Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Effects of CuO additives and sol-gel technique on NiNb2O6 dielectric ceramics for LTCC application

The effects of CuO additives and sol–gel method synthesis on the sintering behavior, microstructure and the microwave dielectric properties of NiNb2O6 ceramics were investigated systematically. The NiNb2O6 ceramics were synthesized with traditional solid state method and sol–gel method, and the CuO additives were used in the solid state method for comparison. The sintering temperature of NiNb2O6 ceramics with the highest densification can be effectively reduced from about 1275 °C to 1050 and 1100 °C respectively by using CuO additions and sol–gel technique. To study their applicability in low temperature co-fired ceramic technology, dielectric properties have been characterized. The dielectric properties exhibited a significant dependence on the sintering condition, composition and crystal structure of the ceramics. In particular, the 2.5 wt% CuO-doped NiNb2O6 ceramics sintered at 1050 °C have excellent microwave dielectric properties: εr = 21.45, Q × f = 23,531 GHz, τf = −27.9 ppm/°C. While the NiNb2O6 ceramics prepared by sol–gel method obtain microwave dielectric properties as: εr = 19.16, Q × f = 11,149 GHz, τf = −27.3 ppm/°C after sintered at 1100 °C for 2 h

Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer

Background Squamous cell lung carcinomas account for approximately 25% of new lung carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma. Methodology/Principal Findings Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genes–WHSC1L1, LETM2, and FGFR1–is amplified in 3% of lung adenocarcinomas and 21% of squamous cell lung carcinomas. Furthermore, we demonstrated that a non-small cell lung carcinoma cell line harboring focal amplification of FGFR1 is dependent on FGFR1 activity for cell growth, as treatment of this cell line either with FGFR1-specific shRNAs or with FGFR small molecule enzymatic inhibitors leads to cell growth inhibition. Conclusions/Significance These studies show that FGFR1 amplification is common in squamous cell lung cancer, and that FGFR1 may represent a promising therapeutic target in non-small cell lung cancer.Novartis Pharmaceuticals CorporationAmerican Lung AssociationUniting Against Lung CancerSara Thomas Monopoli FundSeaman FoundationIndia. Dept. of BiotechnologyNational Lung Cancer Partnershi

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Altered processing of sensory stimuli in patients with migraine

Migraine is a cyclic disorder, in which functional and morphological brain changes fluctuate over time, culminating periodically in an attack. In the migrainous brain, temporal processing of external stimuli and sequential recruitment of neuronal networks are often dysfunctional. These changes reflect complex CNS dysfunction patterns. Assessment of multimodal evoked potentials and nociceptive reflex responses can reveal altered patterns of the brain's electrophysiological activity, thereby aiding our understanding of the pathophysiology of migraine. In this Review, we summarize the most important findings on temporal processing of evoked and reflex responses in migraine. Considering these data, we propose that thalamocortical dysrhythmia may be responsible for the altered synchronicity in migraine. To test this hypothesis in future research, electrophysiological recordings should be combined with neuroimaging studies so that the temporal patterns of sensory processing in patients with migraine can be correlated with the accompanying anatomical and functional changes

The role of inflammation in epilepsy.

Epilepsy is the third most common chronic brain disorder, and is characterized by an enduring predisposition to generate seizures. Despite progress in pharmacological and surgical treatments of epilepsy, relatively little is known about the processes leading to the generation of individual seizures, and about the mechanisms whereby a healthy brain is rendered epileptic. These gaps in our knowledge hamper the development of better preventive treatments and cures for the approximately 30% of epilepsy cases that prove resistant to current therapies. Here, we focus on the rapidly growing body of evidence that supports the involvement of inflammatory mediators-released by brain cells and peripheral immune cells-in both the origin of individual seizures and the epileptogenic process. We first describe aspects of brain inflammation and immunity, before exploring the evidence from clinical and experimental studies for a relationship between inflammation and epilepsy. Subsequently, we discuss how seizures cause inflammation, and whether such inflammation, in turn, influences the occurrence and severity of seizures, and seizure-related neuronal death. Further insight into the complex role of inflammation in the generation and exacerbation of epilepsy should yield new molecular targets for the design of antiepileptic drugs, which might not only inhibit the symptoms of this disorder, but also prevent or abrogate disease pathogenesis

Identification of Serum MicroRNAs as Novel Non-Invasive Biomarkers for Early Detection of Gastric Cancer

BACKGROUND: To investigate the potential of serum miRNAs as biomarkers for early detection of gastric cancer (GC), a population-based study was conducted in Linqu, a high-risk area of GC in China. METHODOLOGY/PRINCIPAL FINDINGS: All subjects were selected from two large cohort studies. Differential miRNAs were identified in serum pools of GC and control using TaqMan low density array, and validated in individual from 82 pairs of GC and control, and 46 pairs of dysplasia and control by real-time quantitative reverse transcription-polymerase chain reaction. The temporal trends of identified serum miRNA expression were further explored in a retrospective study on 58 GC patients who had at least one pre-GC diagnosis serum sample based on the long-term follow-up population. The miRNA profiling results demonstrated that 16 miRNAs were markedly upregulated in GC patients compared to controls. Further validation identified a panel of three serum miRNAs (miR-221, miR-744, and miR-376c) as potential biomarkers for GC detection, and receiver operating characteristic (ROC) curve-based risk assessment analysis revealed that this panel could distinguish GCs from controls with 82.4% sensitivity and 58.8% specificity. MiR-221 and miR-376c demonstrated significantly positive correlation with poor differentiation of GC, and miR-221 displayed higher level in dysplasia than in control. Furthermore, the retrospective study revealed an increasing trend of these three miRNA levels during GC development (P for trend<0.05), and this panel could classify serum samples collected up to 5 years ahead of clinical GC diagnosis with 79.3% overall accuracy. CONCLUSIONS/SIGNIFICANCE: These data suggest that serum miR-221, miR-376c and miR-744 have strong potential as novel non-invasive biomarkers for early detection of GC

Concurrent codes:a holographic-type encoding robust against noise and loss

Concurrent coding is an encoding scheme with 'holographic' type properties that are shown here to be robust against a significant amount of noise and signal loss. This single encoding scheme is able to correct for random errors and burst errors simultaneously, but does not rely on cyclic codes. A simple and practical scheme has been tested that displays perfect decoding when the signal to noise ratio is of order -18dB. The same scheme also displays perfect reconstruction when a contiguous block of 40% of the transmission is missing. In addition this scheme is 50% more efficient in terms of transmitted power requirements than equivalent cyclic codes. A simple model is presented that describes the process of decoding and can determine the computational load that would be expected, as well as describing the critical levels of noise and missing data at which false messages begin to be generated

A complementary method for detecting qi vacuity

<p>Abstract</p> <p>Background</p> <p>Qi vacuity (QV) is defined by traditional Chinese medicine as a loss of energy in the human body. An objective method for detecting QV was not available until recently, however. The automatic reflective diagnosis system (ARDK) is a device that detects human bioenergy through measuring skin conductance at 24 special acupoints on the wrists and ankles.</p> <p>Methods</p> <p>This study used the ARDK to measure skin conductance on 193 patients with QV and 89 sex- and age-matched healthy controls to investigate whether the device is useful in detecting QV. Patients diagnosed with QV have three or more of five symptoms or signs; symptom severity is measured on 5 levels and scored from 0 to 4 points. We compared the difference in the mean ARDK values between patients with QV and healthy controls, and further used linear regression analysis to investigate the correlation between the mean ARDK values and QV scores in patients diagnosed with QV.</p> <p>Results</p> <p>The mean ARDK values in patients with QV (30.2 ± 16.8 μA) are significantly lower than those of healthy controls (37.7 ± 10.8 μA; <it>P </it>< 0.001). A negative correlation was found between the mean ARDK values and QV scores (<it>r </it>coefficient = -0.61; <it>P </it>< 0.001). After adjusting for age, the decreased mean ARDK values in patients with QV showed a significant correlation with the QV scores.</p> <p>Conclusion</p> <p>These results suggest that the mean ARDK values reflect the severity of QV in patients diagnosed with the disorder. They also suggest that the bioenergy level of the human body can be measured by skin conductance. ARDK is a safe and effective complementary method for detecting and diagnosing QV.</p

Macular and serum carotenoid concentrations in patients with malabsorption syndromes

The carotenoids lutein and zeaxanthin are believed to protect the human macula by absorbing blue light and quenching free radicals. Intestinal malabsorption syndromes such as celiac and Crohn’s disease are known to cause deficiencies of lipid-soluble nutrients. We hypothesized that subjects with nutrient malabsorption syndromes will demonstrate lower carotenoid levels in the macula and blood, and that these lower levels may correlate with early-onset maculopathy. Resonance Raman spectrographic (RRS) measurements of macular carotenoid levels were collected from subjects with and without a history of malabsorption syndromes. Carotenoids were extracted from serum and analyzed by high performance liquid chromatography (HPLC). Subjects with malabsorption (n = 22) had 37% lower levels of macular carotenoids on average versus controls (n = 25, P < 0.001). Malabsorption was not associated with decreased serum carotenoid levels. Convincing signs of early maculopathy were not observed. We conclude that intestinal malabsorption results in lower macular carotenoid levels