QOL assessment tools assessed social and physical functioning, psychological, and emotional well-being. Patient perceptions and support networks had a major impact on QOL scores. Surgery negatively affected social functioning in younger patients, while radiation therapy had a variable impact. Any intervention appeared to have a greater negative impact on physical functioning compared to observation. CONCLUSION: Younger patients with meningiomas appear to be more vulnerable within social and physical functioning domains. All of these findings must be interpreted with great caution due to great clinical heterogeneity, limited generalizability, and risk of bias. For meningioma patients, the ideal QOL questionnaire would present outcomes that can be easily measured, presented, and compared across studies. Existing scales can be the foundation upon which a comprehensive, standard, and simple meningioma-specific survey can be prospectively developed and validated.
Background: Venous thromboembolism (VTE) is a serious complication following severe TBI, however, anticoagulant prophylaxis is often withheld over concerns of intracranial hemorrhage (ICH) progression. We analyzed practice patterns and outcomes among severe TBI patients and systematically reviewed the literature for studies of anticoagulant prophylaxis after severe TBI. Methods: We prospectively screened consecutive patients with severe TBI (highest GCS≤8 from time of injury to ICU admission) admitted to a Level-I trauma centre between Oct 1,2015–Sept 30,2016 to assess type/timing of anticoagulant prophylaxis, rates of new VTE and ICH progression. Results: We identified 64 eligible patients with severe TBI. Most (53;83%) received anticoagulant prophylaxis, initiated ≥3d after TBI in 67%. Ten (16%) developed VTE during hospitalization; 8 started prophylaxis prior to VTE. No significant difference was observed in VTE incidence or ICH progression between patients with early prophylaxis (<3d) vs.later (≥3d). Our systematic review identified 5 studies of heterogeneous quality/design, with reported VTE incidence of 11-30% in patients without anticoagulant prophylaxis and 5-10% in patients with prophylaxis. Conclusions: VTE is a common complication after severe TBI despite routine use of anticoagulant prophylaxis. Anticoagulant prophylaxis is often started late (≥3d) post-injury. The relative benefits of early prophylaxis versus possible risks of ICH progression should be directly compared in an appropriately powered RCT.
Glioblastomas are the most frequent and aggressive primary brain tumor in adults and despite recent therapeutic advances, they are resistant to treatment. Increasing malignancy of gliomas correlates with an increase in cellularity and a poorly organized tumor vasculature, leading to insufficient blood supply, hypoxic areas, and ultimately to the formation of necrosis. Hypoxia induces direct or indirect changes in the biology of solid tumor and their microenvironment through the activation of HIF transcription factors, leading to increased aggressiveness and tumor resistance to therapy. Not much is known about the epigenetic alterations induced by hypoxia and how they could alter tumor biology. In the present study, we have utilized PIMO as a specific marker of hypoxia in glioblastoma patients, treated with PIMO preoperatively. We have estimated PIMO positivity in each tumor (5-45%) and determined that it positively correlates with the hypoxia marker CA IX (r=0.57). In addition, 10 surgical PIMO cases were dissociated, immune labeled using PIMO antibody, followed by DNA isolation and methylation profiling. Our analysis of differentially top 4000 differentially methylated probes suggests that PIMO-positive (hypoxic) cells are differentially methylated compared to the PIMO-negative cells and these changes are associated with genes involved in hypoxic cellular response. We will validate these findings in additional glioblastoma cases and assess the mechanism of these epigenetic alterations in vitro in glioma stem cell culture conditions and upon exposure of the cells hypoxic conditions.
Observational studies reported potential associations between different dietary patterns and the risk of metabolic syndrome (MetS); however, a consistent perspective has not been established to date. The current systematic review and meta-analysis aimed to evaluate the relationship between a posteriori dietary patterns and MetS by pooling available data.
MEDLINE and EMBASE databases were searched for relevant articles published up to July 2015 with no time restriction and with English language restriction. Two independent reviewers completed study selection and data extraction. Random-effects models (DerSimonian–Laird method) were used to pool effect sizes of eligible studies. The potential sources of heterogeneity were assessed using the I2 statistic.
Nineteen papers that identified dietary patterns using an a posteriori method were selected and included in the meta-analysis. The ‘Healthy/Prudent’ dietary pattern was inversely associated with risk of MetS (OR=0·89; 95 % CI 0·84, 0·94, P=0·002). In contrast, the ‘Unhealthy/Western’ dietary pattern had a significant positive association with risk of MetS (OR=1·16; 95 % CI 1·11, 1·22, P<0·001).
Our findings provide evidence that greater adherence to a healthy/prudent dietary pattern is associated with a lower risk of MetS, while an unhealthy/Western dietary pattern is associated with increased risk of MetS. These data suggest that a diet based on healthy food choices is also beneficial for prevention of MetS.