Increased serum levels of eotaxin/CCL11 in late-stage patients with bipolar disorder: an accelerated aging biomarker?

BACKGROUND: Bipolar disorder (BD) is commonly comorbid with many medical disorders including atopy, and appears characterized by progressive social, neurobiological, and functional impairment associated with increasing number of episodes and illness duration. Early and late stages of BD may present different biological features and may therefore require different treatment strategies. Consequently, the aim of this study was to evaluate serum levels of eotaxin/CCL11, eotaxin-2/CCL24, IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, IFNγ, BDNF, TBARS, carbonyl, and GPx in a sample of euthymic patients with BD at early and late stages compared to controls. METHODS: Early-stage BD patients, 12 late-stage patients, and 25 controls matched for sex and age were selected. 10mL of peripheral blood was drawn from all subjects by venipuncture. Serum levels of BDNF, TBARS, carbonyl content, glutathione-peroxidase activity (GPx), cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and IFNγ), and chemokines (eotaxin/CCL11 and eotaxin-2/CCL24) were measured. RESULTS: There were no demographic differences between patients and controls. No significant differences were found for any of the biomarkers, except chemokine eotaxin/CCL11, whose serum levels were higher in late-stage patients with BD when compared to controls (p=0.022; Mann-Whitney U test). LIMITATIONS: Small number of subjects and use of medication may have influenced in our results. CONCLUSION: The present study suggests a link between biomarkers of atopy and eosinophil function and bipolar disorder. These findings are also in line with progressive biological changes partially mediated by inflammatory imbalance, a process referred to as neuroprogression.

A new design concept for knitted external vein-graft support mesh

Autologous vein-graft failure significantly limits the long-term efficacy of coronary artery bypass procedures. The major cause behind this complication is biomechanical mismatch between the vein and coronary artery. The implanted vein experiences a sudden increase (10-12 fold) in luminal pressures. The resulting vein over-distension or 'ballooning' initiates wall thickening phenomenon and ultimate occlusion. Therefore, a primary goal in improving the longevity of a coronary bypass procedure is to inhibit vein over-distension using mechanical constriction. The idea of using an external vein-graft support mesh has demonstrated sustained benefits and wide acceptance in experimental studies. Nitinol based knitted structures have offered more promising mechanical features than other mesh designs owing to their unique loosely looped construction. However, the conventional plain knit construction still exhibits limitations (radial compliance, deployment ease, flexibility, and bending stresses) which limit this design from proving its real clinical advantage. The new knitted mesh design presented in this study is based on the concept of composite knitting utilising high modulus (nitinol and polyester) and low modulus (polyurethane) material components. The experimental comparison of the new design with a plain knit design demonstrated significant improvement in biomechanical (compliance, flexibility, extensibility, viscoelasticity) and procedural (deployment limit) parameters. The results are indicative of the promising role of new mesh in restoring the lost compliance and pulsatility of vein-graft at high arterial pressures. This way it can assist in controlled vein-graft remodelling and stepwise restoration of vein mechanical homoeostasis. Also, improvement in deployment limit parameter offers more flexibility for a surgeon to use a wide range of vein diameters, which may otherwise be rendered unusable for a plain knit mesh.

The concept of physical limitations in knee osteoarthritis: as viewed by patients and health professionals

Objective: To comprehensively identify components of the physical limitation concept in knee osteoarthritis (OA) and to rate the clinical importance of these using perspectives of both patients and health professionals.Design: Concept mapping, a structured group process, was used to identify and organize data in focus groups (patients) and via a global web-based survey (professionals). Ideas were elicited through a nominal group technique and then organized using multidimensional scaling, cluster analysis, participant validation, rating of clinical importance, and thematic analyses to generate a conceptual model of physical limitations in knee OA. Results: Fifteen Danish patients and 200 international professionals contributed to generating the conceptual model. Five clusters emerged: ‘Limitations/physical deficits’; ‘Everyday hurdles’; ‘You’re not the person you used to be’; ‘Need to adjust way of living’; and ‘External limitations,’ each with sub-clusters. Patients generally found their limitations more important than the professionals did. Conclusion: Patients and professionals agreed largely on the physical limitation concept in knee OA. Some limitations of high importance to patients were lower rated by the professionals, highlighting the importance of including patients when conceptualizing patient outcomes. These data offer new knowledge to guide selection of clinically relevant outcomes and development of outcome measures in knee OA.

Genomics based biomarker discovery in oral squamous cell carcinoma

 The present thesis showed signaling mechanisms and pathways essential for oral cancer progression through genomics approach. It has identified markers that are of diagnostic, prognostic and therapeutic importance. It has also shown that aspirin is a potential drug in oral cancer treatment.

Peripheral vascular endothelial growth factor as a novel depression biomarker: a meta-analysis

BACKGROUND: The neurotrophic hypothesis of major depressive disorder (MDD) postulates that the pathology of this illness incorporates a down-regulation of neurotrophin signaling. Brain-derived neurotrophic factor (BDNF) is the most studied neurotrophic mediator regarding the neurobiology of MDD. Nevertheless, emerging evidence has implicated the multi-competent angiogenic and neurogenic molecule - vascular endothelial growth factor (VEGF) - in hippocampal neurogenesis and depression pathophysiology. OBJECTIVE: To compare peripheral levels of VEGF between individuals with MDD and healthy controls. METHODS: We performed a systematic review and meta-analysis of original studies measuring peripheral levels of VEGF in participants with MDD compared to healthy controls. We searched the Pubmed/MEDLINE, EMBASE and PsycInfo databases for studies published in any language through December 16th, 2014. RESULTS: Fourteen studies met eligibility criteria (N=1633). VEGF levels were significantly elevated in individuals with MDD when compared to healthy controls (Hedges's g=0.343; 95% CI: 0.146-0.540; P<0.01). Funnel plot inspection and the Egger's test did not provide evidence of publication bias. A significant degree of heterogeneity was observed (Q=38.355, df=13, P<0.001; I(2)=66.1%), which was explored through meta-regression and subgroup analyses. Overall methodological quality, sample for assay (plasma versus serum), as well as the matching of MDD and control samples for age and gender emerged as significant sources of heterogeneity. CONCLUSIONS: Taken together, extant data indicate that VEGF shows promise as a biomarker for MDD, and supports that this mediator may be involved in neuroplasticity mechanisms underlying the pathophysiology of MDD.

Regional homogeneity of resting-state brain abnormalities in violent juvenile offenders: A biomarker of brain immaturity?

The authors investigated whether male violent juvenile offenders demonstrate any differences in local functional connectivity indicative of delayed maturation of the brain that may serve as a biomarker of violence. Twenty-nine violent juvenile offenders and 28 age-matched controls were recruited. Regional homogeneity (ReHo) method was used to analyze resting-state magnetic resonance images. Violent offenders showed significantly lower ReHo values in the right caudate, right medial prefrontal cortex, and left precuneus, and higher values in the right supramarginal gyrus than the controls. These regions had both high sensitivity and specificity in distinguishing between the two groups suggesting that dysfunction in these regions can be used to correctly classify those individuals who are violent. Dysfunction in the right medial prefrontal-caudate circuit may, therefore, represent an important biomarker of violence juvenile males.

Modeling intermittent cycling performance in hypoxia using the critical power concept

PURPOSE: This study investigated the efficacy of an intermittent critical power model, termed the "work-balance" (W'BAL) model, during high-intensity exercise in hypoxia. METHODS: Eleven trained, male cyclists (mean ± SD; age 27 ± 6.6 yr, V[Combining Dot Above]O2peak 4.79 ± 0.56 L.min) completed a maximal ramp test and a 3 min "all-out" test to determine critical power (CP) and work performed above CP (W'). On another day an intermittent exercise test to task failure was performed. All procedures were performed in normoxia (NORM) and hypoxia (HYPO; FiO2 ≈ 0.155) in a single-blind, randomized and counter-balanced experimental design. The W'BAL model was used to calculate the minimum W' (W'BALmin) achieved during the intermittent test. W'BALmin in HYPO was also calculated using CP + W' derived in NORM (N+H). RESULTS: In HYPO there was an 18% decrease in V[Combining Dot Above]O2peak (4.79 ± 0.56 vs 3.93 ± 0.47 L.min ; P<0.001) and a 9% decrease in CP (347 ± 45 vs 316 ± 46 W; P<0.001). No significant change for W' occurred (13.4 ± 3.9 vs 13.7 ± 4.9 kJ; P=0.69; NORM vs HYPO). The change in V[Combining Dot Above]O2peak was significantly correlated with the change in CP (r = 0.72; P=0.01). There was no difference between NORM and HYPO for W'BALmin (1.1 ± 0.9 kJ vs 1.2 ± 0.6 kJ). The N+H analysis grossly overestimated W'BALmin (7.8 ± 3.4 kJ) compared with HYPO (P<0.001). CONCLUSION: The W'BAL model produced similar results in hypoxia and normoxia, but only when model parameters were determined under the same environmental conditions as the performance task. Application of the W'BAL model at altitude requires a modification of the model, or that CP and W' are measured at altitude.